Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

PubMed Central

Zhang, Wenli; Muck-Hausl, Martin; Wang, Jichang; Sun, Chuanbo; Gebbing, Maren; Miskey, Csaba; Ivics, Zoltan; Izsvak, Zsuzsanna; Ehrhardt, Anja

2013-01-01

We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models. PMID:24124483

Time Safety Margin: Theory and Practice

DTIC Science & Technology

2016-09-01

Basic Dive Recovery Terminology The Simplest Definition of TSM: Time Safety Margin is the time to directly travel from the worst-case vector to an...Safety Margin (TSM). TSM is defined as the time in seconds to directly travel from the worst case vector (i.e. worst case combination of parameters...invoked by this AFI, base recovery planning and risk management upon the calculated TSM. TSM is the time in seconds to di- rectly travel from the worst case

42 CFR 71.54 - Etiological agents, hosts, and vectors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Etiological agents, hosts, and vectors. 71.54 Section 71.54 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING FOREIGN QUARANTINE Importations § 71.54 Etiological agents, hosts, and vectors. (a) A...

42 CFR 71.54 - Etiological agents, hosts, and vectors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Etiological agents, hosts, and vectors. 71.54 Section 71.54 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING FOREIGN QUARANTINE Importations § 71.54 Etiological agents, hosts, and vectors. (a) A...

42 CFR 71.54 - Etiological agents, hosts, and vectors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Etiological agents, hosts, and vectors. 71.54 Section 71.54 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING FOREIGN QUARANTINE Importations § 71.54 Etiological agents, hosts, and vectors. (a) A...

Vector-borne pathogens: New and emerging arboviral diseases affecting public health

USDA-ARS?s Scientific Manuscript database

Dengue and Zika have quickly become two of the most important vector-borne diseases affecting Public health around the world. This presentation will introduce vector-borne diseases and all the vectors implicated. A focus will be made on the most important arboviral diseases (Zika and dengue) describ...

Annual Insecticide Loadings

EPA Pesticide Factsheets

Pesticides, Herbicides, Fungicides...etc, are used for a variety of purposes, including control of household, lawn, and garden pests; for control of mosquitoes and other insect vectors of animal and human diseases; for control of brush in rangelands, on roadsides, and along power line rights-of-way; as wood preservatives; as disinfectants; and in golf courses, parks and forest lands. The toxicity that makes pesticides useful in agriculture, silviculture, disease vector, and nuisance control can, however, also endanger humans, nontarget wildlife, and ecosystems. EPA carries the mandated responsibility for solving this policy and regulatory dilemma, first through registering pesticides so that their labels explain how to avoid unreasonable risks when using them, and second by setting allowable levels of pesticide residues to ensure the safety of drinking water and the food supply (Schierow 1996). More information about these resources, including the variables used in this study, may be found here: https://edg.epa.gov/data/Public/ORD/NERL/ReVA/ReVA_Data.zip.

Annual Fungicide Loadings

EPA Pesticide Factsheets

Pesticides, Herbicides, Fungicides...etc, are used for a variety of purposes, including control of household, lawn, and garden pests; for control of mosquitoes and other insect vectors of animal and human diseases; for control of brush in rangelands, on roadsides, and along power line rights-of-way; as wood preservatives; as disinfectants; and in golf courses, parks and forest lands. The toxicity that makes pesticides useful in agriculture, silviculture, disease vector, and nuisance control can, however, also endanger humans, nontarget wildlife, and ecosystems. EPA carries the mandated responsibility for solving this policy and regulatory dilemma, first through registering pesticides so that their labels explain how to avoid unreasonable risks when using them, and second by setting allowable levels of pesticide residues to ensure the safety of drinking water and the food supply (Schierow 1996). More information about these resources, including the variables used in this study, may be found here: https://edg.epa.gov/data/Public/ORD/NERL/ReVA/ReVA_Data.zip.

Enhancing Global Competitiveness: Benchmarking Airline Operational Performance in Highly Regulated Environments

NASA Technical Reports Server (NTRS)

Bowen, Brent D.; Headley, Dean E.; Kane, Karisa D.

1998-01-01

Enhancing competitiveness in the global airline industry is at the forefront of attention with airlines, government, and the flying public. The seemingly unchecked growth of major airline alliances is heralded as an enhancement to global competition. However, like many mega-conglomerates, mega-airlines will face complications driven by size regardless of the many recitations of enhanced efficiency. Outlined herein is a conceptual model to serve as a decision tool for policy-makers, managers, and consumers of airline services. This model is developed using public data for the United States (U.S.) major airline industry available from the U/S. Department of Transportation, Federal Aviation Administration, the National Aeronautics and Space Administration, the National Transportation Safety Board, and other public and private sector sources. Data points include number of accidents, pilot deviations, operational performance indicators, flight problems, and other factors. Data from these sources provide opportunity to develop a model based on a complex dot product equation of two vectors. A row vector is weighted for importance by a key informant panel of government, industry, and consumer experts, while a column vector is established with the factor value. The resulting equation, known as the national Airline Quality Rating (AQR), where Q is quality, C is weight, and V is the value of the variables, is stated Q=C[i1-19] x V[i1-19]. Looking at historical patterns of AQR results provides the basis for establishment of an industry benchmark for the purpose of enhancing airline operational performance. A 7 year average of overall operational performance provides the resulting benchmark indicator. Applications from this example can be applied to the many competitive environments of the global industry and assist policy-makers faced with rapidly changing regulatory challenges.

Survey of Blood Collection Centers and Implementation of Guidance for Prevention of Transfusion-Transmitted Zika Virus Infection--Puerto Rico, 2016.

PubMed

Vasquez, Amber M; Sapiano, Mathew R P; Basavaraju, Sridhar V; Kuehnert, Matthew J; Rivera-Garcia, Brenda

2016-04-15

Since November 2015, Puerto Rico has reported active mosquito-borne transmission of Zika virus. Because of the potential for Zika virus to be transmitted through transfusion of blood components, and because a high percentage of persons infected with Zika virus are asymptomatic, the Food and Drug Administration (FDA) recommended that blood collections cease in areas of the United States affected by active vector-borne transmission of Zika virus until laboratory screening of blood donations or pathogen reduction technology (PRT) for treatment of blood components can be implemented. To inform efforts to maintain the safety and availability of the blood supply in Puerto Rico, CDC, in collaboration with the Puerto Rico Department of Health, conducted a rapid assessment of blood collection and use on the island. A total of 139,369 allogeneic red blood cell (RBC) units, 45,243 platelet units, and 56,466 plasma units were collected in or imported to Puerto Rico during 2015, and 135,966 allogeneic RBC units, 13,526 therapeutic platelet units, and 25,775 plasma units were transfused. Because of the potential for local Zika virus transmission in areas with a competent mosquito vector, other areas of the United States should develop plans to ensure local blood safety and adequacy. Blood collection organizations and public health agencies should collaborate to maintain the safety and availability of local blood supplies in accordance with FDA guidance.

Regulated Apoptosis of Genetically-Modified Hematopoietic Stem and Progenitor Cells via an Inducible Caspase-9 Suicide Gene in Rhesus Macaques

PubMed Central

Barese, Cecilia N.; Felizardo, Tania C.; Sellers, Stephanie E.; Keyvanfar, Keyvan; Di Stasi, Antonio; Metzger, Mark E.; Krouse, Allen E.; Donahue, Robert E.; Spencer, David M.; Dunbar, Cynthia E.

2014-01-01

The high risk of insertional oncogenesis reported in clinical trials utilizing integrating retroviral vectors to genetically-modify hematopoietic stem and progenitor cells (HSPC) requires the development of safety strategies to minimize risks associated with novel cell and gene therapies. The ability to ablate genetically modified cells in vivo is desirable, should an abnormal clone emerge. Inclusion of “suicide genes” in vectors to facilitate targeted ablation of vector-containing abnormal clones in vivo is one potential safety approach. We tested whether the inclusion of the “inducible Caspase-9” (iCasp9) suicide gene in a gamma-retroviral vector facilitated efficient elimination of vector-containing HSPCs and their hematopoietic progeny in vivo long-term, in an autologous non-human primate transplantation model. Following stable engraftment of iCasp9 expressing hematopoietic cells in rhesus macaques, administration of AP1903, a chemical inducer of dimerization able to activate iCasp9, specifically eliminated vector-containing cells in all hematopoietic lineages long-term, suggesting activity at the HSPC level. Between 75–94% of vector-containing cells were eliminated by well-tolerated AP1903 dosing, but lack of complete ablation was linked to lower iCasp9 expression in residual cells. Further investigation of resistance mechanisms demonstrated upregulation of Bcl-2 in hematopoietic cell lines transduced with the vector and resistant to AP1903 ablation. These results demonstrate both the potential and the limitations of safety approaches utilizing iCasp9 to HSPC-targeted gene therapy settings, in a model with great relevance to clinical development. PMID:25330775

Retrovirus-based vectors for transient and permanent cell modification.

PubMed

Schott, Juliane W; Hoffmann, Dirk; Schambach, Axel

2015-10-01

Retroviral vectors are commonly employed for long-term transgene expression via integrating vector technology. However, three alternative retrovirus-based platforms are currently available that allow transient cell modification. Gene expression can be mediated from either episomal DNA or RNA templates, or selected proteins can be directly transferred through retroviral nanoparticles. The different technologies are functionally graded with respect to safety, expression magnitude and expression duration. Improvement of the initial technologies, including modification of vector designs, targeted increase in expression strength and duration as well as improved safety characteristics, has allowed maturation of retroviral systems into efficient and promising tools that meet the technological demands of a wide variety of potential application areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy.

PubMed

Zarogoulidis, P; Hohenforst-Schmidt, W; Darwiche, K; Krauss, L; Sparopoulou, D; Sakkas, L; Gschwendtner, A; Huang, H; Turner, F J; Freitag, L; Zarogoulidis, K

2013-10-01

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

Major emerging vector-borne zoonotic diseases of public health importance in Canada

PubMed Central

Kulkarni, Manisha A; Berrang-Ford, Lea; Buck, Peter A; Drebot, Michael A; Lindsay, L Robbin; Ogden, Nicholas H

2015-01-01

In Canada, the emergence of vector-borne diseases may occur via international movement and subsequent establishment of vectors and pathogens, or via northward spread from endemic areas in the USA. Re-emergence of endemic vector-borne diseases may occur due to climate-driven changes to their geographic range and ecology. Lyme disease, West Nile virus (WNV), and other vector-borne diseases were identified as priority emerging non-enteric zoonoses in Canada in a prioritization exercise conducted by public health stakeholders in 2013. We review and present the state of knowledge on the public health importance of these high priority emerging vector-borne diseases in Canada. Lyme disease is emerging in Canada due to range expansion of the tick vector, which also signals concern for the emergence of human granulocytic anaplasmosis, babesiosis, and Powassan virus. WNV has been established in Canada since 2001, with epidemics of varying intensity in following years linked to climatic drivers. Eastern equine encephalitis virus, Jamestown Canyon virus, snowshoe hare virus, and Cache Valley virus are other mosquito-borne viruses endemic to Canada with the potential for human health impact. Increased surveillance for emerging pathogens and vectors and coordinated efforts among sectors and jurisdictions will aid in early detection and timely public health response. PMID:26954882

Major emerging vector-borne zoonotic diseases of public health importance in Canada.

PubMed

Kulkarni, Manisha A; Berrang-Ford, Lea; Buck, Peter A; Drebot, Michael A; Lindsay, L Robbin; Ogden, Nicholas H

2015-06-10

In Canada, the emergence of vector-borne diseases may occur via international movement and subsequent establishment of vectors and pathogens, or via northward spread from endemic areas in the USA. Re-emergence of endemic vector-borne diseases may occur due to climate-driven changes to their geographic range and ecology. Lyme disease, West Nile virus (WNV), and other vector-borne diseases were identified as priority emerging non-enteric zoonoses in Canada in a prioritization exercise conducted by public health stakeholders in 2013. We review and present the state of knowledge on the public health importance of these high priority emerging vector-borne diseases in Canada. Lyme disease is emerging in Canada due to range expansion of the tick vector, which also signals concern for the emergence of human granulocytic anaplasmosis, babesiosis, and Powassan virus. WNV has been established in Canada since 2001, with epidemics of varying intensity in following years linked to climatic drivers. Eastern equine encephalitis virus, Jamestown Canyon virus, snowshoe hare virus, and Cache Valley virus are other mosquito-borne viruses endemic to Canada with the potential for human health impact. Increased surveillance for emerging pathogens and vectors and coordinated efforts among sectors and jurisdictions will aid in early detection and timely public health response.

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

PubMed Central

Zarogouldis, Paul; Karamanos, Nikos K.; Porpodis, Konstantinos; Domvri, Kalliopi; Huang, Haidong; Hohenforst-Schimdt, Wolfgang; Goldberg, Eugene P.; Zarogoulidis, Konstantinos

2012-01-01

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer. PMID:23109824

Novel approaches to develop Rift Valley fever vaccines

PubMed Central

Indran, Sabarish V.; Ikegami, Tetsuro

2012-01-01

Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed. PMID:23112960

Novel approaches to develop Rift Valley fever vaccines.

PubMed

Indran, Sabarish V; Ikegami, Tetsuro

2012-01-01

Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed.

Protective immunity against tularemia provided by an adenovirus-vectored vaccine expressing Tul4 of Francisella tularensis.

PubMed

Kaur, Ravinder; Chen, Shan; Arévalo, Maria T; Xu, Qingfu; Chen, Yanping; Zeng, Mingtao

2012-03-01

Francisella tularensis, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad/opt-Tul4, carrying a codon-optimized gene for expression of a membrane protein, Tul4, of F. tularensis LVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1 × 10(7) PFU) of Ad/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100 × 50% lethal dose (LD(50)) F. tularensis LVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5 μg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad/opt-Tul4 vaccine was more effective than the protein vaccine, and protection was dose dependent. Compared to LVS, the protection rate is lower, but an adenovirus-vectored vaccine may be more attractive due to its enhanced safety profile and mucosal route of delivery. Furthermore, simple genetic modification of the vaccine may potentially produce antibodies protective against a fully virulent strain of F. tularensis. Our data support the development and further research of an adenovirus-vectored vaccine against Tul4 of F. tularensis LVS.

Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials.

PubMed

Will, Elke; Bailey, Jeff; Schuesler, Todd; Modlich, Ute; Balcik, Brenden; Burzynski, Ben; Witte, David; Layh-Schmitt, Gerlinde; Rudolph, Cornelia; Schlegelberger, Brigitte; von Kalle, Christof; Baum, Christopher; Sorrentino, Brian P; Wagner, Lars M; Kelly, Patrick; Reeves, Lilith; Williams, David A

2007-04-01

Although retroviral vectors are one of the most widely used vehicles for gene transfer, there is no uniformly accepted pre-clinical model defined to assess their safety, in particular their risk related to insertional mutagenesis. In the murine pre-clinical study presented here, 40 test and 10 control mice were transplanted with ex vivo manipulated bone marrow cells to assess the long-term effects of the transduction of hematopoietic cells with the retroviral vector MSCV-MGMT(P140K)wc. Test mice had significant gene marking 8-12 months post-transplantation with an average of 0.93 vector copies per cell and 41.5% of peripheral blood cells expressing the transgene MGMT(P140K), thus confirming persistent vector expression. Unexpectedly, six test mice developed malignant lymphoma. No vector was detected in the tumor cells of five animals with malignancies, indicating that the malignancies were not caused by insertional mutagenesis or MGMT(P140K) expression. Mice from a concurrent study with a different transgene also revealed additional cases of vector-negative lymphomas of host origin. We conclude that the background tumor formation in this mouse model complicates safety determination of retroviral vectors and propose an improved study design that we predict will increase the relevance and accuracy of interpretation of pre-clinical mouse studies.

Employing a gain-of-function factor IX variant R338L to advance the efficacy and safety of hemophilia B human gene therapy: preclinical evaluation supporting an ongoing adeno-associated virus clinical trial.

PubMed

Monahan, Paul E; Sun, Junjiang; Gui, Tong; Hu, Genlin; Hannah, William B; Wichlan, David G; Wu, Zhijian; Grieger, Joshua C; Li, Chengwen; Suwanmanee, Thipparat; Stafford, Darrel W; Booth, Carmen J; Samulski, Jade J; Kafri, Tal; McPhee, Scott W J; Samulski, R Jude

2015-02-01

Vector capsid dose-dependent inflammation of transduced liver has limited the ability of adeno-associated virus (AAV) factor IX (FIX) gene therapy vectors to reliably convert severe to mild hemophilia B in human clinical trials. These trials also identified the need to understand AAV neutralizing antibodies and empty AAV capsids regarding their impact on clinical success. To address these safety concerns, we have used a scalable manufacturing process to produce GMP-grade AAV8 expressing the FIXR338L gain-of-function variant with minimal (<10%) empty capsid and have performed comprehensive dose-response, biodistribution, and safety evaluations in clinically relevant hemophilia models. The scAAV8.FIXR338L vector produced greater than 6-fold increased FIX specific activity compared with wild-type FIX and demonstrated linear dose responses from doses that produced 2-500% FIX activity, associated with dose-dependent hemostasis in a tail transection bleeding challenge. More importantly, using a bleeding model that closely mimics the clinical morbidity of hemophilic arthropathy, mice that received the scAAV8.FIXR338L vector developed minimal histopathological findings of synovitis after hemarthrosis, when compared with mice that received identical doses of wild-type FIX vector. Hemostatically normal mice (n=20) and hemophilic mice (n=88) developed no FIX antibodies after peripheral intravenous vector delivery. No CD8(+) T cell liver infiltrates were observed, despite the marked tropism of scAAV8.FIXR338L for the liver in a comprehensive biodistribution evaluation (n=60 animals). With respect to the role of empty capsids, we demonstrated that in vivo FIXR338L expression was not influenced by the presence of empty AAV particles, either in the presence or absence of various titers of AAV8-neutralizing antibodies. Necropsy of FIX(-/-) mice 8-10 months after vector delivery revealed no microvascular or macrovascular thrombosis in mice expressing FIXR338L (plasma FIX activity, 100-500%). These preclinical studies demonstrate a safety:efficacy profile supporting an ongoing phase 1/2 human clinical trial of the scAAV8.FIXR338L vector (designated BAX335).

Ecological approaches to informing public health policy and risk assessments on emerging vector-borne zoonoses

PubMed Central

Medlock, JM; Jameson, LJ

2010-01-01

Pathogens associated with vector-borne zoonoses occur in enzootic cycles within nature. They are driven by a combination of vertebrate host and invertebrate vector population dynamics, which in turn respond to changes in environmental stimuli. Human involvement in these cycles, and hence the occurrence of human disease, is often to act as incidental host. From a public health perspective our ability to better predict human outbreaks of these diseases and prepare intervention and mitigation strategies relies on understanding the natural cycle of pathogen transmission. This requires consideration of, for example, invertebrate and vertebrate ecology and biology, climatology, land use and habitat change. Collectively, these can be referred to as medical entomology and medical ecology. This article reviews the importance for inclusion of such disciplines when assessing the public health risk from vector-borne zoonoses and summarizes the possible future challenges and driving forces for changes in vector status and vector-borne zoonoses emergence, with a particular focus on a UK and European context. PMID:22460391

Application of a support vector machine algorithm to the safety precaution technique of medium-low pressure gas regulators

NASA Astrophysics Data System (ADS)

Hao, Xuejun; An, Xaioran; Wu, Bo; He, Shaoping

2018-02-01

In the gas pipeline system, safe operation of a gas regulator determines the stability of the fuel gas supply, and the medium-low pressure gas regulator of the safety precaution system is not perfect at the present stage in the Beijing Gas Group; therefore, safety precaution technique optimization has important social and economic significance. In this paper, according to the running status of the medium-low pressure gas regulator in the SCADA system, a new method for gas regulator safety precaution based on the support vector machine (SVM) is presented. This method takes the gas regulator outlet pressure data as input variables of the SVM model, the fault categories and degree as output variables, which will effectively enhance the precaution accuracy as well as save significant manpower and material resources.

Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle.

PubMed

Barrera, J; Brake, D A; Kamicker, B J; Purcell, C; Kaptur, R; Schieber, T; Lechtenberg, K; Miller, T D; Ettyreddy, D; Brough, D E; Butman, B T; Colby, M; Neilan, J G

2018-04-01

The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs. The fourth safety study conducted in 10 lactating cows using an AdtA24 vaccine serial showed that the vaccine was completely absent from milk. The fifth safety study was conducted under typical U.S. production field conditions in 500 healthy beef and dairy cattle using two AdtA24 vaccine serials. These results demonstrated that the vaccine was safe when used per the product label recommendations. Additional data collected during these five studies confirmed that AdtA24 vaccinees developed FMDV A24 and the HAd5 vaccine vector serum neutralization antibodies that test negative in a FMDV non-structural protein antibody test, confirming AdtA24 vaccine's capability to differentiate infected from vaccinated animals (DIVA). In conclusion, results from this comprehensive set of cattle studies demonstrated the safety of the replication-deficient AdtA24 vaccine and fulfilled safety-related requirements for U.S. regulatory requirements. © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

Practical utilization of recombinant AAV vector reference standards: focus on vector genomes titration by free ITR qPCR.

PubMed

D'Costa, Susan; Blouin, Veronique; Broucque, Frederic; Penaud-Budloo, Magalie; François, Achille; Perez, Irene C; Le Bec, Christine; Moullier, Philippe; Snyder, Richard O; Ayuso, Eduard

2016-01-01

Clinical trials using recombinant adeno-associated virus (rAAV) vectors have demonstrated efficacy and a good safety profile. Although the field is advancing quickly, vector analytics and harmonization of dosage units are still a limitation for commercialization. AAV reference standard materials (RSMs) can help ensure product safety by controlling the consistency of assays used to characterize rAAV stocks. The most widely utilized unit of vector dosing is based on the encapsidated vector genome. Quantitative polymerase chain reaction (qPCR) is now the most common method to titer vector genomes (vg); however, significant inter- and intralaboratory variations have been documented using this technique. Here, RSMs and rAAV stocks were titered on the basis of an inverted terminal repeats (ITRs) sequence-specific qPCR and we found an artificial increase in vg titers using a widely utilized approach. The PCR error was introduced by using single-cut linearized plasmid as the standard curve. This bias was eliminated using plasmid standards linearized just outside the ITR region on each end to facilitate the melting of the palindromic ITR sequences during PCR. This new "Free-ITR" qPCR delivers vg titers that are consistent with titers obtained with transgene-specific qPCR and could be used to normalize in-house product-specific AAV vector standards and controls to the rAAV RSMs. The free-ITR method, including well-characterized controls, will help to calibrate doses to compare preclinical and clinical data in the field.

An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation

PubMed Central

Ryu, Byoung Y.; Evans-Galea, Marguerite V.; Gray, John T.; Bodine, David M.; Persons, Derek A.

2008-01-01

Pathogenic activation of the LMO2 proto-oncogene by an oncoretroviral vector insertion in a clinical trial for X-linked severe combined immunodeficiency (X-SCID) has prompted safety concerns. We used an adeno-associated virus vector to achieve targeted insertion of a γ-retroviral long terminal repeat (LTR) driving a GFP expression cassette with flanking loxP sites in a human T-cell line at the precise location of vector integration in one of the patients with X-SCID. The LTR-GFP cassette was inserted into the first intron of the LMO2 gene, resulting in strong activation of LMO2. Cre-mediated cassette exchange was used to replace the original LTR-GFP cassette with one flanked by insulator elements leading to a several fold reduction in LMO2 expression. The LTR-GFP cassette was also replaced with a globin gene regulatory cassette that failed to activate the LMO2 gene in lymphoid cells. A γ-retroviral vector with 2 intact LTRs resulted in activation of the LMO2 gene when inserted into the first intron, but a self-inactivating lentiviral vector with an internal cellular promoter and flanking insulator elements did not activate the LMO2 gene. Thus, this system is useful for comparing the safety profiles of vector cassettes with various regulatory elements for their potential for proto-oncogene activation. PMID:17991809

Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans

PubMed Central

Borggren, Marie; Nielsen, Jens; Bragstad, Karoline; Karlsson, Ingrid; Krog, Jesper S; Williams, James A; Fomsgaard, Anders

2015-01-01

The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines. PMID:25746201

Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques

PubMed Central

2013-01-01

Background Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown. Results This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells. Conclusions Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge. PMID:24041113

Synthetic biology and occupational risk.

PubMed

Howard, John; Murashov, Vladimir; Schulte, Paul

2017-03-01

Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

Ub-ISAP: a streamlined UNIX pipeline for mining unique viral vector integration sites from next generation sequencing data.

PubMed

Kamboj, Atul; Hallwirth, Claus V; Alexander, Ian E; McCowage, Geoffrey B; Kramer, Belinda

2017-06-17

The analysis of viral vector genomic integration sites is an important component in assessing the safety and efficiency of patient treatment using gene therapy. Alongside this clinical application, integration site identification is a key step in the genetic mapping of viral elements in mutagenesis screens that aim to elucidate gene function. We have developed a UNIX-based vector integration site analysis pipeline (Ub-ISAP) that utilises a UNIX-based workflow for automated integration site identification and annotation of both single and paired-end sequencing reads. Reads that contain viral sequences of interest are selected and aligned to the host genome, and unique integration sites are then classified as transcription start site-proximal, intragenic or intergenic. Ub-ISAP provides a reliable and efficient pipeline to generate large datasets for assessing the safety and efficiency of integrating vectors in clinical settings, with broader applications in cancer research. Ub-ISAP is available as an open source software package at https://sourceforge.net/projects/ub-isap/ .

Return of epidemic dengue in the United States: implications for the public health practitioner.

PubMed

Bouri, Nidhi; Sell, Tara Kirk; Franco, Crystal; Adalja, Amesh A; Henderson, D A; Hynes, Noreen A

2012-01-01

Conditions that facilitate sustained dengue transmission exist in the United States, and outbreaks have occurred during the past decade in Texas, Hawaii, and Florida. More outbreaks can also be expected in years to come. To combat dengue, medical and public health practitioners in areas with mosquito vectors that are competent to transmit the virus must be aware of the threat of reemergent dengue, and the need for early reporting and control to reduce the impact of dengue outbreaks. Comprehensive dengue control includes human and vector surveillance, vector management programs, and community engagement efforts. Public health, medical, and vector-control communities must collaborate to prevent and control disease spread. Policy makers should understand the role of mosquito abatement and community engagement in the prevention and control of the disease.

Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

PubMed Central

Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. PMID:25446819

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

PubMed

Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. Copyright © 2014. Published by Elsevier Ltd.

LASIK versus photorefractive keratectomy for high myopic (> 3 diopter) astigmatism.

PubMed

Katz, Toam; Wagenfeld, Lars; Galambos, Peter; Darrelmann, Benedikt Große; Richard, Gisbert; Linke, Stephan Johannes

2013-12-01

To compare the efficacy, safety, predictability, and vector analysis indices of LASIK and photorefractive keratectomy (PRK) for correction of high cylinder of greater than 3 diopters (D) in myopic eyes. The efficacy, safety, and predictability of LASIK or PRK performed in 114 consecutive randomly selected myopic eyes with an astigmatism of greater than 3 D were retrospectively analyzed at the 2- to 6-month follow-up visits. Vector analysis of the cylindrical correction was compared between the treatment groups. A total of 57 eyes receiving PRK and 57 eyes receiving LASIK of 114 refractive surgery candidates were enrolled in the study. No statistically significant difference in efficacy [efficacy index = 0.76 (±0.32) for PRK vs 0.74 (±0.19) for LASIK (P = .82)], safety [safety index = 1.10 (±0.26) for PRK vs 1.01 (±0.17) for LASIK (P = .121)], or predictability [achieved astigmatism < 1 D in 39% of PRK- and 54% of LASIK-treated eyes, and < 2 D in 88% of PRK- and 89% of LASIK-treated eyes (P = .218)] was demonstrated. Using Alpins vector analysis, the surgically induced astigmatism and difference vector were not significantly different between the surgery methods, whereas the correction index showed a slight and significant advantage of LASIK over PRK (1.25 for PRK and 1.06 for LASIK, P < .001). LASIK and PRK are comparably safe, effective, and predictable procedures for excimer laser correction of high astigmatism of greater than 3 D in myopic eyes. Predictability of the correction of the cylindrical component is lower than that of the spherical equivalent. Copyright 2013, SLACK Incorporated.

Economic development, mobility and traffic accidents in Algeria.

PubMed

Bougueroua, M; Carnis, L

2016-07-01

The aim of this contribution is to estimate the impact of road economic conditions and mobility on traffic accidents for the case of Algeria. Using the cointegration approach and vector error correction model (VECM), we will examine simultaneously short term and long-term impacts between the number of traffic accidents, fuel consumption and gross domestic product (GDP) per capital, over the period 1970-2013. The main results of the estimation show that the number of traffic accidents in Algeria is positively influenced by the GDP per capita in the short and long term. It implies that a higher economic development worsens the road safety situation. However, the new traffic rules adopted in 2009 have an impact on the forecast trend of traffic accidents, meaning efficient public policy could improve the situation. This result calls for a strong political commitment with effective countermeasures for avoiding the further deterioration of road safety record in Algeria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sleeping Beauty Transposon Vectors in Liver-directed Gene Delivery of LDLR and VLDLR for Gene Therapy of Familial Hypercholesterolemia

PubMed Central

Turunen, Tytteli A K; Kurkipuro, Jere; Heikura, Tommi; Vuorio, Taina; Hytönen, Elisa; Izsvák, Zsuzsanna; Ylä-Herttuala, Seppo

2016-01-01

Plasmid-based Sleeping Beauty (SB) transposon vectors were developed and used to deliver genes for low-density lipoprotein and very-low-density lipoprotein receptors (LDLR and VLDLR, respectively) or lacZ reporter into liver of an LDLR-deficient mouse model of familial hypercholesterolemia (FH). SB transposase, SB100x, was used to integrate the therapeutic transposons into mice livers for evaluating the feasibility of the vectors in reducing high blood cholesterol and the progression of atherosclerosis. Hydrodynamic gene delivery of transposon-VLDLR into the livers of the mice resulted in initial 17–19% reductions in plasma cholesterol, and at the later time points, in a significant stabilization of the cholesterol level for the 6.5-month duration of the study compared to the control mice. Transposon-LDLR-treated animals also demonstrated a trend of stabilization in the cholesterol levels in the long term. Vector-treated mice had slightly less lipid accumulation in the liver and reduced aortic atherosclerosis. Clinical chemistry and histological analyses revealed normal liver function and morphology comparable to that of the controls during the follow-up with no safety issues regarding the vector type, transgenes, or the gene transfer method. The study demonstrates the safety and potential benefits of the SB transposon vectors in the treatment of FH. PMID:26670130

CRITICAL EVALUATION OF THE EFFECTIVENESS OF SEWAGE SLUDGE DISINFECTION AND VECTOR ATTRACTION REDUCTION PROCESSES

EPA Science Inventory

What is the current state of management practices for biosolids production and application, and how can those be made more effective? How effective are Class B disinfection and vector attraction processes, and public access and harvesting restrictions at reducing the public's exp...

Community Response to a Public Health Threat-VEE

ERIC Educational Resources Information Center

McDonald, John L.; Vuturo, Anthony F.

1975-01-01

After identifying the mosquito as the Venezuelan equine encephalitis vector, health officials worked with the community to eliminate mosquito breeding sites. By educating the public first, cooperation was received in opening drainage areas and stocking water collection areas with mosquito eating fish to interrupt the host-vector-recipient cycle.…

[Public health pests. Arthropods and rodents as causative disease agents as well as reservoirs and vectors of pathogens].

PubMed

Faulde, M; Freise, J

2014-05-01

Globally, infectious diseases pose the most important cause of death. Among known human pathogenic diseases, approximately 50 % are zoonoses. When considering emerging infectious diseases separately 73 % currently belong to the group of zoonoses. In Central Europe, hard ticks show by far the biggest potential as vectors of agents of human disease. Lyme borreliosis, showing an estimated annual incidence between 60,000 and 214,000 cases is by far the most frequent tick-borne disease in Germany. Continually, formerly unknown disease agents could be discovered in endemic vector species. Additionally, introduction of new arthropod vectors and/or agents of disease occur constantly. Recently, five mosquito species of the genus Aedes have been newly introduced to Europe where they are currently spreading in different regions. Uncommon autochthonous transmission of dengue and chikungunya fever viruses in Southern Europe could be directly linked to these vector species and of these Ae. albopictus and Ae. japonicus are currently reported to occur in Germany. The German Protection against Infection Act only covers the control of public health pests which are either active hematophagous vectors or mechanical transmitters of agents of diseases. Use of officially recommended biocidal products aiming to interrupt transmission cycles of vector-borne diseases, is confined to infested buildings only, including sewage systems in the case of Norway rat control. Outdoor vectors, such as hard ticks and mosquitoes, are currently not taken into consideration. Additionally, adjustments of national public health regulations, detailed arthropod vector and rodent reservoir mapping, including surveillance of vector-borne disease agents, are necessary in order to mitigate future disease risks.

Assessing the threat of chikungunya virus emergence in Australia.

PubMed

Viennet, Elvina; Knope, Katrina; Faddy, Helen M; Williams, Craig R; Harley, David

2013-06-30

Chikungunya virus (CHIKV) is a major threat to Australia given the distribution of competent vectors, and the large number of travellers returning from endemic regions. We describe current knowledge of CHIKV importations into Australia, and quantify reported viraemic cases, with the aim of facilitating the formulation of public health policy and ensuring maintenance of blood safety. Cases reported to the National Notifiable Disease Surveillance System (NNDSS) from 2002 to 2012 were analysed by place, month of acquisition, and place of residence. Rates of chikungunya importation were estimated based on reported cases and on the numbers of short-term movements. Between 2002 and 2012, there were 168 cases of chikungunya virus (CHIKV) imported into Australia. Victoria and New South Wales had the largest number of notifications. The main sources were Indonesia, India and Malaysia. The number of cases increased from 2008 to reach a peak in 2010 (n=64; 40%). Although Indonesia accounted for the majority of CHIKV notifications in Australia, travel from India had the highest CHIKV importation rate (number of imported cases per 100,000 travellers). The Australian population is increasingly at risk from CHIKV. Arrivals from endemic countries have increased concurrently with vector incursions via imported goods, as well as via local movement from the Torres Strait to North Queensland ports. An outbreak of CHIKV could have a significant impact on health, the safety of the blood supply and on tourism. Case and vector surveillance as well as population health responses are crucial for minimising any potential impact of CHIKV establishment in Australia. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.

Fall 1998 200 East area biological vector contamination report

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

CONNELL, D.J.

The purpose of this report is to document the investigation into the cause of the spread of radioactive contamination in September and October 1998 at the Hanford Site's 200 East Area and its subsequent spread to the City of Richland Landfill; identify the source of the contamination; and present corrective actions. The focus and thrust of managing the incident was based on the need to accomplish the following, listed in order of importance: (1) protect the health and safety of the Site workers and the public; (2) contain and control the spread of contamination; (3) identify the source of contaminationmore » and the pathways for its spread; and (4) identify the causal factors enabling the contamination.« less

76 FR 71081 - Public Aircraft Oversight Safety Forum

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... NATIONAL TRANSPORTATION SAFETY BOARD Public Aircraft Oversight Safety Forum The National Transportation Safety Board (NTSB) will convene a Public Aircraft Oversight Safety Forum which will begin at 9 a... ``Public Aircraft Oversight Forum: Ensuring Safety for Critical Missions'', are to (1) raise awareness of...

Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T-cells

PubMed Central

Scholler, John; Brady, Troy L.; Binder-Scholl, Gwendolyn; Hwang, Wei-Ting; Plesa, Gabriela; Hege, Kristen M.; Vogel, Ashley N.; Kalos, Michael; Riley, James L.; Deeks, Steven G.; Mitsuyasu, Ronald T.; Bernstein, Wendy B.; Aronson, Naomi E.; Levine, Bruce L.; Bushman, Frederic D.; June, Carl H.

2015-01-01

The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. Here we report long term results from three clinical trials to evaluate gammaretroviral vector engineered T-cells for HIV. The vector encoded a chimeric antigen receptor (CAR) comprised of CD4 linked to the CD3-ζ signaling chain (CD4ζ). CAR T-cells were detected in 98% of samples tested for at least 11 years post-infusion at frequencies that exceed average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells as integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells have stable levels of engraftment, with decay half-lives that exceed 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression prior to T cell transfer is not required in order to achieve long term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient years of follow up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long term delivery of protein based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases. PMID:22553251

Analysis of the clonal repertoire of gene-corrected cells in gene therapy.

PubMed

Paruzynski, Anna; Glimm, Hanno; Schmidt, Manfred; Kalle, Christof von

2012-01-01

Gene therapy-based clinical phase I/II studies using integrating retroviral vectors could successfully treat different monogenetic inherited diseases. However, with increased efficiency of this therapy, severe side effects occurred in various gene therapy trials. In all cases, integration of the vector close to or within a proto-oncogene contributed substantially to the development of the malignancies. Thus, the in-depth analysis of integration site patterns is of high importance to uncover potential clonal outgrowth and to assess the safety of gene transfer vectors and gene therapy protocols. The standard and nonrestrictive linear amplification-mediated PCR (nrLAM-PCR) in combination with high-throughput sequencing exhibits technologies that allow to comprehensively analyze the clonal repertoire of gene-corrected cells and to assess the safety of the used vector system at an early stage on the molecular level. It enables clarifying the biological consequences of the vector system on the fate of the transduced cell. Furthermore, the downstream performance of real-time PCR allows a quantitative estimation of the clonality of individual cells and their clonal progeny. Here, we present a guideline that should allow researchers to perform comprehensive integration site analysis in preclinical and clinical studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes.

PubMed

Ellinwood, N Matthew; Ausseil, Jérôme; Desmaris, Nathalie; Bigou, Stéphanie; Liu, Song; Jens, Jackie K; Snella, Elizabeth M; Mohammed, Eman E A; Thomson, Christopher B; Raoul, Sylvie; Joussemet, Béatrice; Roux, Françoise; Chérel, Yan; Lajat, Yaouen; Piraud, Monique; Benchaouir, Rachid; Hermening, Stephan; Petry, Harald; Froissart, Roseline; Tardieu, Marc; Ciron, Carine; Moullier, Philippe; Parkes, Jennifer; Kline, Karen L; Maire, Irène; Vanier, Marie-Thérèse; Heard, Jean-Michel; Colle, Marie-Anne

2011-02-01

Recent trials in patients with neurodegenerative diseases documented the safety of gene therapy based on adeno-associated virus (AAV) vectors deposited into the brain. Inborn errors of the metabolism are the most frequent causes of neurodegeneration in pre-adulthood. In Sanfilippo syndrome, a lysosomal storage disease in which heparan sulfate oligosaccharides accumulate, the onset of clinical manifestation is before 5 years. Studies in the mouse model showed that gene therapy providing the missing enzyme α-N-acetyl-glucosaminidase to brain cells prevents neurodegeneration and improves behavior. We now document safety and efficacy in affected dogs. Animals received eight deposits of a serotype 5 AAV vector, including vector prepared in insect Sf9 cells. As shown previously in dogs with the closely related Hurler syndrome, immunosuppression was necessary to prevent neuroinflammation and elimination of transduced cells. In immunosuppressed dogs, vector was efficiently delivered throughout the brain, induced α-N-acetyl-glucosaminidase production, cleared stored compounds and storage lesions. The suitability of the procedure for clinical application was further assessed in Hurler dogs, providing information on reproducibility, tolerance, appropriate vector type and dosage, and optimal age for treatment in a total number of 25 treated dogs. Results strongly support projects of human trials aimed at assessing this treatment in Sanfilippo syndrome.

High-capacity 'gutless' adenoviral vectors.

PubMed

Kochanek, S; Schiedner, G; Volpers, C

2001-10-01

Adenoviral vectors are promising gene transfer vehicles for different gene therapy applications. High-capacity adenoviral (HC-Ad) vectors address some of the problems that have been observed with replication-defective, E1-deleted first-generation adenoviral vectors: toxicity and immunogenicity due to viral gene expression and 7 to 8 kb capacity limit for the transport of therapeutic DNA. This review summarizes HC-Ad vector-related publications from the past 18 months that are mainly concerned with vector design/production and in vivo applications in different murine models.

The evolution of adenoviral vectors through genetic and chemical surface modifications.

PubMed

Capasso, Cristian; Garofalo, Mariangela; Hirvinen, Mari; Cerullo, Vincenzo

2014-02-17

A long time has passed since the first clinical trial with adenoviral (Ad) vectors. Despite being very promising, Ad vectors soon revealed their limitations in human clinical trials. The pre-existing immunity, the marked liver tropism and the high toxicity of first generation Ad (FG-Ad) vectors have been the main challenges for the development of new approaches. Significant effort toward the development of genetically and chemically modified adenoviral vectors has enabled researchers to create more sophisticated vectors for gene therapy, with an improved safety profile and a higher transduction ability of different tissues. In this review, we will describe the latest findings in the high-speed, evolving field of genetic and chemical modifications of adenoviral vectors, a field in which different disciplines, such as biomaterial research, virology and immunology, co-operate synergistically to create better gene therapy tools for modern challenges.

Legal aspects of public health: difficulties in controlling vector-borne and zoonotic diseases in Brazil.

PubMed

Mendes, Marcílio S; de Moraes, Josué

2014-11-01

In recent years, vector-borne and zoonotic diseases have become a major challenge for public health. Dengue fever and leptospirosis are the most important communicable diseases in Brazil based on their prevalence and the healthy life years lost from disability. The primary strategy for preventing human exposure to these diseases is effective insect and rodent control in and around the home. However, health authorities have difficulties in controlling vector-borne and zoonotic diseases because residents often refuse access to their homes. This study discusses aspects related to the activities performed by Brazilian health authorities to combat vector-borne and zoonotic diseases, particularly difficulties in relation to the legal aspect, which often impede the quick and effective actions of these professionals. How might it be possible to reconcile the need to preserve public health and the rule on the inviolability of the home, especially in the case of abandoned properties or illegal residents and the refusal of residents to allow the health authority access? Do residents have the right to hinder the performance of health workers even in the face of a significant and visible focus of disease transmission? This paper argues that a comprehensive legal plan aimed at the control of invasive vector-borne and zoonotic diseases including synanthropic animals of public health importance should be considered. In addition, this paper aims to bridge the gap between lawyers and public health professionals and to facilitate communication between them. Copyright © 2014 Elsevier B.V. All rights reserved.

Viruses vector control proposal: genus Aedes emphasis.

PubMed

Reis, Nelson Nogueira; Silva, Alcino Lázaro da; Reis, Elma Pereira Guedes; Silva, Flávia Chaves E; Reis, Igor Guedes Nogueira

The dengue fever is a major public health problem in the world. In Brazil, in 2015, there were 1,534,932 cases, being 20,320 cases of severe form, and 811 deaths related to this disease. The distribution of Aedes aegypti, the vector, is extensive. Recently, Zika and Chikungunya viruses had arisen, sharing the same vector as dengue and became a huge public health issue. Without specific treatment, it is urgently required as an effective vector control. This article is focused on reviewing vector control strategies, their effectiveness, viability and economical impact. Among all, the Sterile Insect Technique is highlighted as the best option to be adopted in Brazil, once it is largely effectively used in the USA and Mexico for plagues related to agribusiness. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Unstoppable The Gap Between Public Safety and Traffic Safety in the Age of Driverless Cars

DTIC Science & Technology

2017-03-01

themselves, what will the increase in traffic safety cost society in terms of public safety? • What can public safety and homeland security...industry. Safer products are more marketable products, and companies that work with law enforcement for the benefit of public safety may have an...secondary public safety benefit of crime suppression. Reasonable suspicion to stop a vehicle would be an infrequent occurrence, and the legal authority

Replication-Competent Controlled Herpes Simplex Virus

PubMed Central

Bloom, David C.; Feller, Joyce; McAnany, Peterjon; Vilaboa, Nuria

2015-01-01

ABSTRACT We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. IMPORTANCE The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate, stringent regulation of multiple replication-essential genes. By directing activating heat to the region of virus administration, replication is strictly confined to infected cells within this region. The requirement for antiprogestin provides an additional level of safety, ensuring that virus replication cannot be triggered inadvertently. Replication-competent controlled vectors such as HSV-GS3 may have the potential to be superior to conventional attenuated HSV vaccine and oncolytic vectors without sacrificing safety. PMID:26269179

Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

PubMed

Grigg, Patricia; Titong, Allison; Jones, Leslie A; Yilma, Tilahun D; Verardi, Paulo H

2013-09-17

Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunocompromised individuals or in those with other predisposing conditions. VACVs constitutively expressing interferon-γ (IFN-γ) replicate in cell culture indistinguishably from control viruses; however, they replicate in vivo to low or undetectable levels, and are rapidly cleared even in immunodeficient animals. In an effort to develop safe and highly effective replication-competent VACV vectors, we established a system to inducibly express IFN-γ. Our SMART (safety mechanism assisted by the repressor of tetracycline) vectors are designed to express the tetracycline repressor under a constitutive VACV promoter and IFN-γ under engineered tetracycline-inducible promoters. Immunodeficient SCID mice inoculated with VACVs not expressing IFN-γ demonstrated severe weight loss, whereas those given VACVs expressing IFN-γ under constitutive VACV promoters showed no signs of infection. Most importantly, mice inoculated with a VACV expressing the IFN-γ gene under an inducible promoter remained healthy in the presence of doxycycline, but exhibited severe weight loss in the absence of doxycycline. In this study, we developed a safety mechanism for VACV based on the conditional expression of IFN-γ under a tightly controlled tetracycline-inducible VACV promoter for use in vaccines and oncolytic cancer therapies.

Adeno-associated virus Rep-mediated targeting of integrase-defective retroviral vector DNA circles into human chromosome 19

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

Huang, Shuohao; Kawabe, Yoshinori; Ito, Akira

2012-01-06

Highlights: Black-Right-Pointing-Pointer Adeno-associated virus (AAV) is capable of targeted integration in human cells. Black-Right-Pointing-Pointer Integrase-defective retroviral vector (IDRV) enables a circular DNA delivery. Black-Right-Pointing-Pointer A targeted integration system of IDRV DNA using the AAV integration mechanism. Black-Right-Pointing-Pointer Targeted IDRV integration ameliorates the safety concerns for retroviral vectors. -- Abstract: Retroviral vectors have been employed in clinical trials for gene therapy owing to their relative large packaging capacity, alterable cell tropism, and chromosomal integration for stable transgene expression. However, uncontrollable integrations of transgenes are likely to cause safety issues, such as insertional mutagenesis. A targeted transgene integration system for retroviral vectors,more » therefore, is a straightforward way to address the insertional mutagenesis issue. Adeno-associated virus (AAV) is the only known virus capable of targeted integration in human cells. In the presence of AAV Rep proteins, plasmids possessing the p5 integration efficiency element (p5IEE) can be integrated into the AAV integration site (AAVS1) in the human genome. In this report, we describe a system that can target the circular DNA derived from non-integrating retroviral vectors to the AAVS1 site by utilizing the Rep/p5IEE integration mechanism. Our results showed that after G418 selection 30% of collected clones had retroviral DNA targeted at the AAVS1 site.« less

Exploiting the potential of vector control for disease prevention.

PubMed

Townson, H; Nathan, M B; Zaim, M; Guillet, P; Manga, L; Bos, R; Kindhauser, M

2005-12-01

Although vector control has proven highly effective in preventing disease transmission, it is not being used to its full potential, thereby depriving disadvantaged populations of the benefits of well tried and tested methods. Following the discovery of synthetic residual insecticides in the 1940s, large-scale programmes succeeded in bringing many of the important vector-borne diseases under control. By the late 1960s, most vector-borne diseases--with the exception of malaria in Africa--were no longer considered to be of primary public health importance. The result was that control programmes lapsed, resources dwindled, and specialists in vector control disappeared from public health units. Within two decades, many important vector-borne diseases had re-emerged or spread to new areas. The time has come to restore vector control to its key role in the prevention of disease transmission, albeit with an increased emphasis on multiple measures, whether pesticide-based or involving environmental modification, and with a strengthened managerial and operational capacity. Integrated vector management provides a sound conceptual framework for deployment of cost-effective and sustainable methods of vector control. This approach allows for full consideration of the complex determinants of disease transmission, including local disease ecology, the role of human activity in increasing risks of disease transmission, and the socioeconomic conditions of affected communities.

Exploiting the potential of vector control for disease prevention.

PubMed Central

Townson, H.; Nathan, M. B.; Zaim, M.; Guillet, P.; Manga, L.; Bos, R.; Kindhauser, M.

2005-01-01

Although vector control has proven highly effective in preventing disease transmission, it is not being used to its full potential, thereby depriving disadvantaged populations of the benefits of well tried and tested methods. Following the discovery of synthetic residual insecticides in the 1940s, large-scale programmes succeeded in bringing many of the important vector-borne diseases under control. By the late 1960s, most vector-borne diseases--with the exception of malaria in Africa--were no longer considered to be of primary public health importance. The result was that control programmes lapsed, resources dwindled, and specialists in vector control disappeared from public health units. Within two decades, many important vector-borne diseases had re-emerged or spread to new areas. The time has come to restore vector control to its key role in the prevention of disease transmission, albeit with an increased emphasis on multiple measures, whether pesticide-based or involving environmental modification, and with a strengthened managerial and operational capacity. Integrated vector management provides a sound conceptual framework for deployment of cost-effective and sustainable methods of vector control. This approach allows for full consideration of the complex determinants of disease transmission, including local disease ecology, the role of human activity in increasing risks of disease transmission, and the socioeconomic conditions of affected communities. PMID:16462987

Mosquito vector biology and control in latin america-a 24th symposium.

PubMed

Clark, Gary G; Fernández-Salas, Ildefonso

2014-09-01

The 24th Annual Latin American Symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 80th Annual Meeting in Seattle, WA, in February 2014. The principal objective, for the previous 23 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 26 presentations that were given orally in Spanish or presented as posters by participants from Colombia, Mexico, and the USA. Topics addressed in the symposium included: surveillance, ecology, chemical control, studies of dengue viruses, and insecticide resistance associated with Aedes aegypti; Anopheles vectors of malaria; essential oils; and ethnic groups and vector-borne diseases.

Current status of Plasmodium knowlesi vectors: a public health concern?

PubMed

Vythilingam, I; Wong, M L; Wan-Yussof, W S

2018-01-01

Plasmodium knowlesi a simian malaria parasite is currently affecting humans in Southeast Asia. Malaysia has reported the most number of cases and P. knowlesi is the predominant species occurring in humans. The vectors of P. knowlesi belong to the Leucosphyrus group of Anopheles mosquitoes. These are generally described as forest-dwelling mosquitoes. With deforestation and changes in land-use, some species have become predominant in farms and villages. However, knowledge on the distribution of these vectors in the country is sparse. From a public health point of view it is important to know the vectors, so that risk factors towards knowlesi malaria can be identified and control measures instituted where possible. Here, we review what is known about the knowlesi malaria vectors and ascertain the gaps in knowledge, so that future studies could concentrate on this paucity of data in-order to address this zoonotic problem.

Application of eco-friendly tools and eco-bio-social strategies to control dengue vectors in urban and peri-urban settings in Thailand

PubMed Central

Kittayapong, Pattamaporn; Thongyuan, Suporn; Olanratmanee, Phanthip; Aumchareoun, Worawit; Koyadun, Surachart; Kittayapong, Rungrith; Butraporn, Piyarat

2012-01-01

Background Dengue is considered one of the most important vector-borne diseases in Thailand. Its incidence is increasing despite routine implementation of national dengue control programmes. This study, conducted during 2010, aimed to demonstrate an application of integrated, community-based, eco-bio-social strategies in combination with locally-produced eco-friendly vector control tools in the dengue control programme, emphasizing urban and peri-urban settings in eastern Thailand. Methodology Three different community settings were selected and were randomly assigned to intervention and control clusters. Key community leaders and relevant governmental authorities were approached to participate in this intervention programme. Ecohealth volunteers were identified and trained in each study community. They were selected among active community health volunteers and were trained by public health experts to conduct vector control activities in their own communities using environmental management in combination with eco-friendly vector control tools. These trained ecohealth volunteers carried out outreach health education and vector control during household visits. Management of public spaces and public properties, especially solid waste management, was efficiently carried out by local municipalities. Significant reduction in the pupae per person index in the intervention clusters when compared to the control ones was used as a proxy to determine the impact of this programme. Results Our community-based dengue vector control programme demonstrated a significant reduction in the pupae per person index during entomological surveys which were conducted at two-month intervals from May 2010 for the total of six months in the intervention and control clusters. The programme also raised awareness in applying eco-friendly vector control approaches and increased intersectoral and household participation in dengue control activities. Conclusion An eco-friendly dengue vector control programme was successfully implemented in urban and peri-urban settings in Thailand, through intersectoral collaboration and practical action at household level, with a significant reduction in vector densities. PMID:23318236

Ecological, biological and social dimensions of dengue vector breeding in five urban settings of Latin America: a multi-country study.

PubMed

Quintero, Juliana; Brochero, Helena; Manrique-Saide, Pablo; Barrera-Pérez, Mario; Basso, César; Romero, Sonnia; Caprara, Andrea; De Lima Cunha, Jane Cris; Beltrán-Ayala, Efraín; Mitchell-Foster, Kendra; Kroeger, Axel; Sommerfeld, Johannnes; Petzold, Max

2014-01-21

Dengue is an increasingly important public health problem in most Latin American countries and more cost-effective ways of reducing dengue vector densities to prevent transmission are in demand by vector control programs. This multi-centre study attempted to identify key factors associated with vector breeding and development as a basis for improving targeted intervention strategies. In each of 5 participant cities in Mexico, Colombia, Ecuador, Brazil and Uruguay, 20 clusters were randomly selected by grid sampling to incorporate 100 contiguous households, non-residential private buildings (businesses) and public spaces. Standardized household surveys, cluster background surveys and entomological surveys specifically targeted to obtain pupal indices for Aedes aegypti, were conducted in the dry and wet seasons. The study clusters included mainly urban low-middle class populations with satisfactory infrastructure and -except for Uruguay- favourable climatic conditions for dengue vector development. Household knowledge about dengue and "dengue mosquitoes" was widespread, mainly through mass media, but there was less awareness around interventions to reduce vector densities. Vector production (measured through pupal indices) was favoured when water containers were outdoor, uncovered, unused (even in Colombia and Ecuador where the large tanks used for household water storage and washing were predominantly productive) and -particularly during the dry season- rainwater filled. Larval infestation did not reflect productive container types. All productive container types, including those important in the dry season, were identified by pupal surveys executed during the rainy season. A number of findings are relevant for improving vector control: 1) there is a need for complementing larval surveys with occasional pupal surveys (to be conducted during the wet season) for identifying and subsequently targeting productive container types; 2) the need to raise public awareness about useful and effective interventions in productive container types specific to their area; and 3) the motivation for control services that-according to this and similar studies in Asia- dedicated, targeted vector management can make a difference in terms of reducing vector abundance.

Application of eco-friendly tools and eco-bio-social strategies to control dengue vectors in urban and peri-urban settings in Thailand.

PubMed

Kittayapong, Pattamaporn; Thongyuan, Suporn; Olanratmanee, Phanthip; Aumchareoun, Worawit; Koyadun, Surachart; Kittayapong, Rungrith; Butraporn, Piyarat

2012-12-01

Dengue is considered one of the most important vector-borne diseases in Thailand. Its incidence is increasing despite routine implementation of national dengue control programmes. This study, conducted during 2010, aimed to demonstrate an application of integrated, community-based, eco-bio-social strategies in combination with locally-produced eco-friendly vector control tools in the dengue control programme, emphasizing urban and peri-urban settings in eastern Thailand. Three different community settings were selected and were randomly assigned to intervention and control clusters. Key community leaders and relevant governmental authorities were approached to participate in this intervention programme. Ecohealth volunteers were identified and trained in each study community. They were selected among active community health volunteers and were trained by public health experts to conduct vector control activities in their own communities using environmental management in combination with eco-friendly vector control tools. These trained ecohealth volunteers carried out outreach health education and vector control during household visits. Management of public spaces and public properties, especially solid waste management, was efficiently carried out by local municipalities. Significant reduction in the pupae per person index in the intervention clusters when compared to the control ones was used as a proxy to determine the impact of this programme. Our community-based dengue vector control programme demonstrated a significant reduction in the pupae per person index during entomological surveys which were conducted at two-month intervals from May 2010 for the total of six months in the intervention and control clusters. The programme also raised awareness in applying eco-friendly vector control approaches and increased intersectoral and household participation in dengue control activities. An eco-friendly dengue vector control programme was successfully implemented in urban and peri-urban settings in Thailand, through intersectoral collaboration and practical action at household level, with a significant reduction in vector densities.

Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

USDA-ARS?s Scientific Manuscript database

The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

Transduction of Photoreceptors With Equine Infectious Anemia Virus Lentiviral Vectors: Safety and Biodistribution of StarGen for Stargardt Disease

PubMed Central

Binley, Katie; Widdowson, Peter; Loader, Julie; Kelleher, Michelle; Iqball, Sharifah; Ferrige, Georgina; de Belin, Jackie; Carlucci, Marie; Angell-Manning, Diana; Hurst, Felicity; Ellis, Scott; Miskin, James; Fernandes, Alcides; Wong, Paul; Allikmets, Rando; Bergstrom, Christopher; Aaberg, Thomas; Yan, Jiong; Kong, Jian; Gouras, Peter; Prefontaine, Annick; Vezina, Mark; Bussieres, Martin; Naylor, Stuart; Mitrophanous, Kyriacos A.

2013-01-01

Purpose. StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. Methods. Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. Results. Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. Conclusions. In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration. PMID:23620430

Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

PubMed Central

2017-01-01

Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971

47 CFR 90.20 - Public Safety Pool.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Public Safety Pool. 90.20 Section 90.20 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.20 Public Safety Pool. (a) Eligibility. The following are eligible to hold authorizations in...

47 CFR 90.20 - Public Safety Pool.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Public Safety Pool. 90.20 Section 90.20 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.20 Public Safety Pool. (a) Eligibility. The following are eligible to hold authorizations in...

47 CFR 90.20 - Public Safety Pool.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Public Safety Pool. 90.20 Section 90.20 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.20 Public Safety Pool. (a) Eligibility. The following are eligible to hold authorizations in...

Public safety training as a force multiplier.

PubMed

Potter, Anthony N; Woodruff, Craig A

2012-01-01

The training of public safety officers to meet the many and varied demands of today's healthcare environment is the second step in developing and maintaining a world class public safety service. Working closely with the corporate training department, and utilizing the latest adult education techniques, the public safety director can ensure that all officers are capable of meeting the challenges threatening the safety and security of his healthcare facilities. This is the second in a series of articles on all aspects of public safety personnel administration.

Historical Perspective on the Current Renaissance for Hematopoietic Stem Cell Gene Therapy.

PubMed

Kohn, Donald B

2017-10-01

Gene therapy using hematopoietic stem cells (HSC) has developed over the past 3 decades, with progressive improvements in the efficacy and safety. Autologous transplantation of HSC modified with murine gammaretroviral vectors first showed clinical benefits for patients with several primary immune deficiencies, but some of these patients suffered complications from vector-related genotoxicity. Lentiviral vectors have been used recently for gene addition to HSC and have yielded clinical benefits for primary immune deficiencies, metabolic diseases, and hemoglobinopathies, without vector-related complications. Gene editing using site-specific endonucleases is emerging as a promising technology for gene therapy and is moving into clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Animal Models of Tick-Borne Hemorrhagic Fever Viruses

PubMed Central

Zivcec, Marko; Safronetz, David; Feldmann, Heinz

2013-01-01

Tick-borne hemorrhagic fever viruses (TBHFV) are detected throughout the African and Eurasian continents and are an emerging or re-emerging threat to many nations. Due to the largely sporadic incidences of these severe diseases, information on human cases and research activities in general have been limited. In the past decade, however, novel TBHFVs have emerged and areas of endemicity have expanded. Therefore, the development of countermeasures is of utmost importance in combating TBHFV as elimination of vectors and interrupting enzootic cycles is all but impossible and ecologically questionable. As in vivo models are the only way to test efficacy and safety of countermeasures, understanding of the available animal models and the development and refinement of animal models is critical in negating the detrimental impact of TBHFVs on public and animal health. PMID:25437041

Natural disasters and communicable diseases in the Americas: contribution of veterinary public health.

PubMed

Schneider, Maria Cristina; Tirado, Maria Cristina; Rereddy, Shruthi; Dugas, Raymond; Borda, Maria Isabel; Peralta, Eduardo Alvarez; Aldighieri, Sylvain; Cosivi, Ottorino

2012-01-01

The consequences of natural disasters on the people living in the Americas are often amplified by socio-economic conditions. This risk may be increased by climate-related changes. The public health consequences of natural disasters include fatalities as well as an increased risk of communicable diseases. Many of these diseases are zoonotic and foodborne diseases. The aim of this article is to provide an overview of the importance of natural disasters for the Americas and to emphasise the contribution of veterinary public health (VPH) to the management of zoonotic and foodborne disease risks. An analysis was conducted of natural disasters that occurred in the Americas between 2004 and 2008. Five cases studies illustrating the contributions of VPH in situations of disaster are presented. The data shows that natural disasters, particularly storms and floods, can create very important public health problems. Central America and the Caribbean, particularly Haiti, presented a higher risk than the other areas of the Americas. Two priority areas of technical cooperation are recommended for this region, namely: reducing the risk of leptospirosis and other vector-borne disease outbreaks related to floods and hurricanes and improving food safety. The contribution of different disciplines and sectors in disaster preparedness and response is of paramount importance to minimise morbidity and mortality.

HIV-1 vaccine strategies utilizing viral vectors including antigen- displayed inoviral vectors.

PubMed

Hassapis, Kyriakos A; Kostrikis, Leondios G

2013-12-01

Antigen-presenting viral vectors have been extensively used as vehicles for the presentation of antigens to the immune system in numerous vaccine strategies. Particularly in HIV vaccine development efforts, two main viral vectors have been used as antigen carriers: (a) live attenuated vectors and (b) virus-like particles (VLPs); the former, although highly effective in animal studies, cannot be clinically tested in humans due to safety concerns and the latter have failed to induce broadly neutralizing anti-HIV antibodies. For more than two decades, Inoviruses (non-lytic bacterial phages) have also been utilized as antigen carriers in several vaccine studies. Inoviral vectors are important antigen-carriers in vaccine development due to their ability to present an antigen on their outer architecture in many copies and to their natural high immunogenicity. Numerous fundamental studies have been conducted, which have established the unique properties of antigen-displayed inoviral vectors in HIV vaccine efforts. The recent isolation of new, potent anti-HIV broadly neutralizing monoclonal antibodies provides a new momentum in this emerging technology.

The Adenovirus Genome Contributes to the Structural Stability of the Virion

PubMed Central

Saha, Bratati; Wong, Carmen M.; Parks, Robin J.

2014-01-01

Adenovirus (Ad) vectors are currently the most commonly used platform for therapeutic gene delivery in human gene therapy clinical trials. Although these vectors are effective, many researchers seek to further improve the safety and efficacy of Ad-based vectors through detailed characterization of basic Ad biology relevant to its function as a vector system. Most Ad vectors are deleted of key, or all, viral protein coding sequences, which functions to not only prevent virus replication but also increase the cloning capacity of the vector for foreign DNA. However, radical modifications to the genome size significantly decreases virion stability, suggesting that the virus genome plays a role in maintaining the physical stability of the Ad virion. Indeed, a similar relationship between genome size and virion stability has been noted for many viruses. This review discusses the impact of the genome size on Ad virion stability and emphasizes the need to consider this aspect of virus biology in Ad-based vector design. PMID:25254384

Vaccination strategies for SIR vector-transmitted diseases.

PubMed

Cruz-Pacheco, Gustavo; Esteva, Lourdes; Vargas, Cristobal

2014-08-01

Vector-borne diseases are one of the major public health problems in the world with the fastest spreading rate. Control measures have been focused on vector control, with poor results in most cases. Vaccines should help to reduce the diseases incidence, but vaccination strategies should also be defined. In this work, we propose a vector-transmitted SIR disease model with age-structured population subject to a vaccination program. We find an expression for the age-dependent basic reproductive number R(0), and we show that the disease-free equilibrium is locally stable for R(0) ≤ 1, and a unique endemic equilibrium exists for R(0) > 1. We apply the theoretical results to public data to evaluate vaccination strategies, immunization levels, and optimal age of vaccination for dengue disease.

Novel Nonreplicating Vaccinia Virus Vector Enhances Expression of Heterologous Genes and Suppresses Synthesis of Endogenous Viral Proteins.

PubMed

Wyatt, Linda S; Xiao, Wei; Americo, Jeffrey L; Earl, Patricia L; Moss, Bernard

2017-06-06

Viruses are used as expression vectors for protein synthesis, immunology research, vaccines, and therapeutics. Advantages of poxvirus vectors include the accommodation of large amounts of heterologous DNA, the presence of a cytoplasmic site of transcription, and high expression levels. On the other hand, competition of approximately 200 viral genes with the target gene for expression and immune recognition may be disadvantageous. We describe a vaccinia virus (VACV) vector that uses an early promoter to express the bacteriophage T7 RNA polymerase; has the A23R intermediate transcription factor gene deleted, thereby restricting virus replication to complementing cells; and has a heterologous gene regulated by a T7 promoter. In noncomplementing cells, viral early gene expression and DNA replication occurred normally but synthesis of intermediate and late proteins was prevented. Nevertheless, the progeny viral DNA provided templates for abundant expression of heterologous genes regulated by a T7 promoter. Selective expression of the Escherichia coli lac repressor gene from an intermediate promoter reduced transcription of the heterologous gene specifically in complementing cells, where large amounts might adversely impact VACV replication. Expression of heterologous proteins mediated by the A23R deletion vector equaled that of a replicating VACV, was higher than that of a nonreplicating modified vaccinia virus Ankara (MVA) vector used for candidate vaccines in vitro and in vivo , and was similarly immunogenic in mice. Unlike the MVA vector, the A23R deletion vector still expresses numerous early genes that can restrict immunogenicity as demonstrated here by the failure of the prototype vector to induce interferon alpha. By deleting immunomodulatory genes, we anticipate further improvements in the system. IMPORTANCE Vaccines provide an efficient and effective way of preventing infectious diseases. Nevertheless, new and better vaccines are needed. Vaccinia virus, which was used successfully as a live vaccine to eradicate smallpox, has been further attenuated and adapted as a recombinant vector for immunization against other pathogens. However, since the initial description of this vector system, only incremental improvements largely related to safety have been implemented. Here we described novel modifications of the platform that increased expression of the heterologous target gene and decreased expression of endogenous vaccinia virus genes while providing safety by preventing replication of the candidate vaccine except in complementing cells used for vector propagation. Copyright © 2017 Wyatt et al.

Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

PubMed

Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

2018-03-16

RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

Safety of gene therapy: new insights to a puzzling case.

PubMed

Rothe, Michael; Schambach, Axel; Biasco, Luca

2014-01-01

Over the last few years, the transfer of therapeutic genes via gammaretro- or lentiviral vector systems has proven its virtue as an alternative treatment for a series of genetic disorders. The number of approved phase I/II clinical trials, especially for rare diseases, is steadily increasing, but the overall hurdles to become a broadly acceptable therapy remain numerous. The efforts by clinicians and basic scientists have tremendously improved the knowledge available about feasibility and biosafety of gene therapy. Nonetheless, despite the generation of a plethora of clinical and preclinical safety data, we still lack sufficiently powerful assays to predictively assess the exact levels of toxicity that might be observed in any given clinical gene therapy. Insertional mutagenesis is one of the major concerns when using integrating vectors for permanent cell modification, and the occurrence of adverse events related to genotoxicity, in early gene therapy trials, has refrained the field of gene therapy from emerging further. In this review, we provided a comprehensive overview on the basic principles and potential co-factors concurring in the generation of adverse events reported in gene therapy clinical trials using integrating vectors. Additionally, we summarized the available systems to assess genotoxicity at the preclinical level and we shed light on the issues affecting the predictive value of these assays when translating their results into the clinical arena. In the last section of the review we briefly touched on the future trends and how they could increase the safety of gene therapy employing integrating vector technology to take it to the next level.

78 FR 10689 - Pipeline Safety: Public Forum State One-Call Exemptions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-14

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No... Safety, Pipeline and Hazardous Materials Safety Administration, DOT. ACTION: Notice; public forum. SUMMARY: The Pipeline and Hazardous Materials Safety Administration will sponsor a public forum on state...

47 CFR 0.192 - Emergency Response Interoperability Center.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Organization Public Safety and Homeland Security Bureau § 0.192 Emergency Response Interoperability Center. (a... Public Safety and Homeland Security Bureau to develop, recommend, and administer policy goals, objectives... and procedures for the 700 MHz public safety broadband wireless network and other public safety...

47 CFR 0.192 - Emergency Response Interoperability Center.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Organization Public Safety and Homeland Security Bureau § 0.192 Emergency Response Interoperability Center. (a... Public Safety and Homeland Security Bureau to develop, recommend, and administer policy goals, objectives... and procedures for the 700 MHz public safety broadband wireless network and other public safety...

Genotoxicity of retroviral hematopoietic stem cell gene therapy

PubMed Central

Trobridge, Grant D

2012-01-01

Introduction Retroviral vectors have been developed for hematopoietic stem cell (HSC) gene therapy and have successfully cured X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency (ADA-SCID), adrenoleukodystrophy, and Wiskott-Aldrich syndrome. However, in HSC gene therapy clinical trials, genotoxicity mediated by integrated vector proviruses has led to clonal expansion, and in some cases frank leukemia. Numerous studies have been performed to understand the molecular basis of vector-mediated genotoxicity with the aim of developing safer vectors and safer gene therapy protocols. These genotoxicity studies are critical to advancing HSC gene therapy. Areas covered This review provides an introduction to the mechanisms of retroviral vector genotoxicity. It also covers advances over the last 20 years in designing safer gene therapy vectors, and in integration site analysis in clinical trials and large animal models. Mechanisms of retroviral-mediated genotoxicity, and the risk factors that contribute to clonal expansion and leukemia in HSC gene therapy are introduced. Expert opinion Continued research on virus–host interactions and next-generation vectors should further improve the safety of future HSC gene therapy vectors and protocols. PMID:21375467

Malaria vector control at a crossroads: public health entomology and the drive to elimination.

PubMed

Mnzava, Abraham P; Macdonald, Michael B; Knox, Tessa B; Temu, Emmanuel A; Shiff, Clive J

2014-09-01

Vector control has been at the core of successful malaria control. However, a dearth of field-oriented vector biologists threatens to undermine global reductions in malaria burden. Skilled cadres are needed to manage insecticide resistance, to maintain coverage with current interventions, to develop new paradigms for tackling 'residual' transmission and to target interventions as transmission becomes increasingly heterogeneous. Recognising this human resource crisis, in September 2013, WHO Global Malaria Programme issued guidance for capacity building in entomology and vector control, including recommendations for countries and implementing partners. Ministries were urged to develop long-range strategic plans for building human resources for public health entomology and vector control (including skills in epidemiology, geographic information systems, operational research and programme management) and to set in place the requisite professional posts and career opportunities. Capacity building and national ownership in all partner projects and a clear exit strategy to sustain human and technical resources after project completion were emphasised. Implementing partners were urged to support global and regional efforts to enhance public health entomology capacity. While the challenges inherent in such capacity building are great, so too are the opportunities to establish the next generation of public health entomologists that will enable programmes to continue on the path to malaria elimination. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

47 CFR 90.1432 - Conditions for waiver to allow limited and temporary wideband operations in the 700 MHz public...

Code of Federal Regulations, 2011 CFR

2011-10-01

... temporary wideband operations in the 700 MHz public safety spectrum. 90.1432 Section 90.1432... and temporary wideband operations in the 700 MHz public safety spectrum. (a) Wideband operations in the 700 MHz Public Safety spectrum. Wideband operations are prohibited in the public safety allocation...

47 CFR 90.1432 - Conditions for waiver to allow limited and temporary wideband operations in the 700 MHz public...

Code of Federal Regulations, 2012 CFR

2012-10-01

... temporary wideband operations in the 700 MHz public safety spectrum. 90.1432 Section 90.1432... and temporary wideband operations in the 700 MHz public safety spectrum. (a) Wideband operations in the 700 MHz Public Safety spectrum. Wideband operations are prohibited in the public safety allocation...

47 CFR 90.1432 - Conditions for waiver to allow limited and temporary wideband operations in the 700 MHz public...

Code of Federal Regulations, 2010 CFR

2010-10-01

... temporary wideband operations in the 700 MHz public safety spectrum. 90.1432 Section 90.1432... and temporary wideband operations in the 700 MHz public safety spectrum. (a) Wideband operations in the 700 MHz Public Safety spectrum. Wideband operations are prohibited in the public safety allocation...

44 CFR 150.5 - Joint Public Safety Awards Board.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Joint Public Safety Awards Board. 150.5 Section 150.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY FIRE PREVENTION AND CONTROL PUBLIC SAFETY AWARDS TO PUBLIC SAFETY OFFICERS...

[Going into the 21st century: should one dream or act?].

PubMed

Coosemans, M

1991-01-01

A historical review of vector control is made. Despite the available tools, vector borne diseases are still a priority in Public Health. Magic tools, like DDT, were often misused. Adapted strategies and structures for vector control are now required. Progress will mainly result from research and evaluation done in the framework of vector control programmes. Discovery of new tools will find in these operational programmes a point of fall for their application.

50 CFR 25.71 - Public safety.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Public safety. 25.71 Section 25.71... NATIONAL WILDLIFE REFUGE SYSTEM ADMINISTRATIVE PROVISIONS Safety Regulations § 25.71 Public safety. Persons using national wildlife refuges shall comply with the safety requirements which are established under...

50 CFR 25.71 - Public safety.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Public safety. 25.71 Section 25.71... NATIONAL WILDLIFE REFUGE SYSTEM ADMINISTRATIVE PROVISIONS Safety Regulations § 25.71 Public safety. Persons using national wildlife refuges shall comply with the safety requirements which are established under...

Disease Severity and Exercise Testing Reduce Subcutaneous Implantable Cardioverter-Defibrillator Left Sternal ECG Screening Success in Hypertrophic Cardiomyopathy.

PubMed

Srinivasan, Neil T; Patel, Kiran H; Qamar, Kashif; Taylor, Amy; Bacà, Marco; Providência, Rui; Tome-Esteban, Maria; Elliott, Perry M; Lambiase, Pier D

2017-04-01

The features of the hypertrophic cardiomyopathy (HCM) ECG make it a challenge for subcutaneous implantable cardioverter-defibrillator (S-ICD) screening. We aimed to investigate the causes of screening failure at rest and on exercise to inform optimal S-ICD ECG vector development. One hundred and thirty-one HCM patients (age, 50±16 years; 92 males and 39 females) with ≥1 HCM risk factor for sudden death underwent S-ICD ECG screening at rest and on exercise. Fifty patients (38%) were ineligible for S-ICD because of screening failure in every lead vector: 33 (66%) failed in the supine position, 12 (24%) failed in the standing position, and 5 (10%) failed on exercise. In patients who could exercise and passed screening at rest, 31 (44%) had 1 vector safety, 16 (23%) had 2 vector safety, and 24 (33%) had 3 vector safety. Increased R:T wave ratio in the S-ICD screening ECG (odds ratio, 4.0; confidence interval, 3.0-5.3; P <0.001) was associated with screening failure, while R/T ratio <3 in aVF (odds ratio, 0.3; confidence interval, 0.12-0.69; P =0.006) and increasing age (odds ratio, 0.97; confidence interval, 0.95-0.99; P =0.03) was associated with reduced screening failure. European Society of Cardiology risk score was higher in those failing screening (risk score 5.5% [interquartile range, 3.2-8.7] in failed versus 4.5% [interquartile range, 2.9-7.4] in passed; P =0.04). HCM patients have a significant incidence of screening failure, which is determined primarily by the increased R:T ratio on the screening ECG and lead aVF. High-risk patients have an increased screening failure rate. Optimization of sensing algorithms is required to ensure that the highest risk HCM patients can benefit from S-ICD implantation. © 2017 American Heart Association, Inc.

GLOBE Observer Mosquito Habitat Mapper: Geoscience and Public Health Connections

NASA Astrophysics Data System (ADS)

Low, R.; Boger, R. A.

2017-12-01

The global health crisis posed by vector-borne diseases is so great in scope that it is clearly insurmountable without the active help of tens-or hundreds- of thousands of individuals, working to identify and eradicate risk in communities around the world. Mobile devices equipped with data collection capabilities and visualization opportunities are lowering the barrier for participation in data collection efforts. The GLOBE Observer Mosquito Habitat Mapper (MHM) provides citizen scientists with an easy to use mobile platform to identify and locate mosquito breeding sites in their community. The app also supports the identification of vector taxa in the larvae development phase via a built-in key, which provides important information for scientists and public health officials tracking the rate of range expansion of invasive vector species and associated health threats. GO Mosquito is actively working with other citizen scientist programs across the world to ensure interoperability of data through standardization of metadata fields specific to vector monitoring, and through the development of APIs that allow for data exchange and shared data display through a UN-sponsored proof of concept project, Global Mosquito Alert. Avenues of application for mosquito vector data-both directly, by public health entities, and by modelers who employ remotely sensed environmental data to project mosquito population dynamics and epidemic disease will be featured.

A National Partnership for Careers in Public Safety and Security

ERIC Educational Resources Information Center

Coffee, Joseph

2007-01-01

A partnership of state, local and federal public safety agencies, secondary and postsecondary educational institutions, and professional and educational associations, the National Partnership for Careers in Law, Public Safety, Corrections and Security also serves as the lead organization for the Law, Public Safety, Corrections and Security Career…

Climate change, vector-borne diseases and working population.

PubMed

Vonesch, Nicoletta; D'Ovidio, Maria Concetta; Melis, Paola; Remoli, Maria Elena; Ciufolini, Maria Grazia; Tomao, Paola

2016-01-01

Risks associated with climate change are increasing worldwide and the global effects include altered weather and precipitation patterns, rising temperatures and others; human health can be affected directly and indirectly. This paper is an overview of literature regarding climate changes, their interaction with vector-borne diseases and impact on working population. Articles regarding climate changes as drivers of vector-borne diseases and evidences of occupational cases have been picked up by public databank. Technical documents were also included in the study. Evidences regarding the impact of climate changes on vector-borne diseases in Europe, provided by the analysis of the literature, are presented. Climate-sensitive vector-borne diseases are likely to be emerging due to climate modifications, with impacts on public and occupational health. However, other environmental and anthropogenic drivers such as increasing travelling and trade, deforestation and reforestation, altered land use and urbanization can influence their spread. Further studies are necessary to better understand the phenomenon and implementation of adaptation strategies to protect human health should be accelerated and strengthened.

77 FR 68070 - Implementing Public Safety Broadband Provisions of the Middle Class Tax Relief and Job Creation...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

...; announcement of effective date. SUMMARY: On October 15, 2012, the Public Safety and Homeland Security Bureau...: Gene Fullano, Federal Communications Commission, Public Safety and Homeland Security Bureau, 445 12th... . SUPPLEMENTARY INFORMATION: On October 15, 2012, the Public Safety and Homeland Security Bureau (Bureau) of the...

10 CFR 871.2 - Public health and safety exemption.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Public health and safety exemption. 871.2 Section 871.2 Energy DEPARTMENT OF ENERGY AIR TRANSPORTATION OF PLUTONIUM § 871.2 Public health and safety exemption... property damage, or other significant threat to the public health and safety. [42 FR 48332, Sept. 23, 1977...

10 CFR 871.2 - Public health and safety exemption.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Public health and safety exemption. 871.2 Section 871.2 Energy DEPARTMENT OF ENERGY AIR TRANSPORTATION OF PLUTONIUM § 871.2 Public health and safety exemption... property damage, or other significant threat to the public health and safety. [42 FR 48332, Sept. 23, 1977...

10 CFR 871.2 - Public health and safety exemption.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Public health and safety exemption. 871.2 Section 871.2 Energy DEPARTMENT OF ENERGY AIR TRANSPORTATION OF PLUTONIUM § 871.2 Public health and safety exemption... property damage, or other significant threat to the public health and safety. [42 FR 48332, Sept. 23, 1977...

10 CFR 871.2 - Public health and safety exemption.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Public health and safety exemption. 871.2 Section 871.2 Energy DEPARTMENT OF ENERGY AIR TRANSPORTATION OF PLUTONIUM § 871.2 Public health and safety exemption... property damage, or other significant threat to the public health and safety. [42 FR 48332, Sept. 23, 1977...

25 CFR 559.7 - May the Chairman request Indian lands or environmental and public health and safety documentation...

Code of Federal Regulations, 2012 CFR

2012-04-01

... and public health and safety documentation regarding any gaming place, facility, or location where... environmental and public health and safety documentation regarding any gaming place, facility, or location where gaming will occur? A tribe shall provide Indian lands or environmental and public health and safety...

10 CFR 871.2 - Public health and safety exemption.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Public health and safety exemption. 871.2 Section 871.2 Energy DEPARTMENT OF ENERGY AIR TRANSPORTATION OF PLUTONIUM § 871.2 Public health and safety exemption... property damage, or other significant threat to the public health and safety. [42 FR 48332, Sept. 23, 1977...

76 FR 10295 - Implementing a Nationwide, Broadband, Interoperable Public Safety Network in the 700 MHz Band

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-24

... Docket 07-100; FCC 11-6] Implementing a Nationwide, Broadband, Interoperable Public Safety Network in the... framework for the nationwide public safety broadband network. This document considers and proposes... broadband networks operating in the 700 MHz band. This document addresses public safety broadband network...

25 CFR 559.7 - May the Chairman request Indian lands or environmental and public health and safety documentation...

Code of Federal Regulations, 2010 CFR

2010-04-01

... and public health and safety documentation regarding any gaming place, facility, or location where... environmental and public health and safety documentation regarding any gaming place, facility, or location where gaming will occur? A tribe shall provide Indian lands or environmental and public health and safety...

25 CFR 559.7 - May the Chairman request Indian lands or environmental and public health and safety documentation...

Code of Federal Regulations, 2011 CFR

2011-04-01

... and public health and safety documentation regarding any gaming place, facility, or location where... environmental and public health and safety documentation regarding any gaming place, facility, or location where gaming will occur? A tribe shall provide Indian lands or environmental and public health and safety...

Traffic De-Anonymizer

DTIC Science & Technology

2014-11-01

November 2014 © Her Majesty the Queen in Right of Canada, as represented by the Minister of National Defence, 2014 © Sa Majesté la Reine (en droit du...partnership with Public Safety Canada. The project was led by Public Safety Canada in partnership with Dalhousie University. Canadian Safety and...Development Canada’s Centre for Security Science in partnership with Public Safety Canada. The project was led by Public Safety Canada in partnership with

Ecological, biological and social dimensions of dengue vector breeding in five urban settings of Latin America: a multi-country study

PubMed Central

2014-01-01

Background Dengue is an increasingly important public health problem in most Latin American countries and more cost-effective ways of reducing dengue vector densities to prevent transmission are in demand by vector control programs. This multi-centre study attempted to identify key factors associated with vector breeding and development as a basis for improving targeted intervention strategies. Methods In each of 5 participant cities in Mexico, Colombia, Ecuador, Brazil and Uruguay, 20 clusters were randomly selected by grid sampling to incorporate 100 contiguous households, non-residential private buildings (businesses) and public spaces. Standardized household surveys, cluster background surveys and entomological surveys specifically targeted to obtain pupal indices for Aedes aegypti, were conducted in the dry and wet seasons. Results The study clusters included mainly urban low-middle class populations with satisfactory infrastructure and –except for Uruguay- favourable climatic conditions for dengue vector development. Household knowledge about dengue and “dengue mosquitoes” was widespread, mainly through mass media, but there was less awareness around interventions to reduce vector densities. Vector production (measured through pupal indices) was favoured when water containers were outdoor, uncovered, unused (even in Colombia and Ecuador where the large tanks used for household water storage and washing were predominantly productive) and –particularly during the dry season- rainwater filled. Larval infestation did not reflect productive container types. All productive container types, including those important in the dry season, were identified by pupal surveys executed during the rainy season. Conclusions A number of findings are relevant for improving vector control: 1) there is a need for complementing larval surveys with occasional pupal surveys (to be conducted during the wet season) for identifying and subsequently targeting productive container types; 2) the need to raise public awareness about useful and effective interventions in productive container types specific to their area; and 3) the motivation for control services that-according to this and similar studies in Asia- dedicated, targeted vector management can make a difference in terms of reducing vector abundance. PMID:24447796

Correction of murine hemophilia A following nonmyeloablative transplantation of hematopoietic stem cells engineered to encode an enhanced human factor VIII variant using a safety-augmented retroviral vector

PubMed Central

Ramezani, Ali

2009-01-01

Insertional mutagenesis by retroviral vectors is a major impediment to the clinical application of hematopoietic stem cell gene transfer for the treatment of hematologic disorders. We recently developed an insulated self-inactivating gammaretroviral vector, RMSinOFB, which uses a novel enhancer-blocking element that significantly decreases genotoxicity of retroviral integration. In this study, we used the RMSinOFB vector to evaluate the efficacy of a newly bioengineered factor VIII (fVIII) variant (efVIII)—containing a combination of A1 domain point mutations (L303E/F309S) and an extended partial B domain for improved secretion plus A2 domain mutations (R484A/R489A/P492A) for reduced immunogenicity—toward successful treatment of murine hemophilia A. In cell lines, efVIII was secreted at up to 6-fold higher levels than an L303E/F309S A1 domain–only fVIII variant (sfVIIIΔB). Most important, when compared with a conventional gammaretroviral vector expressing sfVIIIΔB, lower doses of RMSin-efVIII-OFB–transduced hematopoietic stem cells were needed to generate comparable curative fVIII levels in hemophilia A BALB/c mice after reduced-intensity total body irradiation or nonmyeloablative chemotherapy conditioning regimens. These data suggest that the safety-augmented RMSin-efVIII-OFB platform represents an encouraging step in the development of a clinically appropriate gene addition therapy for hemophilia A. PMID:19470695

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector

PubMed Central

Lichtenstein, DL; Spencer, JF; Doronin, K; Patra, D; Meyer, JM; Shashkova, EV; Kuppuswamy, M; Dhar, D; Thomas, MA; Tollefson, AE; Zumstein, LA; Wold, WSM; Toth, K

2012-01-01

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 × 1010 viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007. PMID:19197324

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.

PubMed

Lichtenstein, D L; Spencer, J F; Doronin, K; Patra, D; Meyer, J M; Shashkova, E V; Kuppuswamy, M; Dhar, D; Thomas, M A; Tollefson, A E; Zumstein, L A; Wold, W S M; Toth, K

2009-08-01

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 x 10(10) viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007.

43 CFR 8365.1-4 - Public health, safety and comfort.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Public health, safety and comfort. 8365.1-4 Section 8365.1-4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.1-4 Public health, safety and comfort. (a) No person shall cause a public disturbance or create a...

43 CFR 8365.1-4 - Public health, safety and comfort.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Public health, safety and comfort. 8365.1-4 Section 8365.1-4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.1-4 Public health, safety and comfort. (a) No person shall cause a public disturbance or create a...

43 CFR 8365.1-4 - Public health, safety and comfort.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Public health, safety and comfort. 8365.1-4 Section 8365.1-4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.1-4 Public health, safety and comfort. (a) No person shall cause a public disturbance or create a...

43 CFR 8365.1-4 - Public health, safety and comfort.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Public health, safety and comfort. 8365.1-4 Section 8365.1-4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.1-4 Public health, safety and comfort. (a) No person shall cause a public disturbance or create a...

Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs.

PubMed

Jaén, Maria Luisa; Vilà, Laia; Elias, Ivet; Jimenez, Veronica; Rodó, Jordi; Maggioni, Luca; Ruiz-de Gopegui, Rafael; Garcia, Miguel; Muñoz, Sergio; Callejas, David; Ayuso, Eduard; Ferré, Tura; Grifoll, Iris; Andaluz, Anna; Ruberte, Jesus; Haurigot, Virginia; Bosch, Fatima

2017-09-15

Diabetes is a complex metabolic disease that exposes patients to the deleterious effects of hyperglycemia on various organs. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We developed a gene therapy approach to control diabetic hyperglycemia based on co-expression of the insulin and glucokinase genes in skeletal muscle. Previous studies proved the feasibility of gene delivery to large diabetic animals with adeno-associated viral (AAV) vectors. Here, we report the long-term (∼8 years) follow-up after a single administration of therapeutic vectors to diabetic dogs. Successful, multi-year control of glycemia was achieved without the need of supplementation with exogenous insulin. Metabolic correction was demonstrated through normalization of serum levels of fructosamine, triglycerides, and cholesterol and remarkable improvement in the response to an oral glucose challenge. The persistence of vector genomes and therapeutic transgene expression years after vector delivery was documented in multiple samples from treated muscles, which showed normal morphology. Thus, this study demonstrates the long-term efficacy and safety of insulin and glucokinase gene transfer in large animals and especially the ability of the system to respond to the changes in metabolic needs as animals grow older.

Management of arthropod pathogen vectors in North America: Minimizing adverse effects on pollinators

USGS Publications Warehouse

Ginsberg, Howard; Bargar, Timothy A.; Hladik, Michelle L.; Lubelczyk, Charles

2017-01-01

Tick and mosquito management is important to public health protection. At the same time, growing concerns about declines of pollinator species raise the question of whether vector control practices might affect pollinator populations. We report the results of a task force of the North American Pollinator Protection Campaign (NAPPC) that examined potential effects of vector management practices on pollinators, and how these programs could be adjusted to minimize negative effects on pollinating species. The main types of vector control practices that might affect pollinators are landscape manipulation, biocontrol, and pesticide applications. Some current practices already minimize effects of vector control on pollinators (e.g., short-lived pesticides and application-targeting technologies). Nontarget effects can be further diminished by taking pollinator protection into account in the planning stages of vector management programs. Effects of vector control on pollinator species often depend on specific local conditions (e.g., proximity of locations with abundant vectors to concentrations of floral resources), so planning is most effective when it includes collaborations of local vector management professionals with local experts on pollinators. Interventions can then be designed to avoid pollinators (e.g., targeting applications to avoid blooming times and pollinator nesting habitats), while still optimizing public health protection. Research on efficient targeting of interventions, and on effects on pollinators of emerging technologies, will help mitigate potential deleterious effects on pollinators in future management programs. In particular, models that can predict effects of integrated pest management on vector-borne pathogen transmission, along with effects on pollinator populations, would be useful for collaborative decision-making.

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

PubMed Central

Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

43 CFR 8365.2-5 - Public health, safety and comfort.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Public health, safety and comfort. 8365.2-5 Section 8365.2-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.2-5 Public health, safety and comfort. On developed recreation sites and areas, unless otherwise...

43 CFR 8365.2-5 - Public health, safety and comfort.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Public health, safety and comfort. 8365.2-5 Section 8365.2-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.2-5 Public health, safety and comfort. On developed recreation sites and areas, unless otherwise...

43 CFR 8365.2-5 - Public health, safety and comfort.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Public health, safety and comfort. 8365.2-5 Section 8365.2-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.2-5 Public health, safety and comfort. On developed recreation sites and areas, unless otherwise...

43 CFR 8365.2-5 - Public health, safety and comfort.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Public health, safety and comfort. 8365.2-5 Section 8365.2-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... § 8365.2-5 Public health, safety and comfort. On developed recreation sites and areas, unless otherwise...

Analysis of Particle Content of Recombinant Adeno-Associated Virus Serotype 8 Vectors by Ion-Exchange Chromatography

PubMed Central

Lock, Martin; Alvira, Mauricio R.

2012-01-01

Abstract Advances in adeno-associated virus (AAV)-mediated gene therapy have brought the possibility of commercial manufacturing of AAV vectors one step closer. To realize this prospect, a parallel effort with the goal of ever-increasing sophistication for AAV vector production technology and supporting assays will be required. Among the important release assays for a clinical gene therapy product, those monitoring potentially hazardous contaminants are most critical for patient safety. A prominent contaminant in many AAV vector preparations is vector particles lacking a genome, which can substantially increase the dose of AAV capsid proteins and lead to possible unwanted immunological consequences. Current methods to determine empty particle content suffer from inconsistency, are adversely affected by contaminants, or are not applicable to all serotypes. Here we describe the development of an ion-exchange chromatography-based assay that permits the rapid separation and relative quantification of AAV8 empty and full vector particles through the application of shallow gradients and a strong anion-exchange monolith chromatography medium. PMID:22428980

Gene delivery with viral vectors for cerebrovascular diseases

PubMed Central

Gan, Yu; Jing, Zheng; Stetler, R. Anne; Cao, Guodong

2017-01-01

Recent achievements in the understanding of molecular events involved in the pathogenesis of central nervous system (CNS) injury have made gene transfer a promising approach for various neurological disorders, including cerebrovascular diseases. However, special obstacles, including the post-mitotic nature of neurons and the blood-brain barrier (BBB), constitute key challenges for gene delivery to the CNS. Despite the various limitations in current gene delivery systems, a spectrum of viral vectors has been successfully used to deliver genes to the CNS. Furthermore, recent advancements in vector engineering have improved the safety and delivery of viral vectors. Numerous viral vector-based clinical trials for neurological disorders have been initiated. This review will summarize the current implementation of viral gene delivery in the context of cerebrovascular diseases including ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage (SAH). In particular, we will discuss the potentially feasible ways in which viral vectors can be manipulated and exploited for use in neural delivery and therapy. PMID:23276981

Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

PubMed

Morille, Marie; Passirani, Catherine; Vonarbourg, Arnaud; Clavreul, Anne; Benoit, Jean-Pierre

2008-01-01

Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection and for multi-located tumor sites, i.e. metastases. Non-viral vectors based on the use of cationic lipids or polymers appear to have promising potential, given the problems of safety encountered with viral vectors. Using these non-viral vectors, the current challenge is to obtain a similarly effective transfection to viral ones. Based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers, the aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer.

Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

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

Barkhouse, Darryll A.; Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107; Faber, Milosz

Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4more » RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.« less

41 CFR 50-204.2 - General safety and health standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true General safety and health... Public Contracts PUBLIC CONTRACTS, DEPARTMENT OF LABOR 204-SAFETY AND HEALTH STANDARDS FOR FEDERAL SUPPLY CONTRACTS General Safety and Health Standards § 50-204.2 General safety and health standards. (a) Every...

47 CFR 27.303 - Upper 700 MHz commercial and public safety coordination zone.

Code of Federal Regulations, 2010 CFR

2010-10-01

... operators are required, prior to commencing operations on fixed or base station transmitters on the 776-787 MHz and 788-793 MHz bands that are located within 500 meters of existing or planned public safety base... license. Public safety base stations are considered “planned” when public safety operators have notified...

76 FR 51271 - Implementing a Nationwide, Broadband, Interoperable Public Safety Network in the 700 MHz Band

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... Docket 07-100; FCC 11-6] Implementing a Nationwide, Broadband, Interoperable Public Safety Network in the... interoperable public safety broadband network. The establishment of a common air interface for 700 MHz public safety broadband networks will create a foundation for interoperability and provide a clear path for the...

25 CFR 1000.304 - What is imminent jeopardy to public health and safety?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 2 2011-04-01 2011-04-01 false What is imminent jeopardy to public health and safety...-DETERMINATION AND EDUCATION ACT Reassumption § 1000.304 What is imminent jeopardy to public health and safety? Imminent jeopardy to public health and safety means an immediate and significant threat of serious harm to...

25 CFR 1000.304 - What is imminent jeopardy to public health and safety?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false What is imminent jeopardy to public health and safety...-DETERMINATION AND EDUCATION ACT Reassumption § 1000.304 What is imminent jeopardy to public health and safety? Imminent jeopardy to public health and safety means an immediate and significant threat of serious harm to...

Applications and challenges of multivalent recombinant vaccines

PubMed Central

Naim, Hussein Y.

2013-01-01

The exceptional discoveries of antigen/gene delivery systems have allowed the development of novel prophylactic and therapeutic vaccine candidates. The vaccine candidates employ various antigen-delivery systems, particularly recombinant viral vectors. Recombinant viral vectors are experimental vaccines similar to DNA vaccines, but they use attenuated viruses or bacterium as a carrier “vector” to introduce microbial DNA to cells of the body. They closely mimic a natural infection and therefore can efficiently stimulate the immune system. Although such recombinant vectors may face extensive preclinical testing and will possibly have to meet stringent regulatory requirements, some of these vectors (e.g. measles virus vectors) may benefit from the profound industrial and clinical experience of the parent vaccine. Most notably, novel vaccines based on live attenuated viruses combine the induction of broad, strong and persistent immune responses with acceptable safety profiles. We assess certain technologies in light of their use against human immunodeficiency virus (HIV). PMID:23249651

Curing genetic disease with gene therapy.

PubMed

Williams, David A

2014-01-01

Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile.

Overcoming preexisting humoral immunity to AAV using capsid decoys.

PubMed

Mingozzi, Federico; Anguela, Xavier M; Pavani, Giulia; Chen, Yifeng; Davidson, Robert J; Hui, Daniel J; Yazicioglu, Mustafa; Elkouby, Liron; Hinderer, Christian J; Faella, Armida; Howard, Carolann; Tai, Alex; Podsakoff, Gregory M; Zhou, Shangzhen; Basner-Tschakarjan, Etiena; Wright, John Fraser; High, Katherine A

2013-07-17

Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery.

Curing Genetic Disease with Gene Therapy

PubMed Central

Williams, David A.

2014-01-01

Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile. PMID:25125725

Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys

PubMed Central

Anguela, Xavier M.; Pavani, Giulia; Chen, Yifeng; Davidson, Robert J.; Hui, Daniel J.; Yazicioglu, Mustafa; Elkouby, Liron; Hinderer, Christian J.; Faella, Armida; Howard, Carolann; Tai, Alex; Podsakoff, Gregory M.; Zhou, Shangzhen; Basner-Tschakarjan, Etiena; Wright, John Fraser

2014-01-01

Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery. PMID:23863832

78 FR 53790 - Public Forum-Safety Culture: Enhancing Transportation Safety

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... NATIONAL TRANSPORTATION SAFETY BOARD Public Forum--Safety Culture: Enhancing Transportation Safety On Tuesday and Wednesday, September 10-11, 2013, the National Transportation Safety Board (NTSB) will convene a forum titled, ``Safety Culture: Enhancing Transportation Safety.'' The forum will begin at 9:00...

1980 survey of public perceptions on highway safety.

DOT National Transportation Integrated Search

1980-09-01

The 1980 survey again found a wide discrepancy between public attitudes : and perceptions about safety belts and the public's usage of safety : belts. While it is widely believed that safety belts may help to : prevent serious injury in an automobile...

Ebola and Human Rights: Post-9/11 Public Health and Safety in Epidemics.

PubMed

Annas, George J

2016-05-01

In public health practice, the concepts of health and safety are often conflated. However, protecting and promoting health is radically different from protecting and promoting safety. Since 9/11, the distinctions between health and safety have changed and are in the process of merging. In our terrorism-obsessed world, public health has been increasingly militarized and enlisted, often without protest, into the service of protecting the safety of the public and the security of the nation. But safety and security are the proper purposes of law enforcement and the military, not of public health. More importantly, using public health to combat terrorism is often counterproductive to the population's health, and undermines human rights. Using the Ebola epidemic of 2014, this Article suggests how the post-9/11 reframing of public health goals as including disaster preparedness and counterterrorism, and the new military metaphors we have adopted to describe public health, have deformed our public health agencies, and have made them less trusted by the public. In turn, these agencies are therefore less able to prevent and respond to new infectious diseases. The United States' response to Ebola gives us an opportunity to reconsider the merger of public health and public safety domestically and globally. This Article suggests that a deeper commitment to human rights, especially to the right to health, has the theoretical and practical strength to act as a countervailing force and refocus public health on the health of populations rather than on safety and national security.

Novel Propulsion and Power Concepts for 21st Century Aviation

NASA Technical Reports Server (NTRS)

Sehra, Arun K.

2003-01-01

The air transportation for the new millennium will require revolutionary solutions to meeting public demand for improving safety, reliability, environmental compatibility, and affordability. NASA s vision for 21st Century Aircraft is to develop propulsion systems that are intelligent, virtually inaudible (outside the airport boundaries), and have near zero harmful emissions (CO2 and NO(x)). This vision includes intelligent engines that will be capable of adapting to changing internal and external conditions to optimally accomplish the mission with minimal human intervention. The distributed vectored propulsion will replace two to four wing mounted or fuselage mounted engines by a large number of small, mini, or micro engines. And the electric drive propulsion based on fuel cell power will generate electric power, which in turn will drive propulsors to produce the desired thrust. Such a system will completely eliminate the harmful emissions.

Augmented Reality Based Doppler Lidar Data Visualization: Promises and Challenges

NASA Astrophysics Data System (ADS)

Cherukuru, N. W.; Calhoun, R.

2016-06-01

Augmented reality (AR) is a technology in which the enables the user to view virtual content as if it existed in real world. We are exploring the possibility of using this technology to view radial velocities or processed wind vectors from a Doppler wind lidar, thus giving the user an ability to see the wind in a literal sense. This approach could find possible applications in aviation safety, atmospheric data visualization as well as in weather education and public outreach. As a proof of concept, we used the lidar data from a recent field campaign and developed a smartphone application to view the lidar scan in augmented reality. In this paper, we give a brief methodology of this feasibility study, present the challenges and promises of using AR technology in conjunction with Doppler wind lidars.

Handbook for Public Playground Safety.

ERIC Educational Resources Information Center

Consumer Product Safety Commission, Washington, DC.

Playgrounds, being a fundamental part of the childhood experience, should be safe havens for children. This handbook includes technical safety guidelines for designing, constructing, operating, and maintaining public playgrounds. It also includes a "Public Playground Safety Checklist" to highlight some of the most important safety issues…

Canine vector-borne diseases in Brazil

PubMed Central

Dantas-Torres, Filipe

2008-01-01

Canine vector-borne diseases (CVBDs) are highly prevalent in Brazil and represent a challenge to veterinarians and public health workers, since some diseases are of great zoonotic potential. Dogs are affected by many protozoa (e.g., Babesia vogeli, Leishmania infantum, and Trypanosoma cruzi), bacteria (e.g., Anaplasma platys and Ehrlichia canis), and helminths (e.g., Dirofilaria immitis and Dipylidium caninum) that are transmitted by a diverse range of arthropod vectors, including ticks, fleas, lice, triatomines, mosquitoes, tabanids, and phlebotomine sand flies. This article focuses on several aspects (etiology, transmission, distribution, prevalence, risk factors, diagnosis, control, prevention, and public health significance) of CVBDs in Brazil and discusses research gaps to be addressed in future studies. PMID:18691408

An agent-vector-host-environment model for controlling small arms and light weapons.

PubMed

Pinto, Andrew D; Sharma, Malika; Muggah, Robert

2011-05-01

Armed violence is a significant public health problem. It results in fatal and non-fatal injuries and disrupts social and economic processes that are essential to the health of individuals and communities. We argue that an agent-vector-host-environment model can be helpful in understanding and describing the availability and misuse of small arms and light weapons. Moreover, such a model can assist in identifying potential control points and in developing mitigation strategies. These concepts have been developed from analogous vector control programs and are applied to controlling arms to reduce their misuse. So-called 'denormalization' and 'de-legitimization' campaigns that focus on the vector - including the industry producing these commodities - can be based on the experience of public health in controlling tobacco use and exposure. This model can assist health professionals, civil society and governments in developing comprehensive strategies to limit the production, distribution and misuse of small arms and light weapons.

Optimized Lentiviral Vector Design Improves Titer and Transgene Expression of Vectors Containing the Chicken β-Globin Locus HS4 Insulator Element

PubMed Central

Hanawa, Hideki; Yamamoto, Motoko; Zhao, Huifen; Shimada, Takashi; Persons, Derek A

2009-01-01

Hematopoietic cell gene therapy using retroviral vectors has achieved success in clinical trials. However, safety issues regarding vector insertional mutagenesis have emerged. In two different trials, vector insertion resulted in the transcriptional activation of proto-oncogenes. One strategy for potentially diminishing vector insertional mutagenesis is through the use of self-inactivating lentiviral vectors containing the 1.2-kb insulator element derived from the chicken β-globin locus. However, use of this element can dramatically decrease both vector titer and transgene expression, thereby compromising its practical use. Here, we studied lentiviral vectors containing either the full-length 1.2-kb insulator or the smaller 0.25-kb core element in both orientations in the partially deleted long-terminal repeat. We show that use of the 0.25-kb core insulator rescued vector titer by alleviating a postentry block to reverse transcription associated with the 1.2-kb element. In addition, in an orientation-dependent manner, the 0.25-kb core element significantly increased transgene expression from an internal promoter due to improved transcriptional termination. This element also demonstrated barrier activity, reducing variability of expression due to position effects. As it is known that the 0.25-kb core insulator has enhancer-blocking activity, this particular insulated lentiviral vector design may be useful for clinical application. PMID:19223867

Ribosomal DNA Integrating rAAV-rDNA Vectors Allow for Stable Transgene Expression

PubMed Central

Lisowski, Leszek; Lau, Ashley; Wang, Zhongya; Zhang, Yue; Zhang, Feijie; Grompe, Markus; Kay, Mark A

2012-01-01

Although recombinant adeno-associated virus (rAAV) vectors are proving to be efficacious in clinical trials, the episomal character of the delivered transgene restricts their effectiveness to use in quiescent tissues, and may not provide lifelong expression. In contrast, integrating vectors enhance the risk of insertional mutagenesis. In an attempt to overcome both of these limitations, we created new rAAV-rDNA vectors, with an expression cassette flanked by ribosomal DNA (rDNA) sequences capable of homologous recombination into genomic rDNA. We show that after in vivo delivery the rAAV-rDNA vectors integrated into the genomic rDNA locus 8–13 times more frequently than control vectors, providing an estimate that 23–39% of the integrations were specific to the rDNA locus. Moreover, a rAAV-rDNA vector containing a human factor IX (hFIX) expression cassette resulted in sustained therapeutic levels of serum hFIX even after repeated manipulations to induce liver regeneration. Because of the relative safety of integration in the rDNA locus, these vectors expand the usage of rAAV for therapeutics requiring long-term gene transfer into dividing cells. PMID:22990671

A qualitative exploration of the perceptions and information needs of public health inspectors responsible for food safety

PubMed Central

2010-01-01

Background In Ontario, local public health inspectors play an important frontline role in protecting the public from foodborne illness. This study was an in-depth exploration of public health inspectors' perceptions of the key food safety issues in public health, and their opinions and needs with regards to food safety information resources. Methods Four focus group discussions were conducted with public health inspectors from the Central West region of Ontario, Canada during June and July, 2008. A questioning route was used to standardize qualitative data collection. Audio recordings of sessions were transcribed verbatim and data-driven content analysis was performed. Results A total of 23 public health inspectors participated in four focus group discussions. Five themes emerged as key food safety issues: time-temperature abuse, inadequate handwashing, cross-contamination, the lack of food safety knowledge by food handlers and food premise operators, and the lack of food safety information and knowledge about specialty foods (i.e., foods from different cultures). In general, participants reported confidence with their current knowledge of food safety issues and foodborne pathogens. Participants highlighted the need for a central source for food safety information, access to up-to-date food safety information, resources in different languages, and additional food safety information on specialty foods. Conclusions The information gathered from these focus groups can provide a basis for the development of resources that will meet the specific needs of public health inspectors involved in protecting and promoting food safety. PMID:20553592

49 CFR 190.239 - Safety orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pipeline integrity risk to public safety, property, or the environment, the Associate Administrator may... existence of a condition that poses a pipeline integrity risk to public safety, property, or the environment... public safety, property, or the environment. (5) Post-hearing action. Following a hearing under this...

14 CFR 437.81 - Public safety responsibility.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Public safety responsibility. 437.81 Section 437.81 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... an experimental permit is safe, and must protect public health and safety and the safety of property. ...

14 CFR 437.81 - Public safety responsibility.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Public safety responsibility. 437.81 Section 437.81 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... an experimental permit is safe, and must protect public health and safety and the safety of property. ...

Novel lipophilic chloroquine analogues for a highly efficient gene transfer into gynecological tumors.

PubMed

Keil, O; Bojar, H; Prisack, H B; Dall, P

2001-10-08

Liposomal vectors based on cationic lipids have been proven to be an attractive alternative to viral vectors in gene therapy protocols with regard to safety and manufacturing concerns. In order to improve the transfection efficiency we have synthesized two novel carboxycholesteryl-modified chloroquine analogues. Due to their potential endosomal buffering capacity these compounds enable the efficient transfection of various gynecological tumors and therefore are promising reagents in gene therapy applications.

Successes and failures of sixty years of vector control in French Guiana: what is the next step?

PubMed

Epelboin, Yanouk; Chaney, Sarah C; Guidez, Amandine; Habchi-Hanriot, Nausicaa; Talaga, Stanislas; Wang, Lanjiao; Dusfour, Isabelle

2018-03-12

Since the 1940s, French Guiana has implemented vector control to contain or eliminate malaria, yellow fever, and, recently, dengue, chikungunya, and Zika. Over time, strategies have evolved depending on the location, efficacy of the methods, development of insecticide resistance, and advances in vector control techniques. This review summarises the history of vector control in French Guiana by reporting the records found in the private archives of the Institute Pasteur in French Guiana and those accessible in libraries worldwide. This publication highlights successes and failures in vector control and identifies the constraints and expectations for vector control in this French overseas territory in the Americas.

Liver-Directed Lentiviral Gene Therapy in a Dog Model of Hemophilia B

PubMed Central

Bartholomae, Cynthia C.; Volpin, Monica; Della Valle, Patrizia; Sanvito, Francesca; Sergi Sergi, Lucia; Gallina, Pierangela; Benedicenti, Fabrizio; Bellinger, Dwight; Raymer, Robin; Merricks, Elizabeth; Bellintani, Francesca; Martin, Samia; Doglioni, Claudio; D’Angelo, Armando; VandenDriessche, Thierry; Chuah, Marinee K.; Schmidt, Manfred; Nichols, Timothy; Montini, Eugenio; Naldini, Luigi

2017-01-01

We investigated the safety and efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B, and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We show that gene therapy using lentiviral vectors targeting expression of a canine factor IX transgene to hepatocytes was well-tolerated and provided stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we show that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be useful for the treatment of hemophilia. PMID:25739762

[Biomedical foundation for human safety in aviation].

PubMed

Ushakov, I B

2004-01-01

According to the author, preventive medical issues of providing human safety in aviation are related to the fundamental biomedical and socio-psychological problems of human beings in the present-day world. Factual material for analysis was compiled in the study performed at the State Research and Test Institute of Military Medicine. Outlined are main vectors of the future attack on the problem.

Bioterrorism Preparedness for Infectious Disease (BTPID) Proposal

DTIC Science & Technology

2007-01-01

approximately $210,000/ year x 5 years. (Pending) Safety, Tolerability and Immunogenicity of ACAM3000 Modified Vaccinia Ankara (MVA) Small Pox ...Hospital. • (Pending) Safety, Tolerability and Immunogenicity of ACAM3000 Modified Vaccinia Ankara (MVA) Small Pox Vaccine in HIV-Seropositive...choosing optimal pox virus derived vectors as vaccines in terms of reducing clinical reactogenicity and inducing dendritic cell (DC) aturation. 2006 Elsevier

Derivation of improved load transformation matrices for launchers-spacecraft coupled analysis, and direct computation of margins of safety

NASA Technical Reports Server (NTRS)

Klein, M.; Reynolds, J.; Ricks, E.

1989-01-01

Load and stress recovery from transient dynamic studies are improved upon using an extended acceleration vector in the modal acceleration technique applied to structural analysis. Extension of the normal LTM (load transformation matrices) stress recovery to automatically compute margins of safety is presented with an application to the Hubble space telescope.

Research on public participant urban infrastructure safety monitoring system using smartphone

NASA Astrophysics Data System (ADS)

Zhao, Xuefeng; Wang, Niannian; Ou, Jinping; Yu, Yan; Li, Mingchu

2017-04-01

Currently more and more people concerned about the safety of major public security. Public participant urban infrastructure safety monitoring and investigation has become a trend in the era of big data. In this paper, public participant urban infrastructure safety protection system based on smart phones is proposed. The system makes it possible to public participant disaster data collection, monitoring and emergency evaluation in the field of disaster prevention and mitigation. Function of the system is to monitor the structural acceleration, angle and other vibration information, and extract structural deformation and implement disaster emergency communications based on smartphone without network. The monitoring data is uploaded to the website to create urban safety information database. Then the system supports big data analysis processing, the structure safety assessment and city safety early warning.

Epidemic Potential for Local Transmission of Zika Virus in 2015 and 2016 in Queensland, Australia.

PubMed

Viennet, Elvina; Mincham, Gina; Frentiu, Francesca D; Jansen, Cassie C; Montgomery, Brian L; Harley, David; Flower, Robert L P; Williams, Craig R; Faddy, Helen M

2016-12-13

Zika virus could be transmitted in the state of Queensland, Australia, in parts of the state where the mosquito vectors are established. We assessed the epidemic potential of Zika in Queensland from January 2015 to August 2016, and estimate the epidemic potential from September to December 2016, by calculating the temperature-dependent relative vectorial capacity (rVc), based on empirical and estimated parameters. Through 2015, we estimated a rVc of 0.119, 0.152, 0.170, and 0.175, respectively in the major cities of Brisbane, Rockhampton, Cairns, and Townsville. From January to August 2016, the epidemic potential trend was similar to 2015, however the highest epidemic potential was in Cairns. During September to November 2016, the epidemic potential is consistently the highest in Cairns, followed by Townsville, Rockhampton and Brisbane. Then, from November to December 2016, Townsville has the highest estimated epidemic potential. We demonstrate using a vectorial capacity model that ZIKV could have been locally transmitted in Queensland, Australia during 2015 and 2016. ZIKV remains a threat to Australia for the upcoming summer, during the Brazilian Carnival season, when the abundance of vectors is relatively high. Understanding the epidemic potential of local ZIKV transmission will allow better management of threats to blood safety and assessment of public health risk.

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines

PubMed Central

Kim, Shin-Hee; Samal, Siba K.

2016-01-01

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens. PMID:27384578

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.

PubMed

Kim, Shin-Hee; Samal, Siba K

2016-07-04

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

PubMed Central

2011-01-01

Background The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed. Results Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented. Conclusions This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps. PMID:21612587

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis.

PubMed

Sinka, Marianne E; Bangs, Michael J; Manguin, Sylvie; Chareonviriyaphap, Theeraphap; Patil, Anand P; Temperley, William H; Gething, Peter W; Elyazar, Iqbal R F; Kabaria, Caroline W; Harbach, Ralph E; Hay, Simon I

2011-05-25

The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed. Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented. This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.

Public health and vector-borne diseases - a new concept for risk governance.

PubMed

Schmidt, K; Dressel, K M; Niedrig, M; Mertens, M; Schüle, S A; Groschup, M H

2013-12-01

Public Health is defined as an interdisciplinary multilevel approach that deals with questions of preventing diseases at the population level. In this context, this paper focuses on vector-borne diseases as an important threat with an increasing impact on human and animal health. Emphasis is laid on an integrated health approach ('One-Health' initiative) as it recognizes the interrelated nature of both human and animal health. The importance of vector-borne diseases to new and emerging diseases in Europe was demonstrated, for example, by the recent outbreak of West Nile virus infections in Greece, Northern Italy and Hungary; the spread of Crimean-Congo haemorrhagic fever virus across Turkey, south-western countries of the former USSR and the Balkans; the dramatic increase in hantavirus infections in Germany in 2012; and the dengue virus outbreak in Portugal in the same year. This paper provides a systematic approach for the analysis, assessment and governance of emerging health risks attributed to vector-borne diseases by using a holistic approach developed by the International Risk Governance Council (IRGC), called the 'IRGC Risk Governance Framework'. It can be used by decision-makers and general Public Health authorities in order to evaluate the situation regarding any specific pathogen or Public Health risk and to decide if additional measures should be implemented. © 2013 Blackwell Verlag GmbH.

41 CFR 50-204.2 - General safety and health standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... health standards. 50-204.2 Section 50-204.2 Public Contracts and Property Management Other Provisions Relating to Public Contracts PUBLIC CONTRACTS, DEPARTMENT OF LABOR 204-SAFETY AND HEALTH STANDARDS FOR FEDERAL SUPPLY CONTRACTS General Safety and Health Standards § 50-204.2 General safety and health...

42 CFR 3.208 - Continued protection of patient safety work product.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Continued protection of patient safety work product. 3.208 Section 3.208 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Confidentiality and...

78 FR 12042 - Public Availability of Defense Nuclear Facilities Safety Board FY 2011 Service Contract Inventory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Public Availability of Defense Nuclear Facilities Safety Board FY 2011 Service Contract Inventory Analysis/FY 2012 Service Contract Inventory AGENCY: Defense Nuclear Facilities Safety Board (DNFSB). ACTION: Notice of Public Availability of FY 2011 Service Contract...

76 FR 5354 - Public Availability of Defense Nuclear Facilities Safety Board FY 2010 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-31

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Public Availability of Defense Nuclear Facilities Safety Board FY 2010 Service Contract Inventory AGENCY: Defense Nuclear Facilities Safety Board (Board). ACTION: Notice of public availability of FY 2010 Service Contract Inventories. SUMMARY: In accordance with...

77 FR 7139 - Public Availability of Defense Nuclear Facilities Safety Board; FY 2010 Service Contract...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Public Availability of Defense Nuclear Facilities Safety Board; FY 2010 Service Contract Inventory Analysis/FY 2011 Service Contract Inventory AGENCY: Defense Nuclear Facilities Safety Board (DNFSB). ACTION: Notice of Public Availability of FY 2010 Service Contract...

Will integrated surveillance systems for vectors and vector-borne diseases be the future of controlling vector-borne diseases? A practical example from China.

PubMed

Wu, Y; Ling, F; Hou, J; Guo, S; Wang, J; Gong, Z

2016-07-01

Vector-borne diseases are one of the world's major public health threats and annually responsible for 30-50% of deaths reported to the national notifiable disease system in China. To control vector-borne diseases, a unified, effective and economic surveillance system is urgently needed; all of the current surveillance systems in China waste resources and/or information. Here, we review some current surveillance systems and present a concept for an integrated surveillance system combining existing vector and vector-borne disease monitoring systems. The integrated surveillance system has been tested in pilot programmes in China and led to a 21·6% cost saving in rodent-borne disease surveillance. We share some experiences gained from these programmes.

Comparing SVM and ANN based Machine Learning Methods for Species Identification of Food Contaminating Beetles.

PubMed

Bisgin, Halil; Bera, Tanmay; Ding, Hongjian; Semey, Howard G; Wu, Leihong; Liu, Zhichao; Barnes, Amy E; Langley, Darryl A; Pava-Ripoll, Monica; Vyas, Himansu J; Tong, Weida; Xu, Joshua

2018-04-25

Insect pests, such as pantry beetles, are often associated with food contaminations and public health risks. Machine learning has the potential to provide a more accurate and efficient solution in detecting their presence in food products, which is currently done manually. In our previous research, we demonstrated such feasibility where Artificial Neural Network (ANN) based pattern recognition techniques could be implemented for species identification in the context of food safety. In this study, we present a Support Vector Machine (SVM) model which improved the average accuracy up to 85%. Contrary to this, the ANN method yielded ~80% accuracy after extensive parameter optimization. Both methods showed excellent genus level identification, but SVM showed slightly better accuracy  for most species. Highly accurate species level identification remains a challenge, especially in distinguishing between species from the same genus which may require improvements in both imaging and machine learning techniques. In summary, our work does illustrate a new SVM based technique and provides a good comparison with the ANN model in our context. We believe such insights will pave better way forward for the application of machine learning towards species identification and food safety.

Spatially explicit multi-criteria decision analysis for managing vector-borne diseases

PubMed Central

2011-01-01

The complex epidemiology of vector-borne diseases creates significant challenges in the design and delivery of prevention and control strategies, especially in light of rapid social and environmental changes. Spatial models for predicting disease risk based on environmental factors such as climate and landscape have been developed for a number of important vector-borne diseases. The resulting risk maps have proven value for highlighting areas for targeting public health programs. However, these methods generally only offer technical information on the spatial distribution of disease risk itself, which may be incomplete for making decisions in a complex situation. In prioritizing surveillance and intervention strategies, decision-makers often also need to consider spatially explicit information on other important dimensions, such as the regional specificity of public acceptance, population vulnerability, resource availability, intervention effectiveness, and land use. There is a need for a unified strategy for supporting public health decision making that integrates available data for assessing spatially explicit disease risk, with other criteria, to implement effective prevention and control strategies. Multi-criteria decision analysis (MCDA) is a decision support tool that allows for the consideration of diverse quantitative and qualitative criteria using both data-driven and qualitative indicators for evaluating alternative strategies with transparency and stakeholder participation. Here we propose a MCDA-based approach to the development of geospatial models and spatially explicit decision support tools for the management of vector-borne diseases. We describe the conceptual framework that MCDA offers as well as technical considerations, approaches to implementation and expected outcomes. We conclude that MCDA is a powerful tool that offers tremendous potential for use in public health decision-making in general and vector-borne disease management in particular. PMID:22206355

Criteria for the prioritization of public health interventions for climate-sensitive vector-borne diseases in Quebec.

PubMed

Hongoh, Valerie; Gosselin, Pierre; Michel, Pascal; Ravel, André; Waaub, Jean-Philippe; Campagna, Céline; Samoura, Karim

2017-01-01

Prioritizing resources for optimal responses to an ever growing list of existing and emerging infectious diseases represents an important challenge to public health. In the context of climate change, there is increasing anticipated variability in the occurrence of infectious diseases, notably climate-sensitive vector-borne diseases. An essential step in prioritizing efforts is to identify what considerations and concerns to take into account to guide decisions and thus set disease priorities. This study was designed to perform a comprehensive review of criteria for vector-borne disease prioritization, assess their applicability in a context of climate change with a diverse cross-section of stakeholders in order to produce a baseline list of considerations to use in this decision-making context. Differences in stakeholder choices were examined with regards to prioritization of these criteria for research, surveillance and disease prevention and control objectives. A preliminary list of criteria was identified following a review of the literature. Discussions with stakeholders were held to consolidate and validate this list of criteria and examine their effects on disease prioritization. After this validation phase, a total of 21 criteria were retained. A pilot vector-borne disease prioritization exercise was conducted using PROMETHEE to examine the effects of the retained criteria on prioritization in different intervention domains. Overall, concerns expressed by stakeholders for prioritization were well aligned with categories of criteria identified in previous prioritization studies. Weighting by category was consistent between stakeholders overall, though some significant differences were found between public health and non-public health stakeholders. From this exercise, a general model for climate-sensitive vector-borne disease prioritization has been developed that can be used as a starting point for further public health prioritization exercises relating to research, surveillance, and prevention and control interventions in a context of climate change. Multi-stakeholder engagement in prioritization can help broaden the range of criteria taken into account, offer opportunities for early identification of potential challenges and may facilitate acceptability of any resulting decisions.

Prisoner reentry: a public health or public safety issue for social work practice?

PubMed

Patterson, George T

2013-01-01

A significant literature identifies the policy, economic, health, and social challenges that confront released prisoners. This literature also describes the public health and public safety risks associated with prisoner reentry, provides recommendations for improving the reentry process, and describes the effectiveness of prison-based programs on recidivism rates. Public health and public safety risks are particularly significant in communities where large numbers of prisoners are released and few evidence-based services exist. The purpose of this article is to describe the public health and public safety risks that released prisoners experience when they reenter communities, and to discuss the social justice issues relevant for social work practice.

Alcohol/safety public information materials catalog. Number 5

DOT National Transportation Integrated Search

1981-06-01

Author's abstract: The Alcohol/Safety Public Information Materials Catalog is designed for use by persons developing public information programs on alcohol and highway safety. It lists materials produced for campaigns along with journal articles and ...

Commercial wireless technologies for public safety users

DOT National Transportation Integrated Search

2000-07-01

This report on commercial wireless for public safety addresses the issues associated with the use of commercial services for public safety. It then reviews available wireless services for wide area data services: cellular, personal communication and ...

Application of patient safety indicators internationally: a pilot study among seven countries.

PubMed

Drösler, Saskia E; Klazinga, Niek S; Romano, Patrick S; Tancredi, Daniel J; Gogorcena Aoiz, Maria A; Hewitt, Moira C; Scobie, Sarah; Soop, Michael; Wen, Eugene; Quan, Hude; Ghali, William A; Mattke, Soeren; Kelley, Edward

2009-08-01

To explore the potential for international comparison of patient safety as part of the Health Care Quality Indicators project of the Organization for Economic Co-operation and Development (OECD) by evaluating patient safety indicators originally published by the US Agency for Healthcare Research and Quality (AHRQ). A retrospective cross-sectional study. Acute care hospitals in the USA, UK, Sweden, Spain, Germany, Canada and Australia in 2004 and 2005/2006. Routine hospitalization-related administrative data from seven countries were analyzed. Using algorithms adapted to the diagnosis and procedure coding systems in place in each country, authorities in each of the participating countries reported summaries of the distribution of hospital-level and overall (national) rates for each AHRQ Patient Safety Indicator to the OECD project secretariat. Each country's vector of national indicator rates and the vector of American patient safety indicators rates published by AHRQ (and re-estimated as part of this study) were highly correlated (0.821-0.966). However, there was substantial systematic variation in rates across countries. This pilot study reveals that AHRQ Patient Safety Indicators can be applied to international hospital data. However, the analyses suggest that certain indicators (e.g. 'birth trauma', 'complications of anesthesia') may be too unreliable for international comparisons. Data quality varies across countries; undercoding may be a systematic problem in some countries. Efforts at international harmonization of hospital discharge data sets as well as improved accuracy of documentation should facilitate future comparative analyses of routine databases.

21 CFR 25.16 - Public health and safety emergencies.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Public health and safety emergencies. 25.16... ENVIRONMENTAL IMPACT CONSIDERATIONS Agency Actions Requiring Environmental Consideration § 25.16 Public health... importance to the public health or safety, may make full adherence to the procedural provisions of NEPA and...

21 CFR 25.16 - Public health and safety emergencies.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Public health and safety emergencies. 25.16... ENVIRONMENTAL IMPACT CONSIDERATIONS Agency Actions Requiring Environmental Consideration § 25.16 Public health... importance to the public health or safety, may make full adherence to the procedural provisions of NEPA and...

21 CFR 25.16 - Public health and safety emergencies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Public health and safety emergencies. 25.16... ENVIRONMENTAL IMPACT CONSIDERATIONS Agency Actions Requiring Environmental Consideration § 25.16 Public health... importance to the public health or safety, may make full adherence to the procedural provisions of NEPA and...

21 CFR 25.16 - Public health and safety emergencies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Public health and safety emergencies. 25.16... ENVIRONMENTAL IMPACT CONSIDERATIONS Agency Actions Requiring Environmental Consideration § 25.16 Public health... importance to the public health or safety, may make full adherence to the procedural provisions of NEPA and...

Gene Therapy for Skin Diseases

PubMed Central

Gorell, Emily; Nguyen, Ngon; Lane, Alfred; Siprashvili, Zurab

2014-01-01

The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene therapy widely available clinically. PMID:24692191

Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

PubMed

Becker, P S; Taylor, J A; Trobridge, G D; Zhao, X; Beard, B C; Chien, S; Adair, J; Kohn, D B; Wagner, J E; Shimamura, A; Kiem, H-P

2010-10-01

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA.

33 CFR 164.72 - Navigational-safety equipment, charts or maps, and publications required on towing vessels.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Navigational-safety equipment, charts or maps, and publications required on towing vessels. 164.72 Section 164.72 Navigation and... NAVIGATION SAFETY REGULATIONS § 164.72 Navigational-safety equipment, charts or maps, and publications...

78 FR 61251 - The National Public Transportation Safety Plan, the Public Transportation Agency Safety Plan, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... Transportation Agency Safety Plan, and the Public Transportation Safety Certification Training Program; Transit... systems are in a state of good repair, and provide increased transparency into agencies' budgetary... October 2001, mail received through the U.S. Postal Service may be subject to delays. Parties submitting...

Vector excitation speech or audio coder for transmission or storage

NASA Technical Reports Server (NTRS)

Davidson, Grant (Inventor); Gersho, Allen (Inventor)

1989-01-01

A vector excitation coder compresses vectors by using an optimum codebook designed off line, using an initial arbitrary codebook and a set of speech training vectors exploiting codevector sparsity (i.e., by making zero all but a selected number of samples of lowest amplitude in each of N codebook vectors). A fast-search method selects a number N.sub.c of good excitation vectors from the codebook, where N.sub.c is much smaller tha ORIGIN OF INVENTION The invention described herein was made in the performance of work under a NASA contract, and is subject to the provisions of Public Law 96-517 (35 USC 202) under which the inventors were granted a request to retain title.

Disruptive Technology for Vector Control: the Innovative Vector Control Consortium and the US Military Join Forces to Explore Transformative Insecticide Application Technology for Mosquito Control Programmes

DTIC Science & Technology

2015-09-26

Forces Pest Management Board (AFPMB) focused on public health pesticide application technology. Three main top- ics were discussed: the limitations...industry, the World Health Organization, the Bill and Melinda Gates Foundation and others. Keywords: Pesticide application, Indoor residual spraying (IRS...Navy Entomology Center of Excel- lence (NECE), and industry as part of a joint workshop focused on public health pesticide application technology

Resurgent vector-borne diseases as a global health problem.

PubMed Central

Gubler, D. J.

1998-01-01

Vector-borne infectious diseases are emerging or resurging as a result of changes in public health policy, insecticide and drug resistance, shift in emphasis from prevention to emergency response, demographic and societal changes, and genetic changes in pathogens. Effective prevention strategies can reverse this trend. Research on vaccines, environmentally safe insecticides, alternative approaches to vector control, and training programs for health-care workers are needed. PMID:9716967

40 CFR 257.3-8 - Safety.

Code of Federal Regulations, 2012 CFR

2012-07-01

... application and compaction of soil or other suitable material over disposed solid waste at the end of each... disease vectors' access to the waste. (7) Putrescible wastes means solid waste which contains organic...

40 CFR 257.3-8 - Safety.

Code of Federal Regulations, 2014 CFR

2014-07-01

... application and compaction of soil or other suitable material over disposed solid waste at the end of each... disease vectors' access to the waste. (7) Putrescible wastes means solid waste which contains organic...

40 CFR 257.3-8 - Safety.

Code of Federal Regulations, 2010 CFR

2010-07-01

... application and compaction of soil or other suitable material over disposed solid waste at the end of each... disease vectors' access to the waste. (7) Putrescible wastes means solid waste which contains organic...

40 CFR 257.3-8 - Safety.

Code of Federal Regulations, 2011 CFR

2011-07-01

... application and compaction of soil or other suitable material over disposed solid waste at the end of each... disease vectors' access to the waste. (7) Putrescible wastes means solid waste which contains organic...

40 CFR 257.3-8 - Safety.

Code of Federal Regulations, 2013 CFR

2013-07-01

... application and compaction of soil or other suitable material over disposed solid waste at the end of each... disease vectors' access to the waste. (7) Putrescible wastes means solid waste which contains organic...

Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

PubMed

Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

2014-11-01

The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

77 FR 60507 - Motor Carrier Safety Advisory Committee (MCSAC): Public Subcommittee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee (MCSAC): Public Subcommittee Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Meeting of Compliance, Safety...

75 FR 29384 - Motor Carrier Safety Advisory Committee Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-25

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2010-0143] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee meeting. SUMMARY: FMCSA...

Achieving the Proper Balance Between Crew and Public Safety

NASA Technical Reports Server (NTRS)

Gowan, John; Silvestri, Ray; Stahl, Ben; Rosati, Paul; Wilde, Paul

2011-01-01

A paramount objective of all human-rated launch and reentry vehicle developers is to ensure that the risks to both the crew onboard and the public are minimized within reasonable cost, schedule, and technical constraints. Past experience has shown that proper attention to range safety requirements necessary to ensure public safety must be given early in the design phase to avoid additional operational complexities or threats to the safety of people onboard, and the design engineers must give these requirements the same consideration as crew safety requirements. For human spaceflight, the primary purpose and operational concept for any flight safety system is to protect the public while maximizing the likelihood of crew survival. This paper will outline the policy considerations, technical issues, and operational impacts regarding launch and reentry vehicle failure scenarios where crew and public safety are intertwined and thus addressed optimally in an integrated manner. An overview of existing range and crew safety policy requirements will be presented. Application of these requirements and lessons learned from both the Space Shuttle and Constellation Programs will also be discussed. Using these past programs as examples, the paper will detail operational, design, and analysis approaches to mitigate and balance the risks to people onboard and in the public. Manned vehicle perspectives from the Federal Aviation Administration (FAA) and Air Force organizations that oversee public safety will be summarized as well. Finally, the paper will emphasize the need to factor policy, operational, and analysis considerations into the early design trades of new vehicles to help ensure that both crew and public safety are maximized to the greatest extent possible.

Achieving the Proper Balance between Crew & Public Safety

NASA Astrophysics Data System (ADS)

Wilde, P.; Gowan, J.; Silvestri, R.; Stahl, B.; Rosati, P.

2012-01-01

A paramount objective of all human-rated launch and reentry vehicle developers is to ensure that the risks to both the crew onboard and the public are minimized within reasonable cost, schedule, and technical constraints. Past experience has shown that proper attention to range safety requirements necessary to ensure public safety must be given early in the design phase to avoid additional operational complexities or threats to the safety of people onboard, and the design engineers must give these requirements the same consideration as crew safety requirements. For human spaceflight, the primary purpose and operational concept for any flight safety system is to protect the public while maximizing the likelihood of crew survival. This paper will outline the policy considerations, technical issues, and operational impacts regarding launch and reentry vehicle failure scenarios where crew and public safety are intertwined and thus addressed optimally in an integrated manner. An overview of existing range and crew safety policy requirements will be presented. Application of these requirements and lessons learned from both the Space Shuttle and Constellation Programs will also be discussed. Using these past programs as examples, the paper will detail operational, design, and analysis approaches to mitigate and balance the risks to people onboard and in the public. Crewed vehicle perspectives from the Federal Aviation Administration and Air Force organizations that oversee public safety will be summarized as well. Finally, the paper will emphasize the need to factor policy, operational, and analysis considerations into the early design trades of new vehicles to help ensure that both crew and public safety are maximized to the greatest extent possible.

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.

PubMed

Okamoto, Kenichi W; Gould, Fred; Lloyd, Alun L

2016-03-01

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest perturbations induced by weak interventions can exhibit strong, albeit transient, epidemiological effects. This, together with our finding that under some conditions combining strategies could have transient adverse epidemiological effects suggests that a relatively long time horizon may be necessary to discern the efficacy of alternative intervention strategies.

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases

PubMed Central

Okamoto, Kenichi W.; Gould, Fred; Lloyd, Alun L.

2016-01-01

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences—consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest perturbations induced by weak interventions can exhibit strong, albeit transient, epidemiological effects. This, together with our finding that under some conditions combining strategies could have transient adverse epidemiological effects suggests that a relatively long time horizon may be necessary to discern the efficacy of alternative intervention strategies. PMID:26962871

78 FR 67212 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... the safety of public transportation systems. DATES: The TRACS meeting will be held on November 21... Letter Report on the Development of the National Public Transportation Safety Plan (4) Review of the Draft Letter Report on Public Transportation Agency Plans (5) Public Comments (6) Wrap Up As previously...

78 FR 66420 - Proposed Enhancements to the Motor Carrier Safety Measurement System (SMS) Public Web Site

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

...-0392] Proposed Enhancements to the Motor Carrier Safety Measurement System (SMS) Public Web Site AGENCY... on the Agency's Safety Measurement System (SMS) public Web site. FMCSA first announced the... public Web site that are the direct result of feedback from stakeholders regarding the information...

Assessing the potential for AAV vector genotoxicity in a murine model

PubMed Central

Li, Hojun; Malani, Nirav; Hamilton, Shari R.; Schlachterman, Alexander; Bussadori, Giulio; Edmonson, Shyrie E.; Shah, Rachel; Arruda, Valder R.; Mingozzi, Federico; Fraser Wright, J.; Bushman, Frederic D.

2011-01-01

Gene transfer using adeno-associated virus (AAV) vectors has great potential for treating human disease. Recently, questions have arisen about the safety of AAV vectors, specifically, whether integration of vector DNA in transduced cell genomes promotes tumor formation. This study addresses these questions with high-dose liver-directed AAV-mediated gene transfer in the adult mouse as a model (80 AAV-injected mice and 52 controls). After 18 months of follow-up, AAV-injected mice did not show a significantly higher rate of hepatocellular carcinoma compared with controls. Tumors in mice treated with AAV vectors did not have significantly different amounts of vector DNA compared with adjacent normal tissue. A novel high-throughput method for identifying AAV vector integration sites was developed and used to clone 1029 integrants. Integration patterns in tumor tissue and adjacent normal tissue were similar to each other, showing preferences for active genes, cytosine-phosphate-guanosine islands, and guanosine/cysteine-rich regions. Gene expression data showed that genes near integration sites did not show significant changes in expression patterns compared with genes more distal to integration sites. No integration events were identified as causing increased oncogene expression. Thus, we did not find evidence that AAV vectors cause insertional activation of oncogenes and subsequent tumor formation. PMID:21106988

Development of replication-competent viral vectors for HIV vaccine delivery

PubMed Central

Parks, Christopher L.; Picker, Louis J.; King, C. Richter

2014-01-01

Purpose of review Briefly describe some of the replication-competent (RC) vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. Recent findings RC viral vectors have advanced to the stage were decisions can be made regarding future development of HIV vaccines. The viruses being used as RC vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. RC viral vectors encoding SIV or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of pre-existing immunity. Summary A variety of DNA and RNA viruses are being used to develop RC viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be safe and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials. PMID:23925000

10 CFR 1703.105 - Requests for board records not available through the public reading room (FOIA requests).

Code of Federal Regulations, 2014 CFR

2014-01-01

... public reading room (FOIA requests). 1703.105 Section 1703.105 Energy DEFENSE NUCLEAR FACILITIES SAFETY... address for such requests is: Designated FOIA Officer, Defense Nuclear Facilities Safety Board, 625... pertain to an immediate source of risk to the public health and safety or worker safety at a defense...

10 CFR 1703.105 - Requests for board records not available through the public reading room (FOIA requests).

Code of Federal Regulations, 2013 CFR

2013-01-01

... public reading room (FOIA requests). 1703.105 Section 1703.105 Energy DEFENSE NUCLEAR FACILITIES SAFETY... address for such requests is: Designated FOIA Officer, Defense Nuclear Facilities Safety Board, 625... pertain to an immediate source of risk to the public health and safety or worker safety at a defense...

10 CFR 1703.105 - Requests for board records not available through the public reading room (FOIA requests).

Code of Federal Regulations, 2012 CFR

2012-01-01

... public reading room (FOIA requests). 1703.105 Section 1703.105 Energy DEFENSE NUCLEAR FACILITIES SAFETY... address for such requests is: Designated FOIA Officer, Defense Nuclear Facilities Safety Board, 625... pertain to an immediate source of risk to the public health and safety or worker safety at a defense...

10 CFR 1703.105 - Requests for board records not available through the public reading room (FOIA requests).

Code of Federal Regulations, 2010 CFR

2010-01-01

... public reading room (FOIA requests). 1703.105 Section 1703.105 Energy DEFENSE NUCLEAR FACILITIES SAFETY... address for such requests is: Designated FOIA Officer, Defense Nuclear Facilities Safety Board, 625... pertain to an immediate source of risk to the public health and safety or worker safety at a defense...

10 CFR 1703.105 - Requests for board records not available through the public reading room (FOIA requests).

Code of Federal Regulations, 2011 CFR

2011-01-01

... public reading room (FOIA requests). 1703.105 Section 1703.105 Energy DEFENSE NUCLEAR FACILITIES SAFETY... address for such requests is: Designated FOIA Officer, Defense Nuclear Facilities Safety Board, 625... pertain to an immediate source of risk to the public health and safety or worker safety at a defense...

47 CFR 27.303 - Upper 700 MHz commercial and public safety coordination zone.

Code of Federal Regulations, 2011 CFR

2011-10-01

... safety coordinator. (1) The description must include, at a minimum; (i) The frequency or frequencies on... 47 Telecommunication 2 2011-10-01 2011-10-01 false Upper 700 MHz commercial and public safety... Rules for WCS § 27.303 Upper 700 MHz commercial and public safety coordination zone. (a) General. CMRS...

78 FR 17751 - Motor Carrier Safety Advisory Committee (MCSAC): Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee (MCSAC): Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Meeting of Motor Carrier Safety Advisory Committee...

76 FR 32390 - Motor Carrier Safety Advisory Committee Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... Measurement System (SafeStat), CSMS quantifies the on-road safety performance of carriers to identify... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety...

Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy

PubMed Central

Kallert, Sandra M.; Darbre, Stephanie; Bonilla, Weldy V.; Kreutzfeldt, Mario; Page, Nicolas; Müller, Philipp; Kreuzaler, Matthias; Lu, Min; Favre, Stéphanie; Kreppel, Florian; Löhning, Max; Luther, Sanjiv A.; Zippelius, Alfred; Merkler, Doron; Pinschewer, Daniel D.

2017-01-01

Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTLeff) responses. Conversely, the induction of protective tumour-specific CTLeff and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTLeff responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTLeff influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy. PMID:28548102

Multiple sensor fault diagnosis for dynamic processes.

PubMed

Li, Cheng-Chih; Jeng, Jyh-Cheng

2010-10-01

Modern industrial plants are usually large scaled and contain a great amount of sensors. Sensor fault diagnosis is crucial and necessary to process safety and optimal operation. This paper proposes a systematic approach to detect, isolate and identify multiple sensor faults for multivariate dynamic systems. The current work first defines deviation vectors for sensor observations, and further defines and derives the basic sensor fault matrix (BSFM), consisting of the normalized basic fault vectors, by several different methods. By projecting a process deviation vector to the space spanned by BSFM, this research uses a vector with the resulted weights on each direction for multiple sensor fault diagnosis. This study also proposes a novel monitoring index and derives corresponding sensor fault detectability. The study also utilizes that vector to isolate and identify multiple sensor faults, and discusses the isolatability and identifiability. Simulation examples and comparison with two conventional PCA-based contribution plots are presented to demonstrate the effectiveness of the proposed methodology. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Reducing vector-borne disease by empowering farmers in integrated vector management.

PubMed

van den Berg, Henk; von Hildebrand, Alexander; Ragunathan, Vaithilingam; Das, Pradeep K

2007-07-01

Irrigated agriculture exposes rural people to health risks associated with vector-borne diseases and pesticides used in agriculture and for public health protection. Most developing countries lack collaboration between the agricultural and health sectors to jointly address these problems. We present an evaluation of a project that uses the "farmer field school" method to teach farmers how to manage vector-borne diseases and how to improve rice yields. Teaching farmers about these two concepts together is known as "integrated pest and vector management". An intersectoral project targeting rice irrigation systems in Sri Lanka. Project partners developed a new curriculum for the field school that included a component on vector-borne diseases. Rice farmers in intervention villages who graduated from the field school took vector-control actions as well as improving environmental sanitation and their personal protection measures against disease transmission. They also reduced their use of agricultural pesticides, especially insecticides. The intervention motivated and enabled rural people to take part in vector-management activities and to reduce several environmental health risks. There is scope for expanding the curriculum to include information on the harmful effects of pesticides on human health and to address other public health concerns. Benefits of this approach for community-based health programmes have not yet been optimally assessed. Also, the institutional basis of the integrated management approach needs to be broadened so that people from a wider range of organizations take part. A monitoring and evaluation system needs to be established to measure the performance of integrated management initiatives.

The National Map - Orthoimagery Layer

USGS Publications Warehouse

,

2007-01-01

Many Federal, State, and local agencies use a common set of framework geographic information databases as a tool for economic and community development, land and natural resource management, and health and safety services. Emergency management and homeland security applications rely on this information. Private industry, nongovernmental organizations, and individual citizens use the same geographic data. Geographic information underpins an increasingly large part of the Nation's economy. The U.S. Geological Survey (USGS) is developing The National Map to be a seamless, continually maintained, and nationally consistent set of online, public domain, framework geographic information databases. The National Map will serve as a foundation for integrating, sharing, and using data easily and consistently. The data will be the source of revised paper topographic maps. The National Map includes digital orthorectified imagery; elevation data; vector data for hydrography, transportation, boundary, and structure features; geographic names; and land cover information.

Detecting dominant motion patterns in crowds of pedestrians

NASA Astrophysics Data System (ADS)

Saqib, Muhammad; Khan, Sultan Daud; Blumenstein, Michael

2017-02-01

As the population of the world increases, urbanization generates crowding situations which poses challenges to public safety and security. Manual analysis of crowded situations is a tedious job and usually prone to errors. In this paper, we propose a novel technique of crowd analysis, the aim of which is to detect different dominant motion patterns in real-time videos. A motion field is generated by computing the dense optical flow. The motion field is then divided into blocks. For each block, we adopt an Intra-clustering algorithm for detecting different flows within the block. Later on, we employ Inter-clustering for clustering the flow vectors among different blocks. We evaluate the performance of our approach on different real-time videos. The experimental results show that our proposed method is capable of detecting distinct motion patterns in crowded videos. Moreover, our algorithm outperforms state-of-the-art methods.

Revolutionary Propulsion Systems for 21st Century Aviation

NASA Technical Reports Server (NTRS)

Sehra, Arun K.; Shin, Jaiwon

2003-01-01

The air transportation for the new millennium will require revolutionary solutions to meeting public demand for improving safety, reliability, environmental compatibility, and affordability. NASA's vision for 21st Century Aircraft is to develop propulsion systems that are intelligent, virtually inaudible (outside the airport boundaries), and have near zero harmful emissions (CO2 and Knox). This vision includes intelligent engines that will be capable of adapting to changing internal and external conditions to optimally accomplish the mission with minimal human intervention. The distributed vectored propulsion will replace two to four wing mounted or fuselage mounted engines by a large number of small, mini, or micro engines, and the electric drive propulsion based on fuel cell power will generate electric power, which in turn will drive propulsors to produce the desired thrust. Such a system will completely eliminate the harmful emissions. This paper reviews future propulsion and power concepts that are currently under development at NASA Glenn Research Center.

Emerging Vector-Borne Diseases – Incidence through Vectors

PubMed Central

Savić, Sara; Vidić, Branka; Grgić, Zivoslav; Potkonjak, Aleksandar; Spasojevic, Ljubica

2014-01-01

Vector-borne diseases use to be a major public health concern only in tropical and subtropical areas, but today they are an emerging threat for the continental and developed countries also. Nowadays, in intercontinental countries, there is a struggle with emerging diseases, which have found their way to appear through vectors. Vector-borne zoonotic diseases occur when vectors, animal hosts, climate conditions, pathogens, and susceptible human population exist at the same time, at the same place. Global climate change is predicted to lead to an increase in vector-borne infectious diseases and disease outbreaks. It could affect the range and population of pathogens, host and vectors, transmission season, etc. Reliable surveillance for diseases that are most likely to emerge is required. Canine vector-borne diseases represent a complex group of diseases including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, and leishmaniosis. Some of these diseases cause serious clinical symptoms in dogs and some of them have a zoonotic potential with an effect to public health. It is expected from veterinarians in coordination with medical doctors to play a fundamental role at primarily prevention and then treatment of vector-borne diseases in dogs. The One Health concept has to be integrated into the struggle against emerging diseases. During a 4-year period, from 2009 to 2013, a total number of 551 dog samples were analyzed for vector-borne diseases (borreliosis, babesiosis, ehrlichiosis, anaplasmosis, dirofilariosis, and leishmaniasis) in routine laboratory work. The analysis was done by serological tests – ELISA for borreliosis, dirofilariosis, and leishmaniasis, modified Knott test for dirofilariosis, and blood smear for babesiosis, ehrlichiosis, and anaplasmosis. This number of samples represented 75% of total number of samples that were sent for analysis for different diseases in dogs. Annually, on average more then half of the samples brought to the laboratory to analysis for different infectious diseases are analyzed for vector-borne diseases. In the region of Vojvodina (northern part of Serbia), the following vector-borne infectious diseases have been found in dogs so far borreliosis, babesiosis, dirofilariosis, leishmaniasis, and anaplasmosis. PMID:25520951

Emerging Vector-Borne Diseases - Incidence through Vectors.

PubMed

Savić, Sara; Vidić, Branka; Grgić, Zivoslav; Potkonjak, Aleksandar; Spasojevic, Ljubica

2014-01-01

Vector-borne diseases use to be a major public health concern only in tropical and subtropical areas, but today they are an emerging threat for the continental and developed countries also. Nowadays, in intercontinental countries, there is a struggle with emerging diseases, which have found their way to appear through vectors. Vector-borne zoonotic diseases occur when vectors, animal hosts, climate conditions, pathogens, and susceptible human population exist at the same time, at the same place. Global climate change is predicted to lead to an increase in vector-borne infectious diseases and disease outbreaks. It could affect the range and population of pathogens, host and vectors, transmission season, etc. Reliable surveillance for diseases that are most likely to emerge is required. Canine vector-borne diseases represent a complex group of diseases including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, and leishmaniosis. Some of these diseases cause serious clinical symptoms in dogs and some of them have a zoonotic potential with an effect to public health. It is expected from veterinarians in coordination with medical doctors to play a fundamental role at primarily prevention and then treatment of vector-borne diseases in dogs. The One Health concept has to be integrated into the struggle against emerging diseases. During a 4-year period, from 2009 to 2013, a total number of 551 dog samples were analyzed for vector-borne diseases (borreliosis, babesiosis, ehrlichiosis, anaplasmosis, dirofilariosis, and leishmaniasis) in routine laboratory work. The analysis was done by serological tests - ELISA for borreliosis, dirofilariosis, and leishmaniasis, modified Knott test for dirofilariosis, and blood smear for babesiosis, ehrlichiosis, and anaplasmosis. This number of samples represented 75% of total number of samples that were sent for analysis for different diseases in dogs. Annually, on average more then half of the samples brought to the laboratory to analysis for different infectious diseases are analyzed for vector-borne diseases. In the region of Vojvodina (northern part of Serbia), the following vector-borne infectious diseases have been found in dogs so far borreliosis, babesiosis, dirofilariosis, leishmaniasis, and anaplasmosis.

Risk perception, risk management and safety assessment: what can governments do to increase public confidence in their vaccine system?

PubMed

MacDonald, Noni E; Smith, Jennifer; Appleton, Mary

2012-09-01

For decades vaccine program managers and governments have devoted many resources to addressing public vaccine concerns, vaccine risk perception, risk management and safety assessment. Despite ever growing evidence that vaccines are safe and effective, public concerns continue. Education and evidence based scientific messages have not ended concerns. How can governments and programs more effectively address the public's vaccine concerns and increase confidence in the vaccine safety system? Vaccination hesitation has been attributed to concerns about vaccine safety, perceptions of high vaccine risks and low disease risk and consequences. Even when the public believes vaccines are important for protection many still have concerns about vaccine safety. This overview explores how heuristics affect public perception of vaccines and vaccine safety, how the public finds and uses vaccine information, and then proposes strategies for changes in the approach to vaccine safety communications. Facts and evidence confirming the safety of vaccines are not enough. Vaccine beliefs and behaviours must be shaped. This will require a shift in the what, when, how and why of vaccine risk and benefit communication content and practice. A change to a behavioural change strategy such as the WHO COMBI program that has been applied to disease eradication efforts is suggested. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

Arboviruses and their vectors in the Pacific--status report.

PubMed

Guillaumot, Laurent

2005-09-01

Three arboviruses have already caused epidemics in various Pacific Island countries and territories, and currently represent a direct threat to public health. The diseases concerned are all mosquito-borne and should be kept under careful surveillance. Dengue fever, which is a worldwide major public health problem, is mainly transmitted in the Pacific by the Aedes aegypti vector but also by other mosquitoes of this genus with varying ranges. Epidemic polyarthritis due to the Ross River virus is endemic in Australia. At least one major epidemic has occurred in the Pacific where various vector mosquito species occur. Japanese encephalitis is a zoonosis that can be transmitted to humans by mosquitoes of the genus Culex. Its area of distribution in Asia is expanding and the possibility of fresh incursions into the region should be borne in mind. This paper reviews the situation regarding these diseases in the Pacific and provides information on the way they are transmitted as well as on the biology of the mosquito vectors.

Assembly and Functional Analysis of an S/MAR Based Episome with the Cystic Fibrosis Transmembrane Conductance Regulator Gene.

PubMed

De Rocco, Davide; Pompili, Barbara; Castellani, Stefano; Morini, Elena; Cavinato, Luca; Cimino, Giuseppe; Mariggiò, Maria A; Guarnieri, Simone; Conese, Massimo; Del Porto, Paola; Ascenzioni, Fiorentina

2018-04-17

Improving the efficacy of gene therapy vectors is still an important goal toward the development of safe and efficient gene therapy treatments. S/MAR (scaffold/matrix attached region)-based vectors are maintained extra-chromosomally in numerous cell types, which is similar to viral-based vectors. Additionally, when established as an episome, they show a very high mitotic stability. In the present study we tested the idea that addition of an S/MAR element to a CFTR (cystic fibrosis transmembrane conductance regulator) expression vector, may allow the establishment of a CFTR episome in bronchial epithelial cells. Starting from the observation that the S/MAR vector pEPI-EGFP (enhanced green fluorescence protein) is maintained as an episome in human bronchial epithelial cells, we assembled the CFTR vector pBQ-S/MAR. This vector, transfected in bronchial epithelial cells with mutated CFTR , supported long term wt CFTR expression and activity, which in turn positively impacted on the assembly of tight junctions in polarized epithelial cells. Additionally, the recovery of intact pBQ-S/MAR, but not the parental vector lacking the S/MAR element, from transfected cells after extensive proliferation, strongly suggested that pBQ-S/MAR was established as an episome. These results add a new element, the S/MAR, that can be considered to improve the persistence and safety of gene therapy vectors for cystic fibrosis pulmonary disease.

Safety Information, Transportation & Public Facilities, State of Alaska

Science.gov Websites

Department of Transportation & Public Facilities/ Safety Information Search DOT&PF State of Alaska DOT&PF> Safety Information DOT&PF Safety Information link to 511 511.alaska.gov - Traveler Information link to AHSO Alaska Highway Safety Office link to HSIP Highway Safety Improvement Program link to

Compositional Verification with Abstraction, Learning, and SAT Solving

DTIC Science & Technology

2015-05-01

arithmetic, and bit-vectors (currently, via bit-blasting). The front-end is based on an existing tool called UFO [8] which converts C programs to the Horn...supports propositional logic, linear arithmetic, and bit-vectors (via bit-blasting). The front-end is based on the tool UFO [8]. It encodes safety of...tool UFO [8]. The encoding in Horn-SMT only uses the theory of Linear Rational Arithmetic. All experiments were carried out on an Intel R© CoreTM2 Quad

77 FR 34123 - Pipeline Safety: Public Meeting on Integrity Management of Gas Distribution Pipelines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No. PHMSA-2012-0100] Pipeline Safety: Public Meeting on Integrity Management of Gas Distribution Pipelines AGENCY: Office of Pipeline Safety, Pipeline and Hazardous Materials Safety Administration, DOT. ACTION...

Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions

DTIC Science & Technology

2012-10-26

viruses and vectors isolated over different geographic regions promote understanding of virus-vector co-evolution and the impact on dengue virus...AFRIMS Virology field site in KPP to be a participant in a regional phase 3 dengue vaccine efficacy trial. The trial is scheduled to begin in 2Q...important human pathogen producing severe illness known as dengue hemorrhagic fever (DHF). Dengue is considered an emerged global public health

Achieving the Proper Balance Between Crew and Public Safety

NASA Technical Reports Server (NTRS)

Gowan, John; Rosati, Paul; Silvestri, Ray; Stahl, Ben; Wilde, Paul

2011-01-01

A paramount objective of all human-rated launch and reentry vehicle developers is to ensure that the risks to both the crew onboard and the public are minimized within reasonable cost, schedule, and technical constraints. Past experience has shown that proper attention to range safety requirements necessary to ensure public safety must be given early in the design phase to avoid additional operational complexities or threats to the safety of people onboard. This paper will outline the policy considerations, technical issues, and operational impacts regarding launch and reentry vehicle failure scenarios where crew and public safety are intertwined and thus addressed optimally in an integrated manner. Historical examples and lessons learned from both the Space Shuttle and Constellation Programs will be presented. Using these examples as context, the paper will discuss some operational, design, and analysis approaches to mitigate and balance the risks to people onboard and in the public. Manned vehicle perspectives from the FAA and Air Force organizations that oversee public safety will also be summarized. Finally, the paper will emphasize the need to factor policy, operational, and analysis considerations into the early design trades of new vehicles to help ensure that both crew and public safety are maximized to the greatest extent possible.

QuickMap: a public tool for large-scale gene therapy vector insertion site mapping and analysis.

PubMed

Appelt, J-U; Giordano, F A; Ecker, M; Roeder, I; Grund, N; Hotz-Wagenblatt, A; Opelz, G; Zeller, W J; Allgayer, H; Fruehauf, S; Laufs, S

2009-07-01

Several events of insertional mutagenesis in pre-clinical and clinical gene therapy studies have created intense interest in assessing the genomic insertion profiles of gene therapy vectors. For the construction of such profiles, vector-flanking sequences detected by inverse PCR, linear amplification-mediated-PCR or ligation-mediated-PCR need to be mapped to the host cell's genome and compared to a reference set. Although remarkable progress has been achieved in mapping gene therapy vector insertion sites, public reference sets are lacking, as are the possibilities to quickly detect non-random patterns in experimental data. We developed a tool termed QuickMap, which uniformly maps and analyzes human and murine vector-flanking sequences within seconds (available at www.gtsg.org). Besides information about hits in chromosomes and fragile sites, QuickMap automatically determines insertion frequencies in +/- 250 kb adjacency to genes, cancer genes, pseudogenes, transcription factor and (post-transcriptional) miRNA binding sites, CpG islands and repetitive elements (short interspersed nuclear elements (SINE), long interspersed nuclear elements (LINE), Type II elements and LTR elements). Additionally, all experimental frequencies are compared with the data obtained from a reference set, containing 1 000 000 random integrations ('random set'). Thus, for the first time a tool allowing high-throughput profiling of gene therapy vector insertion sites is available. It provides a basis for large-scale insertion site analyses, which is now urgently needed to discover novel gene therapy vectors with 'safe' insertion profiles.

Schools as Potential Risk Sites for Vector-Borne Disease Transmission: Mosquito Vectors in Rural Schools in Two Municipalities in Colombia.

PubMed

Olano, Víctor Alberto; Matiz, María Inés; Lenhart, Audrey; Cabezas, Laura; Vargas, Sandra Lucía; Jaramillo, Juan Felipe; Sarmiento, Diana; Alexander, Neal; Stenström, Thor Axel; Overgaard, Hans J

2015-09-01

Dengue and other vector-borne diseases are of great public health importance in Colombia. Vector surveillance and control activities are often focused at the household level. Little is known about the importance of nonhousehold sites, including schools, in maintaining vector-borne disease transmission. The objectives of this paper were to determine the mosquito species composition in rural schools in 2 municipalities in Colombia and to assess the potential risk of vector-borne disease transmission in school settings. Entomological surveys were carried out in rural schools during the dry and rainy seasons of 2011. A total of 12 mosquito species were found: Aedes aegypti, Anopheles pseudopunctipennis, Culex coronator, Cx. quinquefasciatus, and Limatus durhamii in both immature and adult forms; Ae. fluviatilis, Cx. nigripalpus, Cx. corniger, and Psorophora ferox in immature forms only; and Ae. angustivittatus, Haemagogus equinus, and Trichoprosopon lampropus in adult forms only. The most common mosquito species was Cx. quinquefasciatus. Classrooms contained the greatest abundance of adult female Ae. aegypti and Cx. quinquefasciatus. The most common Ae. aegypti breeding sites were containers classified as "others" (e.g., cans), followed by containers used for water storage. A high level of Ae. aegypti infestation was found during the wet season. Our results suggest that rural schools are potentially important foci for the transmission of dengue and other mosquito-borne diseases. We propose that public health programs should be implemented in rural schools to prevent vector-borne diseases.

Participatory Risk Mapping of Malaria Vector Exposure in Northern South America using Environmental and Population Data

PubMed Central

Fuller, D.O.; Troyo, A.; Alimi, T.O.; Beier, J.C.

2014-01-01

Malaria elimination remains a major public health challenge in many tropical regions, including large areas of northern South America. In this study, we present a new high spatial resolution (90 × 90 m) risk map for Colombia and surrounding areas based on environmental and human population data. The map was created through a participatory multi-criteria decision analysis in which expert opinion was solicited to determine key environmental and population risk factors, different fuzzy functions to standardize risk factor inputs, and variable factor weights to combine risk factors in a geographic information system. The new risk map was compared to a map of malaria cases in which cases were aggregated to the municipio (municipality) level. The relationship between mean municipio risk scores and total cases by muncípio showed a weak correlation. However, the relationship between pixel-level risk scores and vector occurrence points for two dominant vector species, Anopheles albimanus and An. darlingi, was significantly different (p < 0.05) from a random point distribution, as was a pooled point distribution for these two vector species and An. nuneztovari. Thus, we conclude that the new risk map derived based on expert opinion provides an accurate spatial representation of risk of potential vector exposure rather than malaria transmission as shown by the pattern of malaria cases, and therefore it may be used to inform public health authorities as to where vector control measures should be prioritized to limit human-vector contact in future malaria outbreaks. PMID:24976656

Insights from agriculture for the management of insecticide resistance in disease vectors.

PubMed

Sternberg, Eleanore D; Thomas, Matthew B

2018-04-01

Key to contemporary management of diseases such as malaria, dengue, and filariasis is control of the insect vectors responsible for transmission. Insecticide-based interventions have contributed to declines in disease burdens in many areas, but this progress could be threatened by the emergence of insecticide resistance in vector populations. Insecticide resistance is likewise a major concern in agriculture, where insect pests can cause substantial yield losses. Here, we explore overlaps between understanding and managing insecticide resistance in agriculture and in public health. We have used the Global Plan for Insecticide Resistance Management in malaria vectors, developed under the auspices of the World Health Organization Global Malaria Program, as a framework for this exploration because it serves as one of the few cohesive documents for managing a global insecticide resistance crisis. Generally, this comparison highlights some fundamental differences between insect control in agriculture and in public health. Moreover, we emphasize that the success of insecticide resistance management strategies is strongly dependent on the biological specifics of each system. We suggest that the biological, operational, and regulatory differences between agriculture and public health limit the wholesale transfer of knowledge and practices from one system to the other. Nonetheless, there are some valuable insights from agriculture that could assist in advancing the existing Global Plan for Insecticide Resistance Management framework.

Competence of Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus Mosquitoes as Zika Virus Vectors, China.

PubMed

Liu, Zhuanzhuan; Zhou, Tengfei; Lai, Zetian; Zhang, Zhenhong; Jia, Zhirong; Zhou, Guofa; Williams, Tricia; Xu, Jiabao; Gu, Jinbao; Zhou, Xiaohong; Lin, Lifeng; Yan, Guiyun; Chen, Xiao-Guang

2017-07-01

In China, the prevention and control of Zika virus disease has been a public health threat since the first imported case was reported in February 2016. To determine the vector competence of potential vector mosquito species, we experimentally infected Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus mosquitoes and determined infection rates, dissemination rates, and transmission rates. We found the highest vector competence for the imported Zika virus in Ae. aegypti mosquitoes, some susceptibility of Ae. albopictus mosquitoes, but no transmission ability for Cx. quinquefasciatus mosquitoes. Considering that, in China, Ae. albopictus mosquitoes are widely distributed but Ae. aegypti mosquito distribution is limited, Ae. albopictus mosquitoes are a potential primary vector for Zika virus and should be targeted in vector control strategies.

Competence of Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus Mosquitoes as Zika Virus Vectors, China

PubMed Central

Liu, Zhuanzhuan; Zhou, Tengfei; Lai, Zetian; Zhang, Zhenhong; Jia, Zhirong; Zhou, Guofa; Williams, Tricia; Xu, Jiabao; Gu, Jinbao; Zhou, Xiaohong; Lin, Lifeng; Yan, Guiyun

2017-01-01

In China, the prevention and control of Zika virus disease has been a public health threat since the first imported case was reported in February 2016. To determine the vector competence of potential vector mosquito species, we experimentally infected Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus mosquitoes and determined infection rates, dissemination rates, and transmission rates. We found the highest vector competence for the imported Zika virus in Ae. aegypti mosquitoes, some susceptibility of Ae. albopictus mosquitoes, but no transmission ability for Cx. quinquefasciatus mosquitoes. Considering that, in China, Ae. albopictus mosquitoes are widely distributed but Ae. aegypti mosquito distribution is limited, Ae. albopictus mosquitoes are a potential primary vector for Zika virus and should be targeted in vector control strategies. PMID:28430562

14 CFR 431.71 - Public safety responsibility.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Public safety responsibility. 431.71 Section 431.71 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Requirements-Reusable Launch Vehicle Mission License Terms and Conditions § 431.71 Public safety responsibility...

14 CFR 431.71 - Public safety responsibility.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Public safety responsibility. 431.71 Section 431.71 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Requirements-Reusable Launch Vehicle Mission License Terms and Conditions § 431.71 Public safety responsibility...

14 CFR 431.71 - Public safety responsibility.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Public safety responsibility. 431.71 Section 431.71 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Requirements-Reusable Launch Vehicle Mission License Terms and Conditions § 431.71 Public safety responsibility...

43 CFR 3162.5 - Environment and safety.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Environment and safety. 3162.5 Section 3162.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... for Operating Rights Owners and Operators § 3162.5 Environment and safety. ...

43 CFR 3162.5 - Environment and safety.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Environment and safety. 3162.5 Section 3162.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... for Operating Rights Owners and Operators § 3162.5 Environment and safety. ...

43 CFR 3162.5 - Environment and safety.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Environment and safety. 3162.5 Section 3162.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... for Operating Rights Owners and Operators § 3162.5 Environment and safety. ...

43 CFR 3162.5 - Environment and safety.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Environment and safety. 3162.5 Section 3162.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... for Operating Rights Owners and Operators § 3162.5 Environment and safety. ...

47 CFR 90.15 - Scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... emergency repair of public communications facilities. Entities not meeting these eligibility criteria may... FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.15 Scope. The Public Safety Radio Pool covers the licensing of the...

47 CFR 90.15 - Scope.

Code of Federal Regulations, 2014 CFR

2014-10-01

... emergency repair of public communications facilities. Entities not meeting these eligibility criteria may... FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.15 Scope. The Public Safety Radio Pool covers the licensing of the...

47 CFR 90.15 - Scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

... emergency repair of public communications facilities. Entities not meeting these eligibility criteria may... FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.15 Scope. The Public Safety Radio Pool covers the licensing of the...

47 CFR 90.15 - Scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

... emergency repair of public communications facilities. Entities not meeting these eligibility criteria may... FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.15 Scope. The Public Safety Radio Pool covers the licensing of the...

47 CFR 90.15 - Scope.

Code of Federal Regulations, 2012 CFR

2012-10-01

... emergency repair of public communications facilities. Entities not meeting these eligibility criteria may... FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Public Safety Radio Pool § 90.15 Scope. The Public Safety Radio Pool covers the licensing of the...

A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera)

PubMed Central

Ribeiro, José M. C.; Schwarz, Alexandra; Francischetti, Ivo M. B.

2015-01-01

Saliva of blood-sucking arthropods contains a complex cocktail of pharmacologically active compounds that assists feeding by counteracting their hosts’ hemostatic and inflammatory reactions. Panstrongylus megistus (Burmeister) is an important vector of Chagas disease in South America, but despite its importance there is only one salivary protein sequence publicly deposited in GenBank. In the present work, we used Illumina technology to disclose and publicly deposit 3,703 coding sequences obtained from the assembly of >70 million reads. These sequences should assist proteomic experiments aimed at identifying pharmacologically active proteins and immunological markers of vector exposure. A supplemental file of the transcriptome and deducted protein sequences can be obtained from http://exon.niaid.nih.gov/transcriptome/P_megistus/Pmeg-web.xlsx. PMID:26334808

41 CFR 50-204.75 - Transportation safety.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Transportation safety. 50... Contracts PUBLIC CONTRACTS, DEPARTMENT OF LABOR 204-SAFETY AND HEALTH STANDARDS FOR FEDERAL SUPPLY CONTRACTS Transportation Safety § 50-204.75 Transportation safety. Any requirements of the U.S. Department of...

41 CFR 50-204.75 - Transportation safety.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Transportation safety. 50... Contracts PUBLIC CONTRACTS, DEPARTMENT OF LABOR 204-SAFETY AND HEALTH STANDARDS FOR FEDERAL SUPPLY CONTRACTS Transportation Safety § 50-204.75 Transportation safety. Any requirements of the U.S. Department of...

Gene correction of induced pluripotent stem cells derived from a murine model of X-linked chronic granulomatous disorder.

PubMed

Mukherjee, Sayandip; Thrasher, Adrian J

2014-01-01

Gene therapy presents an attractive alternative to allogeneic haematopoietic stem cell transplantation (HSCT) for treating patients suffering from primary immunodeficiency disorder (PID). The conceptual advantage of gene correcting a patient's autologous HSCs lies in minimizing or completely avoiding immunological complications arising from allogeneic transplantation while conferring the same benefits of immune reconstitution upon long-term engraftment. Clinical trials targeting X-linked chronic granulomatous disorder (X-CGD) have shown promising results in this context. However, long-term clinical benefits in these patients have been limited by issues of poor engraftment of gene-transduced cells coupled with transgene silencing and vector induced clonal proliferation. Novel vectors incorporating safety features such as self-inactivating (SIN) mutations in the long terminal repeats (LTRs) along with synthetic promoters driving lineage-restricted sustainable expression of the gp91phox transgene are expected to resolve the current pitfalls and require rigorous preclinical testing. In this chapter, we have outlined a protocol in which X-CGD mouse model derived induced pluripotent stem cells (iPSCs) have been utilized to develop a platform for investigating the efficacy and safety profiles of novel vectors prior to clinical evaluation.

Public acceptability of highway safety countermeasures : volume IV, pedestrian measures.

DOT National Transportation Integrated Search

1981-06-01

This volume is part of a larger study providing information about public attitudes : towards proposed highway safety countermeasures in three program areas: alcohol : and drugs, unsafe driving behaviors, and pedestrian safety. Pedestrian safety : cou...

Renewal: New Aspects of Acceleration and Transport of Solar Energetic Particles (SEPs) from the Sun to the Earth

DTIC Science & Technology

2014-10-31

Hole .......................................................4 2. SOHO EIT Image with Coronal Holes and FPA Vector...Diagram of CME Deflection by a Coronal Hole Figure 2: SOHO EIT Image with Coronal Holes and FPA Vector Approved for public release; distribution

Assessment of patient safety culture in private and public hospitals in Peru.

PubMed

Arrieta, Alejandro; Suárez, Gabriela; Hakim, Galed

2018-04-01

To assess the patient safety culture in Peruvian hospitals from the perspective of healthcare professionals, and to test for differences between the private and public healthcare sectors. Patient safety is defined as the avoidance and prevention of patient injuries or adverse events resulting from the processes of healthcare delivery. A non-random cross-sectional study conducted online. An online survey was administered from July to August 2016, in Peru. This study reports results from Lima and Callao, which are the capital and the port region of Peru. A total of 1679 healthcare professionals completed the survey. Participants were physicians, medical residents and nurses working in healthcare facilities from the private sector and public sector. Assessment of the degree of patient safety and 12 dimensions of patient safety culture in hospital units as perceived by healthcare professionals. Only 18% of healthcare professionals assess the degree of patient safety in their unit of work as excellent or very good. Significant differences are observed between the patient safety grades in the private sector (37%) compared to the public sub-sectors (13-15%). Moreover, in all patient safety culture dimensions, healthcare professionals from the private sector give more favorable responses for patient safety, than those from the public sub-systems. The most significant difference in support comes from patient safety administrators through communication and information about errors. Overall, the degree of patient safety in Peru is low, with significant gaps that exist between the private and the public sectors.

Prevalence of Zoonotic and Vector-Borne Infections Among Afghan National Army Recruits in Afghanistan.

PubMed

Todd, Catherine S; Mansoor, Ghulam Farooq; Buhler, Cyril; Rahimi, Habiburrahman; Zekria, Rohullah; Fernandez, Stefan; Mikhail, Amy F W; Scott, Paul T; Yingst, Samuel L

2016-08-01

To measure prevalence of prior/current Plasmodium vivax and Plasmodium falciparum (PV and PF), Brucella spp. (BR), dengue virus (DENV), Leishmania donovani (visceral leishmaniasis; VL), and Crimean-Congo hemorrhagic fever (CCHF) virus exposure among Afghan National Army (ANA) recruits. Randomly chosen, nationally representative serum samples from consenting men aged 18-40 years and who were screened between February 2010 and January 2011 were tested, with ∼25 samples/province. Samples were screened for PV and PF antigens and VL antibody with rapid diagnostic tests. Reactive malaria screening results were confirmed with polymerase chain reaction assay. Enzyme-linked immunosorbent assays were used to screen for CCHF and DENV antibodies; reactive DENV samples were confirmed with the plaque-reduction neutralization test. BR screening and confirmatory testing was performed with slide and tube agglutination, respectively. Correlates of BR titres >1:80 were analyzed using logistic regression. Of 809 participants contributing specimens, 62% had previously lived outside Afghanistan, predominantly in Pakistan and Iran. CCHF (4.1%, n = 33), DENV (2.1%, n = 17), and VL (1.0%, n = 8) antibody prevalence was low. For PV and PF, only 7 out of 56 reactive samples had detectable nucleic acid. For BR, 8.0% (n = 65) of samples had screening titers >1:40, of which 83.1% had confirmatory titers >1:80. Participants from Kabul and surrounding provinces had lower odds (OR = 0.19, 95% CI: 0.04-1.00) of BR antibody compared with other regions. BR exposure was relatively common with a nearly national distribution, whereas geographic distribution for other pathogens aligned roughly with the expected vector distribution. Public health protection measures should include vector control, food safety, and enhanced diagnostics for acute febrile illness.

Safety and immunogenicity of mammalian cell derived and Modified Vaccinia Ankara vectored African swine fever subunit antigens in swine.

PubMed

Lopera-Madrid, Jaime; Osorio, Jorge E; He, Yongqun; Xiang, Zuoshuang; Adams, L Garry; Laughlin, Richard C; Mwangi, Waithaka; Subramanya, Sandesh; Neilan, John; Brake, David; Burrage, Thomas G; Brown, William Clay; Clavijo, Alfonso; Bounpheng, Mangkey A

2017-03-01

A reverse vaccinology system, Vaxign, was used to identify and select a subset of five African Swine Fever (ASF) antigens that were successfully purified from human embryonic kidney 293 (HEK) cells and produced in Modified vaccinia virus Ankara (MVA) viral vectors. Three HEK-purified antigens [B646L (p72), E183L (p54), and O61R (p12)], and three MVA-vectored antigens [B646L, EP153R, and EP402R (CD2v)] were evaluated using a prime-boost immunization regimen swine safety and immunogenicity study. Antibody responses were detected in pigs following prime-boost immunization four weeks apart with the HEK-293-purified p72, p54, and p12 antigens. Notably, sera from the vaccinees were positive by immunofluorescence on ASFV (Georgia 2007/1)-infected primary macrophages. Although MVA-vectored p72, CD2v, and EP153R failed to induce antibody responses, interferon-gamma (IFN-γ + ) spot forming cell responses against all three antigens were detected one week post-boost. The highest IFN-γ + spot forming cell responses were detected against p72 in pigs primed with MVA-p72 and boosted with the recombinant p72. Antigen-specific (p12, p72, CD2v, and EP153R) T-cell proliferative responses were also detected post-boost. Collectively, these results are the first demonstration that ASFV subunit antigens purified from mammalian cells or expressed in MVA vectors are safe and can induce ASFV-specific antibody and T-cell responses following a prime-boost immunization regimen in swine. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

PubMed

Fuchs, Jonathan D; Bart, Pierre-Alexandre; Frahm, Nicole; Morgan, Cecilia; Gilbert, Peter B; Kochar, Nidhi; DeRosa, Stephen C; Tomaras, Georgia D; Wagner, Theresa M; Baden, Lindsey R; Koblin, Beryl A; Rouphael, Nadine G; Kalams, Spyros A; Keefer, Michael C; Goepfert, Paul A; Sobieszczyk, Magdalena E; Mayer, Kenneth H; Swann, Edith; Liao, Hua-Xin; Haynes, Barton F; Graham, Barney S; McElrath, M Juliana

2015-05-01

Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.

42 CFR 86.35 - Payments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Payments. 86.35 Section 86.35 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and...

42 CFR 86.15 - Payments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Payments. 86.15 Section 86.15 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and...

42 CFR 86.15 - Payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Payments. 86.15 Section 86.15 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and...

42 CFR 86.35 - Payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Payments. 86.35 Section 86.35 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and...

75 FR 57081 - Revised Draft Safety Culture Policy Statement: Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

... on Safety Culture at the Health Physics Society Annual Meeting, and presentations on the development... holders \\2\\ establish and maintain a positive safety culture that protects public health and safety and... public health and safety, the Commission has required the regulated entity involved to determine the...

76 FR 34773 - Final Safety Culture Policy Statement

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-14

... Special Joint Session on Safety Culture at the Health Physics Society Annual Meeting, and presentations on... safety-first focus in nuclear work environments for public health and safety. The Commission's emphasis... operations, if attacked, could have an impact on public health and safety. During the early years of...

76 FR 64110 - Safety and Health Management Programs for Mines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-17

... DEPARTMENT OF LABOR Mine Safety and Health Administration RIN 1219-AB71 Safety and Health Management Programs for Mines AGENCY: Mine Safety and Health Administration, Labor. ACTION: Notice of public meetings. SUMMARY: The Mine Safety and Health Administration (MSHA) is holding a public meeting, and plans...

75 FR 74022 - Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD [Recommendation 2010-1] Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers AGENCY: Defense Nuclear Facilities Safety Board... Nuclear Facilities Safety Board has made a recommendation to the Secretary of Energy requesting an...

Aviation safety data accessibility study index: a report on the issues related to public interest in aviation safety data

DOT National Transportation Integrated Search

1997-01-20

This paper reviews aviation safety data and measurement issues relevant to the determination of the best means of providing safety information to the public while ensuring the integrity of the aviation safety system. In addition , the paper examines ...

Tumor-Free Transplantation of Patient-Derived Induced Pluripotent Stem Cell Progeny for Customized Islet Regeneration.

PubMed

El Khatib, Moustafa M; Ohmine, Seiga; Jacobus, Egon J; Tonne, Jason M; Morsy, Salma G; Holditch, Sara J; Schreiber, Claire A; Uetsuka, Koji; Fusaki, Noemi; Wigle, Dennis A; Terzic, Andre; Kudva, Yogish C; Ikeda, Yasuhiro

2016-05-01

Human induced pluripotent stem cells (iPSCs) and derived progeny provide invaluable regenerative platforms, yet their clinical translation has been compromised by their biosafety concern. Here, we assessed the safety of transplanting patient-derived iPSC-generated pancreatic endoderm/progenitor cells. Transplantation of progenitors from iPSCs reprogrammed by lentiviral vectors (LV-iPSCs) led to the formation of invasive teratocarcinoma-like tumors in more than 90% of immunodeficient mice. Moreover, removal of primary tumors from LV-iPSC progeny-transplanted hosts generated secondary and metastatic tumors. Combined transgene-free (TGF) reprogramming and elimination of residual pluripotent cells by enzymatic dissociation ensured tumor-free transplantation, ultimately enabling regeneration of type 1 diabetes-specific human islet structures in vivo. The incidence of tumor formation in TGF-iPSCs was titratable, depending on the oncogenic load, with reintegration of the cMYC expressing vector abolishing tumor-free transplantation. Thus, transgene-free cMYC-independent reprogramming and elimination of residual pluripotent cells are mandatory steps in achieving transplantation of iPSC progeny for customized and safe islet regeneration in vivo. Pluripotent stem cell therapy for diabetes relies on the safety as well as the quality of derived insulin-producing cells. Data from this study highlight prominent tumorigenic risks of induced pluripotent stem cell (iPSC) products, especially when reprogrammed with integrating vectors. Two major underlying mechanisms in iPSC tumorigenicity are residual pluripotent cells and cMYC overload by vector integration. This study also demonstrated that combined transgene-free reprogramming and enzymatic dissociation allows teratoma-free transplantation of iPSC progeny in the mouse model in testing the tumorigenicity of iPSC products. Further safety assessment and improvement in iPSC specification into a mature β cell phenotype would lead to safe islet replacement therapy for diabetes. ©AlphaMed Press.

EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat.

PubMed

Zallocchi, Marisa; Binley, Katie; Lad, Yatish; Ellis, Scott; Widdowson, Peter; Iqball, Sharifah; Scripps, Vicky; Kelleher, Michelle; Loader, Julie; Miskin, James; Peng, You-Wei; Wang, Wei-Min; Cheung, Linda; Delimont, Duane; Mitrophanous, Kyriacos A; Cosgrove, Dominic

2014-01-01

Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.

Good Laboratory Practice Preclinical Safety Studies for GSK2696273 (MLV Vector-Based Ex Vivo Gene Therapy for Adenosine Deaminase Deficiency Severe Combined Immunodeficiency) in NSG Mice.

PubMed

Carriglio, Nicola; Klapwijk, Jan; Hernandez, Raisa Jofra; Vezzoli, Michela; Chanut, Franck; Lowe, Rhiannon; Draghici, Elena; Nord, Melanie; Albertini, Paola; Cristofori, Patrizia; Richards, Jane; Staton, Hazel; Appleby, Jonathan; Aiuti, Alessandro; Sauer, Aisha V

2017-03-01

GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Ex vivo gene therapy of patient bone-marrow CD34+ cells is an alternative treatment. In order to prepare for a marketing authorization application in the European Union, preclinical safety studies in mice were requested by the European Medicines Agency (EMA). A pilot study and a main biodistribution study were performed according to Good Laboratory Practice (GLP) at the San Raffaele Telethon Institute for Gene Therapy test facility. In the main study, human umbilical cord blood (UCB)-derived CD34+ cells were transduced with gamma-retroviral vector used in the production of GSK2696273. Groups of 10 male and 10 female NOD-SCID gamma (NSG) mice were injected intravenously with a single dose of transduced- or mock-transduced UCB CD34+ cells, and they were observed for 4 months. Engraftment and multilineage differentiation of blood cells was observed in the majority of animals in both groups. There was no significant difference in the level of chimerism between the two groups. In the gene therapy group, vector was detectable in lymphohemopoietic and nonlymphohemopoietic tissues, consistent with the presence of gene-modified human hematopoietic donor cells. Given the absence of relevant safety concerns in the data, the nonclinical studies and the clinical experience with GSK2696273 supported a successful application for market authorization in the European Union for the treatment of ADA-SCID patients, for whom no suitable human leukocyte antigen-matched related donor is available.

Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.

PubMed

Shaw, Kit L; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S; Scharenberg, Andrew; Yang, Otto O; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio; Kohn, Donald B

2017-05-01

Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1-2.6) and granulocytes (VCN = 0.01-0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. ClinicalTrials.gov NCT00794508. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124.

Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency

PubMed Central

Shaw, Kit L.; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E. Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R.; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G. Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B.; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S.; Scharenberg, Andrew; Yang, Otto O.; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio

2017-01-01

BACKGROUND. Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase–deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. RESULTS. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1–2.6) and granulocytes (VCN = 0.01–0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. CONCLUSION. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. TRIAL REGISTRATION. ClinicalTrials.gov NCT00794508. FUNDING. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124. PMID:28346229

77 FR 27669 - Request for Public Comment on Settlement Part Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION 29 CFR Part 2200 Request for Public Comment on Settlement Part Program AGENCY: Occupational Safety and Health Review Commission. ACTION: Request for comment. SUMMARY: The Occupational Safety and Health Review Commission (Review Commission) invites the public to...

78 FR 76391 - Proposed Enhancements to the Motor Carrier Safety Measurement System (SMS) Public Web Site

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

...-0392] Proposed Enhancements to the Motor Carrier Safety Measurement System (SMS) Public Web Site AGENCY... proposed enhancements to the display of information on the Agency's Safety Measurement System (SMS) public Web site. On December 6, 2013, Advocates [[Page 76392

36 CFR 2.32 - Interfering with agency functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and rescue operations, wildlife management operations involving animals that pose a threat to public safety, law enforcement actions, and emergency operations that involve a threat to public safety or park... order and public safety. (3) False information. Knowingly giving a false or fictitious report or other...

36 CFR 1002.32 - Interfering with agency functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... operations, wildlife management operations involving animals that pose a threat to public safety, law enforcement actions, and emergency operations that involve a threat to public safety or resources of the area... necessary to maintain order and public safety. (3) False information. Knowingly giving a false or fictitious...

16 CFR § 1102.10 - Reports of harm.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PUBLICLY AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE Content Requirements § 1102.10 Reports of... they have a public safety purpose. (b) Manner of submission. To be entered into the Database, reports... Commission will publish in the Publicly Available Consumer Product Safety Information Database reports of...

42 CFR 87.1 - To which programs does this regulation apply?

Code of Federal Regulations, 2010 CFR

2010-10-01

... National Institute for Occupational Safety and Health, Centers for Disease Control, of the Public Health... Section 87.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH...

Invasiveness of Aedes aegypti and Aedes albopictus and Vectorial Capacity for Chikungunya Virus

PubMed Central

Lounibos, Leon Philip; Kramer, Laura D.

2016-01-01

In this review, we highlight biological characteristics of Aedes aegypti and Aedes albopictus, 2 invasive mosquito species and primary vectors of chikungunya virus (CHIKV), that set the tone of these species' invasiveness, vector competence, and vectorial capacity (VC). The invasiveness of both species, as well as their public health threats as vectors, is enhanced by preference for human blood. Vector competence, characterized by the efficiency of an ingested arbovirus to replicate and become infectious in the mosquito, depends largely on vector and virus genetics, and most A. aegypti and A. albopictus populations thus far tested confer vector competence for CHIKV. VC, an entomological analog of the pathogen's basic reproductive rate (R0), is epidemiologically more important than vector competence but less frequently measured, owing to challenges in obtaining valid estimates of parameters such as vector survivorship and host feeding rates. Understanding the complexities of these factors will be pivotal in curbing CHIKV transmission. PMID:27920173

Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model

PubMed Central

Simão, Daniel; Pinto, Catarina; Fernandes, Paulo; Peddie, Christopher J.; Piersanti, Stefania; Collinson, Lucy M.; Salinas, Sara; Saggio, Isabella; Schiavo, Giampietro; Kremer, Eric J.; Brito, Catarina; Alves, Paula M.

2017-01-01

Gene therapy is a promising approach with enormous potential for treatment of neurodegenerative disorders. Viral vectors derived from canine adenovirus type 2 (CAV-2) present attractive features for gene delivery strategies in the human brain, by preferentially transducing neurons, are capable of efficient axonal transport to afferent brain structures, have a 30-kb cloning capacity and have low innate and induced immunogenicity in pre-clinical tests. For clinical translation, in-depth pre-clinical evaluation of efficacy and safety in a human setting is primordial. Stem cell-derived human neural cells have a great potential as complementary tools by bridging the gap between animal models, which often diverge considerably from human phenotype, and clinical trials. Herein, we explore helper-dependent CAV-2 (hd-CAV-2) efficacy and safety for gene delivery in a human stem cell-derived 3D neural in vitro model. Assessment of hd-CAV-2 vector efficacy was performed at different multiplicities of infection, by evaluating transgene expression and impact on cell viability, ultrastructural cellular organization and neuronal gene expression. Under optimized conditions, hd-CAV-2 transduction led to stable long-term transgene expression with minimal toxicity. hd-CAV-2 preferentially transduced neurons, while human adenovirus type 5 (HAdV5) showed increased tropism towards glial cells. This work demonstrates, in a physiologically relevant 3D model, that hd-CAV-2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity. PMID:26181626

Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model.

PubMed

Simão, D; Pinto, C; Fernandes, P; Peddie, C J; Piersanti, S; Collinson, L M; Salinas, S; Saggio, I; Schiavo, G; Kremer, E J; Brito, C; Alves, P M

2016-01-01

Gene therapy is a promising approach with enormous potential for treatment of neurodegenerative disorders. Viral vectors derived from canine adenovirus type 2 (CAV-2) present attractive features for gene delivery strategies in the human brain, by preferentially transducing neurons, are capable of efficient axonal transport to afferent brain structures, have a 30-kb cloning capacity and have low innate and induced immunogenicity in preclinical tests. For clinical translation, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. Stem cell-derived human neural cells have a great potential as complementary tools by bridging the gap between animal models, which often diverge considerably from human phenotype, and clinical trials. Herein, we explore helper-dependent CAV-2 (hd-CAV-2) efficacy and safety for gene delivery in a human stem cell-derived 3D neural in vitro model. Assessment of hd-CAV-2 vector efficacy was performed at different multiplicities of infection, by evaluating transgene expression and impact on cell viability, ultrastructural cellular organization and neuronal gene expression. Under optimized conditions, hd-CAV-2 transduction led to stable long-term transgene expression with minimal toxicity. hd-CAV-2 preferentially transduced neurons, whereas human adenovirus type 5 (HAdV5) showed increased tropism toward glial cells. This work demonstrates, in a physiologically relevant 3D model, that hd-CAV-2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity.

Human action classification using procrustes shape theory

NASA Astrophysics Data System (ADS)

Cho, Wanhyun; Kim, Sangkyoon; Park, Soonyoung; Lee, Myungeun

2015-02-01

In this paper, we propose new method that can classify a human action using Procrustes shape theory. First, we extract a pre-shape configuration vector of landmarks from each frame of an image sequence representing an arbitrary human action, and then we have derived the Procrustes fit vector for pre-shape configuration vector. Second, we extract a set of pre-shape vectors from tanning sample stored at database, and we compute a Procrustes mean shape vector for these preshape vectors. Third, we extract a sequence of the pre-shape vectors from input video, and we project this sequence of pre-shape vectors on the tangent space with respect to the pole taking as a sequence of mean shape vectors corresponding with a target video. And we calculate the Procrustes distance between two sequences of the projection pre-shape vectors on the tangent space and the mean shape vectors. Finally, we classify the input video into the human action class with minimum Procrustes distance. We assess a performance of the proposed method using one public dataset, namely Weizmann human action dataset. Experimental results reveal that the proposed method performs very good on this dataset.

76 FR 1137 - Publicly Available Consumer Product Safety Information Database: Notice of Public Web Conferences

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...: Notice of Public Web Conferences AGENCY: Consumer Product Safety Commission. ACTION: Notice. SUMMARY: The Consumer Product Safety Commission (``Commission,'' ``CPSC,'' or ``we'') is announcing two Web conferences... database (``Database''). The Web conferences will be webcast live from the Commission's headquarters in...

25 CFR 559.5 - What must a tribe submit to the Chairman with the copy of each facility license that has been...

Code of Federal Regulations, 2011 CFR

2011-04-01

... on the environment and the public health and safety, as well as mitigating measures the tribe may... environment and public health and safety. ... public health and safety laws, resolutions, codes, policies, standards or procedures applicable to its...

25 CFR 559.5 - What must a tribe submit to the Chairman with the copy of each facility license that has been...

Code of Federal Regulations, 2012 CFR

2012-04-01

... on the environment and the public health and safety, as well as mitigating measures the tribe may... environment and public health and safety. ... public health and safety laws, resolutions, codes, policies, standards or procedures applicable to its...

25 CFR 559.5 - What must a tribe submit to the Chairman with the copy of each facility license that has been...

Code of Federal Regulations, 2010 CFR

2010-04-01

... on the environment and the public health and safety, as well as mitigating measures the tribe may... environment and public health and safety. ... public health and safety laws, resolutions, codes, policies, standards or procedures applicable to its...

78 FR 65293 - Collection of Information; Proposed Extension of Approval; Comment Request-Publicly Available...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... Extension of Approval; Comment Request--Publicly Available Consumer Product Safety Information Database... Publicly Available Consumer Product Safety Information Database. The Commission will consider all comments... intention to seek extension of approval of a collection of information for a database on the safety of...

36 CFR 1004.15 - Safety belts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Safety belts. 1004.15 Section 1004.15 Parks, Forests, and Public Property PRESIDIO TRUST VEHICLES AND TRAFFIC SAFETY § 1004.15 Safety... administered by the Presidio Trust will have the safety belt or child restraint system properly fastened at all...

75 FR 69648 - Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD [Recommendation 2010-1] Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers AGENCY: Defense Nuclear Facilities Safety Board... Facilities Safety Board has made a recommendation to the Secretary of Energy requesting an amendment to the...

36 CFR 1004.15 - Safety belts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Safety belts. 1004.15 Section 1004.15 Parks, Forests, and Public Property PRESIDIO TRUST VEHICLES AND TRAFFIC SAFETY § 1004.15 Safety... administered by the Presidio Trust will have the safety belt or child restraint system properly fastened at all...

Alpharetroviral Vector-mediated Gene Therapy for X-CGD: Functional Correction and Lack of Aberrant Splicing

PubMed Central

Kaufmann, Kerstin B.; Brendel, Christian; Suerth, Julia D.; Mueller-Kuller, Uta; Chen-Wichmann, Linping; Schwäble, Joachim; Pahujani, Shweta; Kunkel, Hana; Schambach, Axel; Baum, Christopher; Grez, Manuel

2013-01-01

Comparative integrome analysis has revealed that the most neutral integration pattern among retroviruses is attributed to alpharetroviruses. We chose X-linked chronic granulomatous disease (X-CGD) as model to evaluate the potential of self-inactivating (SIN) alpharetroviral vectors for gene therapy of monogenic diseases. Therefore, we combined the alpharetroviral vector backbone with the elongation factor-1α short promoter, both considered to possess a low genotoxic profile, to drive transgene (gp91phox) expression. Following efficient transduction transgene expression was sustained and provided functional correction of the CGD phenotype in a cell line model at low vector copy number. Further analysis in a murine X-CGD transplantation model revealed gene-marking of bone marrow cells and oxidase positive granulocytes in peripheral blood. Transduction of human X-CGD CD34+ cells provided functional correction up to wild-type levels and long-term expression upon transplantation into a humanized mouse model. In contrast to lentiviral vectors, no aberrantly spliced transcripts containing cellular exons fused to alpharetroviral sequences were found in transduced cells, implying that the safety profile of alpharetroviral vectors may extend beyond their neutral integration profile. Taken together, this highlights the potential of this SIN alpharetroviral system as a platform for new candidate vectors for future gene therapy of hematopoietic disorders. PMID:23207695

Biosafety challenges for use of lentiviral vectors in gene therapy.

PubMed

Rothe, Michael; Modlich, Ute; Schambach, Axel

2013-12-01

Lentiviral vectors are promising tools for the genetic modification of cells in biomedical research and gene therapy. Their use in recent clinical trials for the treatment of adrenoleukodystrophy, β-thalassemia, Wiskott-Aldrich- Syndrome and metachromatic leukodystrophy underlined their efficacy for therapies especially in case of hereditary diseases. In comparison to gammaretroviral LTR-driven vectors, which were employed in the first clinical trials, lentiviral vectors present with some favorable features like the ability to transduce also non-dividing cells and a potentially safer insertion profile. However, genetic modification with viral vectors in general and stable integration of the therapeutic gene into the host cell genome bear concerns with respect to different levels of personal or environmental safety. Among them, insertional mutagenesis by enhancer mediated dysregulation of neighboring genes or aberrant splicing is still the biggest concern. However, also risks like immunogenicity of vector particles, the phenotoxicity of the transgene and potential vertical or horizontal transmission by replication competent retroviruses need to be taken into account. This review will give an overview on biosafety aspects that are relevant to the use of lentiviral vectors for genetic modification and gene therapy. Furthermore, assay systems aiming at evaluating biosafety in preclinical settings and recent promising clinical trials including efforts of monitoring of patients after gene therapy will be discussed.

Advances in the development of bacterial vector technology.

PubMed

Kochi, Sims K; Killeen, Kevin P; Ryan, Una S

2003-02-01

The demand for new and improved vaccines against human diseases has continued unabated over the past century. While the need continues for traditional vaccines in areas such as infectious diseases, there is an increasing demand for new therapies in nontraditional areas, such as cancer treatment, bioterrorism and food safety. Prompted by these changes, there has been a renewed interest in the application and development of live, attenuated bacteria expressing foreign antigens as vaccines. The application of bacterial vector vaccines to human maladies has been studied most extensively in attenuted strains of Salmonella. Live, attenuated strains of Shigella, Listeria monocytogenes, Mycobacterium bovis-BCG and Vibrio cholerae provide unique alternatives in terms of antigen delivery and immune presentation, however and also show promise as potentially useful bacterial vectors.

Intracellular trafficking of hybrid gene delivery vectors.

PubMed

Keswani, Rahul K; Lazebnik, Mihael; Pack, Daniel W

2015-06-10

Viral and non-viral gene delivery vectors are in development for human gene therapy, but both exhibit disadvantages such as inadequate efficiency, lack of cell-specific targeting or safety concerns. We have recently reported the design of hybrid delivery vectors combining retrovirus-like particles with synthetic polymers or lipids that are efficient, provide sustained gene expression and are more stable compared to native retroviruses. To guide further development of this promising class of gene delivery vectors, we have investigated their mechanisms of intracellular trafficking. Moloney murine leukemia virus-like particles (M-VLPs) were complexed with chitosan (Chi) or liposomes (Lip) comprising DOTAP, DOPE and cholesterol to form the hybrid vectors (Chi/M-VLPs and Lip/M-VLPs, respectively). Transfection efficiency and cellular internalization of the vectors were quantified in the presence of a panel of inhibitors of various endocytic pathways. Intracellular transport and trafficking kinetics of the hybrid vectors were dependent on the synthetic component and used a combination of clathrin- and caveolar-dependent endocytosis and macropinocytosis. Chi/M-VLPs were slower to transfect compared to Lip/M-VLPs due to the delayed detachment of the synthetic component. The synthetic component of hybrid gene delivery vectors plays a significant role in their cellular interactions and processing and is a key parameter for the design of more efficient gene delivery vehicles. Copyright © 2015 Elsevier B.V. All rights reserved.

Protective Immunity and Safety of a Genetically Modified Influenza Virus Vaccine

PubMed Central

Garcia, Cristiana Couto; Filho, Bruno Galvão; Gonçalves, Ana Paula de Faria; Lima, Braulio Henrique Freire; Lopes, Gabriel Augusto Oliveira; Rachid, Milene Alvarenga; Peixoto, Andiara Cristina Cardoso; de Oliveira, Danilo Bretas; Ataíde, Marco Antônio; Zirke, Carla Aparecida; Cotrim, Tatiane Marques; Costa, Érica Azevedo; Almeida, Gabriel Magno de Freitas; Russo, Remo Castro; Gazzinelli, Ricardo Tostes; Machado, Alexandre de Magalhães Vieira

2014-01-01

Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens. PMID:24927156

Expanding integrated vector management to promote healthy environments

PubMed Central

Lizzi, Karina M.; Qualls, Whitney A.; Brown, Scott C.; Beier, John C.

2014-01-01

Integrated Vector Management (IVM) strategies are intended to protect communities from pathogen transmission by arthropods. These strategies target multiple vectors and different ecological and socioeconomic settings, but the aggregate benefits of IVM are limited by the narrow focus of its approach; IVM strategies only aim to control arthropod vectors. We argue that IVM should encompass environmental modifications at early stages, for instance, infrastructural development and sanitation services, to regulate not only vectors but also nuisance-biting arthropods. An additional focus on nuisance-biting arthropods will improve public health, quality of life, and minimize social disparity issues fostered by pests. Optimally, IVM could incorporate environmental awareness and promotion of control methods in order to proactively reduce threats of serious pest situations. PMID:25028090

Criteria for the prioritization of public health interventions for climate-sensitive vector-borne diseases in Quebec

PubMed Central

Gosselin, Pierre; Michel, Pascal; Ravel, André; Waaub, Jean-Philippe; Campagna, Céline; Samoura, Karim

2017-01-01

Prioritizing resources for optimal responses to an ever growing list of existing and emerging infectious diseases represents an important challenge to public health. In the context of climate change, there is increasing anticipated variability in the occurrence of infectious diseases, notably climate-sensitive vector-borne diseases. An essential step in prioritizing efforts is to identify what considerations and concerns to take into account to guide decisions and thus set disease priorities. This study was designed to perform a comprehensive review of criteria for vector-borne disease prioritization, assess their applicability in a context of climate change with a diverse cross-section of stakeholders in order to produce a baseline list of considerations to use in this decision-making context. Differences in stakeholder choices were examined with regards to prioritization of these criteria for research, surveillance and disease prevention and control objectives. A preliminary list of criteria was identified following a review of the literature. Discussions with stakeholders were held to consolidate and validate this list of criteria and examine their effects on disease prioritization. After this validation phase, a total of 21 criteria were retained. A pilot vector-borne disease prioritization exercise was conducted using PROMETHEE to examine the effects of the retained criteria on prioritization in different intervention domains. Overall, concerns expressed by stakeholders for prioritization were well aligned with categories of criteria identified in previous prioritization studies. Weighting by category was consistent between stakeholders overall, though some significant differences were found between public health and non-public health stakeholders. From this exercise, a general model for climate-sensitive vector-borne disease prioritization has been developed that can be used as a starting point for further public health prioritization exercises relating to research, surveillance, and prevention and control interventions in a context of climate change. Multi-stakeholder engagement in prioritization can help broaden the range of criteria taken into account, offer opportunities for early identification of potential challenges and may facilitate acceptability of any resulting decisions. PMID:29281726

The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer

PubMed Central

Boisgérault, Florence; Mingozzi, Federico

2015-01-01

Since the early days of gene therapy, muscle has been one the most studied tissue targets for the correction of enzyme deficiencies and myopathies. Several preclinical and clinical studies have been conducted using adeno-associated virus (AAV) vectors. Exciting progress has been made in the gene delivery technologies, from the identification of novel AAV serotypes to the development of novel vector delivery techniques. In parallel, significant knowledge has been generated on the host immune system and its interaction with both the vector and the transgene at the muscle level. In particular, the role of underlying muscle inflammation, characteristic of several diseases affecting the muscle, has been defined in terms of its potential detrimental impact on gene transfer with AAV vectors. At the same time, feedback immunomodulatory mechanisms peculiar of skeletal muscle involving resident regulatory T cells have been identified, which seem to play an important role in maintaining, at least to some extent, muscle homeostasis during inflammation and regenerative processes. Devising strategies to tip this balance towards unresponsiveness may represent an avenue to improve the safety and efficacy of muscle gene transfer with AAV vectors. PMID:26122097

U.S. Food System Working Conditions as an Issue of Food Safety.

PubMed

Clayton, Megan L; Smith, Katherine C; Pollack, Keshia M; Neff, Roni A; Rutkow, Lainie

2017-02-01

Food workers' health and hygiene are common pathways to foodborne disease outbreaks. Improving food system jobs is important to food safety because working conditions impact workers' health, hygiene, and safe food handling. Stakeholders from key industries have advanced working conditions as an issue of public safety in the United States. Yet, for the food industry, stakeholder engagement with this topic is seemingly limited. To understand this lack of action, we interviewed key informants from organizations recognized for their agenda-setting role on food-worker issues. Findings suggest that participants recognize the work standards/food safety connection, yet perceived barriers limit adoption of a food safety frame, including more pressing priorities (e.g., occupational safety); poor fit with organizational strategies and mission; and questionable utility, including potential negative consequences. Using these findings, we consider how public health advocates may connect food working conditions to food and public safety and elevate it to the public policy agenda.

Thailand Momentum on Policy and Practice in Local Legislation on Dengue Vector Control

PubMed Central

Bhumiratana, Adisak; Intarapuk, Apiradee; Chujun, Suriyo; Kaewwaen, Wuthichai; Sorosjinda-Nunthawarasilp, Prapa; Koyadun, Surachart

2014-01-01

Over a past decade, an administrative decentralization model, adopted for local administration development in Thailand, is replacing the prior centralized (top-down) command system. The change offers challenges to local governmental agencies and other public health agencies at all the ministerial, regional, and provincial levels. A public health regulatory and legislative framework for dengue vector control by local governmental agencies is a national topic of interest because dengue control program has been integrated into healthcare services at the provincial level and also has been given priority in health plans of local governmental agencies. The enabling environments of local administrations are unique, so this critical review focuses on the authority of local governmental agencies responsible for disease prevention and control and on the functioning of local legislation with respect to dengue vector control and practices. PMID:24799896

Socio-economic inequity in demand for insecticide-treated nets, in-door residual house spraying, larviciding and fogging in Sudan.

PubMed

Onwujekwe, Obinna; Malik, El-Fatih Mohamed; Mustafa, Sara Hassan; Mnzava, Abraham

2005-12-15

In order to optimally prioritize and use public and private budgets for equitable malaria vector control, there is a need to determine the level and determinants of consumer demand for different vector control tools. To determine the demand from people of different socio-economic groups for indoor residual house-spraying (IRHS), insecticide-treated nets (ITNs), larviciding with chemicals (LWC), and space spraying/fogging (SS) and the disease control implications of the result. Ratings and levels of willingness-to-pay (WTP) for the vector control tools were determined using a random cross-sectional sample of 720 householdes drawn from two states. WTP was elicited using the bidding game. An asset-based socio-economic status (SES) index was used to explore whether WTP was related to SES of the respondents. IRHS received the highest proportion of highest preferred rating (41.0%) followed by ITNs (23.1%). However, ITNs had the highest mean WTP followed by IRHS, while LWC had the least. The regression analysis showed that SES was positively and statistically significantly related to WTP across the four vector control tools and that the respondents' rating of IRHS and ITNs significantly explained their levels of WTP for the two tools. People were willing to pay for all the vector-control tools, but the demand for the vector control tools was related to the SES of the respondents. Hence, it is vital that there are public policies and financing mechanisms to ensure equitable provision and utilisation of vector control tools, as well as protecting the poor from cost-sharing arrangements.

Electromagnetic Fields of a Uniform Sphere in a Uniform Conducting Medium with Application to Dipole Sources

DTIC Science & Technology

1991-09-01

12b. DISTRIBUTION CODE Approved for public release; distribution is unlimited. 13. ABSTRACT (Maximum 200 words) Vector spherical harmonic expansions are...electric and magnetic field vectors from E rand B - r alone. Genural expressions are given relating the scattered field expansion coefficients to the source...Prescnbed by ANSI Std. Z39-18 29W-102 NCSC TR 426-90 CONTENTS Pag o INTRODUCTION 1 BACKGROUND 1 ANGULAR MOMENTUM OPERATOR AND VECTOR SPHERICAL

Regulatory Oversight of Cell and Gene Therapy Products in Canada.

PubMed

Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

2015-01-01

Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

PubMed

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor

PubMed Central

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M.; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G.; Scholler, John; Levine, Bruce L.; Albelda, Steven M.; June, Carl H.

2010-01-01

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CARs). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week post electroporation. Multiple injections of RNA CAR electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(−/−) mice. Dramatic tumor reduction also occurred when the pre-existing intraperitoneal human-derived tumors, that had been growing in vivo for over 50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes demonstrating that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. PMID:20926399

Therapeutic Gene Editing Safety and Specificity.

PubMed

Lux, Christopher T; Scharenberg, Andrew M

2017-10-01

Therapeutic gene editing is significant for medical advancement. Safety is intricately linked to the specificity of the editing tools used to cut at precise genomic targets. Improvements can be achieved by thoughtful design of nucleases and repair templates, analysis of off-target editing, and careful utilization of viral vectors. Advancements in DNA repair mechanisms and development of new generations of tools improve targeting of specific sequences while minimizing risks. It is important to plot a safe course for future clinical trials. This article reviews safety and specificity for therapeutic gene editing to spur dialogue and advancement. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 23245 - Pesticide Program Dialogue Committee; Notice of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

...: Integrated Pest Management, Comparative Safety Statements, Public Health, and Pollinator Protection. The PPDC... p.m.; Comparative Safety Statements from 1 p.m. to 4 p.m.; Public Health from 1 p.m. to 4 p.m.; and... Management and Pollinator Protection Workgroup meetings. The Comparative Safety Statements [[Page 23246...

77 FR 4731 - Review and Submittal of a Tribe's Facility License Information

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-31

... conducted in a manner which adequately protects the environment and public health and safety.'' 25 U.S.C... conducted in a manner that adequately protects the environment and the public health and safety, as required... that adequately protects the environment and the public health and safety. The proposed rule maintains...

75 FR 8137 - Coordination and Strategic Planning of the Federal Effort Against Intellectual Property...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... jobs. In addition, the IPEC seeks written submissions identifying threats to public health and safety... resulting from intellectual property violations, and the threats to public health and safety created by... violations, and the threats to public health and safety created by infringement. Thus, the IPEC seeks written...

32 CFR 643.22 - Policy-Public safety: Requirement for early identification of lands containing dangerous materials.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Policy-Public safety: Requirement for early identification of lands containing dangerous materials. 643.22 Section 643.22 National Defense Department of...—Public safety: Requirement for early identification of lands containing dangerous materials. (a) DA will...

32 CFR 643.22 - Policy-Public safety: Requirement for early identification of lands containing dangerous materials.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Policy-Public safety: Requirement for early identification of lands containing dangerous materials. 643.22 Section 643.22 National Defense Department of...—Public safety: Requirement for early identification of lands containing dangerous materials. (a) DA will...

Public Safety Core. Integrated Academic and Technical Competencies (ITAC).

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus. Div. of Career-Technical and Adult Education.

This document, which lists the public safety core competencies that are part of the Integrated Academic and Technical Competencies (ITAC) in Ohio, is intended to assist individuals and organizations develop a course to provide students with knowledge and skills applicable to public safety careers, including but not limited to firefighter,…

Implication of vector characteristics of Phlebotomus argentipes in the kala-azar elimination programme in the Indian sub-continent.

PubMed

Chowdhury, Rajib; Kumar, Vijay; Mondal, Dinesh; Das, Murari Lal; Das, Pradeep; Dash, Aditya Prasad; Kroeger, Axel

2016-05-01

Visceral leishmaniasis (VL), also known as kala-azar in the Indian sub-continent (ISC), is a major public health concern in Bangladesh, India, and Nepal, where it is caused by Leishmania donovani transmitted by the sand fly Phlebotomus argentipes. Various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, pH, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. However, more detailed knowledge on vector behavior, such as biting times, breeding places, and preferred hosts are needed to design optimal evidence-based vector control interventions. In order to facilitate rational decisions regarding VL vector control, a systematic review was conducted to identify the prevailing practice and knowledge gaps in relation to vector bionomics and behavior. Search terms included 'sand fly bionomics', 'habitat', and 'visceral leishmaniasis/kala-azar vector control' using the Boolean operator AND to identify the country of interest, namely: Bangladesh, India, and Nepal. Both PubMed and Google search engines were used. Additional unpublished documents in the three countries were also analyzed. Information on the life cycle of VL vectors, their breeding behavior, infection rate with L. donovani, feeding behavior, and seasonal variation are useful for designing vector control operations. Unfortunately, none of the studies on the life cycle of P. argentipes was conducted in field settings of the ISC, so the publications from other locations had to be used for determining the duration of life cycle and development from egg to adult. However, information about breeding places, seasonal variation of vector densities, and 47 out of the selected 51 papers are available from the ISC and can be used for intelligent design of control operations. Vector control services should undertake routine insecticide resistance monitoring and adapt indoor residual spraying rounds to the seasonality of vector densities. Further research is needed on potential animal reservoirs for L. donovani, on the breeding habitat, and life cycle of sand flies in the ISC.

Implication of vector characteristics of Phlebotomus argentipes in the kala-azar elimination programme in the Indian sub-continent

PubMed Central

Chowdhury, Rajib; Kumar, Vijay; Mondal, Dinesh; Das, Murari Lal; Das, Pradeep; Dash, Aditya Prasad

2016-01-01

Background Visceral leishmaniasis (VL), also known as kala-azar in the Indian sub-continent (ISC), is a major public health concern in Bangladesh, India, and Nepal, where it is caused by Leishmania donovani transmitted by the sand fly Phlebotomus argentipes. Various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, pH, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. However, more detailed knowledge on vector behavior, such as biting times, breeding places, and preferred hosts are needed to design optimal evidence-based vector control interventions. Methods In order to facilitate rational decisions regarding VL vector control, a systematic review was conducted to identify the prevailing practice and knowledge gaps in relation to vector bionomics and behavior. Search terms included ‘sand fly bionomics’, ‘habitat’, and ‘visceral leishmaniasis/kala-azar vector control’ using the Boolean operator AND to identify the country of interest, namely: Bangladesh, India, and Nepal. Both PubMed and Google search engines were used. Additional unpublished documents in the three countries were also analyzed. Results Information on the life cycle of VL vectors, their breeding behavior, infection rate with L. donovani, feeding behavior, and seasonal variation are useful for designing vector control operations. Unfortunately, none of the studies on the life cycle of P. argentipes was conducted in field settings of the ISC, so the publications from other locations had to be used for determining the duration of life cycle and development from egg to adult. However, information about breeding places, seasonal variation of vector densities, and 47 out of the selected 51 papers are available from the ISC and can be used for intelligent design of control operations. Conclusion Vector control services should undertake routine insecticide resistance monitoring and adapt indoor residual spraying rounds to the seasonality of vector densities. Further research is needed on potential animal reservoirs for L. donovani, on the breeding habitat, and life cycle of sand flies in the ISC. PMID:27376500

Quantification of vector and host competence for Japanese encephalitis virus: a systematic review of the literature

USDA-ARS?s Scientific Manuscript database

Japanese encephalitis virus (JEV) is a virus of the Flavivirus genus that may result in encephalitis in human hosts. This vector-borne zoonosis occurs in Eastern and Southeastern Asia and an intentional or inadvertent introduction into the United States (US) will have major public health and economi...

Determining an appropriate integrated assessment model of tourism safety risk within the Changbai Mountain Scenic Area

NASA Astrophysics Data System (ADS)

Zhou, Lijun; Liu, Jisheng

2017-03-01

Tourism safety is gradually gaining more attention due to the rapid development of the tourism industry in China. Changbai Mountain is one of the most famous mountainous scenic areas in Northeast Asia. Assessment on Changbai Mountain scenic area’s tourism safety risk could do a favor in detecting influence factor of tourism safety risk and classifying tourism safety risk rank, thereby reducing and preventing associated tourism safety risks. This paper uses the Changbai Mountain scenic area as the study subject. By the means of experts scoring and analytic hierarchy process on quantified relevant evaluation indicator, the grid GIS method is used to vectorize the relevant data within a 1000m grid. It respectively analyzes main indicators associated tourism safety risk in Changbai Mountain scenic area, including hazard, exposure, vulnerability and ability to prevent and mitigate disasters. The integrated tourism safety risk model is used to comprehensively evaluate tourism safety risk in Changbai Mountain scenic area.

Predicting healthcare associated infections using patients' experiences

NASA Astrophysics Data System (ADS)

Pratt, Michael A.; Chu, Henry

2016-05-01

Healthcare associated infections (HAI) are a major threat to patient safety and are costly to health systems. Our goal is to predict the HAI performance of a hospital using the patients' experience responses as input. We use four classifiers, viz. random forest, naive Bayes, artificial feedforward neural networks, and the support vector machine, to perform the prediction of six types of HAI. The six types include blood stream, urinary tract, surgical site, and intestinal infections. Experiments show that the random forest and support vector machine perform well across the six types of HAI.

45 CFR 1310.21 - Safety education.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Safety education. 1310.21 Section 1310.21 Public... PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.21 Safety education. (a) Each agency must... children. The required transportation and pedestrian safety education of children and parents, except for...

45 CFR 1310.21 - Safety education.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Safety education. 1310.21 Section 1310.21 Public... PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.21 Safety education. (a) Each agency must... children. The required transportation and pedestrian safety education of children and parents, except for...

45 CFR 1310.21 - Safety education.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Safety education. 1310.21 Section 1310.21 Public... PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.21 Safety education. (a) Each agency must... children. The required transportation and pedestrian safety education of children and parents, except for...

45 CFR 1310.21 - Safety education.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Safety education. 1310.21 Section 1310.21 Public... PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.21 Safety education. (a) Each agency must... children. The required transportation and pedestrian safety education of children and parents, except for...

45 CFR 1310.21 - Safety education.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Safety education. 1310.21 Section 1310.21 Public... PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.21 Safety education. (a) Each agency must... children. The required transportation and pedestrian safety education of children and parents, except for...

Impact of telemedicine in hospital culture and its consequences on quality of care and safety

PubMed Central

Steinman, Milton; Morbeck, Renata Albaladejo; Pires, Philippe Vieira; Abreu, Carlos Alberto Cordeiro; Andrade, Ana Helena Vicente; Terra, Jose Claudio Cyrineu; Teixeira, José Carlos; Kanamura, Alberto Hideki

2015-01-01

ABSTRACT Objective To describe the impact of the telemedicine application on the clinical process of care and its different effects on hospital culture and healthcare practice. Methods The concept of telemedicine through real time audio-visual coverage was implemented at two different hospitals in São Paulo: a secondary and public hospital, Hospital Municipal Dr. Moysés Deutsch, and a tertiary and private hospital, Hospital Israelita Albert Einstein. Results Data were obtained from 257 teleconsultations records over a 12-month period and were compared to a similar period before telemedicine implementation. For 18 patients (7.1%) telemedicine consultation influenced in diagnosis conclusion, and for 239 patients (92.9%), the consultation contributed to clinical management. After telemedicine implementation, stroke thrombolysis protocol was applied in 11% of ischemic stroke patients. Telemedicine approach reduced the need to transfer the patient to another hospital in 25.9% regarding neurological evaluation. Sepsis protocol were adopted and lead to a 30.4% reduction mortality regarding severe sepsis. Conclusion The application is associated with differences in the use of health services: emergency transfers, mortality, implementation of protocols and patient management decisions, especially regarding thrombolysis. These results highlight the role of telemedicine as a vector for transformation of hospital culture impacting on the safety and quality of care. PMID:26676268

Copy number determination of genetically-modified hematopoietic stem cells.

PubMed

Schuesler, Todd; Reeves, Lilith; Kalle, Christof von; Grassman, Elke

2009-01-01

Human gene transfer with gammaretroviral, murine leukemia virus (MLV) based vectors has been shown to effectively insert and express transgene sequences at a level of therapeutic benefit. However, there are numerous reports of disruption of the normal cellular processes caused by the viral insertion, even of replication deficient gammaretroviral vectors. Current gammaretroviral and lentiviral vectors do not control the site of insertion into the genome, hence, the possibility of disruption of the target cell genome. Risk related to viral insertions is linked to the number of insertions of the transgene into the cellular DNA, as has been demonstrated for replication competent and replication deficient retroviruses in experiments. At high number of insertions per cell, cell transformation due to vector induced activation of proto-oncogenes is more likely to occur, in particular since more than one transforming event is needed for oncogenesis. Thus, determination of the vector copy number in bulk transduced populations, individual colony forming units, and tissue from the recipient of the transduced cells is an increasingly important safety assay and has become a standard, though not straightforward assay, since the inception of quantitative PCR.

Effective delivery of large genes to the retina by dual AAV vectors

PubMed Central

Trapani, Ivana; Colella, Pasqualina; Sommella, Andrea; Iodice, Carolina; Cesi, Giulia; de Simone, Sonia; Marrocco, Elena; Rossi, Settimio; Giunti, Massimo; Palfi, Arpad; Farrar, Gwyneth J; Polishchuk, Roman; Auricchio, Alberto

2014-01-01

Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, AAV's limited cargo capacity prevents its application to therapies of inherited retinal diseases due to mutations of genes over 5 kb, like Stargardt's disease (STGD) and Usher syndrome type IB (USH1B). Previous methods based on ‘forced’ packaging of large genes into AAV capsids may not be easily translated to the clinic due to the generation of genomes of heterogeneous size which raise safety concerns. Taking advantage of AAV's ability to concatemerize, we generated dual AAV vectors which reconstitute a large gene by either splicing (trans-splicing), homologous recombination (overlapping), or a combination of the two (hybrid). We found that dual trans-splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B. Thus, dual AAV trans-splicing or hybrid vectors are an attractive strategy for gene therapy of retinal diseases that require delivery of large genes. PMID:24150896

42 CFR 86.4 - Publications and copyrights.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Publications and copyrights. 86.4 Section 86.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH General § 86.4 Publications and copyrights. Excep...

Global Change and Human Vulnerability to Vector-Borne Diseases

PubMed Central

Sutherst, Robert W.

2004-01-01

Global change includes climate change and climate variability, land use, water storage and irrigation, human population growth and urbanization, trade and travel, and chemical pollution. Impacts on vector-borne diseases, including malaria, dengue fever, infections by other arboviruses, schistosomiasis, trypanosomiasis, onchocerciasis, and leishmaniasis are reviewed. While climate change is global in nature and poses unknown future risks to humans and natural ecosystems, other local changes are occurring more rapidly on a global scale and are having significant effects on vector-borne diseases. History is invaluable as a pointer to future risks, but direct extrapolation is no longer possible because the climate is changing. Researchers are therefore embracing computer simulation models and global change scenarios to explore the risks. Credible ranking of the extent to which different vector-borne diseases will be affected awaits a rigorous analysis. Adaptation to the changes is threatened by the ongoing loss of drugs and pesticides due to the selection of resistant strains of pathogens and vectors. The vulnerability of communities to the changes in impacts depends on their adaptive capacity, which requires both appropriate technology and responsive public health systems. The availability of resources in turn depends on social stability, economic wealth, and priority allocation of resources to public health. PMID:14726459

Survey of spatial distribution of vector-borne disease in neighborhood dogs in southern Brazil.

PubMed

Constantino, Caroline; de Paula, Edson Ferraz Evaristo; Brandão, Ana Pérola Drulla; Ferreira, Fernando; Vieira, Rafael Felipe da Costa; Biondo, Alexander Welker

2017-01-01

Neighborhood dogs may act as reservoirs and disseminators of vector-borne diseases in urban areas. Accordingly, the aim of this study was to ascertain the health status and the vector-borne pathogens infecting dogs living in public areas with high levels of human movement in the city of Curitiba, southern Brazil. Blood samples from 21 neighborhood dogs that were found in nine of 22 bus stations and two public parks were subjected to a complete blood cell (CBC) count, serum biochemical profiling, a commercial rapid ELISA test and a commercial real-time PCR panel of vector-borne diseases. The CBC count and serum biochemical profiling were within the normal range for dogs and only 1/21 (4.7%) of the dogs was seroreactive for Borrelia burgdorferi sensu stricto. The commercial real-time PCR panel showed that 7/21 (33.3%) of the dogs had Mycoplasma haemocanis infection, 9/21 (42.8%) had ' Candidatus Mycoplasma haematoparvum' and 4/21 (19.0%) had both. No statistical association between infected by the agents found here and abnormalities in physical examinations, laboratory tests or ectoparasite presence was found ( p > 0.05). In conclusion, neighborhood dogs showed low prevalence of vector-borne diseases and satisfactory wellbeing, and dogs can be used as sentinels for disease exposure.

Common Host-Derived Chemicals Increase Catches of Disease-Transmitting Mosquitoes and Can Improve Early Warning Systems for Rift Valley Fever Virus

PubMed Central

Tchouassi, David P.; Sang, Rosemary; Sole, Catherine L.; Bastos, Armanda D. S.; Teal, Peter E. A.; Borgemeister, Christian; Torto, Baldwyn

2013-01-01

Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health and veterinary problem in sub-Saharan Africa. Surveillance to monitor mosquito populations during the inter-epidemic period (IEP) and viral activity in these vectors is critical to informing public health decisions for early warning and control of the disease. Using a combination of field bioassays, electrophysiological and chemical analyses we demonstrated that skin-derived aldehydes (heptanal, octanal, nonanal, decanal) common to RVF virus (RVFV) hosts including sheep, cow, donkey, goat and human serve as potent attractants for RVFV mosquito vectors. Furthermore, a blend formulated from the four aldehydes and combined with CO2-baited CDC trap without a light bulb doubled to tripled trap captures compared to control traps baited with CO2 alone. Our results reveal that (a) because of the commonality of the host chemical signature required for attraction, the host-vector interaction appears to favor the mosquito vector allowing it to find and opportunistically feed on a wide range of mammalian hosts of the disease, and (b) the sensitivity, specificity and superiority of this trapping system offers the potential for its wider use in surveillance programs for RVFV mosquito vectors especially during the IEP. PMID:23326620

Interaction of Flavivirus with their mosquito vectors and their impact on the human health in the Americas.

PubMed

Valderrama, Anayansi; Díaz, Yamilka; López-Vergès, Sandra

2017-10-28

Some of the major arboviruses with public health importance, such as dengue, yellow fever, Zika and West Nile virus are mosquito-borne or mosquito-transmitted Flavivirus. Their principal vectors are from the family Culicidae, Aedes aegypti and Aedes albopictus being responsible of the urban cycles of dengue, Zika and yellow fever virus. These vectors are highly competent for transmission of many arboviruses. The genetic variability of the vectors, the environment and the viral diversity modulate the vector competence, in this context, it is important to determine which vector species is responsible of an outbreak in areas where many vectors coexist. As some vectors can transmit several flaviviruses and some flaviviruses can be transmitted by different species of vectors, through this review we expose importance of yellow fever, dengue and Zika virus in the world and the Americas, as well as the updated knowledge about these flaviviruses in their interaction with their mosquito vectors, guiding us on what is probably the beginning of a new stage in which the simultaneity of outbreaks will occur more frequently. Copyright © 2017 Elsevier Inc. All rights reserved.

When They Can't Talk, Lives Are Lost : What Public Officials Need to Know About Interoperability

DOT National Transportation Integrated Search

2003-02-01

This publication was developed to facilitate education and discussion among and between elected and appointed officials, their representative associations, and public safety representatives on public safety wireless communications interoperability. T...

Twenty-Five Years of Gene Therapy for ADA-SCID: From Bubble Babies to an Approved Drug.

PubMed

Ferrua, Francesca; Aiuti, Alessandro

2017-11-01

Twenty-five years have passed since first attempts of gene therapy (GT) in children affected by severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) defect, also known by the general public as bubble babies. ADA-SCID is fatal early in life if untreated. Unconditioned hematopoietic stem cell (HSC) transplant from matched sibling donor represents a curative treatment but is available for few patients. Enzyme replacement therapy can be life-saving, but its chronic use has many drawbacks. This review summarizes the history of ADA-SCID GT over the last 25 years, starting from first pioneering studies in the early 1990s using gamma-retroviral vectors, based on multiple infusions of genetically corrected autologous peripheral blood lymphocytes. HSC represented the ideal target for gene correction to guarantee production of engineered multi-lineage progeny, but it required a decade to achieve therapeutic benefit with this approach. Introduction of low-intensity conditioning represented a crucial step in achieving stable gene-corrected HSC engraftment and therapeutic levels of ADA-expressing cells. Recent clinical trials demonstrated that gamma-retroviral GT for ADA-SCID has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions in patients >13 years after treatment. No abnormal clonal proliferation or leukemia development have been observed in >40 patients treated experimentally in five different centers worldwide. In 2016, the medicinal product Strimvelis™ received marketing approval in Europe for patients affected by ADA-SCID without a suitable human leukocyte antigen-matched related donor. Positive safety and efficacy results have been obtained in GT clinical trials using lentiviral vectors encoding ADA. The results obtained in last 25 years in ADA-SCID GT development fundamentally contributed to improve patients' prognosis, together with earlier diagnosis thanks to newborn screening. These advances open the way to further clinical development of GT as treatment for broader applications, from inherited diseases to cancer.

Construction and Characterization of an in-vivo Linear Covalently Closed DNA Vector Production System

PubMed Central

2012-01-01

Background While safer than their viral counterparts, conventional non-viral gene delivery DNA vectors offer a limited safety profile. They often result in the delivery of unwanted prokaryotic sequences, antibiotic resistance genes, and the bacterial origins of replication to the target, which may lead to the stimulation of unwanted immunological responses due to their chimeric DNA composition. Such vectors may also impart the potential for chromosomal integration, thus potentiating oncogenesis. We sought to engineer an in vivo system for the quick and simple production of safer DNA vector alternatives that were devoid of non-transgene bacterial sequences and would lethally disrupt the host chromosome in the event of an unwanted vector integration event. Results We constructed a parent eukaryotic expression vector possessing a specialized manufactured multi-target site called “Super Sequence”, and engineered E. coli cells (R-cell) that conditionally produce phage-derived recombinase Tel (PY54), TelN (N15), or Cre (P1). Passage of the parent plasmid vector through R-cells under optimized conditions, resulted in rapid, efficient, and one step in vivo generation of mini lcc—linear covalently closed (Tel/TelN-cell), or mini ccc—circular covalently closed (Cre-cell), DNA constructs, separated from the backbone plasmid DNA. Site-specific integration of lcc plasmids into the host chromosome resulted in chromosomal disruption and 105 fold lower viability than that seen with the ccc counterpart. Conclusion We offer a high efficiency mini DNA vector production system that confers simple, rapid and scalable in vivo production of mini lcc DNA vectors that possess all the benefits of “minicircle” DNA vectors and virtually eliminate the potential for undesirable vector integration events. PMID:23216697

Construction and characterization of an in-vivo linear covalently closed DNA vector production system.

PubMed

Nafissi, Nafiseh; Slavcev, Roderick

2012-12-06

While safer than their viral counterparts, conventional non-viral gene delivery DNA vectors offer a limited safety profile. They often result in the delivery of unwanted prokaryotic sequences, antibiotic resistance genes, and the bacterial origins of replication to the target, which may lead to the stimulation of unwanted immunological responses due to their chimeric DNA composition. Such vectors may also impart the potential for chromosomal integration, thus potentiating oncogenesis. We sought to engineer an in vivo system for the quick and simple production of safer DNA vector alternatives that were devoid of non-transgene bacterial sequences and would lethally disrupt the host chromosome in the event of an unwanted vector integration event. We constructed a parent eukaryotic expression vector possessing a specialized manufactured multi-target site called "Super Sequence", and engineered E. coli cells (R-cell) that conditionally produce phage-derived recombinase Tel (PY54), TelN (N15), or Cre (P1). Passage of the parent plasmid vector through R-cells under optimized conditions, resulted in rapid, efficient, and one step in vivo generation of mini lcc--linear covalently closed (Tel/TelN-cell), or mini ccc--circular covalently closed (Cre-cell), DNA constructs, separated from the backbone plasmid DNA. Site-specific integration of lcc plasmids into the host chromosome resulted in chromosomal disruption and 10(5) fold lower viability than that seen with the ccc counterpart. We offer a high efficiency mini DNA vector production system that confers simple, rapid and scalable in vivo production of mini lcc DNA vectors that possess all the benefits of "minicircle" DNA vectors and virtually eliminate the potential for undesirable vector integration events.

Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB-dependent CXCL10 expression.

PubMed

Liu, Qiang; White, Lindsay R; Clark, Sharon A; Heffner, Daniel J; Winston, Brent W; Tibbles, Lee Anne; Muruve, Daniel A

2005-12-01

In gene therapy, the innate immune system is a significant barrier to the effective application of adenovirus (Ad) vectors. In kidney epithelium-derived (REC) cells, serotype 5 Ad vectors induce the expression of the chemokine CXCL10 (IP-10), a response that is dependent on NFkappaB. Compared to the parental vector AdLuc, transduction with the RGD-deleted vector AdL.PB resulted in reduced CXCL10 activation despite increasing titers, implying that RGD-alpha(V) integrin interactions contribute to adenovirus induction of inflammatory genes. Akt, a downstream effector of integrin signaling, was activated within 10 min of transduction with Ad vectors in a dose-dependent manner. Akt activation was not present following transduction with AdL.PB, confirming the importance of capsid-alpha(V) integrin interactions in Ad vector Akt activation. Inhibition of the phosphoinositide-3-OH kinase/Akt pathway by Wortmannin or Ly294002 compounds decreased Ad vector induction of CXCL10 mRNA. Similarly, adenovirus-mediated overexpression of the dominant negative AktAAA decreased CXCL10 mRNA expression compared to the reporter vector AdLacZ alone. The effect of Akt on CXCL10 mRNA expression occurred via NFkappaB-dependent transcriptional activation, since AktAAA overexpression and Ly294002 both inhibited CXCL10 and NFkappaB promoter activation in luciferase reporter experiments. These results show that Akt plays a role in the Ad vector activation of NFkappaB and CXCL10 expression. Understanding the mechanism underlying the regulation of host immunomodulatory genes by adenovirus vectors will lead to strategies that will improve the efficacy and safety of these agents for clinical use.

Critical design criteria for minimal antibiotic-free plasmid vectors necessary to combine robust RNA Pol II and Pol III-mediated eukaryotic expression with high bacterial production yields

PubMed Central

Carnes, Aaron E.; Luke, Jeremy M.; Vincent, Justin M.; Anderson, Sheryl; Schukar, Angela; Hodgson, Clague P.; Williams, James A.

2010-01-01

Background For safety considerations, regulatory agencies recommend elimination of antibiotic resistance markers and nonessential sequences from plasmid DNA-based gene medicines. In the present study we analyzed antibiotic-free (AF) vector design criteria impacting bacterial production and mammalian transgene expression. Methods Both CMV-HTLV-I R RNA Pol II promoter (protein transgene) and murine U6 RNA Pol III promoter (RNA transgene) vector designs were studied. Plasmid production yield was assessed through inducible fed-batch fermentation. RNA Pol II-directed EGFP and RNA Pol III-directed RNA expression were quantified by fluorometry and quantitative real-time polymerase chain reaction (RT-PCR), respectively, after transfection of human HEK293 cells. Results Sucrose-selectable minimalized protein and therapeutic RNA expression vector designs that combined an RNA-based AF selection with highly productive fermentation manufacturing (>1,000 mg/L plasmid DNA) and high level in vivo expression of encoded products were identified. The AF selectable marker was also successfully applied to convert existing kanamycin-resistant DNA vaccine plasmids gWIZ and pVAX1 into AF vectors, demonstrating a general utility for retrofitting existing vectors. A minimum vector size for high yield plasmid fermentation was identified. A strategy for stable fermentation of plasmid dimers with improved vector potency and fermentation yields up to 1,740 mg/L was developed. Conclusions We report the development of potent high yield AF gene medicine expression vectors for protein or RNA (e.g. short hairpin RNA or microRNA) products. These AF expression vectors were optimized to exceed a newly identified size threshold for high copy plasmid replication and direct higher transgene expression levels than alternative vectors. PMID:20806425

Public risk perception of food additives and food scares. The case in Suzhou, China.

PubMed

Wu, Linhai; Zhong, Yingqi; Shan, Lijie; Qin, Wei

2013-11-01

This study examined the factors affecting public risk perception of food additive safety and possible resulting food scares using a survey conducted in Suzhou, Jiangsu Province, China. The model was proposed based on literature relating to the role of risk perception and information perception of public purchase intention under food scares. Structural equation modeling (SEM) was used for data analysis. The results showed that attitude towards behavior, subjective norm and information perception exerted moderate to high effect on food scares, and the effects were also mediated by risk perceptions of additive safety. Significant covariance was observed between attitudes toward behavior, subjective norm and information perception. Establishing an effective mechanism of food safety risk communication, releasing information of government supervision on food safety in a timely manner, curbing misleading media reports on public food safety risk, and enhancing public knowledge of the food additives are key to the development and implementation of food safety risk management policies by the Chinese government. Copyright © 2013 Elsevier Ltd. All rights reserved.

Disentangling Vector-Borne Transmission Networks: A Universal DNA Barcoding Method to Identify Vertebrate Hosts from Arthropod Bloodmeals

PubMed Central

Alcaide, Miguel; Rico, Ciro; Ruiz, Santiago; Soriguer, Ramón; Muñoz, Joaquín; Figuerola, Jordi

2009-01-01

Emerging infectious diseases represent a challenge for global economies and public health. About one fourth of the last pandemics have been originated by the spread of vector-borne pathogens. In this sense, the advent of modern molecular techniques has enhanced our capabilities to understand vector-host interactions and disease ecology. However, host identification protocols have poorly profited of international DNA barcoding initiatives and/or have focused exclusively on a limited array of vector species. Therefore, ascertaining the potential afforded by DNA barcoding tools in other vector-host systems of human and veterinary importance would represent a major advance in tracking pathogen life cycles and hosts. Here, we show the applicability of a novel and efficient molecular method for the identification of the vertebrate host's DNA contained in the midgut of blood-feeding arthropods. To this end, we designed a eukaryote-universal forward primer and a vertebrate-specific reverse primer to selectively amplify 758 base pairs (bp) of the vertebrate mitochondrial Cytochrome c Oxidase Subunit I (COI) gene. Our method was validated using both extensive sequence surveys from the public domain and Polymerase Chain Reaction (PCR) experiments carried out over specimens from different Classes of vertebrates (Mammalia, Aves, Reptilia and Amphibia) and invertebrate ectoparasites (Arachnida and Insecta). The analysis of mosquito, culicoid, phlebotomie, sucking bugs, and tick bloodmeals revealed up to 40 vertebrate hosts, including 23 avian, 16 mammalian and one reptilian species. Importantly, the inspection and analysis of direct sequencing electropherograms also assisted the resolving of mixed bloodmeals. We therefore provide a universal and high-throughput diagnostic tool for the study of the ecology of haematophagous invertebrates in relation to their vertebrate hosts. Such information is crucial to support the efficient management of initiatives aimed at reducing epidemiologic risks of arthropod vector-borne pathogens, a priority for public health. PMID:19768113

Pyrethroid resistance persists after ten years without usage against Aedes aegypti in governmental campaigns: Lessons from São Paulo State, Brazil.

PubMed

Macoris, Maria de Lourdes; Martins, Ademir Jesus; Andrighetti, Maria Teresa Macoris; Lima, José Bento Pereira; Valle, Denise

2018-03-01

Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, public health managers employed pyrethroids against Ae. aegypti adults from 1989 to 2000, when a robust insecticide resistance monitoring system detected resistance to pyrethroids in several Ae. aegypti populations. However, pyrethroids are also the preferred compounds engaged in household applications due to their rapid knockdown effect, lower toxicity to mammals and less irritating smell. We evaluated pyrethroid resistance in Ae. aegypti populations over the course of a decade, from 2004 to 2015, after interruption of pyrethroid public applications in SP. Qualitative bioassays with papers impregnated with a deltamethrin diagnostic dose (DD) performed with insects from seven SP municipalities and evaluated yearly from 2006 to 2014, detected resistance in most of the cases. Quantitative bioassays were also carried out with four populations in 2011, suggesting a positive correlation between resistance level and survivorship in the DD bioassays. Biochemical tests conducted with seven insect populations in 2006 and 2015, detected increasing metabolic alterations of all major classes of detoxifying enzymes, mostly of mixed function oxidases. Genotyping of the voltage-gated sodium channel (AaNaV, the pyrethroid target-site) with a TaqMan real time PCR based technique was performed from 2004 to 2014 in all seven localities. The two kdr mutations, Val1016Ile and Phe1534Cys, known to be spread throughout Brazil, were always present with a severe decrease of the susceptible allele over time. These results are discussed in the context of public and domestic insecticide use, the necessity of implementation of a strong integrated vector control strategy and the conceptual misunderstanding between 'vector control' and 'chemical control of vectors'.

Pyrethroid resistance persists after ten years without usage against Aedes aegypti in governmental campaigns: Lessons from São Paulo State, Brazil

PubMed Central

Andrighetti, Maria Teresa Macoris; Lima, José Bento Pereira; Valle, Denise

2018-01-01

Background Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, public health managers employed pyrethroids against Ae. aegypti adults from 1989 to 2000, when a robust insecticide resistance monitoring system detected resistance to pyrethroids in several Ae. aegypti populations. However, pyrethroids are also the preferred compounds engaged in household applications due to their rapid knockdown effect, lower toxicity to mammals and less irritating smell. Methodology/Principal findings We evaluated pyrethroid resistance in Ae. aegypti populations over the course of a decade, from 2004 to 2015, after interruption of pyrethroid public applications in SP. Qualitative bioassays with papers impregnated with a deltamethrin diagnostic dose (DD) performed with insects from seven SP municipalities and evaluated yearly from 2006 to 2014, detected resistance in most of the cases. Quantitative bioassays were also carried out with four populations in 2011, suggesting a positive correlation between resistance level and survivorship in the DD bioassays. Biochemical tests conducted with seven insect populations in 2006 and 2015, detected increasing metabolic alterations of all major classes of detoxifying enzymes, mostly of mixed function oxidases. Genotyping of the voltage-gated sodium channel (AaNaV, the pyrethroid target-site) with a TaqMan real time PCR based technique was performed from 2004 to 2014 in all seven localities. The two kdr mutations, Val1016Ile and Phe1534Cys, known to be spread throughout Brazil, were always present with a severe decrease of the susceptible allele over time. Conclusions/Significance These results are discussed in the context of public and domestic insecticide use, the necessity of implementation of a strong integrated vector control strategy and the conceptual misunderstanding between 'vector control' and 'chemical control of vectors'. PMID:29601580

75 FR 66384 - Notice of Proposed Information Collection for Public Comment; Exigent Health and Safety...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... provides the property representative with a copy of the ``Notification of Exigent and Fire Safety Hazards... Information Collection for Public Comment; Exigent Health and Safety Deficiency Correction Certification... lists the following information: Title of Proposal: Exigent Health and Safety Deficiency Correction...

49 CFR 350.319 - What are permissible uses of High Priority Activity Funds?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., except that approved public information and education activities may be reimbursed up to 100 percent of... safety regulations. (3) Increase public awareness about CMV safety. (4) Provide education on CMV safety and related issues. (5) Demonstrate new safety related technologies. (b) These funds will be allocated...

49 CFR 350.319 - What are permissible uses of High Priority Activity Funds?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., except that approved public information and education activities may be reimbursed up to 100 percent of... safety regulations. (3) Increase public awareness about CMV safety. (4) Provide education on CMV safety and related issues. (5) Demonstrate new safety related technologies. (b) These funds will be allocated...

49 CFR 350.319 - What are permissible uses of High Priority Activity Funds?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., except that approved public information and education activities may be reimbursed up to 100 percent of... safety regulations. (3) Increase public awareness about CMV safety. (4) Provide education on CMV safety and related issues. (5) Demonstrate new safety related technologies. (b) These funds will be allocated...

49 CFR 350.319 - What are permissible uses of High Priority Activity Funds?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., except that approved public information and education activities may be reimbursed up to 100 percent of... safety regulations. (3) Increase public awareness about CMV safety. (4) Provide education on CMV safety and related issues. (5) Demonstrate new safety related technologies. (b) These funds will be allocated...

78 FR 59413 - International Civil Aviation Organization's (ICAO) Dangerous Goods Panel; Notice of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

..., 2013, in Montreal, Canada, the FAA's Office of Hazardous Materials Safety and the Pipeline and Hazardous Materials Safety Administration's (PHMSA) Office of Hazardous Materials Safety announce a public... directed to Ms. Janet McLaughlin, Deputy Director, Office of Hazardous Materials Safety, ADG-2, Federal...

77 FR 69899 - Public Conference on Geographic Information Systems (GIS) in Transportation Safety

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

... NATIONAL TRANSPORTATION SAFETY BOARD Public Conference on Geographic Information Systems (GIS) in... Geographic Information Systems (GIS) in transportation safety on December 4-5, 2012. GIS is a rapidly... visualization of data. The meeting will bring researchers and practitioners in transportation safety and GIS...

76 FR 8699 - Locomotive Safety Standards; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

.... FRA-2009-0094 and FRA-2009-0095, Notice No. 2] RIN 2130-AC16 Locomotive Safety Standards; Correction... notifying the public that the correct docket number for the Locomotive Safety Standards notice of proposed... locomotive safety standards. See 76 FR 2200. The NPRM established a public docket to receive comments in...

77 FR 23159 - Locomotive Safety Standards; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

.... FRA-2009-0094 and FR-2009-0095, Notice No. 4] RIN 2130-AC16 Locomotive Safety Standards; Correction... notifying the public that the correct docket number for the Locomotive Safety Standards final rule is FRA... rule related to locomotive safety standards. See 77 FR 21312. The final rule established a public...

Data-driven identification of potential Zika virus vectors

PubMed Central

Evans, Michelle V; Dallas, Tad A; Han, Barbara A; Murdock, Courtney C; Drake, John M

2017-01-01

Zika is an emerging virus whose rapid spread is of great public health concern. Knowledge about transmission remains incomplete, especially concerning potential transmission in geographic areas in which it has not yet been introduced. To identify unknown vectors of Zika, we developed a data-driven model linking vector species and the Zika virus via vector-virus trait combinations that confer a propensity toward associations in an ecological network connecting flaviviruses and their mosquito vectors. Our model predicts that thirty-five species may be able to transmit the virus, seven of which are found in the continental United States, including Culex quinquefasciatus and Cx. pipiens. We suggest that empirical studies prioritize these species to confirm predictions of vector competence, enabling the correct identification of populations at risk for transmission within the United States. DOI: http://dx.doi.org/10.7554/eLife.22053.001 PMID:28244371

Gene therapy for cancer: regulatory considerations for approval.

PubMed

Husain, S R; Han, J; Au, P; Shannon, K; Puri, R K

2015-12-01

The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA.

The development of an inherent safety approach to the prevention of domino accidents.

PubMed

Cozzani, Valerio; Tugnoli, Alessandro; Salzano, Ernesto

2009-11-01

The severity of industrial accidents in which a domino effect takes place is well known in the chemical and process industry. The application of an inherent safety approach for the prevention of escalation events leading to domino accidents was explored in the present study. Reference primary scenarios were analyzed and escalation vectors were defined. Inherent safety distances were defined and proposed as a metric to express the intensity of the escalation vectors. Simple rules of thumb were presented for a preliminary screening of these distances. Swift reference indices for layout screening with respect to escalation hazard were also defined. Two case studies derived from existing layouts of oil refineries were selected to understand the potentialities coming from the application in the methodology. The results evidenced that the approach allows a first comparative assessment of the actual domino hazard in a layout, and the identification of critical primary units with respect to escalation events. The methodology developed also represents a useful screening tool to identify were to dedicate major efforts in the design of add-on measures, optimizing conventional passive and active measures for the prevention of severe domino accidents.

Safety of intra-articular transplantation of lentivirally transduced mesenchymal stromal cells for haemophilic arthropathy in a non-human primate.

PubMed

Ohmori, Tsukasa; Mizukami, Hiroaki; Katakai, Yuko; Kawai, Sho; Nakamura, Hitoyasu; Inoue, Makoto; Shu, Tsugumine; Sugimoto, Hideharu; Sakata, Yoichi

2018-05-08

Joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. We previously developed a mesenchymal stromal cell (MSC)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia A. Here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous MSCs in non-human primates. Autologous bone-marrow-derived MSCs transduced with a lentiviral vector expressing coagulation factor VIII (FVIII) were injected into the left knee joint of cynomolgus monkeys. We first conducted codon optimization to increase FVIII production in the cells. Lentiviral transduction of autologous MSCs resulted in a significant increase of FVIII in the culture supernatant before transplantation. We did not find any tumour generation around the knee structure at 11-16 months after injection by magnetic resonance imaging. The proviral sequence of the simian immunodeficiency virus lentiviral vector was not detected in the heart, lungs, spleen, liver, testis, or bone marrow by real-time quantitative PCR. We confirmed the long-term safety of intra-articular injection of transduced MSCs in a non-human primate. The procedure may be an attractive therapeutic approach for joint diseases in haemophilia patients.

Gene therapy for cancer: regulatory considerations for approval

PubMed Central

Husain, S R; Han, J; Au, P; Shannon, K; Puri, R K

2015-01-01

The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA. PMID:26584531

47 CFR 90.421 - Operation of mobile station units not under the control of the licensee.

Code of Federal Regulations, 2010 CFR

2010-10-01

... medical services activities. (3) On the Interoperability Channels in the 700 MHz Public Safety Band (See... in the 700 MHz Public Safety Band or by any licensee holding a license for any other public safety... hand-held and vehicular transmitters in the 700 MHz Band. (b) Industrial/Business Pool. Mobile units...

Partnerships: The Path to Improving Crisis Communication

DTIC Science & Technology

2007-03-01

News Media Perceives Relationships with Public Safety.................32 Table 4. Public Safety SWOT Analysis ...opportunities and threats ( SWOT ) of the Seattle fire and police departments. The SWOT analysis is an assessment tool common to strategic planning for...requirements for training • Lack of strategic planning experience Table 4. Public Safety SWOT Analysis 46 Table 4 compares the strengths and

77 FR 62461 - Implementing Public Safety Broadband Provisions of the Middle Class Tax Relief and Job Creation...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

.... SUMMARY: In this document, the Public Safety and Homeland Security Bureau (Bureau) of the Commission... Spectrum Act) governing deployment of a nationwide public safety broadband network in the 700 MHz band...), and the D Block to the First Responder Network Authority (FirstNet). By eliminating any confusion or...

25 CFR 502.22 - Construction and maintenance of the gaming facility, and the operation of that gaming is...

Code of Federal Regulations, 2011 CFR

2011-04-01

... the public health and safety. 502.22 Section 502.22 Indians NATIONAL INDIAN GAMING COMMISSION... protects the environment and the public health and safety. Construction and maintenance of the gaming... environment and the public health and safety means a tribe has identified and enforces laws, resolutions...

Demand-supply gaps in human resources to combat vector-borne disease in India: capacity-building measures in medical entomology.

PubMed

Pandey, Anuja; Zodpey, Sanjay; Kumar, Raj

2015-01-01

Vector-borne diseases account for a significant proportion of the global burden of infectious disease. They are one of the greatest contributors to human mortality and morbidity in tropical settings, including India. The World Health Organization declared vector-borne diseases as theme for the year 2014, and thus called for renewed commitment to their prevention and control. Human resources are critical to support public health systems, and medical entomologists play a crucial role in public health efforts to combat vector-borne diseases. This paper aims to review the capacity-building initiatives in medical entomology in India, to understand the demand and supply of medical entomologists, and to give future direction for the initiation of need-based training in the country. A systematic, predefined approach, with three parallel strategies, was used to collect and assemble the data regarding medical entomology training in India and assess the demand-supply gap in medical entomologists in the country. The findings suggest that, considering the high burden of vector-borne diseases in the country and the growing need of health manpower specialized in medical entomology, the availability of specialized training in medical entomology is insufficient in terms of number and intake capacity. The demand analysis of medical entomologists in India suggests a wide gap in demand and supply, which needs to be addressed to cater for the burden of vector-borne diseases in the country.

Public-private interactions in global food safety governance.

PubMed

Lin, Ching-Fu

2014-01-01

In response to an apparent decline in global food safety, numerous public and private regulatory initiatives have emerged to restore public confidence. This trend has been particularly marked by the growing influence of private regulators such as multinational food companies, supermarket chains and non-governmental organizations (NGOs), who employ private standards, certification protocols, third-party auditing, and transnational contracting practices. This paper explores how the structure and processes of private food safety governance interact with traditional public governance regimes, focusing on Global Good Agricultural Practices (GlobalGAP) as a primary example of the former. Due to the inefficiency and ineffectiveness of public regulation in the face of global problems, private governance in food safety has gradually replaced states' command-and-control regulation with more flexible, market-oriented mechanisms. The paper concludes by emphasizing the importance of constructive regime interaction instead of institutional boundary building to global food safety governance. Public and private ordering must each play a role as integral parts of a larger, dynamic and evolving governance complex.

Virus-Like-Vaccines against HIV

PubMed Central

Andersson, Anne-Marie C.; Schwerdtfeger, Melanie; Holst, Peter J.

2018-01-01

Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8+ and CD4+ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response. PMID:29439476

A potential targeting gene vector based on biotinylated polyethyleneimine/avidin bioconjugates.

PubMed

Zeng, Xuan; Sun, Yun-Xia; Zhang, Xian-Zheng; Cheng, Si-Xue; Zhuo, Ren-Xi

2009-08-01

To improve the gene delivery efficiency and safety of non-viral vector in liver cells, avidin, which exhibited good biocompatibility and remarkable accumulation in liver, was bioconjugated with biotinylated polyethylenimine to obtain a novel gene vector. Biotinylated polyethyleneimine/avidin bioconjugate (ABP) was synthesized through grafting biotin to high molecular weight branched polyethylenimine (PEI, 25 kDa) and then bioconjugating with avidin by the biotin-avidin interaction. Physiochemical characteristics of ABP/pDNA complexes were analyzed, and in vitro cytotoxicity and transfection of ABP were also evaluated in HepG2, Hela and 293 T cells by using 25 kDa PEI as the control. It was found that ABP was able to condense pDNA efficiently at N/P ratio of 4. The particle sizes of ABP/pDNA complexes were less than 220 nm, and the average surface charges were around 27 mV at the N/P ratio ranging from 2 to 60. Among three different cell lines, ABP and its DNA complexes demonstrated much lower cytotoxicity and higher transfection efficacy in HepG2 cells as compared with 25 kDa PEI. ABP presented higher transfection efficacy and safety in HepG2 cells due to the biocompatibility of avidin and the specific interactions between avidin and HepG2 cells.

Virus-Like-Vaccines against HIV.

PubMed

Andersson, Anne-Marie C; Schwerdtfeger, Melanie; Holst, Peter J

2018-02-11

Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8⁺ and CD4⁺ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response.

The Anopheles gambiae transcriptome - a turning point for malaria control.

PubMed

Domingos, A; Pinheiro-Silva, R; Couto, J; do Rosário, V; de la Fuente, J

2017-04-01

Mosquitoes are important vectors of several pathogens and thereby contribute to the spread of diseases, with social, economic and public health impacts. Amongst the approximately 450 species of Anopheles, about 60 are recognized as vectors of human malaria, the most important parasitic disease. In Africa, Anopheles gambiae is the main malaria vector mosquito. Current malaria control strategies are largely focused on drugs and vector control measures such as insecticides and bed-nets. Improvement of current, and the development of new, mosquito-targeted malaria control methods rely on a better understanding of mosquito vector biology. An organism's transcriptome is a reflection of its physiological state and transcriptomic analyses of different conditions that are relevant to mosquito vector competence can therefore yield important information. Transcriptomic analyses have contributed significant information on processes such as blood-feeding parasite-vector interaction, insecticide resistance, and tissue- and stage-specific gene regulation, thereby facilitating the path towards the development of new malaria control methods. Here, we discuss the main applications of transcriptomic analyses in An. gambiae that have led to a better understanding of mosquito vector competence. © 2017 The Royal Entomological Society.

Invasiveness of Aedes aegypti and Aedes albopictus and Vectorial Capacity for Chikungunya Virus.

PubMed

Lounibos, Leon Philip; Kramer, Laura D

2016-12-15

In this review, we highlight biological characteristics of Aedes aegypti and Aedes albopictus, 2 invasive mosquito species and primary vectors of chikungunya virus (CHIKV), that set the tone of these species' invasiveness, vector competence, and vectorial capacity (VC). The invasiveness of both species, as well as their public health threats as vectors, is enhanced by preference for human blood. Vector competence, characterized by the efficiency of an ingested arbovirus to replicate and become infectious in the mosquito, depends largely on vector and virus genetics, and most A. aegypti and A. albopictus populations thus far tested confer vector competence for CHIKV. VC, an entomological analog of the pathogen's basic reproductive rate (R 0 ), is epidemiologically more important than vector competence but less frequently measured, owing to challenges in obtaining valid estimates of parameters such as vector survivorship and host feeding rates. Understanding the complexities of these factors will be pivotal in curbing CHIKV transmission. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success--a personal perspective.

PubMed

Hastie, Eric; Samulski, R Jude

2015-05-01

Fifty years after the discovery of adeno-associated virus (AAV) and more than 30 years after the first gene transfer experiment was conducted, dozens of gene therapy clinical trials are in progress, one vector is approved for use in Europe, and breakthroughs in virus modification and disease modeling are paving the way for a revolution in the treatment of rare diseases, cancer, as well as HIV. This review will provide a historical perspective on the progression of AAV for gene therapy from discovery to the clinic, focusing on contributions from the Samulski lab regarding basic science and cloning of AAV, optimized large-scale production of vectors, preclinical large animal studies and safety data, vector modifications for improved efficacy, and successful clinical applications.

Optical threshold secret sharing scheme based on basic vector operations and coherence superposition

NASA Astrophysics Data System (ADS)

Deng, Xiaopeng; Wen, Wei; Mi, Xianwu; Long, Xuewen

2015-04-01

We propose, to our knowledge for the first time, a simple optical algorithm for secret image sharing with the (2,n) threshold scheme based on basic vector operations and coherence superposition. The secret image to be shared is firstly divided into n shadow images by use of basic vector operations. In the reconstruction stage, the secret image can be retrieved by recording the intensity of the coherence superposition of any two shadow images. Compared with the published encryption techniques which focus narrowly on information encryption, the proposed method can realize information encryption as well as secret sharing, which further ensures the safety and integrality of the secret information and prevents power from being kept centralized and abused. The feasibility and effectiveness of the proposed method are demonstrated by numerical results.

Public acceptability of highway safety countermeasures. Volume 1, Background of study and methodology

DOT National Transportation Integrated Search

1981-06-01

This study provides information about public attitudes towards proposed highway safety countermeasures in three program areas: alcohol and drugs, unsafe driving behaviors, and pedestrian safety. This volume describes the three research methodologies ...

76 FR 26716 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-09

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Sunshine Act Meeting AGENCY: Defense Nuclear Facilities... Defense Nuclear Facilities Safety Board's (Board) public meeting and hearing. FEDERAL REGISTER CITATIONS... Defense Nuclear Facilities Safety Board, Public Hearing Room, 625 Indiana Avenue, NW., Suite 300...

75 FR 6070 - Notice of Public Meeting on the International Atomic Energy Agency Basic Safety Standards Version...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

... Energy Agency Basic Safety Standards Version 3.0, Draft Safety Requirements DS379 AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Public Meeting on the International Atomic Energy Agency Basic... development of U.S. Government comments on this International Atomic Energy Agency (IAEA) draft General Safety...

41 CFR 102-80.130 - Who must perform the equivalent level of safety analysis?

Code of Federal Regulations, 2010 CFR

2010-07-01

...-SAFETY AND ENVIRONMENTAL MANAGEMENT Accident and Fire Prevention Equivalent Level of Safety Analysis... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Who must perform the equivalent level of safety analysis? 102-80.130 Section 102-80.130 Public Contracts and Property Management...

Vector platforms for gene therapy of inherited retinopathies

PubMed Central

Trapani, Ivana; Puppo, Agostina; Auricchio, Alberto

2014-01-01

Inherited retinopathies (IR) are common untreatable blinding conditions. Most of them are inherited as monogenic disorders, due to mutations in genes expressed in retinal photoreceptors (PR) and in retinal pigment epithelium (RPE). The retina’s compatibility with gene transfer has made transduction of different retinal cell layers in small and large animal models via viral and non-viral vectors possible. The ongoing identification of novel viruses as well as modifications of existing ones based either on rational design or directed evolution have generated vector variants with improved transduction properties. Dozens of promising proofs of concept have been obtained in IR animal models with both viral and non-viral vectors, and some of them have been relayed to clinical trials. To date, recombinant vectors based on the adeno-associated virus (AAV) represent the most promising tool for retinal gene therapy, given their ability to efficiently deliver therapeutic genes to both PR and RPE and their excellent safety and efficacy profiles in humans. However, AAVs’ limited cargo capacity has prevented application of the viral vector to treatments requiring transfer of genes with a coding sequence larger than 5 kb. Vectors with larger capacity, i.e. nanoparticles, adenoviral and lentiviral vectors are being exploited for gene transfer to the retina in animal models and, more recently, in humans. This review focuses on the available platforms for retinal gene therapy to fight inherited blindness, highlights their main strengths and examines the efforts to overcome some of their limitations. PMID:25124745

Recent advances in genetic modification of adenovirus vectors for cancer treatment.

PubMed

Yamamoto, Yuki; Nagasato, Masaki; Yoshida, Teruhiko; Aoki, Kazunori

2017-05-01

Adenoviruses are widely used to deliver genes to a variety of cell types and have been used in a number of clinical trials for gene therapy and oncolytic virotherapy. However, several concerns must be addressed for the clinical use of adenovirus vectors. Selective delivery of a therapeutic gene by adenovirus vectors to target cancer is precluded by the widespread distribution of the primary cellular receptors. The systemic administration of adenoviruses results in hepatic tropism independent of the primary receptors. Adenoviruses induce strong innate and acquired immunity in vivo. Furthermore, several modifications to these vectors are necessary to enhance their oncolytic activity and ensure patient safety. As such, the adenovirus genome has been engineered to overcome these problems. The first part of the present review outlines recent progress in the genetic modification of adenovirus vectors for cancer treatment. In addition, several groups have recently developed cancer-targeting adenovirus vectors by using libraries that display random peptides on a fiber knob. Pancreatic cancer-targeting sequences have been isolated, and these oncolytic vectors have been shown by our group to be associated with a higher gene transduction efficiency and more potent oncolytic activity in cell lines, murine models, and surgical specimens of pancreatic cancer. In the second part of this review, we explain that combining cancer-targeting strategies can be a promising approach to increase the clinical usefulness of oncolytic adenovirus vectors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

West Nile Virus Fitness Costs in Different Mosquito Species.

PubMed

Coffey, Lark L; Reisen, William K

2016-06-01

West Nile virus (WNV) remains an important public health problem causing annual epidemics in the United States. Grubaugh et al. observed that WNV genetic divergence is dependent on the vector mosquito species. This suggests that specific WNV vector-bird species pairings may generate novel genotypes that could promote outbreaks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Divide and Recombine for Large Complex Data

DTIC Science & Technology

2017-12-01

Empirical Methods in Natural Language Processing , October 2014 Keywords Enter keywords for the publication. URL Enter the URL...low-latency data processing systems. Declarative Languages for Interactive Visualization: The Reactive Vega Stack Another thread of XDATA research...for array processing operations embedded in the R programming language . Vector virtual machines work well for long vectors. One of the most

Green-synthesized silver nanoparticles as a novel control tool against dengue virus (DEN-2) and its primary vector Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Dengue is an arthropod-borne viral infection mainly vectored through the bite of Aedes mosquitoes. Recently, its transmission has strongly increased in urban and semi-urban areas of tropical and sub-tropical regions worldwide, becoming a major international public health concern. There is no specifi...

A Look at the Law, Public Safety, Corrections & Security Cluster

ERIC Educational Resources Information Center

Coffee, Joseph N.

2008-01-01

A month after the 9/11 terrorist attack in 2001, an advisory group met in Little Rock, Arkansas, to begin the development of the Law, Public Safety, Corrections and Security (LPSCS) career cluster. At that time there were five pathways of what was then called the Law and Public Safety cluster--fire and emergency services, law enforcement,…

Confinement of Radioactive Materials at Defense Nuclear Facilities

DTIC Science & Technology

2004-10-01

The design of defense nuclear facilities includes systems whose reliable operation is vital to the protection of the public, workers, and the...final safety-class barrier to the release of hazardous materials with potentially serious public consequences. The Defense Nuclear Facilities Safety...the public at certain defense nuclear facilities . This change has resulted in downgrading of the functional safety classification of confinement

The Public Safety Impact of Community Notification Laws: Rearrest of Convicted Sex Offenders

ERIC Educational Resources Information Center

Freeman, Naomi J.

2012-01-01

Sex offender management is one of the highest-profile issues in public safety today. Although states have enacted community notification laws as a means to protect communities from sexual offending, limited research has been conducted to examine the impact of these laws on public safety. As such, this study used a quasi-experimental design to…

77 FR 75186 - Notice of Closure, Target Shooting Public Safety Closure on the Lake Mountains in Utah County, UT

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

... Closure, Target Shooting Public Safety Closure on the Lake Mountains in Utah County, UT AGENCY: Bureau of... Lake Mountains in Utah County, Utah, to recreational target shooting to protect public safety. This... shooting closure within the described area will remain in effect no longer than two years from December 19...

Driving forces behind the Chinese public's demand for improved environmental safety.

PubMed

Wen, Ting; Wang, Jigan; Ma, Zongwei; Bi, Jun

2017-12-15

Over the past decades, the public demand for improved environmental safety keeps increasing in China. This study aims to assess the driving forces behind the increasing public demand for improved environmental safety using a provincial and multi-year (1995, 2000, 2005, 2010, and 2014) panel data and the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model. The potential driving forces investigated included population size, income levels, degrees of urbanization, and educational levels. Results show that population size and educational level are positively (P<0.01) associated with public demand for improved environmental safety. No significant impact on demand was found due to the degree of urbanization. For the impact due to income level, an inverted U-shaped curve effect with the turning point of ~140,000 CNY GDP per capita is indicated. Since per capita GDP of 2015 in China was approximately 50,000 CNY and far from the turning point, the public demand for improved environmental safety will continue rising in the near future. To meet the increasing public demand for improved environmental safety, proactive and risk prevention based environmental management systems coupled with effective environmental risk communication should be established. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibody-mediated targeting of replication-competent retroviral vectors.

PubMed

Tai, Chien-Kuo; Logg, Christopher R; Park, Jinha M; Anderson, W French; Press, Michael F; Kasahara, Noriyuki

2003-05-20

Replication-competent murine leukemia virus (MLV) vectors can be engineered to achieve high efficiency gene transfer to solid tumors in vivo and tumor-restricted replication, however their safety can be further enhanced by redirecting tropism of the virus envelope. We have therefore tested the targeting capability and replicative stability of ecotropic and amphotropic replication-competent retrovirus (RCR) vectors containing two tandem repeats from the immunoglobulin G-binding domain of Staphylococcal protein A inserted into the proline-rich "hinge" region of the envelope, which enables modular use of antibodies of various specificities for vector targeting. The modified envelopes were efficiently expressed and incorporated into virions, were capable of capturing monoclonal anti-HER2 antibodies, and mediated efficient binding of the virus-antibody complex to HER2-positive target cells. While infectivity was markedly reduced by pseudotyping with targeted envelopes alone, coexpression of wild-type envelope rescued efficient cellular entry. Both ecotropic and amphotropic RCR vector/anti-HER2 antibody complexes achieved significant enhancement of transduction on murine target cells overexpressing HER2, which could be competed by preincubation with excess free antibodies. Interestingly, HER2-expressing human breast cancer cells did not show enhancement of transduction despite efficient antibody-mediated cell surface binding, suggesting that target cell-specific parameters markedly affect the efficiency of post-binding entry processes. Serial replication of targeted vectors resulted in selection of Z domain deletion variants, but reduction of the overall size of the vector genome enhanced its stability. Application of antibody-mediated targeting to the initial localization of replication-competent virus vectors to tumor sites will thus require optimized target selection and vector design.

Assaying the Stability and Inactivation of AAV Serotype 1 Vectors

PubMed Central

Howard, Douglas B.; Harvey, Brandon K.

2017-01-01

Adeno-associated virus (AAV) vectors are a commonplace tool for gene delivery ranging from cell culture to human gene therapy. One feature that makes AAV a desirable vector is its stability, in regard to both the duration of transgene expression and retention of infectivity as a viral particle. This study examined the stability of AAV serotype 1 (AAV1) vectors under different conditions. First, transducibility after storage at 4°C decreased 20% over 7 weeks. Over 10 freeze–thaw cycles, the resulting transduction efficiency became variable at 60–120% of a single thaw. Using small stainless steel slugs to mimic a biosafety cabinet or metal lab bench surface, it was found that an AAV1 vector can be reconstituted after 6 days of storage at room temperature. The stability of AAV is a desired feature, but effective decontamination procedures must be available for safety and experimental integrity. Multiple disinfectants commonly used in the laboratory for ability to inactivate an AAV1 vector were tested, and it was found that autoclaving, 0.25% peracetic acid, iodine, or 10% Clorox bleach completely prevented AAV-mediated transgene expression. These data suggest that peracetic acid should be used for inactivating AAV1 vectors on metal-based surfaces or instruments in order to avoid inadvertent transgene expression in human cells or cross-contamination of instruments. PMID:28192678

Socio-economic inequity in demand for insecticide-treated nets, in-door residual house spraying, larviciding and fogging in Sudan

PubMed Central

Onwujekwe, Obinna; Malik, El-Fatih Mohamed; Mustafa, Sara Hassan; Mnzava, Abraham

2005-01-01

Background In order to optimally prioritize and use public and private budgets for equitable malaria vector control, there is a need to determine the level and determinants of consumer demand for different vector control tools. Objectives To determine the demand from people of different socio-economic groups for indoor residual house-spraying (IRHS), insecticide-treated nets (ITNs), larviciding with chemicals (LWC), and space spraying/fogging (SS) and the disease control implications of the result. Methods Ratings and levels of willingness-to-pay (WTP) for the vector control tools were determined using a random cross-sectional sample of 720 householdes drawn from two states. WTP was elicited using the bidding game. An asset-based socio-economic status (SES) index was used to explore whether WTP was related to SES of the respondents. Results IRHS received the highest proportion of highest preferred rating (41.0%) followed by ITNs (23.1%). However, ITNs had the highest mean WTP followed by IRHS, while LWC had the least. The regression analysis showed that SES was positively and statistically significantly related to WTP across the four vector control tools and that the respondents' rating of IRHS and ITNs significantly explained their levels of WTP for the two tools. Conclusion People were willing to pay for all the vector-control tools, but the demand for the vector control tools was related to the SES of the respondents. Hence, it is vital that there are public policies and financing mechanisms to ensure equitable provision and utilisation of vector control tools, as well as protecting the poor from cost-sharing arrangements. PMID:16356177

Species composition of mosquito and public perception about Dengue vector of hemorrhagic fever in Bareng Tenes Malang

NASA Astrophysics Data System (ADS)

Gama, Zulfaidah Penata; Pratiwi, Jenvia Rista

2017-11-01

Dengue Hemorrhagic Fever (DHF) is a mosquito-borne tropical disease caused by the dengue virus. Aedes aegypti and Aedes albopictus are the mosquito vectors of DHF. Malang city was an endemic region of dengue disease in East Java. One of the villages that had a high number of DHF cases was Bareng Tenes. The Case Fatality Rate (CFR) in Malang city totaled 5 patients out of 879 cases (Health Department of Malang city, 2010). Bareng Tenes RW 02 was one of the densely populated regions of Malang city. The objectives of this research were to identify mosquito composition and to analyze the public perception about the DHF vectors in Bareng Tenes RW 02 Malang. This research used two kinds of survey methods of mosquitoes. The first method for collecting larvae was used by direct capture using pipettes from artificial containers and the second method was collecting egg of mosquitoes by using an ovitrap. Public perception was calculated using the questionnaire technique. The accidental sampling technique in this research was Likert scale. The composition of mosquitoes found in Bareng Tenes RW 02 was Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. The mosquito survey showed that Aedes aegypti was the dominant species and the IVI value for the ovitrap survey was 118.06% while the value of IVI for the larval survey was 103.51%. Based on the public perception data, it showed that the community has a very good understanding of DHF knowledge, DHF vectors and ways of DHF prevention, but the undertaken activities by the community have not yet appeared to control the mosquito population especially for their larvae.

Public acceptability of highway safety countermeasures. Volume 3, Alcohol and drug research

DOT National Transportation Integrated Search

1981-06-01

This volume, part of a larger study on public attitudes towards proposed highway safety countermeasures for alcohol and drugs, unsafe driving behaviors, and pedestrian safety, discusses reactions to breath testers, drunk-driving deterrence techniques...

15 CFR 270.352 - Public safety information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE NATIONAL CONSTRUCTION SAFETY TEAMS NATIONAL CONSTRUCTION SAFETY TEAMS Collection and Preservation of Evidence; Information Created Pursuant to an... Team, NIST, and any other investigation participant will not publicly release any information it...

15 CFR 270.352 - Public safety information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE NATIONAL CONSTRUCTION SAFETY TEAMS NATIONAL CONSTRUCTION SAFETY TEAMS Collection and Preservation of Evidence; Information Created Pursuant to an... Team, NIST, and any other investigation participant will not publicly release any information it...

15 CFR 270.352 - Public safety information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE NATIONAL CONSTRUCTION SAFETY TEAMS NATIONAL CONSTRUCTION SAFETY TEAMS Collection and Preservation of Evidence; Information Created Pursuant to an... Team, NIST, and any other investigation participant will not publicly release any information it...

15 CFR 270.352 - Public safety information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE NATIONAL CONSTRUCTION SAFETY TEAMS NATIONAL CONSTRUCTION SAFETY TEAMS Collection and Preservation of Evidence; Information Created Pursuant to an... Team, NIST, and any other investigation participant will not publicly release any information it...

Non-viral gene delivery regulated by stiffness of cell adhesion substrates.

PubMed

Kong, Hyun Joon; Liu, Jodi; Riddle, Kathryn; Matsumoto, Takuya; Leach, Kent; Mooney, David J

2005-06-01

Non-viral gene vectors are commonly used for gene therapy owing to safety concerns with viral vectors. However, non-viral vectors are plagued by low levels of gene transfection and cellular expression. Current efforts to improve the efficiency of non-viral gene delivery are focused on manipulations of the delivery vector, whereas the influence of the cellular environment in DNA uptake is often ignored. The mechanical properties (for example, rigidity) of the substrate to which a cell adheres have been found to mediate many aspects of cell function including proliferation, migration and differentiation, and this suggests that the mechanics of the adhesion substrate may regulate a cell's ability to uptake exogeneous signalling molecules. In this report, we present a critical role for the rigidity of the cell adhesion substrate on the level of gene transfer and expression. The mechanism relates to material control over cell proliferation, and was investigated using a fluorescent resonance energy transfer (FRET) technique. This study provides a new material-based control point for non-viral gene therapy.

Prevention of vector transmitted diseases with clove oil insect repellent.

PubMed

Shapiro, Rochel

2012-08-01

Vector repellent is one element in the prevention of vector-borne diseases. Families that neglect protecting their children against vectors risk their children contracting illnesses such as West Nile virus, eastern equine encephalitis, Lyme disease, malaria, dengue hemorrhagic fever, yellow fever, babesiosis, Crimean-Congo hemorrhagic fever, Rocky Mountain spotted fever, Southern tick-associated rash illness, ehrlichiosis, tick-borne relapsing fever, tularemia, and other insect and arthropod related diseases (CDC, 2011). Identification of families at risk includes screening of the underlying basis for reluctance to apply insect repellent. Nurses and physicians can participate in a positive role by assisting families to determine the proper prophylaxis by recommending insect repellent choices that are economical, safe, and easy to use. A holistic alternative might include the suggestion of clove oil in cases where families might have trepidations regarding the use of DEET on children. This article will explore the safety and effectiveness of clove oil and its use as an insect repellent. Copyright © 2012 Elsevier Inc. All rights reserved.

Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector.

PubMed

Pavot, Vincent; Sebastian, Sarah; Turner, Alison V; Matthews, Jake; Gilbert, Sarah C

2017-01-01

The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to two people per million vaccinated. Modified Vaccinia virus Ankara (MVA) is an attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. MVA can encode one or more foreign antigens and thus can function as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant properties, and induces humoral and cellular immune responses. Many clinical trials of these new vaccines have been conducted, and the safety of MVA is now well documented. Immunogenicity is influenced by the dose and vaccination regimen, and information on the efficacy of MVA-vectored vaccines is now beginning to accumulate. In this chapter, we provide protocols for generation, isolation, amplification, and purification of recombinant MVA for preclinical and clinical evaluation.

VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.

PubMed

Spinozzi, Giulio; Calabria, Andrea; Brasca, Stefano; Beretta, Stefano; Merelli, Ivan; Milanesi, Luciano; Montini, Eugenio

2017-11-25

Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).

Tripartite polyionic complex (PIC) micelles as non-viral vectors for mesenchymal stem cell siRNA transfection.

PubMed

Raisin, Sophie; Morille, Marie; Bony, Claire; Noël, Danièle; Devoisselle, Jean-Marie; Belamie, Emmanuel

2017-08-22

In the context of regenerative medicine, the use of RNA interference mechanisms has already proven its efficiency in targeting specific gene expression with the aim of enhancing, accelerating or, more generally, directing stem cell differentiation. However, achievement of good transfection levels requires the use of a gene vector. For in vivo applications, synthetic vectors are an interesting option to avoid possible issues associated with viral vectors (safety, production costs, etc.). Herein, we report on the design of tripartite polyionic complex micelles as original non-viral polymeric vectors suited for mesenchymal stem cell transfection with siRNA. Three micelle formulations were designed to exhibit pH-triggered disassembly in an acidic pH range comparable to that of endosomes. One formulation was selected as the most promising with the highest siRNA loading capacity while clearly maintaining pH-triggered disassembly properties. A thorough investigation of the internalization pathway of micelles into cells with tagged siRNA was made before showing an efficient inhibition of Runx2 expression in primary bone marrow-derived stem cells. This work evidenced PIC micelles as promising synthetic vectors that allow efficient MSC transfection and control over their behavior, from the perspective of their clinical use.

Safety Considerations in the Chemical Process Industries

NASA Astrophysics Data System (ADS)

Englund, Stanley M.

There is an increased emphasis on chemical process safety as a result of highly publicized accidents. Public awareness of these accidents has provided a driving force for industry to improve its safety record. There has been an increasing amount of government regulation.

42 CFR 86.11 - Eligibility.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Training Grants § 86.11 Eligibility. (a) Eligible applicants. Any public or private...

42 CFR 86.31 - Eligibility; minimum requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

....31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.31 Eligibility; minimum requirements. In...

77 FR 48970 - Sunshine Act Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Sunshine Act Notice AGENCY: Defense Nuclear Facilities... given of the Defense Nuclear Facilities Safety Board's (Board) public meeting and hearing described... (NNSA) efforts to mitigate risks to public and worker safety posed by aging defense nuclear facilities...

Public acceptability of highway safety countermeasures. Volume 2, Safe driving conformance research

DOT National Transportation Integrated Search

1981-06-01

This volume is part of a larger study providing information about public attitudes towards proposed highway safety countermeasures in three program areas: alcohol and drugs, unsafe driving behaviors, and pedestrian safety. Topic areas discussed in th...

47 CFR 90.528 - Public safety broadband license.

Code of Federal Regulations, 2011 CFR

2011-10-01

... licensed if: (i) International agreements require coordination; (ii) Submission of an environmental... 47 Telecommunication 5 2011-10-01 2011-10-01 false Public safety broadband license. 90.528 Section 90.528 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO...

42 CFR 86.11 - Eligibility.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Training Grants § 86.11 Eligibility. (a) Eligible applicants. Any public or private...

42 CFR 86.31 - Eligibility; minimum requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

....31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.31 Eligibility; minimum requirements. In...

Remote Sensing Proxies for Vector-borne Disease Risk Assessment (Invited)

NASA Astrophysics Data System (ADS)

Anyamba, A.

2010-12-01

The spread of re-emerging vector-borne diseases such Rift Valley fever (RVF) and Chikungunya (CHIK) is a major issue of global public health concern. This combined with a variable climate regime has opened an avenue for satellite remote sensing to contribute towards a comprehensive understanding of some of the drivers influencing such vector-borne disease outbreaks. Satellite derived measurements such as vegetation indices, rainfall estimates, and land-surface temperature; can be used to infer the complex mosaic of factors that influence ecology and habitat suitability, emergence and population dynamics of disease vectors. However, there are still some gaps in application including appropriate temporal resolution of remote sensing measurements, the complexity of the virus-vector-disease-ecology system and human components that contribute to disease risk that need to be addressed. Geographic Distribution of Recent Rift Valley fever oubreaks

Launching the first postgraduate diploma in medical entomology and disease vector control in Pakistan.

PubMed

Rathor, H R; Mnzava, A; Bile, K M; Hafeez, A; Zaman, S

2010-01-01

The Health Services Academy has launched a 12-month postgraduate diploma course in medical entomology and disease vector control. The objective is to create a core of experts trained to prevent and control vector-borne diseases. The course is a response to the serious health and socioeconomic burden caused by a number of vector-borne diseases in Pakistan. The persistence, emergence and re-emergence of these diseases is mainly attributed to the scarcity of trained vector-control experts. The training course attempts to fill the gap in trained manpower and thus reduce the morbidity and mortality due to these diseases, resulting in incremental gains to public health. This paper aims to outline the steps taken to establish the course and the perceived challenges to be addressed in order to sustain its future implementation.

76 FR 19375 - Safety and Efficacy of Hypnotic Drugs; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Safety and Efficacy of Hypnotic Drugs; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting. The Food and Drug Administration (FDA) is announcing a public meeting to...

76 FR 58281 - Magnetic Resonance Imaging Safety; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... announcing a public workshop entitled: ``Magnetic Resonance Imaging (MRI) Safety Public Workshop.'' The... (MRI) and approaches to mitigate risks. The overall goal is to discuss strategies to minimize patient and staff risk in the MRI environment. DATES: The public workshop will be held on October 25, 2011...

33 CFR 164.33 - Charts and publications.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Charts and publications. 164.33...) PORTS AND WATERWAYS SAFETY NAVIGATION SAFETY REGULATIONS § 164.33 Charts and publications. (a) Each... extract from, each of the following publications: (i) U.S. Coast Pilot. (ii) Coast Guard Light List. (3...

Development of an automated assessment tool for MedWatch reports in the FDA adverse event reporting system.

PubMed

Han, Lichy; Ball, Robert; Pamer, Carol A; Altman, Russ B; Proestel, Scott

2017-09-01

As the US Food and Drug Administration (FDA) receives over a million adverse event reports associated with medication use every year, a system is needed to aid FDA safety evaluators in identifying reports most likely to demonstrate causal relationships to the suspect medications. We combined text mining with machine learning to construct and evaluate such a system to identify medication-related adverse event reports. FDA safety evaluators assessed 326 reports for medication-related causality. We engineered features from these reports and constructed random forest, L1 regularized logistic regression, and support vector machine models. We evaluated model accuracy and further assessed utility by generating report rankings that represented a prioritized report review process. Our random forest model showed the best performance in report ranking and accuracy, with an area under the receiver operating characteristic curve of 0.66. The generated report ordering assigns reports with a higher probability of medication-related causality a higher rank and is significantly correlated to a perfect report ordering, with a Kendall's tau of 0.24 ( P  = .002). Our models produced prioritized report orderings that enable FDA safety evaluators to focus on reports that are more likely to contain valuable medication-related adverse event information. Applying our models to all FDA adverse event reports has the potential to streamline the manual review process and greatly reduce reviewer workload. Published by Oxford University Press on behalf of the American Medical Informatics Association 2017. This work is written by US Government employees and is in the public domain in the United States.

Wireless communication and spectrum sharing for public safety in the United States.

PubMed

Kapucu, Naim; Haupt, Brittany; Yuksel, Murat

2016-01-01

With the vast number of fragmented, independent public safety wireless communication systems, the United States is encountering major challenges with enhancing interoperability and effectively managing costs while sharing limited availability of critical spectrum. The traditional hierarchical approach of emergency management does not always allow for needed flexibility and is not a mandate. A national system would reduce equipment needs, increase effectiveness, and enrich quality and coordination of response; however, it is dependent on integrating the commercial market. This article discusses components of an ideal national wireless public safety system consists along with key policies in regulating wireless communication and spectrum sharing for public safety and challenges for implementation.

Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

PubMed Central

Xiang, Z.Q.; Greenberg, L.; Ertl, H. C.; Rupprecht, C.E.

2014-01-01

Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. PMID:24503087

47 CFR 90.20 - Public Safety Pool.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Safety Pool to operate radio stations for transmission of communications essential to official activities... operate stations for transmission of communications essential for the delivery or rendition of emergency... Public Safety Pool to operate radio stations for transmission of communications, as listed below. When...

23 CFR 924.9 - Planning.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., management, operation, education, enforcement, and emergency services; (D) Considers safety needs of all public roads; (E) Adopts a strategic safety goal; (F) Identifies key emphasis areas and describes a... infrastructure safety problems and opportunities on all public roads and all users, and focuses resources on...

Safety and business benefit analysis of NASA's aviation safety program

DOT National Transportation Integrated Search

2004-09-20

NASA Aviation Safety Program elements encompass a wide range of products that require both public and private investment. Therefore, two methods of analysis, one relating to the public and the other to the private industry, must be combined to unders...

42 CFR 86.39 - Termination of direct traineeship.

Code of Federal Regulations, 2014 CFR

2014-10-01

....39 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.39 Termination of direct traineeship. (a...

42 CFR 86.36 - Duration and continuation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.36 Duration and continuation. Direct traineeship awards...

42 CFR 86.32 - Application for direct traineeship.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 86.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.32 Application for direct...

14 CFR 417.7 - Public safety responsibility.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Public safety responsibility. 417.7 Section 417.7 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... safety responsibility. A launch operator is responsible for ensuring the safe conduct of a licensed...

14 CFR 417.7 - Public safety responsibility.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Public safety responsibility. 417.7 Section 417.7 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... safety responsibility. A launch operator is responsible for ensuring the safe conduct of a licensed...

42 CFR 86.32 - Application for direct traineeship.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 86.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.32 Application for direct...

42 CFR 86.36 - Duration and continuation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.36 Duration and continuation. Direct traineeship awards...

42 CFR 86.39 - Termination of direct traineeship.

Code of Federal Regulations, 2010 CFR

2010-10-01

....39 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.39 Termination of direct traineeship. (a...

Characteristics of and factors associated with dengue vector breeding sites in the City of Colombo, Sri Lanka

PubMed Central

Kusumawathie, Pad; Palihawadana, Paba; Janaki, Sakoo; Wijemuni, Ruwan; Wilder-Smith, Annelies; Tissera, Hasitha A.

2016-01-01

Introduction Dengue has emerged as a major public health problem in Sri Lanka. Vector control at community level is a frequent and widespread strategy for dengue control. The aim of the study was to assess Aedes mosquito breeding sites and the prevention practices of community members in a heavily urbanized part of Colombo. Methods A cross-sectional entomological survey was conducted from April to June 2013 in 1469 premises located in a subdistrict of the City of Colombo. Types of breeding sites and, where found, their infestation with larvae or pupae were recorded. Furthermore, a questionnaire was administered to the occupants of these premises to record current practices of dengue vector control. Results The surveyed premises consisted of 1341 residential premises and 110 non-residential premises (11 schools, 99 work or public sites), 5 open lands, and 13 non-specified. In these 1469 premises, 15447 potential breeding sites suitable to host larvae of pupae were found; of these sites18.0% contained water. Among the 2775 potential breeding sites that contained water, 452 (16.3%) were positive for larvae and/or pupae. Schools were associated with the proportionally highest number of breeding sites; 85 out of 133 (63.9%) breeding sites were positive for larvae and/or pupae in schools compared with 338 out of 2288 (14.8%) in residential premises. The odds ratio (OR) for schools and work or public sites for being infested with larvae and/or pupae was 2.77 (95% CI 1.58, 4.86), when compared to residential premises. Occupants of 80.8% of the residential premises, 54.5% of the schools and 67.7% of the work or public sites reported using preventive measures. The main prevention practices were coverage of containers and elimination of mosquito breeding places. Occupants of residential premises were much more likely to practice preventive measures than were those of non-residential premises (OR 2.23; 1.49, 3.36). Conclusion Schools and working sites were associated with the highest numbers of breeding sites and lacked preventive measures for vector control. In addition to pursuing vector control measures at residential level, public health strategies should be expanded in schools and work places. PMID:27241954

Innovative technologies targeting vector populations to mitigate the risk of exposure to leishmaniasis and protect deployed U.S. Military personnel in the Middle East

USDA-ARS?s Scientific Manuscript database

Phlebotomine sand flies, including Phlebotomus papatasi, are blood feeders and vectors of significant public health importance because they transmit Leishmania spp., which cause leishmaniasis. Deployed U.S. Military personnel in the Middle East suffer from sand fly bites and are at risk of contract...

Innovative technologies targeting vector populations to mitigate the risk of exposure to leishmaniasis and protect deployed U.S. Military personnel in the Middle East

USDA-ARS?s Scientific Manuscript database

Phlebotomine sand flies, including Phlebotomus papatasi, are blood feeders and vectors of significant public health importance because they transmit Leishmania spp., which cause leishmaniasis. Deployed U.S. Military personnel in the Middle East suffer from sand fly bites and are at risk of contracti...

Laboratory containment practices for arthropod vectors of human and animal pathogens.

PubMed

Tabachnick, Walter J

2006-03-01

Arthropod-borne pathogens have an impact on the health and well-being of humans and animals throughout the world. Research involving arthropod vectors of disease is often dependent on the ability to maintain the specific arthropod species in laboratory colonies. The author reviews current arthropod containment practices and discusses their importance from public health and ecological perspectives.

77 FR 67782 - Proposed Amendment of Class E Airspace; Casper, WY

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-14

..., Natrona County International Airport, Casper, WY, to facilitate vectoring of Instrument Flight Rules (IFR... Range Tactical Air Navigation (VORTAC) has made reconfiguration necessary for the safety and management of aircraft operations at Casper, Natrona County International Airport, Casper, WY. DATES: Comments...

Implications of Organizational Planning for Crisis Relocation.

DTIC Science & Technology

1982-12-01

AD-A 23 956 IMPLICATIONS OF ORGANIZATIDNAL PLANNING FOR CRISIS RELOCATION(U) NORTH CAROLINA DEPT OF CRIME CONTROL AND PUBLIC SAFETY RALEIG.. M A...policies of the Federal Emergency Management Agency. Division of Emergency Management North Carolina Department of Crime Control and Public Safety...North Carolina Department of Crime Control and Work Unit 0 4412 1 Public Safety, 116 W.Jones St. ,Raleigh, NC 27611 II. CONTROLLING OFFICE NAME AND

Dual AAV Vectors for Stargardt Disease.

PubMed

Trapani, Ivana

2018-01-01

Stargardt disease (STGD1), due to mutations in the large ABCA4 gene, is the most common inherited macular degeneration in humans. Attempts at developing gene therapy approaches for treatment of STGD1 are currently ongoing. Among all the vectors available for gene therapy of inherited retinal diseases, those based on adeno-associated viruses (AAV) are the most promising given the efficacy shown in various animal models and their excellent safety profile in humans, as confirmed in many ongoing clinical trials. However, one of the main obstacles for the use of AAV is their limited effective packaging capacity of about 5 kb. Taking advantage of the AAV genome's ability to concatemerize , others and we have recently developed dual AAV vectors to overcome this limit. We tested dual AAV vectors for ABCA4 delivery, and found that they transduce efficiently both mouse and pig photoreceptors , and rescue the Abca4-/- mouse retinal phenotype, indicating their potential for gene therapy of STGD1. This chapter details how we designed dual AAV vectors for the delivery of the ABCA4 gene and describes the techniques that can be explored to evaluate dual AAV transduction efficiency in vitro and in the retina, and their efficacy in the mouse model of STGD1.

Progress on adenovirus-vectored universal influenza vaccines.

PubMed

Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

2015-01-01

Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.

78 FR 25339 - Notice of Funding Availability for the Tribal Transportation Program Safety Funds; and Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

..., activities, and projects on a public road that are consistent with a State strategic highway safety plan and correct or improve a hazardous road location or feature, or address a highway safety problem. Section 202..., activities, or projects on a public road that are consistent with a State Strategic Highway Safety Plan (SHSP...

41 CFR 102-80.105 - What information must be included in an equivalent level of safety analysis?

Code of Federal Regulations, 2011 CFR

2011-01-01

... of Safety Analysis § 102-80.105 What information must be included in an equivalent level of safety... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What information must be included in an equivalent level of safety analysis? 102-80.105 Section 102-80.105 Public Contracts and...

41 CFR 102-80.105 - What information must be included in an equivalent level of safety analysis?

Code of Federal Regulations, 2014 CFR

2014-01-01

... of Safety Analysis § 102-80.105 What information must be included in an equivalent level of safety... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What information must be included in an equivalent level of safety analysis? 102-80.105 Section 102-80.105 Public Contracts and...

41 CFR 102-80.105 - What information must be included in an equivalent level of safety analysis?

Code of Federal Regulations, 2013 CFR

2013-07-01

... of Safety Analysis § 102-80.105 What information must be included in an equivalent level of safety... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What information must be included in an equivalent level of safety analysis? 102-80.105 Section 102-80.105 Public Contracts and...

41 CFR 102-80.105 - What information must be included in an equivalent level of safety analysis?

Code of Federal Regulations, 2012 CFR

2012-01-01

... of Safety Analysis § 102-80.105 What information must be included in an equivalent level of safety... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What information must be included in an equivalent level of safety analysis? 102-80.105 Section 102-80.105 Public Contracts and...

Lentiviral vectors in cancer immunotherapy.

PubMed

Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

2015-01-01

Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

Safety, reliability, maintainability and quality provisions for the Space Shuttle program

NASA Technical Reports Server (NTRS)

1990-01-01

This publication establishes common safety, reliability, maintainability and quality provisions for the Space Shuttle Program. NASA Centers shall use this publication both as the basis for negotiating safety, reliability, maintainability and quality requirements with Shuttle Program contractors and as the guideline for conduct of program safety, reliability, maintainability and quality activities at the Centers. Centers shall assure that applicable provisions of the publication are imposed in lower tier contracts. Centers shall give due regard to other Space Shuttle Program planning in order to provide an integrated total Space Shuttle Program activity. In the implementation of safety, reliability, maintainability and quality activities, consideration shall be given to hardware complexity, supplier experience, state of hardware development, unit cost, and hardware use. The approach and methods for contractor implementation shall be described in the contractors safety, reliability, maintainability and quality plans. This publication incorporates provisions of NASA documents: NHB 1700.1 'NASA Safety Manual, Vol. 1'; NHB 5300.4(IA), 'Reliability Program Provisions for Aeronautical and Space System Contractors'; and NHB 5300.4(1B), 'Quality Program Provisions for Aeronautical and Space System Contractors'. It has been tailored from the above documents based on experience in other programs. It is intended that this publication be reviewed and revised, as appropriate, to reflect new experience and to assure continuing viability.

Highway safety attitudes of Virginians : Results of the 1977 highway safety public opinion poll, final Report.

DOT National Transportation Integrated Search

1978-01-01

In October 1977, the Highway Safety Division of Virginia sponsored a statewide public opinion poll conducted by the Virginia Highway and Transportation Research Council. From the first through the twenty-second of October, approximately 1,700 randoml...

16 CFR 1102.10 - Reports of harm.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE Content Requirements § 1102.10 Reports of harm. (a... they have a public safety purpose. (b) Manner of submission. To be entered into the Database, reports... Commission will publish in the Publicly Available Consumer Product Safety Information Database reports of...

16 CFR 1102.10 - Reports of harm.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE Content Requirements § 1102.10 Reports of harm. (a... they have a public safety purpose. (b) Manner of submission. To be entered into the Database, reports... Commission will publish in the Publicly Available Consumer Product Safety Information Database reports of...

16 CFR 1102.10 - Reports of harm.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE (Eff. Jan. 10, 2011) Content Requirements § 1102.10... they have a public safety purpose. (b) Manner of submission. To be entered into the Database, reports... Commission will publish in the Publicly Available Consumer Product Safety Information Database reports of...

23 CFR 924.9 - Planning.

Code of Federal Regulations, 2011 CFR

2011-04-01

... public roads; (E) Adopts a strategic safety goal; (F) Identifies key emphasis areas and describes a... infrastructure safety problems and opportunities on all public roads and all users, and focuses resources on... approved by the FHWA Division Administrator. (iii) Develop a High Risk Rural Roads program using safety...

47 CFR 90.238 - Telemetry operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... in the Public Safety and Industrial/Business Pools and in accordance with § 90.259). (e) In the 450... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND... MHz band (as available in the Public Safety Pool for bio-medical telemetry operations). (i) For...

47 CFR 90.238 - Telemetry operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... in the Public Safety and Industrial/Business Pools and in accordance with § 90.259). (e) In the 450... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND... MHz band (as available in the Public Safety Pool for bio-medical telemetry operations). (i) For...

75 FR 17825 - Request for Public Comments and OMB Approval of Existing Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-07

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No...: Pipeline and Hazardous Materials Safety Administration. ACTION: Request for Public Comments and OMB... Reduction Act of 1995, the Pipeline and Hazardous Materials Safety Administration (PHMSA) published a notice...

What is the 'true' effect of Trypanosoma rangeli on its triatomine bug vector?

PubMed

Peterson, Jennifer K; Graham, Andrea L

2016-06-01

The phrase, "T. rangeli is pathogenic to its insect vector," is commonly found in peer-reviewed publications on the matter, such that it has become the orthodox view of this interaction. In a literature survey, we identified over 20 papers with almost the exact phrase and several others alluding to it. The idea is of particular importance in triatomine population dynamics and the study of vector-borne T. cruzi transmission, as it could mean that triatomines infected with T. rangeli have lower fitness than uninfected insects. Trypanosoma rangeli pathogenicity was first observed in a series of studies carried out over fifty years ago using the triatomine species Rhodnius prolixus. However, there are few studies of the effect of T. rangeli on its other vector species, and several of the studies were carried out with R. prolixus under non-physiological conditions. Here, we re-evaluate the published studies that led to the conclusion that T. rangeli is pathogenic to its vector, to determine whether or not this indeed is the "true" effect of T. rangeli on its triatomine vector. © 2016 The Society for Vector Ecology.

Virus-Derived Gene Expression and RNA Interference Vector for Grapevine

PubMed Central

Kurth, Elizabeth G.; Peremyslov, Valera V.; Prokhnevsky, Alexey I.; Kasschau, Kristin D.; Miller, Marilyn; Carrington, James C.

2012-01-01

The improvement of the agricultural and wine-making qualities of the grapevine (Vitis vinifera) is hampered by adherence to traditional varieties, the recalcitrance of this plant to genetic modifications, and public resistance to genetically modified organism (GMO) technologies. To address these challenges, we developed an RNA virus-based vector for the introduction of desired traits into grapevine without heritable modifications to the genome. This vector expresses recombinant proteins in the phloem tissue that is involved in sugar transport throughout the plant, from leaves to roots to berries. Furthermore, the vector provides a powerful RNA interference (RNAi) capability of regulating the expression of endogenous genes via virus-induced gene-silencing (VIGS) technology. Additional advantages of this vector include superb genetic capacity and stability, as well as the swiftness of technology implementation. The most significant applications of the viral vector include functional genomics of the grapevine and disease control via RNAi-enabled vaccination against pathogens or invertebrate pests. PMID:22438553

Fuzzy support vector machine: an efficient rule-based classification technique for microarrays.

PubMed

Hajiloo, Mohsen; Rabiee, Hamid R; Anooshahpour, Mahdi

2013-01-01

The abundance of gene expression microarray data has led to the development of machine learning algorithms applicable for tackling disease diagnosis, disease prognosis, and treatment selection problems. However, these algorithms often produce classifiers with weaknesses in terms of accuracy, robustness, and interpretability. This paper introduces fuzzy support vector machine which is a learning algorithm based on combination of fuzzy classifiers and kernel machines for microarray classification. Experimental results on public leukemia, prostate, and colon cancer datasets show that fuzzy support vector machine applied in combination with filter or wrapper feature selection methods develops a robust model with higher accuracy than the conventional microarray classification models such as support vector machine, artificial neural network, decision trees, k nearest neighbors, and diagonal linear discriminant analysis. Furthermore, the interpretable rule-base inferred from fuzzy support vector machine helps extracting biological knowledge from microarray data. Fuzzy support vector machine as a new classification model with high generalization power, robustness, and good interpretability seems to be a promising tool for gene expression microarray classification.

75 FR 29155 - Publicly Available Consumer Product Safety Information Database

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-24

...The Consumer Product Safety Commission (``Commission,'' ``CPSC,'' or ``we'') is issuing a notice of proposed rulemaking that would establish a publicly available consumer product safety information database (``database''). Section 212 of the Consumer Product Safety Improvement Act of 2008 (``CPSIA'') amended the Consumer Product Safety Act (``CPSA'') to require the Commission to establish and maintain a publicly available, searchable database on the safety of consumer products, and other products or substances regulated by the Commission. The proposed rule would interpret various statutory requirements pertaining to the information to be included in the database and also would establish provisions regarding submitting reports of harm; providing notice of reports of harm to manufacturers; publishing reports of harm and manufacturer comments in the database; and dealing with confidential and materially inaccurate information.

Recent advances in phlebotomine sand fly research related to leishmaniasis control.

PubMed

Bates, Paul A; Depaquit, Jerôme; Galati, Eunice A B; Kamhawi, Shaden; Maroli, Michele; McDowell, Mary Ann; Picado, Albert; Ready, Paul D; Salomón, O Daniel; Shaw, Jeffrey J; Traub-Csekö, Yara M; Warburg, Alon

2015-02-27

Phlebotomine sand flies are the subject of much research because of the role of their females as the only proven natural vectors of Leishmania species, the parasitic protozoans that are the causative agents of the neglected tropical disease leishmaniasis. Activity in this field was highlighted by the eighth International Symposium on Phlebotomine Sand flies (ISOPS) held in September 2014, which prompted this review focusing on vector control. Topics reviewed include: Taxonomy and phylogenetics, Vector competence, Genetics, genomics and transcriptomics, Eco-epidemiology, and Vector control. Research on sand flies as leishmaniasis vectors has revealed a diverse array of zoonotic and anthroponotic transmission cycles, mostly in subtropical and tropical regions of Africa, Asia and Latin America, but also in Mediterranean Europe. The challenge is to progress beyond descriptive eco-epidemiology, in order to separate vectors of biomedical importance from the sand fly species that are competent vectors but lack the vectorial capacity to cause much human disease. Transmission modelling is required to identify the vectors that are a public health priority, the ones that must be controlled as part of the integrated control of leishmaniasis. Effective modelling of transmission will require the use of entomological indices more precise than those usually reported in the leishmaniasis literature.

U.S. pharmacy policy: a public health perspective on safety and cost.

PubMed

Rosenau, Pauline Vaillancourt; Lal, Lincy S; Glasser, Jay H

2009-01-01

A public health perspective based on social justice and a population health point of view emphasizes pharmacy policy innovations regarding safety and costs. Such policies that effectively reduce costs include controlling profits, establishing profit targets, extending prescription providers, revising prescription classification schemes, emphasizing generic medications, and establishing formularies. Public education and universal programs may reduce costs, but co-pays and "cost-sharing" do not. Switching medications to over-the-counter (OTC) status, pill splitting, and importing medication from abroad are poor substitutes for authentic public health pharmacy policy. Where policy changes yield savings, public health insists that these savings should be used to increase access and improve population health. In the future, pharmacy policies may emphasize public health accountability more than individual liberty because of potential cost savings to society. Fear of litigation, as an informal mechanism of focusing manufacturer's attention on safety, is inefficient; public health pharmacy policy regarding safety looks toward a more active regulatory role on the part of government. A case study of direct-to-consumer advertising illustrates the complexity of public health pharmacy policy.

Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning.

PubMed

Munkhdalai, Tsendsuren; Liu, Feifan; Yu, Hong

2018-04-25

Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. It shows that classical learning models (SVM) remains advantageous over deep learning models (RNN variants) for clinical relation identification, especially for long-distance intersentential relations. However, RNNs demonstrate a great potential of significant improvement if more training data become available. Our work is an important step toward mining EHRs to improve the efficacy of drug safety surveillance. Most importantly, the annotated data used in this study will be made publicly available, which will further promote drug safety research in the community. ©Tsendsuren Munkhdalai, Feifan Liu, Hong Yu. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 25.04.2018.

Preclinical Demonstration of Lentiviral Vector-mediated Correction of Immunological and Metabolic Abnormalities in Models of Adenosine Deaminase Deficiency

PubMed Central

Carbonaro, Denise A; Zhang, Lin; Jin, Xiangyang; Montiel-Equihua, Claudia; Geiger, Sabine; Carmo, Marlene; Cooper, Aaron; Fairbanks, Lynette; Kaufman, Michael L; Sebire, Neil J; Hollis, Roger P; Blundell, Michael P; Senadheera, Shantha; Fu, Pei-Yu; Sahaghian, Arineh; Chan, Rebecca Y; Wang, Xiaoyan; Cornetta, Kenneth; Thrasher, Adrian J; Kohn, Donald B; Gaspar, H Bobby

2014-01-01

Gene transfer into autologous hematopoietic stem cells by γ-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA)–deficient severe combined immunodeficiency (SCID). However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy (GT), we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA). In ADA−/− mice, LV EFS ADA displayed high-efficiency gene transfer and sufficient ADA expression to rescue ADA−/− mice from their lethal phenotype with good thymic and peripheral T- and B-cell reconstitution. Human ADA-deficient CD34+ cells transduced with 1–5 × 107 TU/ml had 1–3 vector copies/cell and expressed 1–2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV EFS ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV EFS ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, while reducing the potential for vector-mediated insertional mutagenesis. PMID:24256635

Proceedings of the National Transportation Safety Board Public Forum on Air Bags and Child Passenger Safety

DOT National Transportation Integrated Search

1997-01-01

The National Transportation Safety Board convened a 4-day public forum from March 17 to March 20, 1997, to discuss concerns related to the effectiveness of air bags, passenger vulnerability to injuries from air bag deployment, other countries' experi...

42 CFR 86.14 - Evaluation and grant award.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Training Grants § 86.14 Evaluation and grant award. Within the limits of funds...

42 CFR 86.34 - Evaluation and award of direct traineeships.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Section 86.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.34 Evaluation and award of direct...

42 CFR 86.21 - Applicability of 45 CFR part 74.

Code of Federal Regulations, 2014 CFR

2014-10-01

....21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Training Grants § 86.21 Applicability of 45 CFR part 74. The...

75 FR 22817 - Emerging Infectious Diseases: Evaluation to Implementation for Transfusion and Transplantation...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Quantitative Risk Assessment: Blood Safety and Availability; Public Workshops AGENCY: Food and Drug... and Transplantation Safety'' (EID public workshop) and ``Quantitative Risk Assessment: Blood Safety... Research (HFM-302), Food and Drug Administration, 1401 Rockville Pike, Suite 550N, Rockville, MD 20852-1448...

47 CFR 90.243 - Mobile relay stations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND... Service. (b) Special provisions for mobile relay operations: (1) In the Public Safety Pool, systems operating on any of the public safety frequencies listed in § 90.20(c) are permitted to be cross-banded for...

42 CFR 3.306 - Complaints to the Secretary.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.306 Complaints to the Secretary. (a) Right to file a complaint. A person who believes that patient safety work product has been...

42 CFR 3.306 - Complaints to the Secretary.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.306 Complaints to the Secretary. (a) Right to file a complaint. A person who believes that patient safety work product has been...

42 CFR 3.306 - Complaints to the Secretary.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.306 Complaints to the Secretary. (a) Right to file a complaint. A person who believes that patient safety work product has been...

42 CFR 3.306 - Complaints to the Secretary.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.306 Complaints to the Secretary. (a) Right to file a complaint. A person who believes that patient safety work product has been...

42 CFR 86.21 - Applicability of 45 CFR part 74.

Code of Federal Regulations, 2010 CFR

2010-10-01

....21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Training Grants § 86.21 Applicability of 45 CFR part 74. The...

42 CFR 86.34 - Evaluation and award of direct traineeships.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 86.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.34 Evaluation and award of direct...

Risk assessment of vector-borne diseases for public health governance.

PubMed

Sedda, L; Morley, D W; Braks, M A H; De Simone, L; Benz, D; Rogers, D J

2014-12-01

In the context of public health, risk governance (or risk analysis) is a framework for the assessment and subsequent management and/or control of the danger posed by an identified disease threat. Generic frameworks in which to carry out risk assessment have been developed by various agencies. These include monitoring, data collection, statistical analysis and dissemination. Due to the inherent complexity of disease systems, however, the generic approach must be modified for individual, disease-specific risk assessment frameworks. The analysis was based on the review of the current risk assessments of vector-borne diseases adopted by the main Public Health organisations (OIE, WHO, ECDC, FAO, CDC etc…). Literature, legislation and statistical assessment of the risk analysis frameworks. This review outlines the need for the development of a general public health risk assessment method for vector-borne diseases, in order to guarantee that sufficient information is gathered to apply robust models of risk assessment. Stochastic (especially spatial) methods, often in Bayesian frameworks are now gaining prominence in standard risk assessment procedures because of their ability to assess accurately model uncertainties. Risk assessment needs to be addressed quantitatively wherever possible, and submitted with its quality assessment in order to enable successful public health measures to be adopted. In terms of current practice, often a series of different models and analyses are applied to the same problem, with results and outcomes that are difficult to compare because of the unknown model and data uncertainties. Therefore, the risk assessment areas in need of further research are identified in this article. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.

PubMed

Mitsui, Kaoru; Ide, Kanako; Takahashi, Tomoyuki; Kosai, Ken-Ichiro

2017-06-16

Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products. Despite such efforts, guaranteeing the clinical safety of regenerative medicine products remains a key challenge. Given the intrinsic genome instability of hPSCs, selective growth advantage of cancer cells, and lessons learned through failures in previous attempts at hematopoietic stem cell gene therapy, conventional strategies are unlikely to completely overcome issues related to hPSC tumorigenesis. Researchers have recently embarked on studies aimed at locating and directly treating hPSC-derived tumorigenic cells. In particular, novel approaches to directly killing tumorigenic cells by transduction of suicide genes and oncolytic viruses are expected to improve the safety of hPSC-based therapy. This article discusses the current status and future perspectives of methods aimed at directly eradicating undifferentiated tumorigenic hPSCs, with a focus on viral vector transduction.

Development of the First World Health Organization Lentiviral Vector Standard: Toward the Production Control and Standardization of Lentivirus-Based Gene Therapy Products

PubMed Central

Zhao, Yuan; Stepto, Hannah; Schneider, Christian K

2017-01-01

Gene therapy is a rapidly evolving field. So far, there have been >2,400 gene therapy products in clinical trials and four products on the market. A prerequisite for producing gene therapy products is ensuring their quality and safety. This requires appropriately controlled and standardized production and testing procedures that result in consistent safety and efficacy. Assuring the quality and safety of lentivirus-based gene therapy products in particular presents a great challenge because they are cell-based multigene products that include viral and therapeutic proteins as well as modified cells. In addition to the continuous refinement of a product, changes in production sites and manufacturing processes have become more and more common, posing challenges to developers regarding reproducibility and comparability of results. This paper discusses the concept of developing a first World Health Organization International Standard, suitable for the standardization of assays and enabling comparison of cross-trial and cross-manufacturing results for this important vector platform. The standard will be expected to optimize the development of gene therapy medicinal products, which is especially important, given the usually orphan nature of the diseases to be treated, naturally hampering reproducibility and comparability of results. PMID:28747142

Towards an integrated approach in surveillance of vector-borne diseases in Europe

PubMed Central

2011-01-01

Vector borne disease (VBD) emergence is a complex and dynamic process. Interactions between multiple disciplines and responsible health and environmental authorities are often needed for an effective early warning, surveillance and control of vectors and the diseases they transmit. To fully appreciate this complexity, integrated knowledge about the human and the vector population is desirable. In the current paper, important parameters and terms of both public health and medical entomology are defined in order to establish a common language that facilitates collaboration between the two disciplines. Special focus is put on the different VBD contexts with respect to the current presence or absence of the disease, the pathogen and the vector in a given location. Depending on the context, whether a VBD is endemic or not, surveillance activities are required to assess disease burden or threat, respectively. Following a decision for action, surveillance activities continue to assess trends. PMID:21967706

Characteristics of lentiviral vectors harboring the proximal promoter of the vav proto-oncogene: a weak and efficient promoter for gene therapy.

PubMed

Almarza, Elena; Río, Paula; Meza, Nestor W; Aldea, Montserrat; Agirre, Xabier; Guenechea, Guillermo; Segovia, José C; Bueren, Juan A

2007-08-01

Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.

Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

PubMed

De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

2016-11-01

Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

77 FR 60007 - Medical Review Board Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

...-0362] Medical Review Board Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Medical Review Board (MRB) public meeting. SUMMARY: The FMCSA announces that... the Federal Motor Carrier Safety Regulation (FMCSR) medical standards. DATES: Meeting Date: The MRB...

Aviation Safety: FAA Has Begun Efforts to Make Data More Publicly Available

DOT National Transportation Integrated Search

1997-04-25

Public concern about the safety of the nation's aviation system escalated : following the crashes of ValuJet flight 592 and TWA flight 800. The Congress : and the public expressed interest in having the Federal Aviation Administration : (FAA) publish...

Inner Ear Gene Transfection in Neonatal Mice Using Adeno-Associated Viral Vector: A Comparison of Two Approaches

PubMed Central

Xia, Li; Yin, Shankai; Wang, Jian

2012-01-01

Local gene transfection is a promising technique for the prevention and/or correction of inner ear diseases, particularly those resulting from genetic defects. Adeno-associated virus (AAV) is an ideal viral vector for inner ear gene transfection because of its safety, stability, long-lasting expression, and its high tropism for many different cell types. Recently, a new generation of AAV vectors with a tyrosine mutation (mut-AAV) has demonstrated significant improvement in transfection efficiency. A method for inner ear gene transfection via the intact round window membrane (RWM) has been developed in our laboratory. This method has not been tested in neonatal mice, an important species for the study of inherited hearing loss. Following a preliminary study to optimize the experimental protocol in order to reduce mortality, the present study investigated inner ear gene transfection in mice at postnatal day 7. We compared transfection efficiency, the safety of the scala tympani injection via RWM puncture, and the trans-RWM diffusion following partial digestion with an enzyme technique. The results revealed that approximately 47% of inner hair cells (IHCs) and 17% of outer hair cells (OHCs) were transfected via the trans-RWM approach. Transfection efficiency via RWM puncture (58% and 19% for IHCs and OHCs, respectively) was slightly higher, but the difference was not significant. PMID:22912830

Advancing vector biology research: a community survey for future directions, research applications and infrastructure requirements

PubMed Central

Kohl, Alain; Pondeville, Emilie; Schnettler, Esther; Crisanti, Andrea; Supparo, Clelia; Christophides, George K.; Kersey, Paul J.; Maslen, Gareth L.; Takken, Willem; Koenraadt, Constantianus J. M.; Oliva, Clelia F.; Busquets, Núria; Abad, F. Xavier; Failloux, Anna-Bella; Levashina, Elena A.; Wilson, Anthony J.; Veronesi, Eva; Pichard, Maëlle; Arnaud Marsh, Sarah; Simard, Frédéric; Vernick, Kenneth D.

2016-01-01

Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector–pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations. PMID:27677378

Vector Fluxgate Magnetometer (VMAG) Development for DSX

DTIC Science & Technology

2008-05-19

AFRL-RV-HA-TR-2008-1108 Vector Fluxgate Magnetometer (VMAG) Development for DSX Mark B. Moldwin Q. O O O I- UCLA Q Institute of...for Public Release; Distribution Unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT UCLA is building a three-axis fluxgate magnetometer for the Air... fluxgate magnetometer provides the necessary data to support both the Space Weather (SWx) specification and mapping requirements and the WPIx

The house fly, Musca domestica: once again a vector of pathogens of public health significance

USDA-ARS?s Scientific Manuscript database

During the time of Walter Reed in Cuba and in subsequent years of the early 20th century, the house fly lost its image of a being a good fly to have around, and became a dreaded vector of disease-causing organisms. In the U.S., it was dubbed the typhoid fly and many research projects were launched t...

Wolbachia Effects on Rift Valley Virus Infection in Culex tarsalis Mosquitoes

DTIC Science & Technology

2017-04-25

Vector-Borne Disease Section, Division of Communicable Diseases, Center 14" for Infectious Diseases, California Department of Public Health ...Wolbachia. 44" 45" Author Summary 46" An integrated vector management program utilizes several practices, including pesticide 47" application and source...mosquitoes and can block pathogen transmission to humans . 51" Additionally, Wolbachia is maternally-inherited, allowing it to spread quickly through

The house fly, Musca domestica: An overlooked vector of pathogens of public health significance

USDA-ARS?s Scientific Manuscript database

During the time of Walter Reed in Cuba and in subsequent years of the early 20th century, the house fly lost its image of a being a good fly to have around, and became a dreaded vector of disease-causing organisms. In the US, it was dubbed the typhoid fly and many research projects were launched to ...

41 CFR 128-1.8005 - Seismic safety standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Seismic safety standards. 128-1.8005 Section 128-1.8005 Public Contracts and Property Management Federal Property Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program § 128-1.8005...

41 CFR 128-1.8009 - Review of Seismic Safety Program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Review of Seismic Safety Program. 128-1.8009 Section 128-1.8009 Public Contracts and Property Management Federal Property Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program...

76 FR 15982 - Nominations to the Advisory Committee on Blood Safety and Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

... Mr. James Berger, Associate Public Health Advisor for Blood, Organ and Tissue Safety; Office of... Public Health Advisor for Blood, Organ and Tissue Safety. Contact information for Mr. Berger is provided... American Association of Blood Banks); the plasma protein fraction community; one of the two major...

78 FR 52116 - Request for Public Comment on a Review Level Alternative Dispute Resolution Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-22

... OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION 29 CFR Part 2200 Request for Public Comment on a Review Level Alternative Dispute Resolution Program AGENCY: Occupational Safety and Health Review Commission. ACTION: Request for comment. SUMMARY: The Occupational Safety and Health Review Commission...

76 FR 16854 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... Secretary and the Federal Transit Administrator on matters relating to the safety of public transportation... to the safety of public transportation systems. TRACS is composed of 21 members representing a broad... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Notice of Meeting of the Transit Rail...

77 FR 55265 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... Secretary and the Federal Transit Administrator on matters relating to the safety of public transportation... Federal Transit Administration (FTA) on matters relating to the safety of public transportation systems... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Notice of Meeting of the Transit Rail...

76 FR 43534 - Alternative to Minimum Days Off Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

... fatigue does not adversely affect public health and safety and the common defense and security. Among... health and safety and the common defense and security by establishing clear and enforceable requirements... public health and safety and common defense and security. B. Alternative to the Minimum Days Off...

10 CFR 50.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... radium-226 to the public health and safety or the common defense and security; and (ii) Before, on, or... as to affect the protection of health and safety against radiation. Cost of service regulation means... waterway, in case of emergency, to protect the public health and safety. Residence within the exclusion...