Upset susceptibility study employing circuit analysis and digital simulation

This paper describes an approach to predicting the susceptibility of digital systems to signal disturbances. Electrical disturbances on a digital system's input and output lines can be induced by activities and conditions including static electricity, lightning discharge, Electromagnetic Interference (EMI) and Electromagnetic Pulsation (EMP). The electrical signal disturbances employed for the susceptibility study were limited to nondestructive levels, i.e., the system does not sustain partial or total physical damage and reset and/or reload will bring the system to an operational status. The front-end transition from the electrical disturbances to the equivalent digital signals was accomplished by computer-aided circuit analysis. The Super-Sceptre (system for circuit evaluation of transient radiation effects) Program was used. Gate models were developed according to manufacturers' performance specifications and parameters resulting from construction processes characteristic of the technology. Digital simulation at the gate and functional level was employed to determine the impact of the abnormal signals on system performance and to study the propagation characteristics of these signals through the system architecture. Example results are included for an Intel 8080 processor configuration

Perceções dos enfermeiros sobre os erros de medicação no pré-hospitalar

Quase metade da totalidade de eventos adversos evitáveis é consequência de erros de medicação (EM), contudo, não sendo possível evitá-los completamente, estes podem ser minorados. Esta problemática em contexto pré-hospitalar (PH) tem sido pouco estudada a nível internacional e nunca foi abordada em Portugal. O objetivo deste estudo é relacionar as variáveis sociodemográficas, socioprofissionais, formação, conhecimentos e experiências com EM com a perceção dos enfermeiros que exercem no PH relativamente à frequência da ocorrência dos tipos e causas de EM, dos obstáculos ao relato de EM, dos fatores facilitadores do relato de EM e com o grau de concordância sobre divulgação de EM. Métodos: Trata-se de um estudo analítico, descritivo, transversal e correlacional. A amostra é composta por 107 enfermeiros do PH (método snowball), dos quais 56.1% são do sexo masculino. Foi aplicado um questionário eletrónico constituído por uma componente sociodemográfica, escala de conhecimentos, perceções e experiência com erros de medicação (Raimundo, 2011; Maurer, 2010; Bohomol & Ramos, 2006; Mayo & Duncan, 2004; Osborne, Blais & Hayes, 1999; Gladstone, 1995). Resultados: Dos inquiridos 60.7% apresentam fracos a razoáveis conhecimentos sobre EM; mais de 54% perceciona a sua formação académica/contínua sobre EM como sendo inexistente/insuficiente e 52.3% não recebe formação sobre farmacologia há pelo menos 6 anos; 45.8% diz ter experienciado no PH um ou mais EM sem dano para o doente e apenas 14.9% relatou um ou mais EM sem dano para o doente. Os tipos e as causas de EM identificadas ocorrem com uma frequência elevada para mais de 39% dos inquiridos. A maioria dos inquiridos (47.7%) considera que no PH existem grandes obstáculos ao relato de EM e os fatores facilitadores do relato de EM apresentados são considerados por 49.5% dos enfermeiros como altamente prováveis de facilitar o relato. 52,3% dos enfermeiros do PH discordam de uma forma global com a divulgação de EM. O sexo feminino apresenta uma perceção mais elevada da ocorrência das causas primárias de EM (MF=2.68, Dp= 0.60 vs MM=2.36, Dp=0.66) e uma perceção mais elevada dos fatores facilitadores ao relato dos EM (MF=4.40, Dp= 0.64 vs MM=4.12, Dp=0.74). Os enfermeiros que exercem exclusivamente no PH possuem uma melhor perceção da frequência de ocorrência das causas primárias de EM. Quanto maior o conhecimento dos enfermeiros sobre EM, maior é a perceção destes relativamente aos tipos de erros e maior o grau de concordância com a divulgação dos EM. Existe evidência estatisticamente significativa (p<0.05) de que os enfermeiros que experienciaram a ocorrência de pelo menos 1 erro com dano para o doente possuem melhor perceção dos tipos, causas primárias e obstáculos ao relato dos EM, assim como apresenta um maior grau de concordância com a divulgação de EM. Conclusão: A perceção dos enfermeiros sobre a frequência dos tipos e das causas de EM, assim como dos obstáculos e dos fatores facilitadores do relato de EM por parte dos enfermeiros no PH não tem, de uma forma geral, relação com as características sociodemográficas e socioprofissionais, o que demonstra a transversalidade desta problemática. Tão ou mais importante do que avaliar a dimensão e caracterizar a tipologia, causas, obstáculos e fatores facilitadores ao relato dos EM será, com base no conhecimento obtido, definir e implementar ações de gestão de risco que permitam a sua redução ou mesmo a sua supressão. PALAVRAS-CHAVE: Erros de Medicação, Perceção dos Enfermeiros, Pré- Hospitalar.ABSTRACT Almost half of all preventable adverse events is the result of medication errors (ME), however, it’s not possible to avoid them completely, but they can be mitigated. This problem in the prehospital setting (PH) has been little studied internationally and has never been approached in Portugal. The objective of this study is to relate the socio-demographic, professional, training, knowledge and experience variables with ME, with the PH nurse’s perception of the occurrence frequency of the types and causes of ME, obstacles to the reporting of ME, facilitating factors of ME and with the degree of agreement on the disclosure of ME. Methods: Analytical, descriptive, cross-sectional and correlational study. Sample with 107 PH nurses (snowball method), of which 56.1% are male gender. Application of an electronic survey composed by a socio-demographic component, a knowledge scale on ME and a scale on perceptions and experiences on ME (Raymond, 2011; Maurer, 2010; Bohomol & Ramos, 2006; Mayo & Duncan, 2004; Osborne, Blais & Hayes, 1999 ; Gladstone, 1995). Results: 60.7% of the nurses inquired have a poor or reasonable knowledge about ME; over 54% consider their academic/continuous training on ME as inexistent/insufficient and 52.3% have not had any continuous training on this subject for at least 6 years; 45.8% claim to have experienced one or more PH ME with no damage for the patient and only 14.9% reported one or more reported one or ME without any harm to the patient. The identified types and causes for the ME occur with a high frequency for over 39% of the enquired people. Most respondents (47.7%) consider that in the PH setting there are considerable obstacles to the reporting of ME and the facilitating factors of ME reports presented are considered by 49.5% of the nurses as highly likely to facilitate reporting. 52.3% of the PH nurses disagree with the disclosure of ME. Females have a higher perception of the occurrence of the primary causes of ME (MF = 2.68, SD = 0.60 vs MM = 2.36, SD = 0.66) and a higher perception of the facilitating factors for reporting ME (MF = 4.40, SD = 0.64 vs MM = 4.12 SD = 0.74). Nurses that work exclusively in the PH have a better perception of the frequency of occurrence of the primary causes of ME. The higher nurses' knowledge of ME matches to a higher perception of the types of ME and to a higher degree of agreement with the disclosure of ME. There’s statistically significant evidence (p <0.05) that nurses who experienced the occurrence of at least one error with damage to the patient has better perception of types, primary causes and obstacles to reporting of ME, as well as presents a higher degree of agreement with the disclosure of ME Conclusion: The PH nurses’ perception on the frequency of the types and causes of ME, as well on the obstacles and facilitating factors for ME reporting is generally not related to the socio-demographic and socio-professional characteristics, demonstrating the transversality of this issue. Equally or more important than assessing the extent and characterize the types, causes, obstacles and facilitating factors for reporting ME, will be define and implement risk management actions that allow its reduction or even its suppression, based on the knowledge gained. KEY WORDS: Medication Errors; Nurse’s Perception; Prehospital

Preclinical evaluation of cancer immune therapy using patient-derived tumor antigen-specific T cells in a novel xenograft platform.

Objectives: With a rapidly growing list of candidate immune-based cancer therapeutics, there is a critical need to generate highly reliable animal models to preclinically evaluate the efficacy of emerging immune-based therapies, facilitating successful clinical translation. Our aim was to design and validate a novel Methods: Tumor xenografts are established rapidly in the greater omentum of globally immunodeficient NOD- Results: The tumors progress rapidly and disseminate in the mice unless patient-derived tumor-specific T cells are introduced. An initial T cell-mediated tumor arrest is later followed by a tumor escape, which correlates with the upregulation of the checkpoint molecules programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on T cells. Treatment with immune-based therapies that target these checkpoints, such as anti-PD-1 antibody (nivolumab) or interleukin-12 (IL-12), prevented or delayed the tumor escape. Furthermore, IL-12 treatment suppressed PD-1 and LAG3 upregulation on T cells. Conclusion: Together, these results validate the X-mouse model and establish its potential to preclinically evaluate the therapeutic efficacy of immune-based therapies

A Database of Full Body Virtual Interactions Annotated with Expressivity Scores

Abstract Recent technologies enable the exploitation of full body expressions in applications such as interactive arts but are still limited in terms of dyadic subtle interaction patterns. Our project aims at full body expressive interactions between a user and an autonomous virtual agent. The currently available databases do not contain full body expressivity and interaction patterns via avatars. In this paper, we describe a protocol defined to collect a database to study expressive full-body dyadic interactions. We detail the coding scheme for manually annotating the collected videos. Reliability measures for global annotations of expressivity and interaction are also provided

A video guide of five access methods to the splenic flexure: the concept of the splenic flexure box

Aim: The aim of this study was to describe all the possible approaches for laparoscopic splenic flexure mobilization (SFM), each suitable for specific situations, and create an illustrated system to show SFM approaches in an easy and practical way to make it easy to learn and teach. Methods: Two different phases. First part: Cadaver-based study of the colonic splenic flexure anatomy. In order to demonstrate the different approaches, a balloon was placed through the colonic hepatic flexure in the lesser sac without sectioning any of the fixing ligaments of the splenic flexure. Second part: A real case series of laparoscopic SFM. Results: First part: 11 cadavers were dissected. Five potential approaches to SFM were found: anterior, trans-omentum, lateral, medial infra-mesocolic, and medial trans-mesocolic. The illustrative system developed was named: Splenic Flexure “Box”(SFBox). Second part: One of the types of SFM described in first part was used in five patients with colorectal cancer. Each laparoscopic approach to the splenic flexure was illustrated in a video accompanied by illustration aids delineating the access. Conclusion: With the cadaver dissection and subsequent demonstration in real-life laparoscopic surgery, we have shown five types of laparoscopic splenic flexure mobilization. The Splenic Flexure “Box” is a useful way to learn and teach this surgical maneuver

Novel phosphatidylserine-binding molecule enhances antitumor T-cell responses by targeting immunosuppressive exosomes in human tumor microenvironments.

BACKGROUND: The human tumor microenvironment (TME) is a complex and dynamic milieu of diverse acellular and cellular components, creating an immunosuppressive environment, which contributes to tumor progression. We have previously shown that phosphatidylserine (PS) expressed on the surface of exosomes isolated from human TMEs is causally linked to T-cell immunosuppression, representing a potential immunotherapeutic target. In this study, we investigated the effect of ExoBlock, a novel PS-binding molecule, on T-cell responses in the TME. METHODS: We designed and synthesized a new compound, (ZnDPA) RESULTS: ExoBlock was able to bind PS with high avidity and was found to consistently and significantly block the immunosuppressive activity of human ovarian tumor and melanoma-associated exosomes in vitro. ExoBlock was also able to significantly enhance T cell-mediated tumor suppression in vivo in both the X-mouse and the OTX model. In the X-mouse model, ExoBlock suppressed tumor recurrence in a T cell-dependent manner. In the OTX model, ExoBlock treatment resulted in an increase in the number as well as function of CD4 and CD8 T cells in the TME, which was associated with a reduction in tumor burden and metastasis, as well as in the number of circulating PS+ exosomes in tumor-bearing mice. CONCLUSION: Our results establish that targeting exosomal PS in TMEs with ExoBlock represents a promising strategy to enhance antitumor T-cell responses

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products