DEFICIENCIES IN THE REQUIREMENT GENERATION PHASE THAT DELAY THE LEAD TIME OF ARMY CONTRACT ACTIONS

The purpose of this mixed-methodology study is to identify opportunities to reduce administrative requirements lead time for contracting actions at Army Contracting Command (ACC) organizations, at CONUS installation level, for future implementation across ACC units. An analysis of FY19–21 reveals issues in the training resources available to operational contract support personnel that degrade critical contract elements, increasing the procurement action lead time for service requirements. The findings show service contracts have a longer requirements generation phase than supply contracts. The longer requirements generation phase is associated with the level of complexity and required documentation for each contract action. As complexity decreases, requirements lead time also decreases. The research further reveals an inverse relationship between the use of standardized resource tools and requirements lead time; the lead time decreased as utilization rates increased. The results of the research indicate that policy implementation and consolidation of standardized resource tools would have a reductive effect on lead time for contract actions within the ACC. Additionally, the research recommends modifying the training curriculum to focus on the requirements generation phase. Furthermore, the research recommends changing table of organization and equipment (TOE) positions to require the additional skill identifier 3C for all S4s/G4s and supply sergeants at every echelon.Major, United States ArmyMajor, United States ArmyMajor, United States ArmyMajor, United States ArmyMajor, United States ArmyApproved for public release. Distribution is unlimited

Las formas de organización de la enseñanza en el policlínico universitario su conceptualización y abordaje.

Las transformaciones que hoy se proponen en la Educación Médica, dada la descentralización de la enseñanza en los municipios, harán posible un abordaje educacional más innovador, apoyado en las tecnologías de la información y la comunicación (TIC), acercando al estudiante al escenario profesional desde el inicio de la Carrera. Todo ello permitirá un equilibrio entre la docencia, la investigación y la asistencia. Como resultado de este rediseño de programas en las Ciencias Médicas, donde el aprendizaje es a nivel del Policlínico Universitario, se ha hecho necesario realizar transformaciones en las Formas de Organización de la Enseñanza (FOE), en la Atención Primaria de Salud. Con el presente trabajo, pretendemos ofrecer nuestros criterios sobre las características de estas FOE, así como brindar elementos metodológicos para la impartición de algunas de ellas, de forma tal que puedan ser utilizadas por igual por el claustro profesoral y poder elevar la calidad del proceso docente.  Palabras clave: Formas de Organización de la Enseñanza (FOE), Policlínico Universitario, Educación Médica, Videoclase, Tecnología Educativa

Aspectos esenciales en la elaboración de las videoclases en las ciencias de la salud.

Uno de los recursos de aprendizaje más utilizado en la actualidad en los procesos docentes de las Ciencias de la Salud es la Videoclase. Para afrontar la elaboración de estos medios de enseñanza es vital proveer al profesor de herramientas de apoyo sencillas y flexibles que le permitan lograr sus objetivos pedagógicos, ofreciendo a su alumnado el soporte y apoyo adecuado para cubrir sus necesidades.  Este trabajo brinda una serie de recomendaciones para tratar de unificar los criterios acerca de la elaboración de las Videoclases, así como orientar a los profesores que van a enfrentar este reto dentro del proceso docente.  Se analizan los aspectos fundamentales que deben tenerse en cuenta en el momento de la confección de la Videoclase, así como los procesos comunicacionales que están involucrados y las características y responsabilidades que debe tener un teleprofesor.  Palabras clave: Videoclases, Teleprofesor, Policlínico Universitario, Recursos de aprendizaje, Medios de enseñanza, Tecnología educativa

Modeling Parkinson’s disease neuropathology and symptoms by intranigral inoculation of preformed human α-synuclein oligomers

The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson’s disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies

MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML

Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia

The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor gene Wnt5a, belonging to the non-canonical Wnt signaling pathway, was investigated in a large series of 75 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia by methylationspecific polymerase chain reaction. At least one methylated gene was observed in cells from 66% (49/75) of patients (methylated group). Disease-free survival and overall survival at 9 years were 51 and 40%, respectively, for the unmethylated group and 3 and 2%, respectively, for the methylated group (both P < 0.0001). Multivariate analysis demonstrated that the Wnt methylation profile was an independent prognostic factor predicting disease-free survival (P = 0.007) and overall survival (P = 0.039). Abnormal DNA methylation of promoter-associated CpG islands in the Wnt signaling pathway is very common in Philadelphia chromosome-positive acute lymphoblastic leukemia and potentially defines subgroups with distinct clinical characteristics

LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome

BACKGROUND: LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored. DESIGN AND METHODS: We measured LMO2 expression by real time RT-PCR in 247 acute lymphoblastic leukemia patient samples with cytogenetic data (144 of them also with survival and immunophenotypical data) and in normal hematopoietic and lymphoid cells. RESULTS: B-cell acute lymphoblastic leukemia cases expressed variable levels of LMO2 depending on immunophenotypical and cytogenetic features. Thus, the most immature subtype, pro-B cells, displayed three-fold higher LMO2 expression than pre-B cells, common-CD10+ or mature subtypes. Additionally, cases with TEL-AML1 or MLL rearrangements exhibited two-fold higher LMO2 expression compared to cases with BCR-ABL rearrangements or hyperdyploid karyotype. Clinically, high LMO2 expression correlated with better overall survival in adult patients (5-year survival rate 64.8% (42.5%-87.1%) vs. 25.8% (10.9%-40.7%), P= 0.001) and constituted a favorable independent prognostic factor in B-ALL with normal karyotype: 5-year survival rate 80.3% (66.4%-94.2%) vs. 63.0% (46.1%-79.9%) (P= 0.043). CONCLUSIONS: Our data indicate that LMO2 expression depends on the molecular features and the differentiation stage of B-cell acute lymphoblastic leukemia cells. Furthermore, assessment of LMO2 expression in adult patients with a normal karyotype, a group which lacks molecular prognostic factors, could be of clinical relevance

The need for a network to establish and validate predictive biomarkers in cancer immunotherapy.

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and social need. In addition, with several new immunotherapy agents in different phases of development, and approved therapeutics being tested in combination with a variety of different standard of care treatments, there is a requirement to stratify patients and select the most appropriate population in which to assess clinical efficacy. The opportunity to design parallel biomarkers studies that are integrated within key randomized clinical trials could be the ideal solution. Sample collection (fresh and/or archival tissue, PBMC, serum, plasma, stool, etc.) at specific points of treatment is important for evaluating possible biomarkers and studying the mechanisms of responsiveness, resistance, toxicity and relapse. This white paper proposes the creation of a network to facilitate the sharing and coordinating of samples from clinical trials to enable more in-depth analyses of correlative biomarkers than is currently possible and to assess the feasibilities, logistics, and collated interests. We propose a high standard of sample collection and storage as well as exchange of samples and knowledge through collaboration, and envisage how this could move forward using banked samples from completed studies together with prospective planning for ongoing and future clinical trials