25 research outputs found
Understanding Variation in the Practice of Employee Discipline: The Perspective of the First-Line Supervisor
First-line supervisors' responses to employee-related problems can vary widely from one supervisor to another. Assuming fair and consistent disciplinary activity is valued by organizations, then discovery of the factors causing supervisors to respond differently to similar situations is a valuable activity. Using a case study approach for four organizations in Puerto Rico, this article explores how factors such as sector, union presence, and managerial and human resource department support influence the choice of a discipline strategy. When present, some of these factors were found to encourage supervisors to comply with formal disciplinary policy. Organizations can use these findings to assess the degree to which there is consistency in these factors and take strategic action to assure that first-line supervisors receive clear and consistent signals regarding appropriate disciplinary strategies.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Serving the Public Interest?: Federal Experiences with Participation in Strategic Planning
A clause in the Government Performance and Results Act of 1993 instructs federal agencies to “consult with stakeholders during strategic plan development.” This requirement is a type of institutional control designed to ensure access to government operations and to keep government responsive to the public interest. Through structured interviews with representatives of the federal, cabinet-level departments, this research examined agency reactions to the Results Act in four areas: What process did agencies use to develop the strategic plan? Who participated? What mechanisms were used for participation? and What were the impacts of including stakeholders? The results suggest that despite minimal impact on the substantive content of federal agency strategic plans, the consultation requirement may have unintended benefits that, if institutionalized, will make government more responsive to the public interest.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Are we All Touching the Same Camel?: Exploring a Model of Participation in Budgeting
Theory offers a vast quantity of normative prescriptions concerning citizen participation in budget decisions. Yet cities struggle with this activity and report unsatisfactory outcomes. Why does this occur? It may be because, similar to the parable of the blind men describing the different parts of the camel, the extant literature suggests so many variables but does not integrate what we know to see the whole picture, nor does it eliminate variables having little explanatory value and there has been limited systematic testing of hypotheses in this area. To manage the complexity caused by a multiplicity of variables, the authors test a causal model with four different factors (structure, participants, process, and mechanisms) thought to influence effective citizen participation outcomes on cases of two midwestern cities. In this limited application, the model shows promise for predictive validity.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Organization Culture as an Explanation for Employee Discipline Practices
Most supervisors dread employee discipline and often employ strategies not officially sanctioned by the organization. Poorly designed discipline systems cause this variation in discipline practices. Inconsistent discipline can cause losses in productivity and reduce employee morale. Extant literature offers little in the form of guidance for improving this important human resource activity. This article explore where normative literature on organizational culture may have explanatory value for understanding variation in discipline practices. The article suggests two groups of factors that have causal effects on discipline practices. The tangible factors are those describing the formal practices the organization wishes its employees to follow. The intangible factors provide cues for explaining why informal strategies emerge as successful practices for getting things done. Using this conception of organization culture, the article proposes hypotheses for future testing to validate the suspected influence of culture on decisions regarding employee discipline.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation and cognition in fragile X mice
Background Identifying feasible therapeutic interventions is crucial for ameliorating the intellectual disability and other afflictions of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism. Hippocampal glycogen synthase kinase-3 (GSK3) is hyperactive in the mouse model of FXS (FX mice), and hyperactive GSK3 promotes locomotor hyperactivity and audiogenic seizure susceptibility in FX mice, raising the possibility that specific GSK3 inhibitors may improve cognitive processes. Methods We tested if specific GSK3 inhibitors improve deficits in N-methyl-D-aspartate receptor-dependent long-term potentiation at medial perforant path synapses onto dentate granule cells and dentate gyrus-dependent cognitive behavioral tasks. Results GSK3 inhibitors completely rescued deficits in long-term potentiation at medial perforant path-dentate granule cells synapses in FX mice. Furthermore, synaptosomes from the dentate gyrus of FX mice displayed decreased inhibitory serine-phosphorylation of GSK3β compared with wild-type littermates. The potential therapeutic utility of GSK3 inhibitors was further tested on dentate gyrus-dependent cognitive behaviors. In vivo administration of GSK3 inhibitors completely reversed impairments in several cognitive tasks in FX mice, including novel object detection, coordinate and categorical spatial processing, and temporal ordering for visual objects. Conclusions These findings establish that synaptic plasticity and cognitive deficits in FX mice can be improved by intervention with inhibitors of GSK3, which may prove therapeutically beneficial in FXS. © 2014 Society of Biological Psychiatry.Peer Reviewe