Barriers to Providing Quality Care for Pediatric Patients with Autism Spectrum Disorder as Identified by Baccalaureate Prepared Registered Nurses: A Basis to Enhance Professional Practice

The increased prevalence of autism spectrum disorder (ASD) foretells that this sector of the population will be accessing health care services in greater numbers; thus, it behooves healthcare providers to prepare for their impending needs. This qualitative study describes the experiences of baccalaureate prepared registered nurses caring for children and adolescents with ASD in order to identify challenges that hinder providing comprehensive and individualized care. A purposive sample of 10 baccalaureate degreed registered nurses (RNs) who have worked or work in the pediatric unit was used to gather rich descriptive experiences. The qualitative data analyses were based on an interpretive phenomenological approach. The participants identified two significant barriers to the quality care of the individuals with ASD in the pediatric setting. The first barrier, “Knowledge Deficit About ASD,” embodies lack of general knowledge about the ASD population. The second barrier, “Not Knowing the ASD Patient,” entails the importance of having the knowledge needed to individualize the care of individuals with ASD. The unresolved barriers that nurses face when caring for patients with ASD, along with the absence of guidelines, limited educational content, and insufficient in-service training underscores the need to establish evidence-based practice guidelines for individuals with ASD. Additionally, the resounding findings of this study, “Knowledge Deficit About ASD,” and “Not Knowing the ASD Patient,” indicate a need to change nursing education to efficiently train undergraduates, graduates, and faculty to adequately care for patients with ASD

Diastereoselective nickel-catalyzed reductive coupling of alkynes and aldehydes and application towards the B-type amphidinolides

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006.Vita.Includes bibliographical references.The application of recently developed stereoselective nickel-catalyzed reductive coupling reactions of alkynes and aldehydes to the synthesis of complex natural product targets was explored. The "B-Type" amphidinolides were selected as ideal targets owing to their molecular complexity and the paucity of synthetically viable means for their total construction. The diastereoselective nickel-catalyzed reductive coupling of simple aryl-substituted alkynes and a-oxyaldehydes was developed and applied to the construction of the C15-C26 region of amphidinolide H3. ... Alternatively, the nickel-catalyzed reductive coupling reaction of 1,3-enynes and aldehydes was found to be a very effective way of installing the congested 1,3-diene moiety common to all members of this class of natural products. This methodology was further examined as a fragment coupling strategy for the syntheses of amphidinolides G3 and H4. This allowed for a highly convergent and functional group tolerant assembly of these ... molecules and, to date, stands as the most complicated setting for the application of the catalytic reductive coupling reaction.by Chudi O. Ndubaku.Ph.D

Optimizing Hybrid Plate Fixation with a Locked, Oblique End Screw in Osteoporotic Fractures

Background The end screw in a fracture plate creates the greatest resistance to bending. For osteoporotic fractures treated with plates, there is some question as to the optimal screw insertion technique for the screw farthest from the fracture. A locked, oblique end screw was previously shown to increase resistance to periprosthetic fracture. It is unknown, however, how this end screw configuration would resist pullout when subjected to bending. Methods Narrow, low contact 3.5 mm locking compression plates with 6 and 12 holes were anchored to simulated bone material with material properties representing osteoporotic bone. Four configurations were evaluated for the end screw: perpendicular and angulated 30 degrees away from the fracture for both non-locked and locked screws (n=6 per group). The constructs were subjected to 3 point bending until the peak load and finally total construct failure was achieved. Results Peak force, stiffness, energy to peak load, and the failure mode of each construct were determined. All four 12-hole construct groups failed by gross plastic bending deformation of the plate at the fulcrum past a previously established clinically relevant limit for failure (15°). All 12-hole plate constructs failed at statistically higher loads and energy than any of the 6-hole plate constructs, with the exception of the 6-hole locked, oblique construct. Conclusion The locked, oblique end screw provides equivalent pull out strength for 3.5 mm low contact plates regardless of plate length. Combined with its resistance to periprosthetic fracture, this end screw configuration appears to be the best option for the construct integrity of hybrid plating for osteoporotic fractures. Clinical Relevance Osteoporotic fractures are challenging to treat. The current study and the existing literature show that resistance to both bending loads and refracture at the end of a plate are minimized with a locked screw angled away from the fracture

Phosphoinositide 3-Kinase-Dependent Signalling Pathways in Cutaneous Squamous Cell Carcinomas

British Skin Foundation

SMG1 and NIK regulate apoptosis induced by Smac mimetic compounds

Smac mimetic compounds (SMCs) are experimental small molecules that induce tumour necrosis factor alpha (TNFα)-dependent cancer cell death by targeting the inhibitor of apoptosis proteins. However, many cancer cell lines are resistant to SMC-mediated apoptosis despite the presence of TNFα. To add insight into the mechanism of SMC-resistance, we used functional siRNA-based kinomic and focused chemical screens and identified suppressor of morphogenesis in genitalia-1 (SMG1) and NF-κB-inducing kinase (NIK) as novel protective factors. Both SMG1 and NIK prevent SMC-mediated apoptosis likely by maintaining FLICE inhibitory protein (c-FLIP) levels to suppress caspase-8 activation. In SMC-resistant cells, the accumulation of NIK upon SMC treatment enhanced the activity of both the classical and alternative nuclear factor-κB pathways, and increased c-FLIP mRNA levels. In parallel, persistent SMG1 expression in SMC-resistant cells repressed SMC-mediated TNFα-induced JNK activation and c-FLIP levels were sustained. Importantly, SMC-resistance is overcome by depleting NIK and SMG1, which appear to facilitate the downregulation of c-FLIP in response to SMC and TNFα treatment, leading to caspase-8-dependent apoptosis. Collectively, these data show that SMG1 and NIK function as critical repressors of SMC-mediated apoptosis by potentially converging on the regulation of c-FLIP metabolism

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