Diversity Oriented Synthesis, Characterization and Anti-Cancer Activity of Killer Peptide Nucleolipid Bioconjugates

The killer peptide sequence D-(KLAKLAK)2 has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)2 sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption results in membrane lysis and the secretion of cell death markers that ultimately lead to programmed cell death. In order to overcome the limited activity of the D-(KLAKLAK)2 sequence in malignant tumor cell types, we proposed that chemically robust and structurally pre-organized amphiphilic nucleolipids would function to enhance cell permeability and mitochondria localization in tumors, resulting in potent and long-lasting anti-cancer effects. In this study, thymidine-derived nucleolipids were rationally designed to contain 3’-lipid appendages and a reactive 5’-carboxy group. A diversity oriented synthesis approach featuring a reductive amination procedure was developed for making a small library of amphiphilic nucleolipids. Solid phase bioconjugation coupled the nucleolipids with the pro-apoptotic D-(KLAKLAK)2 sequence for exploring structure-activity relationships. The peptide nucleolipid conjugates were found to self-assemble into amphiphilic nanoparticle formulations that promoted anti-cancer activity in a selected panel of cancer cells. This thesis will serve to highlight the most important findings towards the development of peptide-nucleolipid conjugates that effectively serve as potent anti-cancer agents

A Lazy User Perspective to the Voluntary Adoption of Electronic Personal Health Records (PHRs)

Personal Health Records (PHRs) have been imbued with the potential to improve health outcomes for individual healthcare consumers, providers, and the broader healthcare system. With Meaningful Use Stage 2 now mandating the implementation of tethered PHRs, tethered to provider electronic health records (patient portals), will healthcare consumers voluntarily use PHRs and contribute to safety, quality, efficiency and reduced health disparities through engagement? Or will PHR use remain low? In this qualitative study, using grounded theory, we asked users how they currently managed their personal health information (PHI) and why. Using the lazy user model, we found that letting physicians manage healthcare consumers PHI is the least effort-based solution and thus the predominant and preferred solution. Providers as guardians of patient PHI suggests the low use rates may persist yet. We should do more to make these technologies usable and accessible to those with irregular contact with a primary care physician

Healthcare Consumers’ Voluntary Adoption and Non-Adoption of Electronic Personal Health Records

The use and ready availability of electronic health records is broadly purported to have the potential to improve health outcomes for individual healthcare consumers, providers and the healthcare system as a whole. Unlike electronic health records that are created and managed by providers, personal health records (PHR) are controlled by the individual consumer and the persons/entities to which they choose to grant access. Studies show while more healthcare consumers have access to PHRs, their voluntary adoption is lagging. Yet, our understanding of adoption lag is also lacking. In this qualitative study, we investigate: (1) how individual healthcare users in Connecticut currently manage their personal health information, (2) whether they have adopted an electronic PHR and the considerations that influenced the volitional adoption or non-adoption of a PHR. Initial findings casts new and surprising understandings including how healthcare consumers would like to use PHRs

Virtual Learning in New Zealand: Achieving Maturity

This proposal describes a study into the development of virtual learning in New Zealand, specifically the obstacles that e-learning clusters face or have faced in their journey to sustainability and maturity through the lens of the Learning Communities Online Handbook. Using a variety of data collection methods, the researchers identified three common barriers, including a lack of a coherent vision, difficulty in securing the necessary funding and resources, and a lack of collaboration and cooperation within and between clusters. Based on these findings, it is recommended that individual e-learning clusters develop specific strategies to encourage greater collaboration between clusters and work towards greater consistency between their activities, including professional and organizational development and also of the approaches to virtual learning

Primary and Secondary Virtual Learning in New Zealand: Examining Barriers to Achieving Maturity

This paper describes the organisational development of virtual learning in networked rural schools in New Zealand, specifically the obstacles that e-learning clusters of rural schools face in their journey to sustainability and maturity through the lens of the Ministry’s Learning Communities Online Handbook. Analysis of a nationwide purposeful sample identified three common barriers: a lack of a coherent vision; difficulty in sustaining necessary funding and resources; and of the need for more collaboration within and between clusters. Based on these findings, it is recommended that VLN e-learning clusters develop specific strategies to encourage greater collaboration between schools and work towards greater consistency between their activities, including professional and organisational development and also of the approaches to virtual learning

Steering transformations under climate change

In light of the persistent failure to reduce emissions decisively, facilitate long-term resilience against climate change and account for the connectedness of climate change with other social, environmental and economic concerns, we present a conceptual framework of capacities for transformative climate governance. Transformative climate governance enables climate mitigation and adaptation while purposefully steering societies towards low-carbon, resilient and sustainable objectives. The framework provides a systematic analytical tool for understanding and supporting the already ongoing changes of the climate governance landscape towards more experimental approaches that include multi-scale, cross-sectoral and public-private collaborations. It distinguishes between different types of capacities needed to address transformation dynamics, including responding to disturbances (stewarding capacity), phasing-out drivers of path dependency (unlocking capacity), creating and embedding novelties (transformative capacity) and coordinating multi-actor processes (orchestrating capacity). Our case study of climate governance in Rotterdam, the Netherlands, demonstrates how the framework helps to map the activities by which multiple actors create new types of conditions for transformative climate governance, assess the effectiveness of the capacities and identify capacity gaps. Transformative and orchestrating capacities in Rotterdam emerged through the creation of space and informal networks for strategic and operational innovation, which also propelled new types of governance arrangements and structures. Both capacities support stewarding and unlocking by integrating and mainstreaming different goals, connecting actors to each other for the development of solutions and mediating interests. Key challenges across capacities remain because of limited mainstreaming of long-term and integrated thinking into institutional and regulatory frameworks. As the ongoing changes in climate governance open up multiple questions about actor roles, effective governance processes, legitimacy and how effective climate governance in the context of transformations can be supported, we invite future research to apply the capacities framework to explore these questions

The Perception of Stress Pattern in Young Cochlear Implanted Children: An EEG Study

Children with sensorineural hearing loss may (re)gain hearing with a cochlear implant—a device that transforms sounds into electric pulses and bypasses the dysfunctioning inner ear by stimulating the auditory nerve directly with an electrode array. Many implanted children master the acquisition of spoken language successfully, yet we still have little knowledge of the actual input they receive with the implant and specifically which language sensitive cues they hear. This would be important however, both for understanding the flexibility of the auditory system when presented with stimuli after a (life-) long phase of deprivation and for planning therapeutic intervention. In rhythmic languages the general stress pattern conveys important information about word boundaries. Infant language acquisition relies on such cues and can be severely hampered when this information is missing, as seen for dyslexic children and children with specific language impairment. Here we ask whether children with a cochlear implant perceive differences in stress patterns during their language acquisition phase and if they do, whether it is present directly following implant stimulation or if and how much time is needed for the auditory system to adapt to the new sensory modality. We performed a longitudinal ERP study, testing in bimonthly intervals the stress pattern perception of 17 young hearing impaired children (age range: 9–50 months; mean: 22 months) during their first 6 months of implant use. An additional session before the implantation served as control baseline. During a session they passively listened to an oddball paradigm featuring the disyllable “baba,” which was stressed either on the first or second syllable (trochaic vs. iambic stress pattern). A group of age-matched normal hearing children participated as controls. Our results show, that within the first 6 months of implant use the implanted children develop a negative mismatch response for iambic but not for trochaic deviants, thus showing the same result as the normal hearing controls. Even congenitally deaf children show the same developing pattern. We therefore conclude (a) that young implanted children have early access to stress pattern information and (b) that they develop ERP responses similar to those of normal hearing children

The Role of Negotiation in Privacy-Enhanced E-Commerce Transactions

Online vendors use personal information to deliver customized services efficiently to their customers. Both users and vendors value the relationship building made possible using personal data. However, the use of personally identifying data gives rise to the potential for privacy invasion. When consumers must disclose personal information, they are forced to perform a risk-benefit analysis in which the risks of disclosing one\u27s personal information are weighted against the potential benefits of the disclosure. While some researchers note that consumers maximize benefits in deciding whether to disclose personal information, others argue that consumers lack sufficient information and power to make educated, balanced decisions regarding disclosing their private information. We add to the privacy discussion by arguing that a real negotiation position for both parties can help realize the full benefits of online personalization. We propose a model for mitigating the tension between the benefits of personalization and the risks to privacy invasion. This framework informs our future work which seeks to develop rich and deep understandings of negotiated, privacy-concerned personalization

Identifying Inconsistencies and Reporting Deficits in Therapeutic Massage and Bodywork (TMB) Case Reports: A Systematic Review and TMB Adapted CAse REport (CARE) Guidelines Audit

poster abstractIntroduction: Case reports are a fundamental tool through which practitioners in applied disciplines are able to inform research and impact their field by detailing the presentation, treatment, and follow-up of a single individual they’ve encountered in practice. Ideally, published case reports contribute to reductions in the research/practice gap by allowing practitioners to describe current practice situations and outcomes to researchers. Unfortunately, inconsistencies in case reporting across applied disciplines have limited the impact of these fundamental sources of clinical evidence. In 2013, reporting guidelines for case reports (CARE guidelines) were published to standardize the reporting of medical case reports. In recognition of discipline differences and reporting needs, the therapeutic massage and bodywork (TMB) adapted CARE guidelines were published in late 2014 to specifically guide reporting of case reports involving massage therapy applied as a treatment. The TMB adapted CARE guidelines identified 5 primary case report components (pre-manuscript, Introduction, Case Presentation, Results, and Discussion), each with unique subcomponents (e.g., title, keywords, abstract for the pre-manuscript component) ranging in number from 6 - 31. By checking off each component and subcomponent included in any given case report, a summary score for TMB adapted CARE guidelines compliance (range: 0 – 65) can be derived. In order to determine whether the consistency of TMB case reporting is improved after publication of the TMB adapted CARE guidelines, a pre-guideline state of TMB case reports is needed. The current study seeks to provide rich descriptive statistics about the state of TMB related case reports in the literature prior to 2015. Methods: A systematic review using PubMed and CINAHL databases identified 935 unique citations using first the MeSH term “Therapy, Soft Tissue” as the subject heading and publication type “case reports” and then a keyword search in PubMed (acupressure, shiatsu, zhi ya, chih ya, reflexology, rolfing, bodywork, massage, case report, case reports, case study, case studies NOT carotid sinus massage, heart massage, cardiac massage, animals) and CINAHL (subject headings: massage therapists, massage, reflexology, case study). Study inclusion/exclusion criteria required: case report, human, English, peer-reviewed, published prior to 2015. Administered massage treatment(s) had to have been from a professional TMB practitioner who had a role in the case’s reporting and publication. N=34 articles met inclusion criteria and were reviewed by two independent reviewers. Through a REDCap data collection form, components and subcomponents of the TMB adapted CARE reporting guidelines included in each article were identified. Variable coding and descriptive statistics were completed using SAS 9.3 by a non-reviewing team member. TMB adapted CARE reporting compliance scores were determined for each case report. Results: Preliminary results for n=30 (final presentation to include all N=34) indicate mean compliance scores = 40.3 (±9.2) and ranged from 10-50. Article sections with the most robust scoring included pre-manuscript items and introduction with average section scores obtaining 75% and 70% of the possible points, respectively. Case presentation and results sections scored the poorest, obtaining an average of 58% and 53% of the possible points, respectively. Conclusions: Case reports in the TMB field published before possible exposure to the TMB adapted CARE guidelines demonstrate inconsistent and deficient reporting. If case reports in the TMB field are to have an impact, consistent and rigorous reporting must be adopted. In an effort to improve the state and impact of TMB case reports in the literature, TMB practitioners should use the TMB adapted CARE guidelines as a checklist when preparing their case reports for publication

UJI LAIK FUNGSI JALAN SECARA TEKNIS PADA RUAS JALAN MANADO – TOMOHON (SEGMEN BATAS KOTA MANADO – KOTA TOMOHON)

Ruas Jalan Nasional Batas Kota Manado – Kota Tomohon merupakan salah satu akses jalan utama yang menghubungkan kedua kota tersebut dan daerah sekitarnya. Tujuan penelitian ini  adalah untuk menganalisis tingkat kelaikan fungsi jalan serta perbaikan yang diperlukan agar jalan menjadi laik menurut Uji Laik Fungsi Jalan (ULFJ) berdasarkan Peraturan Menteri Pekerjaan Umum nomor.11/PRT/M/2010. Uji laik fungsi jalan adalah kondisi suatu ruas jalan yang memenuhi persyaratan teknis kelaikan jalan untuk memberikan keselamatan bagi penggunanya, dan persyaratan administratif yang memberikan kepastian hukum bagi penyelenggara jalan dan pengguna jalan, sehingga jalan tersebut dapat dioperasikan untuk umum. Analisis uji laik fungsi teknis jalan dilakukan dengan mengukur penyimpangan (deviasi) terhadap kondisi lapangan terhadap standar teknis setiap komponen teknis, meliputi: teknis geometrik jalan, teknis struktur perkerasan jalan, teknis struktur bangunan pelengkap jalan, teknis pemanfaatan ruang bagian-bagian jalan, teknis penyelenggaraan manajemen dan rekayasa lalu lintas, dan teknis perlengkapan jalan. Hasil dari penelitian ini menunjukkan bahwa pada ruas jalan Batas Kota Manado – Kota Tomohon termasuk dalam kategori laik fungsi dengan perbaikan teknis yang harus dipenuhi (LS). Perbaikan teknis yang harus dipenuhi pada ruas jalan tersebut berupa pemeliharaan rutin dan pengadaan komponen jalan yang belum ada, agar supaya ruas jalan Batas Kota Manado – Kota Tomohon dapat menjadi laik fungsi. Kata Kunci : Laik Fungsi, Standar Teknis, Ruas Jalan, Perbaika