Bridging the Gap: Selected Works and TopScholar Galleries

Higher education’s scholars utilize online catalogs and library finding aids with ease. However, for the larger community, accessing scholars’ Selected Works and online galleries with topical themes is a helpful intermediary step. Non-scholars often explore and produce scholarship, seek out obscure online sources and gladly volunteer to document cultural resources.Every day historically valuable ephemera is thrown away due to an ignorance of its value to research. Special Collections Librarians partnering with Scholarly Communication Specialists utilize social media to create a gateway and make certain that taxpaying interested parties do not miss the wealth of primary sources compiled over centuries by librarians and archivists. We hope this ease of access to information will encourage casual researchers to support our academic efforts. It may also result in donations of unique letters, photographs, diaries, ephemera and inaccessible publications. The Special Collections galleries allow exhibits of unique photographs, ephemera, oral histories and manuscripts. Scholars create personal selected works sites to showcase individual research projects and collections. University faculty, teachers, adults, and amateur historians can use these accessible resources to gather information and create items to motivate, entertain or educate others. Technology created the door to Libraries via KenCat and TopScholar. Now the galleries and Selected Works throw open wide resources for all

Best practice for analysis of shared clinical trial data

BACKGROUND: Greater transparency, including sharing of patient-level data for further research, is an increasingly important topic for organisations who sponsor, fund and conduct clinical trials. This is a major paradigm shift with the aim of maximising the value of patient-level data from clinical trials for the benefit of future patients and society. We consider the analysis of shared clinical trial data in three broad categories: (1) reanalysis - further investigation of the efficacy and safety of the randomized 3 intervention, (2) meta-analysis, and (3) supplemental analysis for a research question that is not directly assessing the randomized intervention. DISCUSSION: In order to support appropriate interpretation and limit the risk of misleading findings, analysis of shared clinical trial data should have a pre-specified analysis plan. However, it is not generally possible to limit bias and control multiplicity to the extent that is possible in the original trial design, conduct and analysis, and this should be acknowledged and taken into account when interpreting results. We highlight a number of areas where specific considerations arise in planning, conducting, interpreting and reporting analyses of shared clinical trial data. A key issue is that that these analyses essentially share many of the limitations of any post hoc analyses beyond the original specified analyses. The use of individual patient data in meta-analysis can provide increased precision and reduce bias. Supplemental analyses are subject to many of the same issues that arise in broader epidemiological analyses. Specific discussion topics are addressed within each of these areas. SUMMARY: Increased provision of patient-level data from industry and academic-led clinical trials for secondary research can benefit future patients and society. Responsible data sharing, including transparency of the research objectives, analysis plans and of the results will support appropriate interpretation and help to address the risk of misleading results and avoid unfounded health scares

Patient safety in dentistry: development of a candidate 'never event' list for primary care

Introduction The 'never event' concept is often used in secondary care and refers to an agreed list of patient safety incidents that 'should not happen if the necessary preventative measures are in place'. Such an intervention may raise awareness of patient safety issues and inform team learning and system improvements in primary care dentistry. Objective To identify and develop a candidate never event list for primary care dentistry. Methods A literature review, eight workshops with dental practitioners and a modified Delphi with 'expert' groups were used to identify and agree candidate never events. Results Two-hundred and fifty dental practitioners suggested 507 never events, reduced to 27 distinct possibilities grouped across seven themes. Most frequently occurring themes were: 'checking medical history and prescribing' (119, 23.5%) and 'infection control and decontamination' (71, 14%). 'Experts' endorsed nine candidate never event statements with one graded as 'extreme risk' (failure to check past medical history) and four as 'high risk' (for example, extracting wrong tooth). Conclusion Consensus on a preliminary list of never events was developed. This is the first known attempt to develop this approach and an important step in determining its value to patient safety. Further work is necessary to develop the utility of this method

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effectiveness. Our main research goals are first to explore if SMEs should focus on their their development process effectiveness rather than on their product concept effectiveness to achieve high NPD performance; and second, to explore whether a shared pattern in the organization of the NPD function can be recognized to affect NPD performance positively. The medical devices sector in Spain is used as an example of a\ud highly regulated sector. A structured survey among 11 SMEs, of which 2 were studied also as in in-depth case studies, led to the following results. First of all, indeed the companies in the dataset which focused on the effectiveness of their development process, stood out in NPD performance. Further, the higher performing companies did have a number of commonalities in the organisation of their NPD function: 1) The majority of the higher performing firms had an NPD strategy characterized by a predominantly incremental project portfolio.\ud 2) a) Successful firms with an incremental project portfolio combined this with a functional team structure b) Successful firms with a radical project portfolio combined this with a heavyweight or autonomous team structure.\ud 3) A negative reciprocal relationship exists between formalization of the NPD processes and the climate of the NPD function, in that a formalized NPD process and an innovative climate do not seem to reinforce each other. Innovative climate combined with an informal NPD process does however contribute positively to NPD performance. This effect was stronger in combination with a radical project portfolio. The highest NPD performance was measured for companies focusing mainly on incremental innovation. It is argued that in highly regulated sectors, companies with an incremental product portfolio would benefit from employing a functional structure. Those companies who choose for a more radical project portfolio in highly regulated sectors should be aware\ud that they are likely to excell only in the longer term by focusing on strategic flexibility. In their NPD organization, they might be well advised to combine informal innovation processes with an innovative climate

Evolving narratives on signal functions for monitoring maternal and newborn health services: A meta-narrative inspired review

Emergency obstetric care (EmOC) signal functions are a shortlist of key clinical interventions capable of averting deaths from the five main direct causes of maternal mortality; they have been used since 1997 as a part of an EmOC monitoring framework to track the availability of EmOC services in low- and middle-income settings. Their widespread use and proposed adaptation to include other types of care, such as care for newborns, is testimony to their legacy as part of the measurement architecture within reproductive health. Yet, much has changed in the landscape of maternal and newborn health (MNH) since the initial introduction of EmOC signal functions. As part of a project to revise the EmOC monitoring framework, we carried out a meta-narrative inspired review to reflect on how signal functions have been developed and conceptualised over the past two decades, and how different narratives, which have emerged alongside the evolving MNH landscape, have played a role in the conceptualisation of the signal function measurement. We identified three overarching narrative traditions: 1) clinical 2) health systems and 3) human rights, that dominated the discourse and critique around the use of signal functions. Through an iterative synthesis process including 19 final articles selected for the review, we explored patterns of conciliation and areas of contradiction between the three narrative traditions. We summarised five meta-themes around the use of signal functions: i) framing the boundaries; ii) moving beyond clinical capability; iii) capturing the woods versus the trees; iv) grouping signal functions and v) measurement challenges. We intend for this review to contribute to a better understanding of the discourses around signal functions, and to provide insight for the future roles of this monitoring approach for emergency obstetric and newborn care

Identification of HIV-1 Epitopes that Induce the Synthesis of a R5 HIV-1 Suppression Factor by Human CD4+ T Cells Isolated from HIV-1 Immunized Hu-PBL SCID Mice

We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4+ T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vitro and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4+ but not CD8+ T cells. Human CD4+ T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4+ T cells. Aliquots of these re-stimulated CD4+ T cells were then co-cultured with similar APC's that were previously pulsed with 10 μg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-Υ. The data presented herein show that the HIV-1 primed CD4+ T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4+ T cells. Simultaneous production of human interferon (IFN)-Υ was observed in some cases. These results indicate that human CD4+ T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4+ T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1