Like a Melody It Passes: Dasein and Perinatal Well-being

Abstract In this paper, the text found in Johannes Brahms’ Wie Melodien Zieht Es (Like a Melody It Passes) serves as a metaphor for selected key ideas that comprise Heidegger’s Being and Time. Heidegger’s conceptualization of Dasein (including Being and Temporality) are examined in the context of the poetry and applied to understandings of maternal emotional well-being. There is potential for increased insight based on analysis of these selected key concepts, which are described and related to the experience of becoming a mother. There is also significance in examining birthing because of current realities involved in Maternity Care, which include  standardized approaches to care. The poetry of Wie Melodien Zieht Es guides the flow of ideas that are outlined during the paper. The need for enhanced authentic interactions between nurses and women in the peri-natal period is exposed, engaging Heideggerian thought as a framework for possible enlightenment.             Â

My Life Flashed Before My Eyes

The everyday experience of time can be disrupted by the events in our lives, and disquiet notions of predictability about the passage of time. In this work, I describe an alternate experience of time passing that occurred in the context of a car accident. The phrase "I saw my life flash before my eyes" situates the varietal experience of time in human existence, and invites the use of chosen hermeneutic tenets to explore the phenomena. I describe the mysterious personal experience of time associated with the accident, as well as varietal experiences of time that occur for people during hospitalization, relating to experiences of nursing practice. The  tension associated with the temptation to apply scientific explanations to metaphysical questions, and the inevitability of accepting ongoing wonder about the mysteries of time, are featured throughout

Exploring social-ecological trade-offs in fisheries using a coupled food web and human behavior model

Marine fisheries represent a social-ecological system driven by both complex ecological processes and human interactions. Ecosystem-based fisheries management requires an understanding of both the biological and social components, and management failure can occur when either are excluded. Despite the significance of both, most research has focused on characterizing biological uncertainty rather than on better understanding the impacts of human behavior because of the difficulty of incorporating human behavior into simulation models. In this study, we use the fisheries in Narragansett Bay (Rhode Island, USA) as a case study to demonstrate how coupled modeling can be used to represent interactions between the food web and fishers in a social-ecological system. Narragansett Bay holds both a commercial fishery for forage fish, i.e., Atlantic menhaden (Brevoortia tyrannus) and a recreational fishery for their predators, i.e. striped bass (Morone saxatilis) and bluefish (Pomatomus saltatrix). To explore trade-offs between these two fisheries, we created a food web model and then coupled it to a recreational fishers’ behavior model, creating a dynamic social-ecological representation of the ecosystem. Fish biomass was projected until 2030 in both the stand-alone food web model and the coupled social-ecological model, with results highlighting how the incorporation of fisher behavior in modeling can lead to changes in the ecosystem. We examined how model outputs varied in response to three attributes: (1) the forage fish commercial harvest scenario, (2) the predatory (piscivorous) fish abundance-catch relationship in the recreational fishery, and (3) the rate at which recreational fishers become discouraged (termed “satisfaction loss”). Higher commercial harvest of forage fish led to lower piscivorous fish biomass but had minimal effects on the number of piscivorous fish caught recreationally or recreational fisher satisfaction. Both the abundance-catch relationship and satisfaction loss rate had notable effects on the fish biomass, the number of fish caught recreationally, and recreational fisher satisfaction. Currently, the lack of spatial and location-specific fisher behavior data limits the predictive use of our model. However, our modeling framework shows that fisher behavior can be successfully incorporated into a coupled social-ecological model through the use of agent-based modeling, and our results highlight that its inclusion can influence ecosystem dynamics. Because fisher decision making and the ecosystem can influence one another, social responses to changing ecosystems should be explicitly integrated into ecosystem modeling to improve ecosystem-based fisheries management efforts

Providing Culturally Competent Care in the Face of Health Disparities: Assessment and Training Recommendations

Background: Community health centers are a critical source of care for populations who disproportionally experience health disparities, including the uninsured and underinsured, racial and ethnic minorities, and patients with a preferred language other than English. Optimus Health Care (Optimus) is the second largest health center in Connecticut, with clinics located in Bridgeport and Stamford. Cultural competency, or a set of behaviors, attitudes, and policies that enable professionals to work effectively in cross-cultural situations holds immense potential for improving patient-physician communication and for providing effective service delivery. Objectives: This study sought to (1) better understand the barriers to care faced among patients at Optimus (2) assess staff knowledge, attitudes, and skills regarding cultural competency to make recommendations regarding future cultural competency staff trainings. Methods: Electronic medical records (EMR) of patients seen at Optimus between January 2012 and March 2013 who had a diagnosis of hyperlipidemia, hypertension, and/or diabetes were analyzed to describe characteristics related to insurance status, race/ethnicity, primary language, age, gender, and clinic location. A web-based survey was developed based on the Cultural Competence Self-Assessment Questionnaire (CCSAQ) and distributed electronically to Optimus staff. Survey results were analyzed to compare responses according to staff position type and themes were examined among respondent assessments of the current cultural competency trainings provided by Optimus. Results: The majority of patients included in the EMR analysis receive Medicare or Medicaid (75.8%) and the majority of chronic conditions among the sample were among racial and ethnic minorities. Interestingly, the majority of Optimus patients with a diagnosis of diabetes, hypertension and/or hyperlipidemia were between the ages of 30-54. Cultural Competency survey respondents noted difficulties in providing care due to language barriers, limited knowledge of intra-cultural group differences, and limited knowledge of how the causes of mental health are viewed by different cultural groups (Survey response rate: 22.4%). When asked to critique Optimus’ current cultural competency training, staff members reported efficiency as a strength and lack of applicability to a practical setting as a weakness, emphasizing the need for an interactive training. Conclusions and Recommendations: In concordance with the national trend, the results of our study indicate that Optimus patients of racial and ethnic minorities are disproportionally affected by chronic illness. Several areas were identified that can be targeted for improving the cultural competency knowledge, practice and delivery, and training needs of Optimus staff. Future studies should assess patient perceptions of cultural competency to allow for further insight into this emerging area of research.https://elischolar.library.yale.edu/ysph_pbchrr/1041/thumbnail.jp

Reviews

The following publications have been reviewed by the authors; Programmes of Study for Design & Technology - Reviewed by Jim PattersonManaging Design & Technology in the National Curriculum - Reviewed by David DickinsonFocus on Technology - Reviewed by Ian McLintockAccommodating Technology in Schools - Reviewed byJ.R. MathiasDesigning and Making - Reviewed by Paul SpencerTreasury of Historic Pattern and Design - Reviewed by Geoff SmithDesign & Technology in Process - Reviewed by Jonty CrockettTechnology Through Home Economics - Reviewed by Rhona HumphriesThe Soft Toy Workshop - Reviewed by Margaret Jeavons02 PAGES (Quarterly) - Reviewed by AIf MerricksAdventures in Technology - Reviewed by John EvansDesigning Starts here - Reviewed by Trevor TaylorTechnology Shaping Our World - Reviewed by Alan TruemanIntroducing Design: Technology Across the Curriculum - Reviewed by Norman CassonThe Tapestry Makers - Reviewed by Goeff SmithWoodcut with Rigby Graham - Reviewed by John Lancaste

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood–Onset Retinal Dystrophy

PurposeTo provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.DesignNonrandomized, multicenter clinical trial.ParticipantsEight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood–onset retinal degeneration (SECORD).MethodsPatients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.Main Outcome MeasuresThe primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.ResultsAll patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.ConclusionsTreatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns

5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from years 1-5 in these same patients without any additional recombinant adeno-associated virus serotype-1 alpha-1 antitrypsin vector administration. In addition, we observed partial correction of disease-associated neutrophil defects, including neutrophil elastase inhibition, markers of degranulation, and membrane-bound anti-neutrophil antibodies. There was also evidence of an active T regulatory cell response (similar to the 1 year data) and an exhausted cytotoxic T cell response to adeno-associated virus serotype-1 capsid. These findings suggest that muscle-based alpha-1 antitrypsin gene replacement is tolerogenic and that stable levels of M-AAT may exert beneficial neutrophil effects at lower concentrations than previously anticipated

Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results

Recombinant adeno-associated virus (rAAV) vectors offer promise for the gene therapy of α(1)-antitrypsin (AAT) deficiency. In our prior trial, an rAAV vector expressing human AAT (rAAV1-CB-hAAT) provided sustained, vector-derived AAT expression for \u3e1 year. In the current phase 2 clinical trial, this same vector, produced by a herpes simplex virus complementation method, was administered to nine AAT-deficient individuals by intramuscular injection at doses of 6.0×10(11), 1.9×10(12), and 6.0×10(12) vector genomes/kg (n=3 subjects/dose). Vector-derived expression of normal (M-type) AAT in serum was dose dependent, peaked on day 30, and persisted for at least 90 days. Vector administration was well tolerated, with only mild injection site reactions and no serious adverse events. Serum creatine kinase was transiently elevated on day 30 in five of six subjects in the two higher dose groups and normalized by day 45. As expected, all subjects developed anti-AAV antibodies and interferon-γ enzyme-linked immunospot responses to AAV peptides, and no subjects developed antibodies to AAT. One subject in the mid-dose group developed T cell responses to a single AAT peptide unassociated with any clinical effects. Muscle biopsies obtained on day 90 showed strong immunostaining for AAT and moderate to marked inflammatory cell infiltrates composed primarily of CD3-reactive T lymphocytes that were primarily of the CD8(+) subtype. These results support the feasibility and safety of AAV gene therapy for AAT deficiency, and indicate that serum levels of vector-derived normal human AAT \u3e20 μg/ml can be achieved. However, further improvements in the design or delivery of rAAV-AAT vectors will be required to achieve therapeutic target serum AAT concentrations

A Case Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic and Tractable Biomarkers in Male Breast Cancer

Purpose: Breast cancer (BC) affects both genders, but is understudied in men. Although still rare, male BC is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental design: A transcriptomic investigation of male and female BC was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n=477, training; n=220, validation set) and quantified in pre- and post-treatment samples from a male BC patient receiving Everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were up-regulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (Log rank; p=0.013; HR=1.77, 1.12-2.8 and p=0.035; HR=1.68, 1.03-2.74, respectively), or when co-expressed (p=0.01; HR=2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis (eIF4E p=0.016; HR 2.38 (1.18-4.8), eIF5 p=0.022; HR 2.55 (1.14-5.7); co-expression p=0.001; HR=7.04 (2.22-22.26)). Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/Everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in male BC patients overexpressing eIF4E and eIF5. With mTOR inhibitors which target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required