Youth Transitions Advisory Council Annual Report 2020

https://digitalcommons.memphis.edu/govpubs-tn-youth-transitions-advisory-council/1002/thumbnail.jp

Pathways to a Sustainable Community Health Worker Program in a Rural Native American Community

Introduction: American Indian/Alaska Native (AI/AN) people have some of the greatest health disparities of any other citizen group in the U.S. (National Indian Health Board [NIHB], 2018). As liaisons between community members and health services, community health workers (CHWs) play an important role in reducing disparities in AI/AN communities (Indian Health Service [IHS], 2018). CHWs in the organization of interest are not being used to their full potential as the documentation of their care is not accessible to the primary care providers (PCPs) for care coordination and the program is threatened by issues related to sustainability. Objectives: The purpose of this project was to develop a strategic plan to increase efficiency and sustainability of a CHW program located in a rural Native American community in the Midwest U.S. The long-term goals of this project are to improve care coordination and program sustainability. Methods: The Cultural Care Theory and Pathways HUB Model guided development of this project. The overall project is a multi-phase quality improvement project involving replication of the Pathways Community HUB model in the target organization. The proposed project will be conducted in multiple phases including strategic planning, implementation, and evaluation. Results: This project represents the first phase of the overall project, which is was the development and delivery of a strategic plan to guide implementation of the proposed practice changes. Implications: It is anticipated that the implementation of an evidence-based model of care coordination will increase CHW documentation completion rates and provide a standardized measurement tool to efficiently evaluate patient outcomes and CHW performance. It is also expected that there will be better communication and care coordination across multiple health and social services, thereby increasing efficiency, quality of care, and sustainability of the target organization’s CHW program

COMPARISON OF THE TIMES TO EXHAUSTION, PHYSIOLOGICAL, PERCEPTUAL, AND NEUROMUSUCLAR RESPONSES DURING CONSTANT HEART RATE, CONSTANT VO2, AND CONSTANT POWER EXERCISE

The purposes of this study were to: 1) Determine if there are differences in the sustainability of exercise when anchored at critical heart rate (CHR), the VO2 associated with CHR (VO2CHR), or the power output associated with CHR (PCHR); 2) examine the patterns of responses in power output, metabolic (heart rate [HR], VO2, respiration rate [RR]), neuromuscular (electromyographic [EMG] amplitude [AMP], mean power frequency [MPF], mechanomyographic [MMG] AMP and MPF, perceptual (rating of perceived exertion [RPE]), and muscle oxygenation responses (%SmO2) during exercise anchored by HR, VO2, and power output; and 3) determine if the CHR can be used for exercise prescription based on time to exhaustion (TLim), physiological, perceptual, and neuromuscular responses. Six, moderately trained, subjects performed a graded exercise test (GXT). On separate days, 4 constant power output trials were performed in a randomized order at 85%, 90%, 95%, and 100% of the peak power output (PPO) determined from the GXT. The total number of heart beats (HBLim) for each power output was calculated as the product of the average 5-second HR and TLim for each constant power output trial. The CHR was defined as the slope of the linear regression of the HBLim versus TLim relationship. The VO2CHR was derived from the linear regression equation of the VO2 versus HR relationship from the GXT where VO2CHR was defined as the VO2 corresponding to CHR. Similarly, the PCHR was derived from the linear regression of the power output versus HR relationship from the GXT where the PCHR was defined as the power output corresponding to CHR. The physiological, perceptual, and neuromuscular responses were recorded during trials at CHR, VO2CHR, and PCHR. Polynomial regression analyses were used to examine the patterns of responses for all variables. The HBLim versus TLim (r2 = 0.9946-0.9995), the VO2 versus HR (r2 = 0.8833 – 0.9899), and the power output versus HR (r2 = 0.9600 – 0.9886) relationships were highly linear. The CHR (170 ± 9 beats×min-1, 91 ± 5% HRmax), VO2CHR (31.55 ± 7.85 mL×kg-1×min-1, 81± 10% O2peak), and PCHR (199 ± 70 Watts, 75 ± 11% PPO) were maintained for 46.28 ± 18.49, 28.93 ± 24.41, 22.60 ± 21.61 min, respectively. At CHR, there was no change in HR, quadratic decreases in VO2 (R2 = 0.976) and power output (R2 = 0.900), quadratic increases in RR (R2 = 0.590), EMG MPF (R2 = 0.986), and MMG MPF (R2 = 0.739), linear increases in RPE (r2 = 0.960), %SmO2 (r2 = 0.940), and MMG AMP (r2 = 0.921), and linear decreases in EMG AMP (r2 = 0.935). At VO2CHR, there was no change in EMG AMP, MMG AMP, and MMG MPF, quadratic decreases in power output (R2 = 0.810), quadratic increases in RPE (R2 = 0.964), linear decreases in VO2 (r2 = 0.580) (despite VO2start = 31.15 mL×kg-1×min-1 not being different from VO2end = 30.85 mL×kg-1×min-1), and linear increases in HR (r2 = 0.860, RR (r2 = 0.940), %SmO2 (r2 = 0.390), and EMG MPF (r2 = 1.000). At PCHR, there was no change in power output, and MMG AMP, quadratic decreases in EMG MPF (R2 = 0.700), quadratic increases in VO2 (R2 = 0.839), HR (R2 = 0.960), and RPE (R2 = 0.996), linear increases in RR (r2 = 0.990), and EMG AMP (r2 = 0.500), and linear decreases in %SmO2 (r2 = 0.720), and MMG MPF (r2 = 0.547). These findings indicated the CHR was more sustainable than VO2CHR and PCHR, and may provide a suitable stimulus for cardiorespiratory endurance training

Youth Transitions Advisory Council Annual Report 2019

https://digitalcommons.memphis.edu/govpubs-tn-youth-transitions-advisory-council/1003/thumbnail.jp

Why is Learning from National Working Life Programmes not a Matter of Course?

"Public policy programmes in the field of working life reforms may be needed, but they cannot do more than supplement the genuine dynamics of the working life. They can influence people’s perceptions of the problems and the work forms applied in organizing development. Power relations in private and public organizations, as results of business and societal trends, are obstacles to innovative and anthropocentric oriented reforms in working life. The more participative elements funded projects have been integrated, the more robust are their outcomes. National programme structures have to strive for the establishment of persistent local-level development coalitions, and to support collaboration of all actors concerned in development processes. International networking is possibly a learning facilitator. The implementation of, and learning from, reform programmes from the 1970s to our time is analyzed, with a focus on personal experiences from research, project management and evaluation of Scandinavian and German programmes." (author's abstract

Youth Transitions Advisory Council 2021 Annual Report

https://digitalcommons.memphis.edu/govpubs-tn-youth-transitions-advisory-council/1001/thumbnail.jp

Progress in upscaling Miscanthus biomass production for the European bio-economy with seed-based hybrids

Funded by UK's Biotechnology and Biological Sciences Research Council (BBSRC) Department for Environment, Food and Rural Affairs (DEFRA). Grant Number: LK0863 BBSRC strategic programme Grant on Energy Grasses & Bio-refining. Grant Number: BBS/E/W/10963A01 OPTIMISC. Grant Number: FP7-289159 WATBIO. Grant Number: FP7-311929 Innovate UK/BBSRC ‘MUST’. Grant Number: BB/N016149/1Peer reviewedPublisher PD

Sustaining local level development: What worked and what did not. Lessons from the phasing-out of Norwegian aid to the Hambantota Integrated Rural Development Programme (HIRDEP), Sri Lanka 1992 to 1999

Aid has been successful when it is no longer needed, but we all too often see how aid breeds dependency, and how both donors and recipients have difficulties preparing for termination of the relationship. This is a study of a case of planned phasing-out. Commissioned by the Norwegian Agency for Development Cooperation (NORAD) and the Ministry of Southern Area Development, Government of Sri Lanka, it summarises the main experiences and lessons from twenty years of cooperation in the Hambantota District with a focus on the last phase from 1992 to 1999. The study looks at two broad themes. Firstly, how were the achievements of HIRDEP in building a more responsive public sector sustained within a changing government structure? And secondly, how did HIRDEP contribute to the new policies of the 1990s of strengthening economic growth, and, in particular, promote institutions able to create economic opportunities for the poor? The phasing-out did not go as initially planned. The scalingdown of HIRDEP’s expenditure was not gradual. It first peaked and then nose-dived, which indicate that the HIRDEP-organisation tried to sustain a high level of activity as long as possible. Moreover, NORAD changed the policy course mid-way as new political concerns were brought into the picture – especially private sector development. With the faltering local government reform, it turned out that the new divisions were not capable of replicating and sustaining the development approaches pioneered by HIRDEP. In general, capacity building in public institutions could only be sustained where other financial resources filled some of the vacuum after the withdrawal of HIRDEP. Probably the most lasting impact of HIRDEP will be its efforts in institution building at the grassroots, related to microcredit and the management of local infrastructure – irrigation, drinking water supply, community centres etc. HIRDEP’s attempt to establish new small-scale industries, by-and-large, failed, while its role as a midwife to the birth of Hambantota District Chamber of Commerce is a remarkable success. Twenty years of HIRDEP has demonstrated the virtues of having a development catalyst at sub-national level, and the authors make a strong plea for making use of this experience when, at this juncture, government and donors are preparing for reconstruction and development in the war-torn parts of the island

안전항구 위치에 생체 내 넉인을 이용한 새로운 유전자치료 플렛폼

학위논문 (석사) -- 서울대학교 대학원 : 국제농업기술대학원 국제농업기술학과, 2020. 8. 염수청.As part of efforts to treat the genetic disorder, there have been many advances in the field of in vivo genome editing. However, the low editing efficiency due to technical problems acts as a limitation directly repairing the mutant gene. Thus, I tried to develop a novel gene-editing strategy for curing genetic disorders using knock-in (KI) into safe harbor locus, which exhibited high expression in the liver. Based on the microarray experiment using human hepatocyte, the Apoc3 gene was selected as the locus for KI. A portion of the human Apoc3 gene, which was harboring highly efficient sgRNA binding site of spCas9 and cjCas9, was used to generate genetically human-mimicking animals. B6.Apoc3-hApoc3 KI mice exhibited high gene expression in the liver (300 folds more elevated than the F9 gene) and no alternative splicing. Besides, hemophilia B was selected as a genetic disease to be treated using in vivo gene editing. The hemophilia B model mouse is generated through the deletion of the coagulation factor 9 gene using CRISPR/Cas9 and had a phenotype of clotting disorder similar to hemophilia B patients. After mouse production, three strategies for in vivo therapeutic gene KI into Apoc3 were applied using adeno-associated virus packing CRISPR/cas9 and donor template. First, the homologous recombination strategy was founded to be a failure due to donor auto-expression and extremely low KI efficiency. However, NHEJ mediated KI (HITI or AAV mediated integration) presented human F9 concentration (about 50, 250ng/ml at six weeks after injection) without donor's auto-expression. In conclusion, the model mice for in vivo genome editings such as mApoc3-hApoc3 KI and F9 KO were produced. In the attempts of in vivo genome editing, some indicators presenting the low KI efficiency were found through PCR and ELISA. To increase KI efficiency, a high dose experiment is on-going.유전장애를 치료하는 노력의 일환으로 많은 증상을 환화하기 위한 방법들이 있으나, 주기적인 투여로 인해 환자의 불편 및 경제적 부담을 유발합니다. 이러한 문제점을 해결하기 위한, 생체 내 게놈 편집 분야의 많은 발전에도 불구하고, 여전히 편집 효율이 매우 낮아서 돌연변이 유전자를 직접적으로 수리하는 것에 어려움을 겪고 있습니다. 따라서, 앞선 한계점을 해결하기 위해서 간에서 높은 발현량을 나타내는 안전 항만 좌위로 치료유전자를 녹인하는 전략을 사용하여, 유전장애를 치료하기 위한 새로운 유전자 편집 전략을 개발하려고 노력하였습니다. 인간 간세포를 사용한 마이크로 어레이 실험의 결과를 토대로, 매우 높은 발현량을 가진 Apoc3 유전자가 치료 유전자를 삽입하기 위한 장소로 선택하였습니다. 그러나, 이러한 정보들은 사람에서 유래된 것이기 때문에 바로 동물실험에 적용하기에 적합하지 않았습니다. 사람의 Apoc3 유전자 내에서도, spCas9 및 cjCas9을 위한 높은 효율의 sgRNA 결합 부위를 함유하는 염기서열을 마우스 게놈내로 삽입하여, 유전적으로 인간-모방 마우스를 생산하였습니다. 생산된 B6.Apoc3-hApoc3 KI 마우스 간에서 Apoc3가 질병원인 유전자들보다 40-300배 높은 것을 알 수 있었고, 인간 염기서열의 넉인은 Apoc3의 대안적인 스플라이싱을 유발시키지 않았습니다. 이러한 B6.Apoc3-hApoc3 KI 마우스를 이용하여, 생체 내 편집 기술을 통해 치료할 유전질환은 혈우병 B입니다. 혈우병 B 마우스는 CRISPR/Cas9을 사용하여 응고인자 9 유전자의 결실을 통해 생산되었으며, 혈우병 환자와 비슷한 표현형을 나타내었습니다. 2가지의 모델 마우스의 생산 이후에, CRISPR 및 공여자 주형을 표적세포에 도입시키기 위해서 아데노 관련 바이러스를 치료 유전자의 넉인 전략에 사용하였습니다. 3가지의 전략중에 첫번째 시도에서, 동종 재조합 전략은 매우 낮은 넉인 효율과 공여자 주형에서 발견된 자동발현 문제로 인해 넉인의 증거를 확인할 수 없었습니다. 그러나, 2가지 비동종 말단 연력을 이용한 전략에서는 공여자 주형에서 자동-발현이 없는 발견되지 않았고, 약간의 긍정적인 결과를 얻을 수 있었습니다. 그러나 이 또한 낮은 발현양상을 나타낸다는 문제점을 가지고 있었습니다. 결론적으로 B6.Apoc3-hApoc3 KI 및 B6.F9 KO과 같은 생체 내 게놈 편집을 위한 모델 마우스의 생산에 성공하였고, 생체 내 게놈 편집을 시도하고 있습니다. 현재까지의 데이터에 따르면 낮은 효율로 인해 뚜렷한 넉인의 증거들을 얻지 못하였습니다. 이러한 넉인 효율을 높이기 위해 고용량 실험을 진행중에 있습니다.1. Literature review 1 1.1 Genetic disorder 1 1.2 Treatment for single-gene disorder 5 1.2.1 Plasma derivatives 5 1.2.2 Protein therapy 5 1.2.3 Gene transfer 6 1.3. genome editing 11 1.3.1 Ex vivo genome editing 15 1.3.2 in vivo genome editing 15 2. Introduction 16 3. Materials and methods 18 3.1 Animal 18 3.2 Preparation of sgRNA and ssODN 18 3.3 Animal production with CRISPR/cas9 22 3.4 RT-PCR and quantitative RT PCR 25 3.5 Blood chemistry 25 3.6 PT and aPTT analysis 27 3.7 In vivo bleeding test 27 3.8 Histology of Spleen in B6. F9 KO mouse 28 3.9 AAV-CRISPR and AAV-donor preparation 28 3.10 Human Coagulation Factor 9 ELISA 31 3.11 Statistical analysis 31 4. Result 32 4.1 Producing mice for a new in vivo genome editing strategy 32 4.2 B6 Apoc3hseq/hseq as a suitable model to mimic in vivo gene editing for human 36 4.3 Generation of a mouse model with factor 9 deficiency using CRISPR/Cas9 38 4.4 Similar hematological phenotype in B6.F9 KO with human hemophilia B patient 41 4.5 Extramedullary hematopoiesis and decreased survival rate in F9 KO mice 45 4.6 Effective transduction of AAV serotype 8 into the liver 48 4.7 Extremely low efficiency of homologous recombination-mediated in vivo gene KI 51 4.8 High cross-reactivity between human and mouse F9 56 4.9 Evidence of therapeutic gene expression in NHEJ mediated KI strategy 59 4.10 sustain effects of in vivo AAV8 NHEJ-mediated gene editing in B6. Apoc3hseq/hseq mouse 64 5. Discussion 68Maste

Youth Transitions Advisory Council 2022 Annual Report

https://digitalcommons.memphis.edu/govpubs-tn-youth-transitions-advisory-council/1000/thumbnail.jp