Impact of Biobanks on Research Outcomes in Rare Diseases：A Systematic Review

Rare diseases (RDs) are a global priority yet are still under researched. When combined, RDs are common, with individual diseases numbering approximately 5,000-8,000, equating to approximately 7% of the population in Europe. Extrapolating this figure for Australia suggests that about 1.2 million people are affected by RDs, with about 400,000 of those being children. The WA Rare Diseases Strategic Framework 2015-2018, the first strategy for rare diseases in Australia, recognises that in order to alleviate the significant burden of rare diseases, innovative translational tools that facilitate research into new diagnostic and therapeutic strategies should be given priority. Registries facilitate clinical, epidemiological, and post-marketing surveillance research for RD, collecting information from individuals with a particular disease, and storing these data in an organised system. Registries can lead to a greater understanding of the natural history of disease, consensus-driven treatment protocols, informed policy making and, in turn, improved patient outcomes. Despite these benefits, registries are limited in their capacity to conduct basic research, attributed to the fact that most registries do not collect and store patient and donor specimens appropriately to capture or preserve important biological information (such as DNA, RNA and proteins) for basic research, a prerequisite for translating scientific discoveries into diagnostic tools and therapies for clinical practice. Biobanks (BB) are gradually becoming more recognised as invaluable tools to drive basic and translational research for RDs. BBs collect and store biological specimens with matched clinical data and patient metadata in an organised system, distributing samples and data to the scientific community, enabling “omics” studies. This is especially important considering the field of drug innovation for RDs has, in recent years, become progressively focused on ‘omics-type research, and that more than 80% of RDs have a genetic component RDs have recently been referred to as “fundamental diseases”, highlighting their unique capacity in providing opportunities to investigate the “extremes of human pathology”. For example, research of LDL-receptors in familial hypercholesterolemia, a rare disease, led to the discovery of statins, a drug therapy that is now also routinely used to prevent heart disease. This Masters research thesis examined the research outcomes of two specific research strategies: registries linked to BBs and registries without BBs, and found that whilst registries without BBs had the capacity to uncover the natural history of disease, develop best practice, replace clinical trials, and improve patient outcomes, they were limited in their capacity to conduct basic research. Registries, when annexed to BBs, had the key infrastructure required to make novel Omics discoveries, identify and validate biomarkers, uncover novel genes, and develop new therapeutic strategies. The results of this Masters research thesis suggest that the role of basic research in RD research is vital; scientists must first understand the pathways of disease before they can develop appropriate interventions. Linkage of BBs to RD registries will provide the enhanced resources required for the effective translation of basic research into clinical practice

China\u27s Labor Law Evolution: Towards A New Frontier

The People\u27s Republic of China (P.R.C.) is moving towards becoming the biggest economy in the world

Advancing techniques to promote the welfare of sows utilized in laboratory based lameness models

The first objective for this dissertation was to refine and enhance common techniques conducted in a laboratory setting including drug administration, anesthesia and behavioral modification for laboratory housed sows to improve the welfare of sows specifically by minimizing pain and distress. The second objective of this dissertation was to use an optimal dosing regimen for two non-steroidal anti-inflammatory drugs to determine their efficacy in pain management using nociceptive threshold tests when sows are induced lame through the use of a chemical synovitis model. The expected outcome was that in this lameness pain model, the pain mitigation agents will alleviate pain as assessed by two nociceptive tests. For the first objective, I developed and refined a technique for catheter placement into the auricular vein of sows. This method was quick, effective and reliable, allowing a large drug volume to be administrated successfully without relying on prolonged restraint or general anesthesia of the sow. Research confirmed that Yohimbine is an effective anesthetic reversal agent in mature sows when anesthetized with xylazine, ketamine, and telazol. Yohimbine reduced overall recovery time and maintained physiological parameters closer to normal homeostatic ranges. Lastly, the results of a study assessing behavioral modification in an individual sow demonstrating oral and locomotor stereotypies suggests the promise of environmental enrichment as an effective treatment strategy for mitigating stereotypies performed in a laboratory setting. The second objective of this dissertation was to use an optimal dosing regimen for two non-steroidal anti-inflammatory drugs (flunixin meglumine and meloxicam) to determine their efficacy in pain management using nociceptive threshold tests when lameness was induced through the use of a chemical synovitis model. Results from this study indicate that flunixin meglumine and meloxicam administration mitigated pain sensitivity in lame sows post lameness induction when pain sensitivity was evaluated with pressure algometry and thermal sensitivity tests. These analgesic drugs may be a key tool to manage pain associated with lameness

Impact of biobanks on research outcomes in rare diseases: a systematic review

BACKGROUND: Alleviating the burden of rare diseases requires research into new diagnostic and therapeutic strategies. We undertook a systematic review to identify and compare the impact of stand-alone registries, registries with biobanks, and rare disease biobanks on research outcomes in rare diseases. METHODS: A systematic review and meta-aggregation was conducted using the preferred reporting items for systematic reviews and meta-analyses (the PRISMA statement). English language publications were sourced from PubMed, Medline, Scopus, and Web of Science. Original research papers that reported clinical, epidemiological, basic or translational research findings derived from data contained in stand-alone registries, registries with biobanks, and rare disease biobanks were considered. Articles selected for inclusion were assessed using the critical appraisal instruments by JBI-QARI. Each article was read in its entirety and findings were extracted using the online data extraction software from JBI-QARI. RESULTS: Thirty studies including 28 rare disease resources were included in the review. Of those, 14 registries were not associated to biobank infrastructure, 9 registries were associated with biobank infrastructure, and 6 were rare disease biobank resources. Stand-alone registries had the capacity to uncover the natural history of disease and contributed to evidence-based practice. When annexed to biobank infrastructure, registries could also identify and validate biomarkers, uncover novel genes, elucidate pathogenesis at the Omics level, and develop new therapeutic strategies. Rare disease biobanks in this review had similar capacity for biological investigations, but in addition, had far greater sample numbers and higher quality laboratory techniques for quality assurance processes. DISCUSSION: We examined the research outcomes of three specific populations: stand-alone registries, registries with biobanks, and stand-alone rare disease biobanks and demonstrated that there are key differences among these resources. These differences are a function of the resources\u27 design, aims, and objectives, with each resource having a distinctive and important role in contributing to the body of knowledge for rare disease research. Whilst stand-alone registries had the capacity to uncover the natural history of disease, develop best practice, replace clinical trials, and improve patient outcomes, they were limited in their capacity to conduct basic research. The role of basic research in rare disease research is vital; scientists must first understand the pathways of disease before they can develop appropriate interventions. Rare disease biobanks, on the other hand (particularly larger biobanks), had the key infrastructure required to conduct basic research, making novel Omics discoveries, identify and validate biomarkers, uncover novel genes, and develop new therapeutic strategies. However, these stand-alone rare disease biobanks did not collect comprehensive data or impact on clinical observations like a rare disease registry. Rare disease research is important not only for rare diseases, but also for also common diseases. For example, research of low-density lipoprotein (LDL)-receptors in the rare disease known as familial hypercholesterolemia led to the discovery of statins, a drug therapy that is now used routinely to prevent heart disease. CONCLUSIONS: Rare diseases are still under-researched worldwide. This review made the important observation that registries with biobanks had the function of both stand-alone registries (the capacity to collect comprehensive clinical and epidemiological data) and stand-alone rare disease biobanks (the ability to contribute to Omics research). We found registries with biobanks offer a unique, practical, cost-effective, and impactful solution for rare disease research. Linkage of stand-alone registries to rare disease biobanks will provide the appropriate resources required for the effective translation of basic research into clinical practice. Furthermore, facilitators such as collaboration, engagement, blended recruitment, pro-active marketing, broad consent, and virtual biobank online catalogues will, if utilised, add to the success of these resources. These important observations can serve to direct future rare diseases research efforts, ultimately improve patient outcomes and alleviate the significant burden associated with rare disease for clinicians, hospitals, society, and most importantly, the patients and their families

Força do aperto da mão e ângulo de fase: acurácia diagnóstica para a avaliação da desnutrição em pacientes submetidos à hemodiálise

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Nutrição, Florianópolis, 2012Introdução: Na ausência de uma técnica ideal para avaliar o estado nutricional em pacientes renais, tem-se buscado identificar parâmetros capazes de diagnosticar a desnutrição. O objetivo deste estudo foi verificar a acurácia diagnóstica da força do aperto da mão (FAM) e do ângulo de fase (AF) na avaliação da desnutrição de pacientes submetidos à hemodiálise (HD). Métodos: Estudo de avaliação da acurácia diagnóstica de parâmetros nutricionais com pacientes em HD. A acurácia e os pontos de corte para desnutrição da FAM e do AF foram investigados por meio das curvas ROC (receiver operating characteristic - características de operação do receptor), utilizando como padrão de referência: avaliação subjetiva global (ASG), escore de desnutrição-inflamação (malnutrition-inflammation score - MIS) e rastreamento de risco nutricional 2002 (nutritional risk screening 2002 - NRS 2002). A associação da FAM e do AF com outros parâmetros nutricionais, como o índice de massa corporal (IMC), porcentagem de massa de gordura (% MG), massa livre de gordura (MLG), circunferência do braço (CB), circunferência muscular do braço (CMB) e AF ou FAM, foi verificada por correlação e regressão linear múltipla, considerando como significância P Abstract : Background: In the absence of an ideal technique for assessing the nutritional status in renal patients, researchers have tried to identify appropriate parameters for the diagnosis of malnutrition. The objective of this study was to verify the diagnostic accuracy of the handgrip strength (HGS) and phase angle (PA) in the assessment of malnutrition in patients undergoing hemodialysis (HD). Methods: Validation study of diagnostic tests for HD patients. The HGS and PA accuracy and cutoff values for malnutrition were evaluated by the ROC (receiver operating characteristic) curves, using as reference standards the subjective global assessment (SGA), malnutrition-inflammation score (MIS) and nutritional risk screening 2002 (NRS 2002). The association of HGS and PA with other nutritional parameters, such as the body mass index (BMI), the fat mass percentage (% FM), fat-free mass (FFM), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC) and PA or HGS, was verified by correlation and multiple linear regression, considering P<0.05 as significant. Results: A total of 138 patients on hemodialysis (85 men/53 women), aged between 24 and 84 years (average 55.4 ± 15.2 years) were evaluated. The area under the curve for the HGS and PA showed moderate accuracy in the case of women (HGS: SGA = 0.818; MIS = 0.834; NRS 2002 = 0.882 and PA: SGA = 0.718; MIS = 0.780; NRS 2002 = 0.778) and low accuracy in the case of men (HGS: SGA = 0.646; MIS = 0.606; NRS 2002 = 0.620 and PA: SGA = 0.570; MIS = 0.662 NRS 2002 = 0.668). The cutoff values in the diagnosis of malnutrition according to the reference standard (MIS) were: < 18 kg and < 28.5 kg for HGS; < 6.1° and < 6.5° for PA, for women and men, respectively. The positive and negative predictive values were also higher for women. There was a positive correlation of the PA with HGS (r = 0.396; P <0.001) and with FFM (women: r = 0.340; P < 0,001; men: r = 0.535; P = < 0,001) for both genders and only in the case of men with, MAC (r = 0.384, P < 0.001) and MAMC (r = 0.386, P < 0.001). For men, the AF was positively correlated with the BMI (r = 0.270, P < 0.019), % FM (r = 0.237, P < 0.041), MAC (r = 0.464, P < 0.001) and MAMC (r = 0.335; P < 0.001). Among women, patients diagnosed as malnourished by the HGS had lower values for PA (ß=-1.00), FFM (ß = -3.15) and MAC (ß = -2.80), while in the case of men, the malnourished patients, had lower values for FFM (ß = -4,53), MAC (ß = -1.71) and MAMC (ß = -1.28). The women diagnosed as malnourished by the PA had lower values for %FM (ß = -5.4) and HGS (ß = -5.4), while for the malnourished men lower values were obtained for MAC (ß = -2.57), MAMC (ß = -2.07) and BMI (ß = -2.44). Conclusions: HGS and PA presented accuracy in the diagnosis of malnutrition in women, and there was association with some of the nutritional parameters for both genders, suggesting that these two nutritional parameters may be useful when used as a complement in the assessment of malnutrition in HD patients

Desenvolvimento de firmware para testes de produção de produtos IoT

TCC(graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. Engenharia de Controle e Automação.Este projeto propõe o desenvolvimento de um firmware para automatização de um processo de teste de produtos da linha de gateways de IoT da empresa Khomp. Os testes de produto na empresa são denominados T2 e buscam validar as funcionalida- des de cada módulo do produto quando este já está completamente montado, sendo o último teste realizado antes da expedição ao cliente final. Cada elemento testado demanda o uso de diferentes abordagens e tecnologias. O objetivo que se busca com a implementação deste firmware é reduzir significativamente o tempo empregado para testes de produto da linha ITG substituindo um longo processo manual por outro au- tomático e mais simples, também mitigando possíveis falhas humanas. Para isso, são utilizadas técnicas de programação concorrente, testes de hardware e software e o de- senvolvimento de uma interface web para monitoramento dos testes e direcionamento para as etapas guiadas. O firmware é implementado utilizando a linguagem Golang e a interface web é desenvolvida utilizando Svelte. Três metodologias ágeis pautam o desenvolvimento deste trabalho: SCRUM para gerenciamento de projeto, FDD para definir o desenvolvimento e TDD para garantir a qualidade do software. Para validação dos resultados, são apresentadas análises comparando o tempo de duração de teste entre os processos e também os feedbacks dos usuários.This project proposes the development of a firmware for automating a product testing process from the IoT gateways line from Khomp company. The company’s product tests are called T2 and seek to validate the functionality of each product module when it is already fully assembled, the last test being carried out before shipping to the final cus- tomer. Each element tested requires the use of different approaches and technologies. The objective pursued with the implementation of this firmware is to significantly reduce the time used for product testing of the ITG line, replacing a long manual process with an automatic and simpler one, also mitigating possible human errors. For this, concur- rent programming techniques are used, as well as hardware and software tests and the development of a web interface for monitoring the tests and directing the user to the guided steps. The firmware is implemented using the Golang language and the web interface is developed using Svelte. Three agile methodologies guide the development of this work: SCRUM for project management, FDD to define the development and TDD to guarantee the software quality. To validate the results, analyzes are presented comparing the test duration time between the processes and also the users’ feedbacks

Sistemas de produção de pós-larvas de tilápia do Nilo

The breeding systems are classified according to the structure and strategy of collecting post-larvae used during the tilapias reproduction. The obtaining post-larvae and fingerlings of tilapia in reproduction may occur in ponds, tanks and hapas through the continuous collection of post-larvae in ponds, total collection of post-larvae in hapas, ponds and tanks, or direct collection eggs in the mouths of females and artificial incubation. The study on methodologies and reproductive managements used is critical to the proper functioning of aquaculture ventures, given the continued growth of tilapia fingerlings and the incessant demand for fingerlings. This review aims to evaluate a set of elements and factors that influence the productivity of Nile tilapia fingerlings in different reproduction systems in order to determine the optimal methodology to be employed, highlighting the scientific and technological advances for the tilapia breeding.The breeding systems are classified according to the structure and strategy of collecting post-larvae used during the tilapias reproduction. The obtaining post-larvae and fingerlings of tilapia in reproduction may occur in ponds, tanks and hapas through the continuous collection of post-larvae in ponds, total collection of post-larvae in hapas, ponds and tanks, or direct collection eggs in the mouths of females and artificial incubation. The study on methodologies and reproductive managements used is critical to the proper functioning of aquaculture ventures, given the continued growth of tilapia fingerlings and the incessant demand for fingerlings. This review aims to evaluate a set of elements and factors that influence the productivity of Nile tilapia fingerlings in different reproduction systems in order to determine the optimal methodology to be employed, highlighting the scientific and technological advances for the tilapia breeding

A proactive blueprint to demonstrate on-farm animal welfare

Farm animal welfare has become an increasing area of consumer and customer interest globally and this has resulted in dramatic changes related to on-farm accountability. Some markets are demanding an-on farm, transparent and accountable animal welfare program. Knowing what key elements are required is critical. Key elements range from (a) caretaker qualities; (b) record keeping and standard operating procedures (SOP) (c) animal- and resource based measures (d) communication and (e) caretaker empowerment. The ultimate on-farm welfare program goal is to provide the highest animal care. This review paper will provide context to these key elements that in turn can be used to create or improve an-farm animal welfare program

Soil Moisture and Porosity Affects the Abundance and Distribution of Ageratum houstonianum

Introduction: Ageratum houstonianum is an herbaceous, drought-tolerant plant also known as Blue billygoat weed. It grows well in drained soil and shaded areas. Soil moisture and porosity are two abiotic factors that affect the abundance and distribution of A. houstonianum. An ideal condition for plants to grow includes a greater amount of soil moisture and porosity. Higher porosity would mean that there is a greater number of pores, which would result in more significant plant nutrients because of its ability to retain more water. The purpose of this research was to see how soil moisture and porosity based on the gradient with regards to distance from the tree impact the abundance and distribution of A. houstonianum. Materials and Methods: The belt transect method was used to test the soil moisture and porosity, and three belts with four quadrants in each were formed. For each of the belts, the first two quadrants closer to the tree were called zone 1, and the last two quadrants were labeled as zone 2. We hypothesized that there was an increase in abundance and distribution further away from the tree. Abundance was calculated by finding the density of the total number of species over each quadrant area. Soil samples were collected to test the soil moisture and porosity. Paired two-sample t-tests and ANOVA single factor tests were performed. Results and Conclusion: The t-tests showed a difference between the relationship of abundance/moisture, abundance/porosity, and moisture/porosity. The ANOVA test compared the means of density/moisture/porosity between zone 1 and 2 to see if they were statistically different from each other. Based on the results, there was a decrease in the density as the distance from the tree increased. Soil moisture and porosity also decreased as the distance from the tree increased, which rejected the hypothesis. Closer to the tree, there was an increase in moisture, density, and porosity, which led to the abundance of A. houstonianum species because the ideal conditions were met