Analysis of black holes in our knowledge concerning animal health in the organic food production chain

Although a large body of research on health aspects can be found via the web or in conference proceedings, only few papers reach the peer reviewed literature. This aspect makes it difficult to judge the quality of available data that relate to health aspects associated with organic livestock production. Many data deal with "on farm case type studies" which often do not lead to a direct relation between certain management procedures and incidence of certain health aspects. The principle that organic held animals are in better condition concerning their health as compared to conventionally held animals has not yet been proven. Well-controlled studies are needed to show the effects of organically held animals on innate and adaptive immune responses and disease susceptibility. The conditions in organic livestock production lead to novel challenges concerning social interactions, physical requirements, climatic conditions and infectious burden which requires certain breeds of animals that differ considerably from the conventionally held animals. More research is needed to identify these breeds whereby breeding selection criteria specific to organic conditions and principles should be used. A number of health problems such as infestation with parasites is an important problem that has been noted in organic livestock (poultry and pig) production and more research is needed to both prevent and treat these infections. Although largely recommended, phytotherapy and homeopathy do not have any demonstrated efficacy in managing helminths. A multidisciplinary approach is needed to address these questions. Investigations should be concerned with aspects such as rotation, stocking density, disinfections strategies, genetic predisposition and novel (plant derived or biological) antihelminthics. A major drawback in the use of phytotherapeuticals is the lack of good clinical trials, most claims are based on traditional use, anecdotal evidence or extrapolation of human data. Another problem is the consistency/standardisation of the product; variations exist in the levels of "active" ingredients between lots. Extensive studies have shown that garlic has a beneficial effect on human health and therefore would possibly be a suitable candidate to increase the health of animals in organic production. Further research is needed to substantiate this claim. Although mastitis is not seen more often in organic dairy production compared to conventional farms, it is still frequently encountered and both basic and applied research concerning prevention and cure without the traditional use of antibiotics is needed. More knowledge is needed concerning effects of alternative treatments in organic livestock production. As long as alternative treatments have not formally been proven to be effective, allopathic treatments should be preferred. Studies are needed concerning the welfare aspects of disease and insufficient or postponed treatment in organic animal production systems. It is generally accepted that feather picking and cannibalism is a major problem in organic poultry and more research is needed to counter this unwanted behaviour of the animals. The following aspects including genetic influences, housing environment, feed composition and the presence of external parasites may be involved. Vaccination has been one of the largest success factors in the prevention of disease in production animals. Most vaccines used nowadays are genetically engineered and should thus carry the GMO label. GMO based vaccines produced by incorporating genetic material from bacteria or viruses into plants is an attractive approach but does not comply with the principles of organic farming. Investigations concerning various vaccination strategies with or without GMO approaches should be evaluated to prevent various infectious diseases in organic livestock production systems. Organic livestock production leads to an increase or re-emergence of certain zoonotic diseases ( Campylobacter, toxoplasma). This is a serious drawback concerning claims that organic products are healthier as compared to conventional products and research into the prevalence of certain zoonotic infections, risk factors, farm management, post slaughter decontamination and consumer perception/education is badly needed. Several micro-organisms are described to be present in feeds and could be sources of infections of farm animals. Such pathogens can be either present on the outside of the plant (epiphytes) or on the inside of the plant (endophytes). The incidence of pathogenic bacteria in/on plants used for organic animal feed is not clear and therefore research on the incidence of these pathogens is needed. Biological cycles such as the utilisation of manure from organic farms may potentially lead to the creation of infectious reservoirs. Research is needed to provide evidence for this hypothesis and strategies should be devised to prevent this problem. Little is known about the role of pests in the occurrence of disease in organic livestock production. Research is needed into the efficacy of alternative pest control strategies since current pest control methods are not in agreement with organic production principles (use of anticoagulants for rodent control). The obligatory use of straw bedding in swine household management leads to higher dust and bioareosol (endotoxin) levels in stables. This may affect susceptibility to lung disease (farmer and animal) and investigations concerning measures to reduce dust and bioaerosol levels are needed. Current literature on this subject is not concordant and true differences may exist between management systems from different countries. Piglet mortality is an important problem in organic production systems and research concerning genetic and housing aspects is currently performed but not yet reported in the peer-reviewed literature. Amino acid imbalance and research into novel feed sources with high protein content is needed. More knowledge is known concerning possible anti-nutritive factors in these feeds and the effects of these new nutrients on gut health of the animals. Amino acid imbalance may lead to higher excretion of excess amino acids into the environment. On farm research should be performed to substantiate whether these claims also apply to organic production systems. It has been suggested that organic feeds for animals in organic production systems may contain higher mycotoxin levels thereby adversely affecting their health status. As yet no conclusive data concerning this issue has been published and research into this area is needed to prove or reject this myth. As yet it is not known whether phytase levels in organic feed for pigs are sufficient to allow optimal utilisation of organic phosphor thereby also leading to a lower environmental pollution; further investigations are needed in this area

The impact of macronutritional composition and ketosis on cognitive health : from normal aging to Alzheimer’s disease

Ketogenic diets (KD) are increasingly investigated for the prevention of cognitive decline and Alzheimer’s disease (AD). Without explicitly investigating a KD, this thesis disentangles two of its hallmarks: a reduced dietary carbohydrate/fat-ratio (CFr) and the metabolic state ketosis. Whether health effects from KD are primarily driven by ketosis or from other pathways related macronutritional changes, is not fully understood. Beyond CFr, KD may optionally be modified regarding protein, fat-subtypes, plant/animal-based food proportions, the timing of nutrient intake, and ketogenic supplements. Strategies to induce ketosis in the absence of a carbohydrate restricted diet (Study I) and subsequent associations between induced ketosis and a biomarker essential for brain function (Study II) was investigated in a randomized clinical trial planned and performed within this doctoral project: In a 6-arm cross-over design, 15 healthy older adults (age 65-73, following their usual diet) were exposed to intake of oils with various composition of medium-chain triglycerides (MCT), with and without glucose. Blood levels of ketones (β-hydroxybutyrate, BHB) and brain-derived neurotrophic factor (BDNF) were thereafter monitored for 4 hours. Mature BDNF (mBDNF) and its precursor proBDNF are essential for brain plasticity, and their concentrations in serum have been associated with cognitive health. A methods comparison for measuring blood ketones (Study III) supports the internal validity of Study I and II. The impact of self-reported CFr—in the non-ketogenic range—on cognitive performance (Study IV/V) was investigated by panel analyses on data (year 0, 1, and 2) from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). The sample (n=1259, age 60–77, 47% females) had no substantial cognitive impairment but had risk factors for developing dementia, and cognition at mean level or slightly lower than expected in screening test. Study V added stratified analyses based on genetics (APOE) and insulin status. Study I: A 16-hour non-carbohydrate window and intake of 20 g caprylic acid (C8) contributed roughly equally to induce transient ketosis (0.45 mmol/L, AUC/time venous BHB hour 0-4, when combining the strategies). Coconut oil (which has a ≈7% fraction constituted by C8 and is dominated by lauric acid) did not share the ketogenic properties of purified C8 (difference –0.22 mmol/L, p<0.001). Study II: Contrary to our expectations, change in mBDNF was lower (z-score: β=–0.88, p<0.001) after intake of C8 (higher ketosis) compared to sunflower oil (lower ketosis). Since associations between BHB and mBDNF appeared unrelated (p=0.43) on the individual level, alternative explanations to ketosis as a driver were discussed. In contrast, proBDNF increased more ( β=0.25, p=0.007) after intake of C8 compared to sunflower oil, and individual associations between BHB and proBDNF ( β=0.40, p=0.006) supported ketosis as a mechanistic link. Study III: A handheld ketone meter correlated well with the laboratory method (r=0.91) and agreement was high when applied to venous whole blood (which was our primary outcome). However, absolute values were systematically higher in capillary blood, which should be considered in comparisons between studies. Study IV: A lower CFr (log, z-score) estimated a higher composite z-score on a Neuropsychological Test Battery ( β=–0.022, p=0.011) in linear mixed regression. Methodological advantages of analyzing intake of carbohydrates and fat as a ratio compared to single variables were discussed. No significant associations were found for protein, and the saturated/total fat ratio had non-linear associations with cognitive performance. Study V: APOE (-2/3/4), which is the most important AD risk gene, modified estimates between diet parameters (CFr, protein, saturated/total fat ratio, fiber, composite score) and cognitive performance in a sub-sample with insulin data, excluding diabetics (n=676). By increasing values of a continuous APOE-gradient [–1 (-23), –0.5 (-24), 0 (-33), 1 (-34), 2 (-44)], a less favorable estimate (p<0.0001 for interaction) was found for a Higher-carbohydrates-fiber-Lower-fat-protein composite score. Estimates for -33 were relatively close to zero whereas -44 (with some ambiguity for females) typically had an antagonistic estimate to -23. Relative hypo- and hyper-insulinemia significantly magnified several estimates diet ->cognition in a dose dependent manner, primarily among -34/44. The plant/animal-based proportion of macronutrients was discussed as a potential unmeasured confounder. Conclusions: Macronutritional changes may be an alternative explanation to ketosis for what may drive potential cognitive effects from KD. Time-restricted carbohydrate intake may be considered as an alternative, or a complement, to C8-enriched MCT-oils for achieving mild ketosis. Signaling functions of ketones may be at work in transient mild/moderate ketosis, but whether our BDNF results have any cognitive implications requires further studies. To guide further research, our diet ->cognition analyses have strengthened the case for: (1) a precision nutrition approach based on APOE-genotype and insulin status; (2) not limiting interventions on carbohydrate restriction to the ketogenic range of CFr; (3) considering both ends of the insulin spectrum as representing distinct at-risk types susceptible to diet modifications. APOE-34/44 carriers may be optimal targets for studying potential benefits on brain health from CFr-reduction, and higher protein intake. The concept of universal macronutrient targets may be questioned, and stratified analyses may be encouraged in further studies

Multiagent Systems Engineering: A Methodology for Analysis and Design of Multiagent Systems

This thesis defines a methodology for the creation of multiagent systems, the Multiagent Systems Engineering (MaSE) methodology. The methodology is a key issue in the development of any complex system and there is currently no standard or widely used methodology in the realm of multiagent systems. MaSE covers the entire software lifecycle, starting from an initial prose specification, and creating a set of formal design documents in a graphical style based on a formal syntax. The final product of MaSE is a diagram describing the deployment of a system of intelligent agents that communicate through structured conversations. MaSE was created with the mention of being supported by an automated design tool. The tool built to support MaSE, agent Tool, is a multiagent system development tool for designing and synthesizing complex multiagent systems

Semantic Privacy Policies for Service Description and Discovery in Service-Oriented Architecture

Privacy can be defined as the right of an individual to have information about them accessed and used in conformity with what they consider acceptable. Privacy preservation in Service-Oriented Architecture (SOA) is an open problem. A solution for this problem must include features that support privacy preservation in each area of SOA. This thesis focuses on the areas of service description and discovery. The problems in these areas are that currently it is not possible to describe how a service provider deals with information received from a service consumer as well as discover a service that satisfies the privacy preferences of a consumer. Research has been carried out in these areas, but there is currently no framework which offers a solution that supports a rich description of privacy policies and their integration in the process of service discovery. Thus, the main goal of this thesis is to propose a privacy preservation framework for the areas of service description and discovery in SOA. The framework enhances service description and discovery with the specification and intersection of privacy policies using a base and domain-specific privacy ontologies. Moreover, the framework enhances these areas with an extension to basic SOA that includes roles responsible for implementing a privacy registry as well as mediating the interactions between service consumers and providers and the privacy preservation component. The framework is evaluated through a health care scenario as privacy preservation is an important issue in this domain

JOHN WESLEY WORK III: ARRANGER, PRESERVER, AND HISTORIAN OF AFRICAN AMERICAN TRADITIONAL MUSIC

This study focuses on John Wesley Work III’s life and career in response to the scarcity of existing research and publication devoted to him. To expand the scholarship focused on Work and to deepen the history of African American artistry, this dissertation analyzes his additions to concert repertoire through his arrangements of spirituals, investigates his scholarship, and performance— including his activities as Director of the Fisk Jubilee Singers — and provides a foundation for further analytical study of African- American sacred music. Methodology utilized in this thesis includes construction of a biographical narrative based on primary sources and analysis of his musical career based on personal writings as well as the musical elements present in his arrangements. Work’s writings about spirituals demonstrate his awareness of the changing styles in concert-style arrangements as they evolved through diverse performance contexts, but he also believed in maintaining the original source and meaning. Work’s career was dedicated to the documentation and preservation of Black sacred music and folk songs through transcriptions, recordings, and arrangements that adhered to the spirit of oral tradition as possible. John Wesley Work III is a significant figure who told the story of the African-American experience through performing, recording, arranging, and writing about Black music

Bugs as Features (Part II): A Perspective on Enriching Microbiome-Gut-Brain Axis Analyses with Multidisciplinary Techniques

The microbiome-gut-brain-axis field is multidisciplinary, benefiting from the expertise of microbiology, ecology, psychiatry, computational biology, and epidemiology amongst other disciplines. As the field matures and moves beyond a basic demonstration of its relevance, it is critical that study design and analysis are robust and foster reproducibility. In this companion piece to Bugs as Features (Part 1), we present techniques from adjacent and disparate fields to enrich and inform the analysis of microbiome-gut-brain-axis data. Emerging techniques built specifically for the microbiome-gut-brain axis are also demonstrated. All of these methods are contextualised to inform several common challenges: how do we establish causality? How can we integrate data from multiple 'omics techniques? How might we account for the dynamicism of host-microbiome interactions? This perspective is offered to experienced and emerging microbiome scientists alike, to assist with these questions and others, at the study conception, design, analysis and interpretation stages of research.Comment: For main text: 20 pages, 2 figures; for supplementary analysis: 31 pages and 6 figures. Supplementary analysis generated using Rmarkdown by Thomaz F. S. Bastiaanssen. arXiv admin note: substantial text overlap with arXiv:2207.1247