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Second, the relationship may be influenced by the geographical scope (national versus local) of the medium. Third, as discussed in chapter 2, news media companies are typically organized so as to separate and insulate business operations from editorial activities. Advertisers are serviced by marketing departments of media companies; thus, reporters rarely come into direct contact with advertisers in their media, although this may be more likely to occur in local news media. In the case of larger newspapers and other media, it is possible that news coverage is more likely to influence advertising, rather than the other way around. In other words, an editorial environment that is not hospitable to a product is unlikely to attract advertising for the product, thus limiting the revenue stream for the news medium. With these general principles in mind, the remainder of this section discusses the relationship between revenue from tobacco advertising and publication of tobacco-related content. H o w the N e w s M e d i a I n f l u e n c e To b a c c o U s e smoking-related stories compared with other health topics. The authors concluded that the paucity of antismoking articles was related to the importance of tobacco advertising as a source of revenue for the magazines. They also concluded that magazine news coverage would adequately address tobacco issues only by restricting tobacco advertising. Similar studies have not yet been conducted to determine whether the presence of tobacco advertising influences editorial coverage in daily newspapers, radio, or television. However, anecdotal evidence about the influence of advertising over editorial coverage exists for newspapers and the broadcast media before the removal of cigarette commercials, 85(p. These insights often are fragmentary because documents made public represent an undefined sample of all documents ever produced within the industry. They also frequently raise questions that cannot be addressed because related documents are missing. For example, Philip Morris used the InfoFlow measure to "understand what the public is reading, hearing and seeing in the news related to tobacco and. In 2000, Philip Morris reported to its staff, "Despite some minor movement, InfoFlow has remained decidedly negative. The Role of the Media national introduction of health warnings on cigarettes packages in the early 1970s. However, the following comments illustrate that industry representatives were aware of the potential influence of messages delivered within the media arena. The sixth point I want to make is that we are not using our very considerable clout with the media. The media like the money they make from our advertisements and they are an ally that we can and should exploit. In most societies in the world today public opinion is formed, to a significant extent, by the news media and I believe we should make a concerted effort in our principal markets to influence the media to write articles or editorials positive to the industry position on the various aspects of the smoking controversy. We have already been helped a great deal by the agencies in Hong Kong for example, in our efforts to resist advertising restrictions. For example, in 1994, a Philip Morris official wrote of the news situation in Australia: There is a vast amount of material published in the media which is predominantly negative. These contained 450 unfavourable mentions concerning tobacco not including negative mentions in classified advertisements. In the same month, an examination of 460 magazines published during the month revealed 181 unfavourable articles. The media is biased and sensational, so that Industry responses do not get the headlines that the anti-smokers achieve. Some evidence suggests the industry may try to leverage its considerable advertising contributions to influence editorial coverage in magazines. However, a growing body of research focused on newspapers indicates that several decades of strong and continuing coverage of the negative aspects of tobacco issues is incompatible with any hypothesis that industry influence can seriously affect the ways in which the news media (except for magazine content) approach tobacco matters. As the tobacco control community continues to make strides in limiting the acceptable locales for print advertising, the influence of the tobacco industry even on magazine content is likely to diminish. Further work needs to be done to elucidate the nature of tobacco-related news coverage and its broader impact on public health.

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In addition to the site characteristics mentioned above, sites that have undergone significant staffing changes during a multiyear registry should be considered prime audit targets to help confirm adequate training of new personnel and to quickly address possible inter-rater variability. To minimize any impact on the observational nature of the registry, the audit plan should be documented in the registry manual. Registries that are designed for the evaluation of patient outcomes and the generation of scientific information, and that use medical chart abstracters, should assess inter-rater reliability in data collection with sufficient scientific rigor for their intended purpose(s). For example, in one registry that uses abstractions extensively, a detailed system of assessing inter-rater reliability has been devised and published; in addition to requiring that abstracters achieve a certain level of proficiency, a proportion of charts are scheduled for reabstraction on the basis of predefined criteria. Statistical measures of reliability from such re-abstractions are maintained and reported. As appropriate to meet registry objectives, the sponsor may request corrective actions from the site. Site compliance may also be enhanced with routine communication of data generated from the patient registry system to the site for reconciliation. Pre-established criteria could include monitoring of sites with high patient enrollment or with prior audit history of findings that require attention, or monitoring could be based on level of site experience, rate of serious adverse event reporting, or identified problems. The registry coordinating center may perform monitoring of a sample of sites, which could be focused on one or several areas. This approach could range from reviewing procedures and interviewing site personnel, to checking screening logs, to monitoring individual case records. The importance of having a complete and detailed registry manual that describes policies, structures, and procedures cannot be overemphasized in the context of quality assurance of registry procedures. Such a manual serves both as a basis for conducting the audits and as a means of documenting changes emanating from these audits. As with data quality audits, feedback of the findings of registry procedure audits should be communicated to all stakeholders and documented in the registry manual. The concepts described below are consistent across many software industry standards and health care industry standards. An internal quality assurance function at the registry coordinating center should regularly audit the processes and procedures described. When third parties other than the registry coordinating center perform activities that interact with the registry systems and data, they are typically assessed for risk and are subject to regular audits by the registry coordinating center. In parallel, quality assurance of system development uses approved specifications to create a validation plan for each project. Test cases are created by trained personnel and systematically executed, with results recorded and reviewed. Depending on regulatory requirements, a final validation report is often written and approved. Processes for development and validation should be similarly documented and periodically audited. The information from these audits is captured, summarized, and reviewed with the applicable group, with the aim of ongoing process improvement and quality improvement. In addition, other Federal and State security laws may apply to registry data, depending on who maintains the registry, the type of data maintained, and other circumstances. Aside from what may be required by applicable laws, this section generally discusses some of the components of a security program. Security is achieved not simply through technology but by clear processes and procedures. Some registries may also maintain personal information, such as information needed to contact patients to remind them to gather or submit patient-reported outcome information. Included in the rules are the policies specifying individual accountability for actions, access rights based on the principle of least privilege, and the need for separation of duties. These principles and the accompanying security practices provide the foundation for the confidentiality and integrity of registry data. Standard criteria exist for such assessments and are based on the type of data being collected. Part of the validation process is a security assessment of the systems and operating procedures. One of the goals of such an assessment is effective risk management, based on determining possible threats to the system or data and identifying potential vulnerabilities. Individuals should receive training relating to their specific job responsibilities and document that appropriate training has been received. No individual should be assigned access privileges that exceed job requirements, and no individual should be in a role that includes access rights that would allow circumvention of controls or the repudiation of actions within the system.

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Applicants engaged in single pilot commercial operations carrying passengers clearly require the most careful medical evaluation in order to reduce the risk of in-flight incapacitation. Those engaged in multicrew operations, where there has been effective incapacitation training, may be considered less stringently. In many such cases flight safety may be adequately protected by an operational condition or limitation applied to the licence. When consulting the Medical Manual it should be remembered that it is intended as guidance material only and as such has no regulatory status. Thus an individual Contracting State may have regulations additional to those specified in Annex 1 for some reason particular to that State. Furthermore, the requirements published under any national regulations are the legal requirements of that State, regardless of what may be found in Annex 1. Additional screening measures, apart from having an adverse financial impact on the State or the aviation industry, may not improve flight safety. Stringent national medical requirements can result in unnecessary restrictions or premature retirement of licence holders. They may also have the consequence of licence holders being reluctant to report illness to the medical examiner or the Licensing Authority, and this is important from the flight safety viewpoint since the value of the medical examination relies to a large extent upon an accurate medical history. It encourages "medical tourism" where a licence holder, refused a licence on medical grounds in one State because of stringent medical requirements, seeks to obtain one in another, less demanding State. The main purpose of the Medical Manual is to assist and guide designated medical examiners, medical assessors and Licensing Authorities in decisions relating to the medical fitness of licence applicants as specified in Annex 1. It is, however, envisaged that the manual might also be useful to supplement properly supervised theoretical and practical post-graduate training in aviation medicine. Thus the chapters of the manual have been edited so that it may serve also as a textbook. Part V, Chapter 1, contains detailed guidance on aeromedical training for medical examiners. In this third edition of the Medical Manual, some limitation of contents has been necessary. The scope of the material includes, particularly, guidance on those areas in which difficulties have been experienced by Contracting States. States are invited to assist in improving this manual by submitting comments to the Organization and by suggesting any pertinent additional information which might usefully be included. Anthony Cullen (pathology) Carsten Edmund (ophthalmology) Sally Evans (oncology) Randall M. Giangrande (haematology) John Hastings (neurology) Andrew Hopkirk (fatigue) Ian Hosegood (psychiatry) Ewan Hutchison (human immunodeficiency virus) Raymond V. Johnston (endocrinology) Michael Joy (cardiology) Mads Klokker (otorhinolaryngology) Marvin Lange (psychiatry) Anker Lauridsen (gastroenterology) Jacques Nolin (orthopaedics) Jeb S. I-1-1 I-1-1 I-1-1 I-1-2 I-1-2 I-1-3 I-1-3 I-1-5 I-1-5 I-1-6 I-1-6 I-1-6 I-1-7 I-1-8 I-1-8 I-1-8 I-1-8 I-1-9 I-1-10 I-1-10 I-1-11 I-1-13 I-1-13 I-1-13 I-1-14 I-1-14 I-1-14 I-1-15 1. Safety management as a foundation for evidence-based aeromedical standards and reporting of medical events. Therefore it is strongly recommended that the reader obtain and keep up to date his1 own copy of Annex 1. Aspects relating to medical regulations for licence applicants are included mainly in Annex 1 - Personnel Licensing and to some degree in Annex 2 - Rules of the Air and Annex 6 - Operation of Aircraft. Issues involving preparedness planning for a communicable disease of public health concern are considered in Annex 6, Annex 9 - Facilitation, Annex 11 - Air Traffic Services and Annex 14 - Aerodromes. Any specification for physical characteristics, configuration, materiel, performance, personnel or procedure, the uniform application of which is recognized as necessary for the safety or regularity of international air navigation, and to which Contracting States will conform in accordance with the Convention. Any specification for physical characteristics, configuration, materiel, performance, personnel or procedure, the uniform application of which is recognized as desirable in the interest of safety, regularity or efficiency of international air navigation, and to which Contracting States will endeavour to conform in accordance with the Convention. Civil aviation includes different types of operations which, for convenience, can be divided into three major 1. This category includes all operations conducted with large and sophisticated aircraft which used to be piloted by several crew members. It now consists of two (or occasionally three) members, depending on the type of aircraft. On modern aeroplanes, computers are handling the systems and the pilot is becoming more and more of a systems manager and decision maker rather than a control operator.

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The recommendations made in the present report complement and can be implemented consistent with the vision and recommendations put forth in those reports. Second, two other recent reports address palliative care: Copyright National Academy of Sciences. First, there is good evidence of the effectiveness of a variety of services in relieving the emotional distress-even the debilitating depression and anxiety-experienced by cancer patients. Strong evidence also supports the utility of services aimed at helping individuals adopt behaviors that can minimize disease symptoms and improve overall health. Other psychosocial services, such as transportation to health care or financial assistance to purchase medications or supplies, while not the subject of effectiveness research, have long-standing and wide acceptance as humane approaches to addressing health-related needs. In particular, the strong leadership of organizations in the voluntary sector has created a broad array of psychosocial support services, in some cases available at no cost to the consumer. However, it is not sufficient simply to have effective services; interventions to identify patients with psychosocial health needs and to link them to appropriate services are needed as well. Fortunately, many providers of health services-some in oncology, some delivering health care for other complex health conditions-understand that psychosocial problems can affect health adversely and have developed interventions to address these problems. Some of these interventions are derived from theoretical or conceptual frameworks, some are based on research findings, and some have undergone empirical testing on their own; the best have all three sources of support. Common components of these interventions point to a model for the effective delivery of psychosocial health services (see Figure S-1). This model includes processes that (1) identify psychosocial health needs, (2) link patients and families to needed psychosocial services, (3) support patients and families in managing the illness, (4) coordinate psychosocial and biomedical health care, and (5) follow up on care delivery to monitor the effectiveness of services and make modifications if needed-all of which are facilitated by effective patient­provider communication. Routine implementation of many of these processes is currently under way by a number of exemplary cancer care providers in a variety of settings, attest- Copyright National Academy of Sciences. However, many patients do not have the benefit of these interventions, and more active steps are needed if this lack of access is to become the exception rather fig S-1 and 4-1 than the rule. All components of the health care system that are inoled in cancer care should explicitly incorporate attention to psychosocial needs Cancer Care Copyright National Academy of Sciences. The committee defines psychosocial health services as follows: Psychosocial health serices are psychological and social serices and interentions that enable patients, their families, and health care proiders to optimize biomedical health care and to manage the psychological/behaioral and social aspects of illness and its consequences so as to promote better health. Examples of psychosocial needs and services that can address those needs are listed in Table S-1. Psychosocial interventions necessary for their appropriate provision are portrayed in Figure S-1. The committee offers the following recommendations for making attention to psychosocial health needs an integral part of quality cancer care. This table includes only formal sources of psychosocial support- those that must be secured through the assistance of an organization or agency that in some way enables the provision of needed services (sometimes at no cost or through volunteers). Key participants and leaders in cancer care have major roles to play in promoting and facilitating adherence to this standard of care. All cancer care providers should ensure that every cancer patient within their practice receives Copyright National Academy of Sciences. The committee believes that all providers can and should implement the above recommendation. Individual clinical practices vary by their patient population, their setting, and available resources in their clinical practice and community. Because of this, how individual health care practices implement the standard of care and the level at which it is done may vary. Nevertheless, as this report describes, the committee believes that it is possible for all providers to meet this standard in some way. This report identifies tools and techniques already in use by leading oncology providers to do so. Patient education and advocacy organizations can play a key role in bringing this about. Patient education and advocacy organizations should educate patients with cancer and their family caregivers to expect, and request when necessary, cancer care that meets the standard for psychosocial care. The goals should be to enable patients to participate actively in their care by providing tools and training in how to obtain information, make decisions, solve problems, and communicate more effectively with their health care providers. A large-scale demonstration of the implementation of the standard of care at various sites would provide useful information about how to achieve its implementation more efficiently; reveal approaches to implementation in both resource-rich and non-resource-rich environments; document approaches for successful implementation among vulnerable groups, such as those with low socioeconomic status, ethnic minorities, those with low health literacy, and the socially isolated; and identify different models for reimbursement. A demonstration could also be used to examine how various types of personnel can be used to perform specific interventions encompassed by the standard and how those personnel can best be trained. This program should demonstrate how the standard can be implemented in different settings, with different populations, and with varying personnel and organizational arrangements.

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With respect to microbial taxonomic composition, researchers observed high levels of the Firmicutes families, especially Lachnospiraceae genera. The microbiota in mice that developed clinical illness remained dominated by Proteobacteria over time, while the microbiota of mice that suffered some inflammation but did not become clinically ill eventually reverted to "healthy" Lachnospiraceaedominated communities (Reeves et al. Moreover, colonization resistance was lowered so much that their microbiomes became pure cultures of C. Restoring balance in the community, or preventing imbalance, could be the basis for yet another new therapeutic approach to managing C. For example, Young mentioned the dissertation research of one of his students demonstrating that Lachnospiraceae bacteria are associated with greater colonization resistance. He wondered whether restoring balance might be simply a matter of adding "more bugs" in the "right combination. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. Hemin-dependent modulation of the lipid A structure of Porphyromonas gingivalis lipopolysaccharide. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Clindamycinassociated colitis due to a toxin-producing species of clostridium in hamsters. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. Reported medication use in the neonatal intensive care unit: Data from a large national data set. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: A molecular and culture-based investigation. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis. Targeting the human microbiome with antibiotics, probiotics, and prebiotics: Gastroenterology enters the metagenomics era. The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile infection. Suppression of Clos tridium difficile in the gastrointestinal tract of germ-free mice inoculated with a murine lachnospiraceae isolate. The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Analysis of the activity to induce toll-like receptor (tlr)2- and tlr4-mediated stimulation of supragingival plaque. The Human Microbiome, Diet, and Health: Workshop Summary 4 Influence of the Microbiome on the Metabolism of Diet and Dietary Components A lthough research on the microbiome is considered an emerging science, scientists already have made tremendous progress in understanding the microbial makeup of the microbiome and in associating microbiome diversity with human disease. Moreover, they are beginning to make headway in understanding how the microbiome impacts human health and disease. Growing evidence suggests that gut microbes influence what the human host is able to extract from its diet, both nutritionally and energetically. This chapter summarizes the workshop presentations and discussion that were focused on the influence of the microbiome on diet and dietary components. Despite considerable interindividual variation in gut microbiome species, all individuals share a core set of microbial genes, according to Turnbaugh.

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Among children and adolescents, milk and 100% fruit juice intake is higher for younger children, and soda intake is higher for adolescents. Examples of the Calories in Food Choices That Are Not in Nutrient- Dense Forms and the Calories in Nutrient- Dense Forms of these Foods Calories in nutrient-dense form of the food Regular ground beef patty (75% lean) cooked 3 ounces Breaded fried chicken strips 3 ounces Frosted corn flakes cereal 1 cup Curly french fried potatoes 1 cup Sweetened applesauce 1 cup Whole milk 1 cup 0 Extra lean ground beef patty (90% lean) 184 Baked chicken breast 138 Corn flakes 90 Baked potato 117 Unsweetened applesauce 105 Fat-free milk 83 50 100 Milk fat 66 149 total 150 Calories 200 250 300 Added sugars 68 173 total Added sugars 57 147 total Frying fat 141 258 total Additional calories in food as consumed Beef fat 52 Breading and frying fat 108 246 total 236 total Based on data from the U. Department of Agriculture, Agricultural Research Service, Food and Nutrient Database for Dietary Studies 4. Healthy individuals, in general, have an adequate total water intake to meet their needs when they have regular access to drinking water and other beverages. The combination of thirst and typical behaviors, such as drinking beverages with meals, provides sufficient total water intake. Individual water intake needs vary widely, based in part on level of physical activity and exposure to heat stress. Heat waves have the potential to result in an increased risk of dehydration, especially in older adults. Other beverages, however, such as fat-free or low-fat milk and 100% fruit juice, provide a substantial amount of nutrients along with the calories they contain. Water and unsweetened beverages, such as coffee and tea, contribute to total water intake without adding calories. Follow food safety principles Ensuring food safety is an important principle for building healthy eating patterns. Foodborne illness affects more than 76 million individuals in the United States every year and leads to 325, 000 hospitalizations and 5, 000 deaths. See Appendix 3 for more these behaviors are information about the four highlighted in the four food safety principles and basic food safety prinadditional guidance for ciples that work together specific population groups that are at higher risk of to reduce the risk of foodborne illness. These principles are: Clean hands, food contact surfaces, and vegetables and fruits. These include raw (unpasteurized) milk, cheeses, and juices; raw or undercooked animal foods, such as seafood, meat, poultry, and eggs; and raw sprouts. With the increase in consumption of bottled water, Americans may not be getting enough fluoride to maintain oral health. During the time that sugars and starches are in contact with teeth, they also contribute to dental caries. A combined approach of reducing the amount of time sugars and starches are in the mouth, drinking fluoridated water, and brushing and flossing teeth, is the most effective way to reduce dental caries. Common food allergies include those to milk, eggs, fish, crustacean shellfish, tree nuts, wheat, peanuts, and soybeans. Proteins in these foods trigger an abnormal immune response in persons allergic to the food. In comparison, food intolerances are due to the inability of the body to digest or metabolize a food component. For example, lactose intolerance is caused by a deficiency of the enzyme lactase that breaks down the sugar lactose in milk and milk products. Because food allergies and food intolerances can cause some of the same symptoms. Those who think they may have a food allergy or a food intolerance should be medically evaluated to avoid unnecessarily eliminating foods from their diet. However, for some food intolerances, like lactose intolerance, smaller portions. More information on food allergies and food intolerances can be found at. Americans should aim to meet their nutrient requirements through a healthy eating pattern that includes nutrient-dense forms of foods, while balancing calorie intake with energy expenditure. Dietary supplements or fortification of certain foods may be advantageous in specific situations to increase intake of a specific vitamin or mineral. In some cases, fortification can provide a food-based means for increasing intake of particular nutrients or providing nutrients in highly bioavailable forms. For many years, most fluid milk has been fortified with vitamin D to increase calcium absorption and prevent rickets. Vitamin D-fortified milk is now the major dietary source of vitamin D for many Americans. Other beverages and foods that often are fortified with vitamin D include orange juice, soy beverages, 75 and yogurt.

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Firmicutes, which are gram-positive bacteria, are the predominant bacteria able to deconjugate and dehydroxylate primary bile acids into secondary bile acids. Ruminococcus perform epimerization during the conversion from primary to secondary bile acids. Key Words: bile acids, enterohepatic circulation, lipid metabolism, rumen degradable starch, dairy goats 135 Thymol modulates chemo-sensing receptors and inflammation markers in the gut of weaning pigs. Thymol in vitro anti-oxidant and anti-inflammatory properties have been widely described, although details of the in vivo mechanism of action of thymol as a guthealth promoting agent are still lacking. More specifically, the involvement of thymol in gut chemo-sensing and intestinal function still has to be thoroughly elucidated. One hundred sixty pigs were fed 5 diets (n = 8) for 14 d: a pre-starter without (control, T1) or with thymol at 25. Moreover, data suggest a possible association between the upregulation of these receptors and the modulation of the inflammatory state in the duodenum which was never described before. Chickens were equipped with a Thermochron temperature logger for continuous monitoring of core body temperature. P101 Is the regulation of intestinal inflammation defective in high breast yield strain? The selection for rapid growth was already been associated with dysfunction of immune response in broilers. However, it is not known if animals selected for distinct body yield characteristics show differences in intestinal immunity. All the birds received the same corn/soy based diet formulated to meet or exceed their requirements. Thus, the gene expression of pro-inflammatory cytokines suggest that birds selected for high breast yield present a higher inflammatory status in the intestine. Also, high breast yielding broilers have lower ability of downregulate the intestinal inflammation, especially the ones affected by wooden breast. Key Words: wooden breast, genetic, gut health P102 Investigating intestinal barrier integrity in heat-stressed modern broilers and their ancestor Jungle Fowl. Four chicken populations: Giant Jungle Fowl, Athens Canadian Random Bred (1950s), 1995 Arkansas Random Bred, and Modern Random Bred (2015) were used. Day-old broiler chicks from each population were raised under thermoneutral conditions with feed and water intake measured daily. On d 28 the birds were subjected to 1 of 2 environment conditions: thermoneutral (24°C) or acute heat stress (2 h at 36°C). After the 2 h, samples from each section of the small intestine were harvested from 2 birds per line per treatment and flash frozen in liquid nitrogen. This data provides evidence for a mechanistic understanding of the gut physiology and how it can be influenced by growth-rate and heat stress. Clostridium perfringens is an anaerobic, spore-forming, gram-positive rod-shaped bacterium which is known to cause enteric infections in a variety of hosts, including humans and livestock. Previous research within our lab has found that as total fecal clostridia loads increase within a dairy herd dry-matter intake and milk yields subsequently become highly variable. We have also seen evidence of widely varying total fecal clostridia loads within lactation groups on a single farm, as well as across farms within dairy-producing regions throughout the United States. The aim of this work is to begin to characterize this variation in 11 animals within a single farm over the course of 3 weeks. We attempted to correlate these data with the feed component clostridia community, as well as several atmospheric measurements. We observed a correlation between ambient air temperature 31 at time of fecal sample collection and total clostridia count data (r = -0. We also observed several changes of community composition over the course of the 3 weeks between animals and overall within the farm, and that as the total clostridia load increases, so does the C. Initial community composition data indicates that this herd is primarily challenged by C. Variation within the enumeration data and community data appeared to show no easily discernable pattern within such a small time-scale. P104 Enumeration and identification of Clostridium along the gastrointestinal tract of dairy cows. Previous dairy feed and cow fecal surveys have indicated that the most abundant Clostridium species is C. Fourteen Holstein cows at the University of Illinois at Urbana-Champaign were challenged with a high, medium or low dose of P.

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Relevance the creation of digital twins could completely alter basic, translational and clinical cancer research, treatment, and population health by providing an advanced, in-silico modeling environment across the oncology spectrum. The digital twin would provide researchers with a computational tool to formulate predictions based on hypotheses and approximations that would improve over time with recourse to finer-scale calculations and observations. A digital twin would enable iterative and ensemble "what-if" evaluations of proposed interventions. This would allow physicians to not just better select the most effective treatment, but help patients weigh their treatment choices against their personal priorities and constraints. The digital twin population could identify high-risk populations and allow policymakers to evaluate different screening practices and guidelines. The digital twin capability has the potential to significantly impact policy and population health. In a clinical setting, a digital twin would also be a powerful tool for patient-physician communication to facilitate better informed patient choice and shared decision making. This cancer challenge builds on existing, but uncoordinated, efforts to create the first protodigital twins. For example, German researchers are using a very rudimentary virtual model to select the best treatments for melanoma patients. Collaborative efforts across disciplines are underway, and there is a need to coordinate efforts to deal with rapidly evolving data streams with various quality and time-scale issues. A multi-scale framework will incorporate genomic, molecular, cellular, and population models that are consistent across space and time scales. These models can incorporate social, behavioral and environmental factors such as diet and pollution exposure. One suggested biological framework for the digital twin-model presented by meeting participants is the Hallmarks of Cancer 22. These are defined as phenotypic changes at the cellular level that are shared by most, and possibly all, cancer types. However, these hallmarks of cancer are mostly studied in isolation and have proven to be of limited predictive utility at clinical scales. A digital twin program to computationally integrate these disparate hallmarks of cancer into one coherent model could be a major step toward understanding, predicting, and reducing cancer lethality. At point of care, digital twins could provide personalized evidence to guide treatment decisions. Patients would be able to see their virtual twin across multiple treatment scenarios, providing personalized information of their cancer progression, treatment related side-effects, and quality of life. The use of a population of digital twins, combined with leadership-class computing power, could augment the gold standard randomized clinical trial and enable rapid virtual clinical trials. These might be able to quickly and efficiently identify potential treatment failures and opportunities. The time, resources and cost of conducting current clinical trials make this a compelling alternative, including potentially saving billions of dollars in the development of new drugs. Population models for virtual prevention trials would take place over decades, over the entire space of the U. The biological models will need to be validated and doing so will push the art of verifying models in complex systems. Similarly, a digital twin model would push the frontier of uncertainty quantification and error estimation that reflect both computational and oncological sources of error. Tumors are a mix of heterogeneous cell types, can exist with dozens of slightly different genetic variants and can arise through clonal evolution. Cancers are mobile (metastasis), both infiltrating new tissue and triggering distal tissues to recruit cancer cells. The vision for adaptive treatments involves the development of biological and nano-device-based, personalized drug treatments that adapt to tumors over time. This approach builds on precision medicine, extending it to a new paradigm for cancer treatment. This challenge imagines direct-to-tumor interactive treatments that: Adapt to changing tumor characteristics during treatments; Target and attack metastasizing cancer cells, augmenting the immune system; Deliver novel therapeutics that fabricate molecules in-vivo at the tumor site. Relevance the systemic adaptation and multi-variant behavior of cancer must be addressed in futuregeneration therapies.

References:

  • https://www.ihpa.gov.au/sites/default/files/clinical_update_-_viral_hepatitis.pdf
  • http://www.ijpsi.org/Papers/Vol5(5)/D0505015028.pdf
  • https://www.maine.edu/human-resources/wp-content/uploads/sites/7/2020/02/Public-Information-Document-11.26.19_accessible.pdf
  • https://www.alnylam.com/wp-content/uploads/2018/05/TIDES_Capella-Slides_FINAL05082018.pdf
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