4.4 Interim Financial Statements

2.1 Applicatio

The attachment system and physiology in adulthood: normative processes, individual differences, and implications for health.

Attachment theory provides a conceptual framework for understanding intersections between personality and close relationships in adulthood. Moreover, attachment has implications for stress-related physiology and physical health. We review work on normative processes and individual differences in the attachment behavioral system, as well as their associations with biological mechanisms related to health outcomes. We highlight the need for more basic research on normative processes and physiology and discuss our own research on individual differences in attachment and links with physiology. We then describe a novel perspective on attachment and physiology, wherein stress-related physiological changes may also be viewed as supporting the social-cognitive and emotion regulatory functions of the attachment system through providing additional energy to the brain, which has implications for eating behavior and health. We close by discussing our work on individual differences in attachment and restorative processes, including sleep and skin repair, and by stressing the importance of developing biologically plausible models for describing how attachment may impact chronic illness

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Luminally expressed gastrointestinal biomarkers

Introduction: A biomarker is a measurable indicator of normal biologic processes, pathogenic processes or pharmacological responses. The identification of a useful biomarker is challenging, with several hurdles to overcome before clinical adoption. This review gives a general overview of a range of biomarkers associated with inflammatory bowel disease or colorectal cancer along the gastrointestinal tract. Areas covered: These markers include those that are already clinically accepted, such as inflammatory markers such as faecal calprotectin, S100A12 (Calgranulin C), Fatty Acid Binding Proteins (FABP), malignancy markers such as Faecal Occult Blood, Mucins, Stool DNA, Faecal microRNA (miRNA), other markers such as Faecal Elastase, Faecal alpha-1-antitrypsin, Alpha2-macroglobulin and possible future markers such as microbiota, volatile organic compounds and pH. Expert commentary: There are currently a few biomarkers that have been sufficiently validated for routine clinical use at present such as FC. However, many of these biomarkers continue to be limited in sensitivity and specificity for various GI diseases. Emerging biomarkers have the potential to improve diagnosis and monitoring but further study is required to determine efficacy and validate clinical utility

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

TABLE OF CONTENTS PART I SURFACE WATER STANDARDS WITH GENERAL, STATEWIDE APPLICATION

9 VAC 25-260-10 Designation of Uses page 5 9 VAC 25-260-20 General Criteria/Mixing Zones page

Salivary cytokines as biomarkers of periodontal diseases

Periodontal disease is time consuming and expensive to treat and therefore its prevention, early detection and management are issues which, if effectively addressed, are likely to yield considerable health-care benefit (97). However, despite numerous advances in our understanding of the pathogenesis of chronic inflammatory diseases, periodontitis is still only diagnosed once connective tissue and bone destruction has occurred. Furthermore, monitoring disease progression is a highly skilled and technically demanding process, involving measurement of bleeding on probing, probing depth and attachment loss coupled with radiographic assessment and (subjective) visual observations (76). It would be highly desirable to develop biomarkers for early detection of periodontal disease and to identify progression because current diagnostic approaches do not reflect current disease activity but simply assess the cumulative effects of historical tissue destruction (53). Rational diagnosis would also have concomitant patient benefit because the paucity of evidence-based knowledge of disease progression in individual patients may lead to unintentional clinical mismanagement (97). In addition, studies of the salivary mediators associated with disease may help in the development of novel therapies aimed at controlling cytokine bioavailability (e.g. through anti-cytokine antibodies, antagonists or soluble receptors) or by targeting the intracellular signaling pathways they activate, approaches which have been successful in the treatment of other chronic inflammatory diseases, such as rheumatoid arthritis (60, 91, 95). Cytokines have been defined as soluble factors produced by one (immune) cell that act on another cell within the same milieu (26). However, it is now recognized that the range of molecules with cytokine-like activity can be extended to include, for example, growth factors and adipokines, which also have immunoregulatory functions. Importantly, cytokine functions often overlap or merge, building a complex immunoregulatory network in the immune system that is often perturbed in disease. It is increasingly appreciated that cytokines have vital roles in the development and homeostasis of numerous cell types and, in a wide range of tissues, have roles in resolution of inflammation, wound healing, repair and regeneration. In the following review, the term ‘cytokine’ will be used in this broad context. In addition to direct analysis of cytokines, the levels of molecules such as matrix metalloproteinases and tissue inhibitors of metalloproteinases, which are regulated by cytokines, have also been given considerable attention as potential periodontitis biomarkers, as reviewed elsewhere in this volume of Periodontology 2000

Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important. METHODS: The five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD. DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD