scholarly journals A computational modelling approach for deriving biomarkers to predict cancer risk in premalignant disease

2015 ◽  
Author(s):  
Andrew Dhawan ◽  
Trevor A Graham ◽  
Alexander G Fletcher
Keyword(s):  
Cancer Risk ◽  
Computational Modelling ◽  
Clonal Diversity ◽  
Clinical Problem ◽  
Tissue Sampling ◽  
Prognostic Information ◽  
Premalignant Disease ◽  
Molecular Measures ◽  
Major Clinical Problem ◽  
Predict Cancer Risk

The lack of effective biomarkers for predicting cancer risk in premalignant disease is a major clinical problem. There is a near-limitless list of candidate biomarkers and it remains unclear how best to sample the tissue in space and time. Practical constraints mean that only a few of these candidate biomarker strategies can be evaluated empirically and there is no framework to determine which of the plethora of possibilities is the most promising. Here we have sought to solve this problem by developing a theoretical platform for in silico biomarker development. We construct a simple computational model of carcinogenesis in premalignant disease and use the model to evaluate an extensive list of tissue sampling strategies and different molecular measures of these samples. Our model predicts that: (i) taking more biopsies improves prognostication, but with diminishing returns for each additional biopsy; (ii) longitudinally-collected biopsies provide slightly more prognostic information than a single biopsy collected at the latest possible time-point; (iii) measurements of clonal diversity are more prognostic than measurements of the presence or absence of a particular abnormality and are particularly robust to confounding by tissue sampling; and (iv) the spatial pattern of clonal expansions is a particularly prognostic measure. This study demonstrates how the use of a mechanistic framework provided by computational modelling can diminish empirical constraints on biomarker development.

scholarly journals A Computational Modeling Approach for Deriving Biomarkers to Predict Cancer Risk in Premalignant Disease

2016 ◽  
Vol 9 (4) ◽  
pp. 283-295 ◽  
Author(s):  
Andrew Dhawan ◽  
Trevor A. Graham ◽  
Alexander G. Fletcher
Keyword(s):  
Cancer Risk ◽  
Computational Modeling ◽  
Modeling Approach ◽  
Premalignant Disease ◽  
Predict Cancer Risk

Epidemiology and antimicrobial resistance of Acinetobacter

2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova
Keyword(s):  
Antibiotic Resistance ◽  
Laboratory Testing ◽  
Immunocompromised Host ◽  
Clinical Problem ◽  
Healthcare Associated Infections ◽  
Opportunistic Bacteria ◽  
Acinetobacter Spp ◽  
Healthcare Associated ◽  
Major Clinical Problem

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.

The Pre-dilatation of vessels: A simple method to recruit small caliber veins for creating distal fistulas

2021 ◽  
pp. 112972982098317
Author(s):  
Marcello Napoli ◽  
Anna Zito ◽  
Maria Luisa Lefons ◽  
Paolo Ria ◽  
Emiliana Ferramosca ◽  
...  
Keyword(s):  
Heart Disease ◽  
Arteriovenous Fistula ◽  
Clinical Problem ◽  
Early Failure ◽  
Simple Method ◽  
Maturation Rate ◽  
Vein Diameter ◽  
Major Clinical Problem

Maturation failure remains a major clinical problem of distal arteriovenous fistula (AVF). Early failure (EF) is associated with the small size of the veins. For about 10 years we have used in more than 1000 fistulas, the Vessels Pre-Dilatation (VPD) to increase the recruitment of small veins for creating distal AVFs. The purpose of this study is to highlight if the VPD can reduce the incidence of EF or failure to mature (FTM) in AVFs created with small veins. Data of all the consecutive patients directly admitted to our Department for their first distal AVF from January to December 2019 were collected. The patients were divided in two groups, one with a vein diameter after the tourniquet ⩽2.0 mm (G1) and one >2 mm (G2). Both in G1 then in G2 the vessels had undergone VPD. Immediate failure (IF), EF, FTM, delayed or arrested maturation rate (DAM), unassisted AVFs and matured AFVs were evaluated. The patients recruited totalled 104, 37 in G1, and 67 in G2. The two groups were homogeneous in age, incidence of diabetes, obesity, heart disease, peripheral vasculopathy, and race. Female were more numerous in G1 (51% vs 12%, p < 0.001). In G1 and G2 occurred respectively 3 IF versus zero ( p < 0.05), 10 EF (29%) versus 6 (9%) ( p < 0.05), 6 DAM (16%) versus 6 (9%), 21 unassisted AVFs (57%) versus 57 (85%) ( p < 0.01). Dividing the patients into groups of unassisted and assisted AVFs, female and low vein diameter are more represented in the assisted group. There were 32 matured AVFs (86%) in G1 and 65 (97%) in G2. In order to increase the incidence of the distal AVF, the PDV allows to include small veins. However, more patients require further interventions to achieve maturation of the fistula.

Noradrenergic and serotonergic modulation to treat vasomotor symptoms

2006 ◽  
Vol 12 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Paola Albertazzi
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Clinical Problem ◽  
Hot Flushes ◽  
Estrogen Replacement ◽  
Climacteric Symptoms ◽  
Limited Efficacy ◽  
Noradrenaline Reuptake ◽  
Menopausal Women ◽  
Major Clinical Problem ◽  
Serotonergic Modulation

Hot flushes are a major clinical problem for many menopausal women. Their aetiology is unknown. Centrally acting neurotransmitters are involved, but this involvement is yet to be fully characterized. In clinical trials with optimal patient selection and compliance, estrogen can reduce the frequency of hot flushes by 70–80%, and placebo by 20–40%. For some women, however, there are contraindications to the use of estrogen, and others are unwilling to use it. Furthermore, hot flushes may persist in spite of adequate estrogen replacement, and to improve symptoms physicians then have either to add another drug to the regimen or find an alternative to estrogen. The most commonly used non-hormonal alternatives for climacteric symptoms are neurotransmitter modulators such as the selective serotonin reuptake inhibitors. These reduce the frequency of hot flushes by 60%. The mechanism of this effect appears to differ from that underlying their effect on mood. They are generally well tolerated and rates of adverse events are far lower than those reported in studies of the use of these agents for depression. The limited efficacy of clonidine suggests that adrenergic mechanisms may be involved and data are awaited for more specific selective noradrenaline reuptake inhibitors. Thus, non-hormonal treatments are not as effective as estrogens in relieving hot flushes but may have a place as an alternative.

scholarly journals A Clinical Decision Support Tool to Predict Cancer Risk for Commonly Tested Cancer-Related Germline Mutations

2018 ◽  
Vol 27 (5) ◽  
pp. 1187-1199 ◽  
Author(s):  
Danielle Braun ◽  
Jiabei Yang ◽  
Molly Griffin ◽  
Giovanni Parmigiani ◽  
Kevin S. Hughes
Keyword(s):  
Decision Support ◽  
Cancer Risk ◽  
Clinical Decision Support ◽  
Decision Support Tool ◽  
Clinical Decision ◽  
Germline Mutations ◽  
Support Tool ◽  
Clinical Decision Support Tool ◽  
Predict Cancer Risk

Research Issues in Parenteral Nutrition

2009 ◽  
Vol 23 (4) ◽  
pp. 294-298
Author(s):  
Amit Tagare ◽  
Umesh Vaidya
Keyword(s):  
Parenteral Nutrition ◽  
Research Work ◽  
Research Priorities ◽  
Clinical Problem ◽  
Research Issues ◽  
Nutritional Interventions ◽  
Work Done ◽  
Developed World ◽  
Major Clinical Problem ◽  
Extrauterine Growth Retardation

Extrauterine growth retardation is a major clinical problem in preterm infants. Aggressive nutritional interventions may play an important role to fight this prevalent problem. Parenteral nutrition is almost indispensable part of aggressive nutritional approach in neonates, because of certain limitations of enteral route during first few days of life. Formidable research work done in developed world has resolved certain important issues like dosage regimens. However, still we need to resolve quite a few unanswered queries. This is especially true for Indian context where we deal with a different population of neonates than the developed world. In this article we will discuss both the resolved and unresolved issues regarding neonatal parenteral nutrition and the research priorities for us.

Biomarkers of acute kidney injury: time to learn from implementation

2021 ◽  
Vol 23 (2) ◽  
pp. 137-140
Author(s):  
Zoltán H Endre ◽  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Clinical Problem ◽  
Time To Learn ◽  
Hospital Acquired ◽  
Major Clinical Problem

Acute kidney injury (AKI) is a major clinical problem in the community and in hospital, with hospital-acquired AKI reported in about 20% of adult and 30% of paediatric admissions.

scholarly journals Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1772 ◽  
Author(s):  
Elena Lucarini ◽  
Carmen Parisio ◽  
Jacopo J. V. Branca ◽  
Cristina Segnani ◽  
Chiara Ippolito ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Visceral Pain ◽  
Clinical Problem ◽  
Nerve Fibers ◽  
Morphological Alterations ◽  
Mhc Ii ◽  
Maladaptive Plasticity ◽  
Central Nervous Systems ◽  
Major Clinical Problem

The management of visceral pain is a major clinical problem in patients affected by gastrointestinal disorders. The poor knowledge about pain chronicization mechanisms prompted us to study the functional and morphological alterations of the gut and nervous system in the animal model of persistent visceral pain caused by 2,4-dinitrobenzenesulfonic acid (DNBS). This agent, injected intrarectally, induced a colonic inflammation peaking on day 3 and remitting progressively from day 7. In concomitance with bowel inflammation, the animals developed visceral hypersensitivity, which persisted after colitis remission for up to three months. On day 14, the administration of pain-relieving drugs (injected intraperitoneally and intrathecally) revealed a mixed nociceptive, inflammatory and neuropathic pain originating from both the peripheral and central nervous system. At this time point, the colonic histological analysis highlighted a partial restitution of the tunica mucosa, transmural collagen deposition, infiltration of mast cells and eosinophils, and upregulation of substance P (SP)-positive nerve fibers, which were surrounded by eosinophils and MHC-II-positive macrophages. A significant activation of microglia and astrocytes was observed in the dorsal and ventral horns of spinal cord. These results suggest that the persistence of visceral pain induced by colitis results from maladaptive plasticity of the enteric, peripheral and central nervous systems.

Preliminary Investigation of the Mechanics of a Novel Thoracic Cavity Extra Pulmonary Oxygenation Device

2018 ◽  
Author(s):  
Fariba Aghabaglou ◽  
Keely Buesing ◽  
Nathan D. Legband ◽  
Connor Slagle ◽  
Wanchuan Xie ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Preliminary Investigation ◽  
Clinical Problem ◽  
Large Animal ◽  
Thoracic Cavity ◽  
New Methods ◽  
Injury Model ◽  
Lung Trauma ◽  
Major Clinical Problem

Acute respiratory distress syndrome (ARDS) arising from trauma, sepsis, pneumonia or other diseases has been acknowledged to be a major clinical problem in respiratory medicine. Hypoxia and hypercapnia arising from ARDS are life-threating particularly in children and elderly people. The reported mortality rate for ARDS is high. Current methods for treating patients who have limited or no lung function are ineffective or insufficient and present additional risks to the patients. In this research, we have explored new methods of infusing phospholipid-coated oxygen microbubbles (OMBs) to the thoracic cavity in order to oxygenate patients suffering from ARDS and hypoxemia. In our previous work, OMBs have been shown to be effective in treating hypoxia in models of LPS lung injury and lung trauma in rats and rabbits. In this study, we have developed a novel thoracic cavity extrapulmonary oxygenation devices using OMBs and test this device in a benchtop test and in vivo experiment on a large animal (pig) right pneumothorax injury model.

Cancer-induced bone pain

2015 ◽  
Author(s):  
Lesley A. Colvin ◽  
Marie Fallon
Keyword(s):  
Bone Pain ◽  
Clinical Presentation ◽  
Clinical Problem ◽  
Current Therapy ◽  
Pain Mechanisms ◽  
Pain Syndromes ◽  
Current Therapies ◽  
Underlying Mechanisms ◽  
Laboratory Models ◽  
Major Clinical Problem

Bone is the third most common site of metastatic disease, after liver and lung, with approximately 75% of these patients suffering from related pain. Cancer-induced bone pain (CIBP) is a major clinical problem, with limited options for predictable, rapid, and effective treatment for some of the elements without unacceptable adverse effects. Our understanding of how current therapy acts is based mainly on studies in non-cancer pain syndromes, which are likely to be quite different, not only in clinical presentation, but also in terms of pathophysiology. It can be difficult to study the specific neurobiological changes associated with CIBP, although development of laboratory models of isolated bone metastases has allowed more specific study of pain mechanisms in this syndrome. In order to evaluate our current therapies properly and direct the development of new therapies logically, it is important to understand the underlying mechanisms of CIBP. This chapter discusses pain processing and the mechanisms and management of CIBP.

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