International guideline comparison of lifestyle management for acute coronary syndrome and type 2 diabetes mellitus: A rapid review.

Acute coronary syndrome (ACS) is a life-threatening condition, with ACS-associated morbidity and mortality causing substantial human and economic challenges to the individual and health services. Due to shared disease determinants, those with ACS have a high risk of comorbid Type 2 diabetes mellitus (T2DM). Despite this, the two conditions are managed separately, duplicating workload for staff and increasing the number of appointments and complexity of patient management plans. This rapid review compared current ACS and T2DM guidelines across Australia, Canada, Europe, Ireland, New Zealand, the UK, and the USA. Results highlighted service overlap, repetition, and opportunities for integrated practice for ACS-T2DM lifestyle management across diet and nutrition, physical activity, weight management, clinical and psychological health. Recommendations are made for potential integration of ACS-T2DM service provision to streamline care and reduce siloed care in the context of the health services for ACS-T2DM and similar comorbid conditions.

Canis Familiaris Papillomavirus Type 26: A Novel Papillomavirus of Dogs and the First Canine Papillomavirus within the Omegapapillomavirus Genus.

Domestic dogs are currently recognized as being infected by 25 different canine papillomavirus (CPV) types classified into three genera. A short sequence from a novel CPV type was amplified, along with CPV1, from a papilloma (wart) from the mouth of a dog. The entire 7499 bp genome was amplified, and CPV26 contained putative coding regions that were predicted to produce four early proteins and two late ones. The ORF L1 showed less than 62% similarity for all previously sequenced CPV types but over 69% similarity to multiple Omegapapillomavirus types from a variety of Caniform species including the giant panda, Weddel seal, and polar bear. Phylogenetic analysis confirmed CPV26 clusters within the Omegapapillomavirus genus. Specific primers were used to investigate the presence of CPV26 DNA within a series of 37 canine proliferative lesions. CPV26 DNA was amplified from one lesion, a cutaneous papilloma that also contained CPV6. This is the first time a PV type within the Omegapapillomavirus genus has been detected in a non-domestic species and this provides evidence that the omegapapillomaviruses infected a common ancestor of, and then co-evolved with, the Caniform species. Whether CPV26 causes disease is uncertain, but the absence of an E7 protein may suggest low pathogenicity.

Evaluation of an Innovative Colon Capsule Endoscopy Service in Scotland From the Perspective of Patients: Mixed Methods Study.

BACKGROUND: Colonoscopy is the gold standard for lower gastrointestinal diagnostics. The procedure is invasive, and its demand is high, resulting in long waiting times. Colon capsule endoscopy (CCE) is a procedure that uses a video capsule to investigate the colon, meaning that it can be carried out in a person's own home. This type of "hospital-at-home" service could potentially reduce costs and waiting times, and increase patient satisfaction. Little is currently understood, however, about how CCE is actually experienced and accepted by patients. OBJECTIVE: The aim of this study was to capture and report patient experiences of the CCE technology (the capsule and associated belt and recorder) and of the new clinical pathway for the CCE service being rolled out as part of routine service in Scotland. METHODS: This was a mixed methods service evaluation of patient experiences of a real-world, deployed, managed service for CCE in Scotland. Two hundred and nine patients provided feedback via a survey about their experiences of the CCE service. Eighteen of these patients took part in a further telephone interview to capture more in-depth lived experiences to understand the barriers and opportunities for the further adoption and scaling up of the CCE service in a way that supports the patient experience and journey. RESULTS: Patients overall perceived the CCE service to be of significant value (eg, mentioning reduced travel times, reduced waiting times, and freedom to complete the procedure at home as perceived benefits). Our findings also highlighted the importance of clear and accessible information (eg, what to expect and how to undertake the bowel preparation) and the need for managing expectations of patients (eg, being clear about when results will be received and what happens if a further colonoscopy is required). CONCLUSIONS: The findings led to recommendations for future implementations of managed CCE services in National Health Service (NHS) Scotland that could also apply more widely (United Kingdom and beyond) and at a greater scale (with more patients in more contexts). These include promoting CCE with, for, and among clinical teams to ensure adoption and success; capturing and understanding reasons why patients do and do not opt for CCE; providing clear information in a variety of appropriate ways to patients (eg, around the importance of bowel preparation instructions); improving the bowel preparation (this is not specific to CCE alone); providing flexible options for issuing and returning the kit (eg, dropping off at a pharmacy); and embedding formative evaluation within the service itself (eg, capturing patient-reported experiences via surveys in the information pack when the equipment is returned).

Oxidation state-specific fluorescent copper sensors reveal oncogene-driven redox changes that regulate labile copper(II) pools.

Copper is an essential metal nutrient for life that often relies on redox cycling between Cu(I) and Cu(II) oxidation states to fulfill its physiological roles, but alterations in cellular redox status can lead to imbalances in copper homeostasis that contribute to cancer and other metalloplasias with metal-dependent disease vulnerabilities. Copper-responsive fluorescent probes offer powerful tools to study labile copper pools, but most of these reagents target Cu(I), with limited methods for monitoring Cu(II) owing to its potent fluorescence quenching properties. Here, we report an activity-based sensing strategy for turn-on, oxidation state-specific detection of Cu(II) through metal-directed acyl imidazole chemistry. Cu(II) binding to a metal and oxidation state-specific receptor that accommodates the harder Lewis acidity of Cu(II) relative to Cu(I) activates the pendant dye for reaction with proximal biological nucleophiles and concomitant metal ion release, thus avoiding fluorescence quenching. Copper-directed acyl imidazole 649 for Cu(II) (CD649.2) provides foundational information on the existence and regulation of labile Cu(II) pools, including identifying divalent metal transporter 1 (DMT1) as a Cu(II) importer, labile Cu(II) increases in response to oxidative stress induced by depleting total glutathione levels, and reciprocal increases in labile Cu(II) accompanied by decreases in labile Cu(I) induced by oncogenic mutations that promote oxidative stress.

Policy Considerations to Promote Equitable Cervical Cancer Screening and Treatment in Peru.

Background: Cervical cancer is one of the leading causes of death among Peruvian women. Women seeking screening or treatment services experience delays in receiving screening results provided at community clinics or district hospitals, and lack sufficient resources to pay out-of-pocket to travel to the capital city of Lima for specialized treatment. Continued disparities in health outcomes and systemic barriers to accessing services suggest there are gaps between policy measures and implementation. Objectives: We aim to understand why national policies and clinical pathways that are aligned to global standards have been insufficient in improving cervical cancer screening and treatment in Peru, particularly among women who experience systemic exclusion from health services. Methods: We conducted a policy analysis based on a literature review (2005-2020), in Spanish and English, on PubMed, Global Health, Scopus, EconLit, Lilacs, and Scielo using a value-based care framework. Findings: The main barriers included unequal distribution of health infrastructure and health care workforce, and differences in access to health insurance. Additional barriers, including limited political will and support, limit efforts to prioritize the implementation of cervical cancer policies. We propose policy considersations in redesigning payment models, expanding healthcare workforce, generating costing and policy evidence, and reviewing policies for point-of-care technologies. Conclusions and Recommendations: The barriers identified in this literature review are applicable not only to cervical cancer care, but to primary health care in Peru. Systematic policy changes that address root causes of health inequities and are implemented at scale are needed to advance health reform efforts.

The Accommodation of Bone Anchors Within the Distal Phalanx for Repair of Flexor Digitorum Profundus Avulsions.

PURPOSE: Avulsion injury of the flexor digitorum profundus (FDP) tendon has been traditionally repaired with a pull-out suture over the nail plate. Complication rates with this method and improvements in anchor design have led to the increased use of bone anchors to give a rigid all-inside repair. However, the dimensions of the distal phalanx may limit their use. The primary hypothesis was that 2 micro bone anchors could fit in either perpendicular or 45° proximally angled positions within each distal phalanx. A further hypothesis was that 1 mini bone anchor could fit in similar positions in the distal phalanx. METHODS: Thirty-two fresh frozen fingers were dissected, and the FDP tendon was removed from the distal phalanx footprint. Two bone anchor types were used, mini and micro sizes, and inserted at 2 angles, perpendicular and 45° proximally angled. Observations of dorsal cortex and joint space penetration were recorded. Distal phalanx dimensions were measured for each finger. RESULTS: The micro anchors penetrated the dorsal cortex in perpendicular tests in little fingers only. The micro anchor did not penetrate the joint in any angled tests. The mini bone anchor penetrated the dorsal cortex in 100% of perpendicular tests and the joint in 63% of angled tests, although none of these included the middle finger. CONCLUSIONS: Two micro bone anchors fit within the distal phalanx in all fingers tested, except the little finger, when placed in the perpendicular position. At a 45° angle, the distal phalanx of the little finger can also accommodate micro bone anchors without any evidence of complication when placed 4 mm from the joint. The mini anchors were too large to fit in a perpendicular position within the distal phalanx. In the 45° angled position, the joint was not penetrated by the mini anchor in only middle fingers. CLINICAL RELEVANCE: The study provides anatomical evidence of the accommodation of micro bone anchors within the distal phalanx in perpendicular or 45° angled positions for the repair of FDP tendon avulsion injury.

The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat.

PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of α-galactosidase A to restore lysosomal activity. METHODS: A pharmacogenetic assay was used to identify the α-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity were measured by a good laboratory practice (GLP)-validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies. RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell α-galactosidase A responses to migalastat in male patients showed high sensitivity, specificity, and positive and negative predictive values (≥0.875). GLP HEK assay results were also predictive of decreases in kidney globotriaosylceramide in males and plasma globotriaosylsphingosine in males and females. The clinical study subset of amenable mutations (n = 51) was representative of all 268 amenable mutations identified by the GLP HEK assay. CONCLUSION: The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat.Genet Med 19 4, 430-438.

NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma.

Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels. Engineered T cells expanded, persisted, trafficked to marrow and exhibited a cytotoxic phenotype. Persistence of engineered T cells in blood was inversely associated with NY-ESO-1 levels in the marrow. Disease progression was associated with loss of T cell persistence or antigen escape, in accordance with the expected mechanism of action of the transferred T cells. Encouraging clinical responses were observed in 16 of 20 patients (80%) with advanced disease, with a median progression-free survival of 19.1 months. NY-ESO-1-LAGE-1 TCR-engineered T cells were safe, trafficked to marrow and showed extended persistence that correlated with clinical activity against antigen-positive myeloma.

Heterochromatin protein 1 expression is reduced in human thyroid malignancy.

Owing to the loss of heterochromatin integrity that occurs during thyroid tumorigenesis, the expression of Heterochromatin Protein 1 isoforms HP1α and HP1ß was assessed by immunohistochemistry in 189 thyroid tumors and non-neoplastic tissues. Expression of HP1ß was significantly decreased in all thyroid lesions, except in follicular adenomas, when compared with matched adjacent normal tissue. This loss of HP1ß expression may in part be caused by microRNA dysregulation. An example is miR-205, a microRNA that is abundantly upregulated in thyroid carcinomas and shown to reduce the expression of HP1ß. In contrast to HP1ß, HP1α expression was only reduced in metastatic carcinomas and poorly differentiated lesions. These results suggest the reduction of HP1ß followed by a decrease in HP1α contributes to the pathogenesis of thyroid carcinomas, and their loss is a potential marker of thyroid malignancy and metastatic potential, respectively.

Regulated assembly of vacuolar ATPase is increased during cluster disruption-induced maturation of dendritic cells through a phosphatidylinositol 3-kinase/mTOR-dependent pathway.

The vacuolar (H(+))-ATPases (V-ATPases) are ATP-driven proton pumps composed of a peripheral V1 domain and a membrane-embedded V0 domain. Regulated assembly of V1 and V0 represents an important regulatory mechanism for controlling V-ATPase activity in vivo. Previous work has shown that V-ATPase assembly increases during maturation of bone marrow-derived dendritic cells induced by activation of Toll-like receptors. This increased assembly is essential for antigen processing, which is dependent upon an acidic lysosomal pH. Cluster disruption of dendritic cells induces a semi-mature phenotype associated with immune tolerance. Thus, semi-mature dendritic cells are able to process and present self-peptides to suppress autoimmune responses. We have investigated V-ATPase assembly in bone marrow-derived, murine dendritic cells and observed an increase in assembly following cluster disruption. This increased assembly is not dependent upon new protein synthesis and is associated with an increase in concanamycin A-sensitive proton transport in FITC-loaded lysosomes. Inhibition of phosphatidylinositol 3-kinase with wortmannin or mTORC1 with rapamycin effectively inhibits the increased assembly observed upon cluster disruption. These results suggest that the phosphatidylinositol 3-kinase/mTOR pathway is involved in controlling V-ATPase assembly during dendritic cell maturation.

The segmentation of colorectal MRI images.

One of the key criteria that informs patient management decisions for colorectal cancer is the extent of the shortest distance from the edge of the primary tumour to the edge of the mesorectum, also referred to as circumferential resection margin (CRM). This region is resected during surgery. The CRM is difficult for clinicians to measure accurately, particularly from 2D slice data. We present a method for automatically calculating and visualising the CRM distances in colorectal cancer MR images. We use local phase of the monogenic signal calculated from the MR image intensities to find edge and ridge features within the data. A non-parametric mixture model is then used to describe image intensity values within level set framework in order to segment the mesorectal fascia and the corresponding tumour and lymph nodes, as distinct regions. This segmentation is used to provide an automatic analysis of the shortest distance resection margin, and we show that this is consistent with that of the clinically accepted MERCURY method. We use the segmentation to provide a 3D visualisation of where the resection margin is smallest. Finally, we reconstruct a 3D map of the segmented anatomy. Both the visualisation methods provide a useful tool to aid surgeons in their treatment planning.

Function of a subunit isoforms of the V-ATPase in pH homeostasis and in vitro invasion of MDA-MB231 human breast cancer cells.

It has previously been shown that highly invasive MDA-MB231 human breast cancer cells express vacuolar proton-translocating ATPase (V-ATPases) at the cell surface, whereas the poorly invasive MCF7 cell line does not. Bafilomycin, a specific V-ATPase inhibitor, reduces the in vitro invasion of MB231 cells but not MCF7 cells. Targeting of V-ATPases to different cellular membranes is controlled by isoforms of subunit a. mRNA levels for a subunit isoforms were measured in MB231 and MCF7 cells using quantitative reverse transcription-PCR. The results show that although all four isoforms are detectable in both cell types, levels of a3 and a4 are much higher in MB231 than in MCF7 cells. Isoform-specific small interfering RNAs (siRNA) were employed to selectively reduce mRNA levels for each isoform in MB231 cells. V-ATPase function was assessed using the fluorescent indicators SNARF-1 and pyranine to monitor the pH of the cytosol and endosomal/lysosomal compartments, respectively. Cytosolic pH was decreased only on knockdown of a3, whereas endosome/lysosome pH was increased on knockdown of a1, a2, and a3. Treatment of cells with siRNA to a4 did not affect either cytosolic or endosome/lysosome pH. Measurement of invasion using an in vitro transwell assay revealed that siRNAs to both a3 and a4 significantly inhibited invasion of MB231 cells. Immunofluorescence staining of MB231 cells for V-ATPase distribution revealed extensive intracellular staining, with plasma membrane staining observed in approximately 18% of cells. Knockdown of a4 had the greatest effect on plasma membrane staining, leading to a 32% reduction. These results suggest that the a4 isoform may be responsible for targeting V-ATPases to the plasma membrane of MB231 cells and that cell surface V-ATPases play a significant role in invasion. However, other V-ATPases affecting the pH of the cytosol and intracellular compartments, particularly those containing a3, are also involved in invasion.

V-ATPase functions in normal and disease processes.

Eukaryotic cells have evolved a family of ATP-dependent proton pumps known as the vacuolar (H(+))-ATPases (or V-ATPases) to regulate the pH of intracellular compartments, the extracellular space, and the cytoplasm. V-ATPases present within intracellular compartments are important for such normal cellular processes as receptor-mediated endocytosis and intracellular membrane traffic, protein processing and degradation and coupled transport of small molecules and ions. They also facilitate the entry of a number of envelope viruses and bacterial toxins, including influenza virus and anthrax toxin. V-ATPases present in the plasma membranes of cells are also important in normal physiology. They facilitate bone resorption by osteoclasts, acid secretion by intercalated cells of the kidney, pH homeostasis in macrophages and neutrophils, angiogenesis by endothelial cells, and sperm maturation and storage in the male reproductive tract. In the insect midgut, they establish a membrane potential used to drive K(+) secretion. Plasma membrane V-ATPases are especially important in human disease, with genetic defects in V-ATPases expressed in osteoclasts and intercalated cells leading to the diseases osteopetrosis and renal tubule acidosis, respectively. Plasma membrane V-ATPases have also been implicated in tumor cell invasion. V-ATPases are thus emerging as potential targets in the treatment of diseases such as osteoporosis and cancer.

Cytokine gene polymorphisms in heavy drinkers with and without decompensated liver disease: a case-control study.

BACKGROUND: Twin studies have suggested some genetic predisposition to alcoholic liver disease (ALD). Cytokines may be involved in ALD pathogenesis. Several cytokine genes contain functionally significant polymorphisms. Associations between ALD and polymorphisms on the interleukin-1 (IL-1), IL-10, and tumor necrosis factor-alpha (TNF-alpha) genes have been reported but not confirmed. OBJECTIVE: Comparison of allelic frequencies of cytokine gene polymorphisms between 223 patients with decompensated ALD (a more severe phenotype than in previous studies) and 162 controls with similar lifetime alcohol consumption but without serious liver disease. METHODS: Genotyping of polymorphisms of the genes for IL-1A (+4,845), IL-1B (+3,954 and -511), IL-1 receptor antagonist (+2,018), IL-6 (-174), IL-10 (-574 and -1,117), and TNF-alpha (-238 and -308). RESULTS: There were increases with respect to IL-6 -174 (2 x 3 chi(2)P < 0.1, OR for G allele carriage 1.61[1.05-2.48]) and Il-10 -592 (2 x 3 chi(2) 7.90, P < 0.01, OR for AA genotype carriage 4.85[1.40-16.8]) polymorphisms in patients compared with heavy-drinking controls. Differences were greater with analysis confined to Child's C patients. Genotype distribution for the other seven polymorphisms did not differ significantly between patients and heavy-drinking controls. CONCLUSION: These data are consistent with a modest role for IL-6 -174, and IL-10 -592 polymorphisms in genetic susceptibility to ALD.

The Ras/cAMP/protein kinase A pathway regulates glucose-dependent assembly of the vacuolar (H+)-ATPase in yeast.

Vacuolar (H+)-ATPases (V-ATPases) are ubiquitous, ATP-driven proton pumps that acidify organelles or the extracellular space. A rapid and effective mechanism for regulating V-ATPase activity involves reversible dissociation of the two functional domains of the pump, V1 and V0. This process is best characterized in yeast, where V-ATPases are reversibly disassembled in response to glucose depletion. To identify regulators that control this process in vivo, a genetic screen was performed in yeast to search for mutants that cannot disassemble their V-ATPases when grown in the absence of glucose. This screen identified IRA1 (inhibitory regulator of the Ras/cAMP pathway 1) and IRA2 as essential genes for regulating V-ATPase dissociation in vivo. IRA1 and IRA2 encode GTPase-activating proteins that negatively regulate Ras in nutrient-poor conditions. Down-regulation of Ras lowers cAMP levels by reducing adenylate cyclase activity. Decreased cAMP levels in turn lead to reduced activity of protein kinase A (PKA). Our results show that targeted deletion of IRA2 results in defective disassembly of the V-ATPase in response to glucose depletion, and reexpression of the gene rescues this phenotype. Glucose-dependent dissociation is also blocked in strains expressing the dominant active RAS2val19 allele or in strains deficient for the regulatory subunit of PKA, both of which lead to constitutively active PKA. These results reveal a role for PKA in controlling glucose-dependent V-ATPase assembly in yeast.

A review of the practical advantages of low molecular weight heparin in the treatment of cancer-related venous thromboembolism.

Patients with cancer, particularly those with metastatic cancer, are at high risk of venous thromboembolism (VTE), which places a huge burden on healthcare resources and can adversely affect patients' prognosis. In addition, VTE can have a negative impact on quality of life and increase the management challenges faced by physicians and nurses. Conventional long-term treatment using vitamin K antagonists, such as warfarin, presents many practical problems for cancer patients including frequent monitoring and dose adjustment, drug interactions, and disruption of anticoagulation for invasive procedures. The aim of this article is to review the potential advantages of using low molecular weight heparin (LMWH) in the treatment of cancer-related VTE in comparison to conventional therapy with warfarin or standard heparin. The potential advantages were determined via a literature review. LMWH is at least as effective as standard heparin or warfarin, and has been shown to have several benefits over warfarin in cancer patients. The simplicity of this therapy enables patients to be treated at home, and has been shown to have a positive impact on overall quality of life. The use of LMWH provides a treatment alternative to patients with cancer offering them hope and optimism regarding their care.

Structure and regulation of the vacuolar ATPases.

The vacuolar (H(+))-ATPases (V-ATPases) are ATP-dependent proton pumps responsible for both acidification of intracellular compartments and, for certain cell types, proton transport across the plasma membrane. Intracellular V-ATPases function in both endocytic and intracellular membrane traffic, processing and degradation of macromolecules in secretory and digestive compartments, coupled transport of small molecules such as neurotransmitters and ATP and in the entry of pathogenic agents, including envelope viruses and bacterial toxins. V-ATPases are present in the plasma membrane of renal cells, osteoclasts, macrophages, epididymal cells and certain tumor cells where they are important for urinary acidification, bone resorption, pH homeostasis, sperm maturation and tumor cell invasion, respectively. The V-ATPases are composed of a peripheral domain (V(1)) that carries out ATP hydrolysis and an integral domain (V(0)) responsible for proton transport. V(1) contains eight subunits (A-H) while V(0) contains six subunits (a, c, c', c'', d and e). V-ATPases operate by a rotary mechanism in which ATP hydrolysis within V(1) drives rotation of a central rotary domain, that includes a ring of proteolipid subunits (c, c' and c''), relative to the remainder of the complex. Rotation of the proteolipid ring relative to subunit a within V(0) drives active transport of protons across the membrane. Two important mechanisms of regulating V-ATPase activity in vivo are reversible dissociation of the V(1) and V(0) domains and changes in coupling efficiency of proton transport and ATP hydrolysis. This review focuses on recent advances in our lab in understanding the structure and regulation of the V-ATPases.

Estimating the mesorectal fascia in MRI.

Apart from chemoradiotherapy, surgery by total mesorectal resection is currently the only curative therapy for colorectal cancer. However, this often has a poor outcome, especially if there are affected lymph nodes too close to the resection boundary. The circumferential resection margin (CRM) is defined as the shortest distance from an affected region to the mesorectal fascia (MF), and should be at least 1 mm. However, this 3D distance is normally estimated in 2D (from image slices) and takes no account of uncertainty of the position of the MF. We describe a system able to estimate the location of the MF with a measure at each point along it of the uncertainty in location, and which then estimates the CRM in three dimensions. The MF localisation algorithm combines anatomical knowledge with a level set method based on: a non-parametric representation of the distribution of intensities, and the use of the monogenic signal to detect portions of the boundary.

Cytokine gene polymorphisms involved in chronicity and complications of anterior uveitis.

The aim of this study was to identify key cytokine polymorphisms associated with disease susceptibility, clinical phenotype, and outcome in patients with chronic anterior uveitis (CAU) as compared to those with recurrent self-limiting anterior uveitis (RAU). One hundred fifty seven British Caucasian patients with anterior uveitis were identified and divided into those where the inflammatory process lasted less than 3 months (RAU=118) and those where the inflammation persisted longer than 3 months (CAU=39). Patients with CAU were further sub-divided into idiopathic CAU, CAU associated with systemic disease, CAU with and without complications (posterior synechiae, posterior subcapsular lens opacity, raised intraocular pressure, cystoid macular oedema, and poor response to treatment). Sixty-six healthy controls were ethnically matched. TaqMan PCR amplification was used to genotype five single nucleotide polymorphisms in cytokine genes; IL-1RN+2018, IL-6-174, IL-10-1082, TNF-238, TNF-308 and these were correlated with clinical phenotype.

Simultaneous registration and landmark detection.

We are developing a system for patient management in colorectal cancer, in which a difficult case of non-rigid registration, namely of pre- and post-therapy images, arises. Numerous non-rigid registration algorithms have been proposed in medical image analysis, and we have applied several leading algorithms to our non-rigid registration problem; but with unpromising results. The fundamental reason appears to be that they lack with knowledge of the particular application. We propose a graphical representation of anatomical knowledge relevant for colorectal cancer, and of the ways in which this anatomy may be predicted to change as a result of chemo and radiotherapy. We show how we interleave this representation with an adaptive registration algorithm to make the non-rigid registration result both robust and accurate.