An introduction to the proceedings of the CCP4 Study Weekend held at the University of Warwick on the 5–6 January 2012.
CCP4 Study Weekend 2012
The 69th meeting of the Society was held in Aberdeen on May 22 and 23, 1964. The meetings were held in the University Medical Buildings, Aberdeen, and the President, Mr. G. F. Rowbotham, was in the Chair.
The International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of “population images” that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures.
• New diagnostic technologies are yielding unprecedented amounts of diagnostic information.
• Advanced IT/cloud computing will aid integration and analysis of diagnostic data.
• Better diagnostic algorithms will lead to faster diagnosis and more rapid treatment.
Radiology; Diagnostic techniques and procedures; Informatics; Algorithms; Efficiency; Organizational
Studies investigating genetic risk factors for susceptibility to rheumatoid arthritis (RA) studied anti-citrullinated peptide antibody (CCP)-positive RA more frequently than anti-CCP-negative RA. One of the reasons for this is the perception that anti-CCP-negative RA may include patients that fulfilled criteria for RA but belong to a wide range of diagnoses. We aimed to evaluate the validity of this notion and explored whether clinical subphenotypes can be discerned within anti-CCP-negative RA.
The 318 patients with anti-CCP-negative RA (1987 ACR criteria), included in the Leiden Early Arthritis Clinic between 1993 and 2006, were studied for baseline characteristics and radiologic progression data during a mean follow-up of 5 years. Grouping was studied both at variable and patient levels. Principal components analysis and partial least-squares regression were applied to study for clustering of variables. A cluster analysis was performed to look for clustering of patients.
The simultaneous presence of patient characteristics at disease presentation was observed for several groups; however, the three largest groups of patients' characteristics explained only 26.5% of the total variance. Plotting the contribution of each patient to these three groups did not reveal clustering of patients. Comparable observations were made when data on progression of joint destruction were studied in relation to baseline clinical data. A cluster analysis, evaluating whether patients resemble each other, revealed no grouping of patients. Altogether, no clinically distinguishable subphenotypes were observed.
The current data provide evidence that, for risk-factor studies, anti-CCP-negative RA patients can be studied as one group.
An introduction to the proceedings of the CCP4 study weekend is given.
The 57th meeting of the Society of British Neurological Surgeons was held in Holland as a joint meeting with the Netherlands Society of Neurosurgeons. Meetings were held at St. Ursula Clinic, Wassenaar, on May 9, and at the University Neurosurgical Department, Utrecht, on May 10. The two Presidents, W. R. HENDERSON (Leeds) and H. VERBIEST (Utrecht), occupied the chair in rotation.
The use of epidemiology in documenting the mortality experience in complex emergencies has become pervasive in humanitarian practice. Recent assessments in Iraq and Darfur have provoked much discussion on the assessment of mortality in scientific and policy spheres. In this context, the Centre for Research on the Epidemiology of Disasters and the Harvard Humanitarian Initiative held an inter-disciplinary symposium to examine the topic among epidemiologists, demographers, forensic scientists and legal and human rights investigators.
We aimed to strengthen the scientific understanding of mortality estimation by reviewing progress across fields and building inter-disciplinary bridges. We report on the presentations and discussions here.
The Tumour Board Meeting was held on August 16, 2011, in the Seminar Hall at B.J. Wadia Hospital for children. The panelists of the meeting were Dr. S. Ranganathan, Pediatric Pathologist from Children's Hospital of Pittsburgh; Dr. Archana Swami, Consultant Pediatric Oncologist at Wadia Children's Hospital; Dr. Sajid Qureshi Onco-surgeon (Pediatric) at Tata Memorial Hospital and Dr. Sushmita Bhatnagar.
Solid tumors; children; tumor board meeting; multimodality treatment
The 2011 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Denver, Colorado in advance of the Society of Toxicologic Pathology’s 30th Annual Meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and microgliomas in rats; a diagnostically challenging microcytic, hypochromic, responsive anemia in rats; a review of microcytes and microcytosis; nasal lesions associated with green tea extract and Ginkgo biloba in rats; corneal dystrophy in Dutch belted rabbits; valvulopathy in rats; and lymphoproliferative disease in a cynomolgus monkey.
NTP Satellite Symposium; ameloblastoma; gas gland hyperplasia; stomach cystic hyperplasia; sodium dichromate dihydrate; olfactory neuroblastoma; cynomolgus monkey; adnexal degeneration; parakeratotic hyperkeratosis; oligodendroglioma; microglioma; microcytic hypochromic anemia; microcytosis; spherocytosis; poikilocytosis; green tea; Ginkgo biloba; corneal dystrophy; Dutch belted rabbit valvulitis; valvulopathy; post-transplant lymphoproliferative disease
The first joint Japanese Society of Toxicologic Pathology (JSTP) and National Toxicology
Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held on January
29th at Okura Frontier Hotel in Tsukuba, Ibaraki, Japan, in advance of the
JSTP’s 29th Annual Meeting. The goal of this Symposium was to present current
diagnostic pathology or nomenclature issues to the toxicologic pathology community. This
article presents summaries of the speakers’ presentations, including diagnostic or
nomenclature issues that were presented, select images that were used for audience voting
or discussion, and the voting results. Some lesions and topics covered during the
symposium include: treatment-related atypical hepatocellular foci of cellular alteration
in B6C3F1 mice; purulent ventriculoencephalitis in a young BALB/c mouse; a subcutaneous
malignant schwannoma in a RccHan:WIST rat; spontaneous nasal septum
hyalinosis/eosinophilic substance in B6C3F1 mice; a rare pancreatic ductal cell adenoma in
a young Lewis rat; eosinophilic crystalline pneumonia in a transgenic mouse model; hyaline
glomerulopathy in two female ddY mice; treatment-related intrahepatic erythrocytes in
B6C3F1 mice; treatment-related subendothelial hepatocytes in B6C3F1 mice; spontaneous
thyroid follicular cell vacuolar degeneration in a cynomolgus monkey; congenital hepatic
fibrosis in a 1-year-old cat; a spontaneous adenocarcinoma of the middle ear in a young
Crl:CD(SD) rat; and finally a series of cases illustrating some differences between
cholangiofibrosis and cholangiocarcinoma in Sprague Dawley and F344 rats.
JSTP/NTP Satellite Symposium; atypical foci of cellular alteration; cholangiocarcinoma; cholangiofibrosis; congenital hepatic fibrosis; eosinophilic crystalline pneumonia; eosinophilic substance; epithelioid type of malignant schwannoma; hyaline glomerulopathy; intrahepatocytic erythrocytes; middle ear adenocarcinoma; nasal septum hyalinosis; pancreatic ductal cell adenoma; subendothelial hepatocytes; thyroid follicular cell vacuolar degeneration; ventriculoencephalitis
To examine the effects of market-level managed care activity on the treatment, cost, and outcomes of care for Medicare fee-for-service acute myocardial infarction (AMI) patients.
Data Sources/Study Setting
Patients from the Cooperative Cardiovascular Project (CCP), a sample of Medicare beneficiaries discharged from nonfederal acute-care hospitals with a primary discharge diagnosis of AMI from January 1994 to February 1996.
We estimated models of patient treatment, costs, and outcomes using ordinary least squares and logistic regression. The independent variables of primary interest were market-area managed care penetration and competition. The models included controls for patient, hospital, and other market area characteristics.
Data Collection/Extraction Methods
We merged the CCP data with Medicare claims and other data sources. The study sample included CCP patients aged 65 and older who were admitted during 1994 and 1995 with a confirmed AMI to a nonrural hospital.
Rates of revascularization and cardiac catheterization for Medicare fee-for-service patients with AMI are lower in high-HMO penetration markets than in low-penetration ones. Patients admitted in high-HMO-competition markets, in contrast, are more likely to receive cardiac catheterization for treatment of their AMI and had higher treatment costs than those admitted in low-competition markets.
The level of managed care activity in the health care market affects the process of care for Medicare fee-for-service AMI patients. Spillovers from managed care activity to patients with other types of insurance are more likely when managed care organizations have greater market power.
Managed care penetration; managed care competition; AMI; cost; treatment
The NF Conference is the largest annual gathering of researchers and clinicians focused on neurofibromatosis and has been convened by the Children’s Tumor Foundation for over 20 years. The 2009 NF Conference was held in Portland, Oregon from June 13th – June 16th, 2009 and co-chaired by Kathryn North from the University of Sydney and The Children’s Hospital at Westmead, Sydney, Australia; and Joseph Kissil from the Wistar Institute, Philadelphia. The Conference included 80 platform presentations in 9 sessions over 4 days; over 100 abstracts presented as posters; and three Keynote presentations. To date, there have been tremendous advances in basic research in the pathogenesis of neurofibromatosis, and more recently in progress toward identifying effective drug therapies and the commencement of neurofibromatosis clinical trials. The NF Conference attendees have significantly increased (doubling from 140 in 2005 to 280 attending in 2009) with a significant increase in attendance of physicians and clinical researchers. Correspondingly the NF Conference scope has expanded to include translational research, clinical trials and clinical management issues while retaining a core of basic research. These themes are reflected in the highlights from the 2009 NF Conference presented here.
Neurofibromatosis type 1; neurofibromatosis type 2; NF1; NF2; schwannomatosis; tumor suppressor; Ras/MAPK; learning disabilities; bone dysplasia
The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations > 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.
Vitamin D; 25-Hydroxyvitamin D; Sunlight exposure; Deficiency; Insufficiency; Recommendations
The First International Conference on Toxicogenomics Integrated with Environmental Sciences (TIES-2007) was held at the North Carolina State University McKimmon Center in Raleigh, North Carolina on October 25th and 26th, 2007. Based on the presentations at the conference and the commitment or interest of the presenters to contribute a manuscript of their research, we compiled this collection of articles as proceedings of the conference and an in-depth topical review of the utility of bioinformatics in the fields of toxicogenomics and environmental genomics.
This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005–2006 FASDSG officers, Daniel J. Bonthius (president), Heather Carmichael Olson (vice-president), and Jennifer Thomas (secretary-treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology.
Fetal Alcohol Syndrome; Fetal Alcohol Spectrum Disorders; Ethanol; Prenatal; Teratology
Introduction to Brain mechanisms of selective perception and action. Proceedings of a Discussion Meeting held at the Royal Society of London on 19 and 20 November 1997. Organized and edited by G. W. Humphreys, J. Duncan and A. Treisman.
Introduction to What are the parietal and hippocampal contributions to spatial cognition?, the proceedings of a Discussion held at The Royal Society on 19 and 20 March 1997. Organized by N. Burgess and J. O'Keefe and edited by N. Burgess, K. J. Jeffery and J. O'Keefe.
Parietal Cortex Hippocampus Spatial Cognition
There are now over 30 confirmed loci predisposing to rheumatoid arthritis (RA). Studies have been largely undertaken in patients with anticyclic citrullinated peptide (anti-CCP) positive RA, and some genetic associations appear stronger in this subgroup than in anti-CCP negative disease, although few studies have had adequate power to address the question. The authors therefore investigated confirmed RA susceptibility loci in a large cohort of anti-CCP negative RA subjects.
RA patients and controls, with serological and genetic data, were available from UK Caucasian patients (n=4068 anti-CCP positive, 2040 anti-CCP negative RA) and 13,009 healthy controls. HLA-DRB1 genotypes and 36 single nucleotide polymorphisms were tested for association between controls and anti-CCP positive or negative RA.
The shared epitope (SE) showed a strong association with anti-CCP positive and negative RA, although the effect size was significantly lower in the latter (effect size ratio=3.18, p<1.0E-96). A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing. No significant association with anti-CCP negative RA was detected for other markers (eg, AFF3, CD28, intronic marker at TNFAIP3), though the study power for those markers was over 80%.
In the largest sample size studied to date, the authors have shown that the strength of association, the effect size and the number of known RA susceptibility loci associated with disease is different in the two disease serotypes, confirming the hypothesis that they might be two genetically different subsets.
A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case–control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti-CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA.
The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 28, 2008 in Washington DC, as a satellite to the Research Society on Alcoholism meeting. The FASDSG membership includes clinical, basic and social scientists, who meet to discuss recent advances and issues in FASD research. The main theme of the meeting was “Factors that Influence Brain and Behavioral Development: Implications for Prevention and Intervention.” Two keynote speakers, Dr. Stephen Suomi and Dr. Carl Keen addressed how early environment and nutrition may influence outcome following prenatal alcohol exposure. The final keynote speaker, Kathy Mitchell, addressed issues regarding the relationship between scientists and the families with children with FASD. Members of the FASDSG provided updates on new findings through brief (FASt) data reports, and national agency representative provided updates of activities and funding priorities. Presentations were also made by recipients of the Student Research Merit award and Rosett award.
fetal alcohol syndrome; fetal alcohol spectrum disorders; teratology; ethanol; prenatal
The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 26, 2010 in San Antonio, TX, as a satellite of the Research Society on Alcoholism meeting. The FASDSG membership includes clinical, basic and social scientists who meet to discuss recent advances and issues in FASD research. The central theme of the meeting was “Glia and Neurons: Teamwork in Pathology and Therapy.” Alcohol disruption of neuron development and alcohol-induced neurodegeneration is central to the pathology and clinical expression of FASD. The active role of glia as perpetrator, victim, or bystander in neurotoxicology and neurodegenerative processes has emerged at the forefront of adult CNS disorders and therapy. Glia and neuron-glial interactions hold the potential to elucidate causes and offer treatment of FASD as well. Growing evidence indicates that neurons and glia are direct targets of alcohol, but may also be vulnerable to molecules produced in peripheral systems as a result of alcohol exposure. Diagnostics and therapies can take advantage of these processes and biomarkers, and these may be applicable to CNS pathology in FASD. Two keynote speakers, Howard E. Gendelman, M.D., and Ernest M. Graham, M.D, addressed the role of glia and neuroinflammation in brain development and neurodegeneration. The invited speakers and FASDSG members discussed new paradigms in CNS development and discuss new strategies for understanding and treating neurodegenerative disease. Members of the FASDSG provided updates on new findings through presentation of breaking research in the FASt Data Sessions. Representatives of national agencies provided updates on programs, activities, and funding priorities. The Henry Rosett Award was presented to R. Louise Floyd, R.N., D.S.N. for her career contributions to the field of fetal alcohol research. The Student and Postdoctoral Fellow Research Merit Award was presented to Shonagh O’Leary-Moore, Ph.D. for her contributions to the field as a young investigator.
In June 2008, the American Association for the Study of Liver Diseases (AASLD) sponsored the Henry M. and Lillian Stratton Basic Research Single-Topic Conference on the Pathobiology of Biliary Epithelia and Cholangiocarcinoma, which was held in Atlanta, GA. Attendees from 12 different countries participated in this conference, making it a truly international scientific event. Both oral and poster presentations were given by multidisciplinary experts, who highlighted important areas of current basic and translational research on biliary epithelial cell biology and pathophysiology, and on the etiology, cellular and molecular pathogenesis, and target-based therapy of cholangiocarcinoma. The specific goals and objectives of the conference were: (1) to advance knowledge of basic and molecular mechanisms underlying developmental and proliferative disorders of the biliary tract; (2) to foster a better and more comprehensive understanding of mechanisms regulating biliary epithelial (cholangiocyte) growth and transport, signaling, cell survival, and abnormalities that result in disease; and (3) to understand basic mechanisms of cholangiocarcinoma development and progression, with the added goal of identifying and exploiting potentially critical molecular pathways that may be targeted therapeutically. A number of interrelated themes emerged from the oral and poster sessions that affected current understandings of the complex organization of transcriptional and signaling mechanisms that regulate bile duct development, hepatic progenitor cell expansion, cholangiocyte secretory functions and proliferation, and mechanisms of cholangiocarcinogenesis and malignant cholangiocyte progression. Most notable were the critical questions raised as to how best to exploit aberrant signaling pathways associated with biliary disease as potential targets for therapy.
CcpA is the global mediator of carbon catabolite repression (CCR) in gram-positive bacteria, and growing evidence from several pathogens, including the group A streptococcus (GAS), suggests that CcpA plays an important role in virulence gene regulation. In this study, a deletion of ccpA in an invasive M1 GAS strain was used to test the contribution of CcpA to pathogenesis in mice. Surprisingly, the ΔccpA mutant exhibited a dramatic “hypervirulent” phenotype compared to the parental MGAS5005 strain, reflected as increased lethality in a model of systemic infection (intraperitoneal administration) and larger lesion size in a model of skin infection (subcutaneous administration). Expression of ccpA in trans from its native promoter was able to complement both phenotypes, suggesting that CcpA acts to repress virulence in GAS. To identify the CcpA-regulated gene(s) involved, a transcriptome analysis was performed on mid-logarithmic-phase cells grown in rich medium. CcpA was found to primarily repress 6% of the GAS genome (124 genes), including genes involved in sugar metabolism, transcriptional regulation, and virulence. Notably, the entire sag operon necessary for streptolysin S (SLS) production was under CcpA-mediated CCR, as was SLS hemolytic activity. Purified CcpA-His bound specifically to a cre within sagAp, demonstrating direct repression of the operon. Finally, SLS activity is required for the increased virulence of a ΔccpA mutant during systemic infection but did not affect virulence in a wild-type background. Thus, CcpA acts to repress SLS activity and virulence during systemic infection in mice, revealing an important link between carbon metabolism and GAS pathogenesis.
The CCP11 project  aims to foster bioinformatics
in the UK through conferences, workshops and
the provision of Web resources. In March 2002,
CCP11 held a meeting in Manchester, UK, on the
functional analysis of microarrays. This was part of
Manchester BioinformaticsWeek—three consecutive
short bioinformatics meetings held in the attractive
setting of the Chancellor's Conference Centre
at the University of Manchester. The other meetings
in the series were a workshop on ontologies
and the 12th Annual MASAMB (Mathematical and
Statistical Aspects of Molecular Biology) Conference.
Many delegates were able to attend more than
one meeting, which led to a useful cross-fertilization
of ideas across the bioinformatics community. The
CCP11 meeting shared with MASAMB a strong
emphasis on the statistical analysis and interpretation
of data—most often image intensity data.
For patients with recurrent prostate cancer after radical prostatectomy, salvage radiotherapy is the only potentially curative treatment option. However, until recently there has been a paucity of data on the effectiveness of this approach. In light of recently published studies, the Genito-Urinary Radiation Oncologists of Canada (GUROC) met and crafted a consensus statement regarding the current place of salvage radiotherapy. GUROC also identified gaps in current knowledge and identified ongoing study protocols that will advance our knowledge in this area.
This report summarizes the main conclusions of the meeting and the commentary provided during the consensus-building process, and outlines the consensus statement that was subsequently adopted.