Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis?

Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis? A. Boyde a, G.R. Davis a, D. Mills a, T. Zikmund a, V.L. Adams b, L.R. Ranganath b, N. Jeffery b, J.A. Gallagher b a Dental Physical Sciences, Oral Growth and Development, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK b Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Objectives High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first discovered in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. If these fragment, they could make a significant contribution to joint destruction in osteoarthritis. We looked for them in human material. Methods Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were studied by MRI DESS at 0.23mm resolution and 26 micron resolution high contrast x-ray microtomography (XMT), then sectioned and embedded in PMMA, and block faces polished and the blocks re-imaged with 6 micron resolution XMT. Tissue mineralisation density was imaged qualitatively by backscattered electron SEM (BSE SEM) at 20kV using uncoated samples at 50Pa chamber pressure to achieve charge neutralisation. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. Block surfaces were sequentially repolished and restained. Results Figure: 3D rendering of 6 micron voxel resolution XMT data set showing HDMP complex projecting above subchondral bone plate. Human femoral head removed at arthroplasty. We found examples of HDMP in HAC in human hips. Their 3D shapes are complex and may show cutting blade forms. Their mineral content (a) exceeds that of articular calcified cartilage (ACC), otherwise the densest tissue in the joint and (b) is not uniform. The mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. Cracks within them are frequent. Dense fragments may be found within damaged HAC. Conclusions HDMP arise via the extrusion of an uncharacterised matrix into clefts in HAC. Little evidence of their existence remains after tissue has been decalcified with usual histological protocols. Their formation may be an extension of a normal but poorly recognised crack self-healing mechanism found in bone and ACC. They are surrounded by HAC, are dense and brittle and show innumerable fault lines within them. We provide evidence that they break in vivo by being able to find matching fragments in HAC. We conclude that these hard and sharp particles contribute to the shredding destruction of HAC. The osteoarthritis research community should be aware of their existence so that the frequency and possible clinical significance can be assessed in the future. Larger HDMP can be detected with the best MRI imaging

An iterative algorithm for parametrization of shortest length shift registers over finite rings

The construction of shortest feedback shift registers for a finite sequence S_1,...,S_N is considered over the finite ring Z_{p^r}. A novel algorithm is presented that yields a parametrization of all shortest feedback shift registers for the sequence of numbers S_1,...,S_N, thus solving an open problem in the literature. The algorithm iteratively processes each number, starting with S_1, and constructs at each step a particular type of minimal Gr\"obner basis. The construction involves a simple update rule at each step which leads to computational efficiency. It is shown that the algorithm simultaneously computes a similar parametrization for the reciprocal sequence S_N,...,S_1.Comment: Submitte

Search For Companions Of Nearby Isolated Galaxies

The radial velocities are measured for 45 galaxies located in the neighborhoods of 29 likely isolated galaxies in a new catalog. We find that about 85% of these galaxies actually are well isolated objects. 4% of nearby galaxies with V_LG<3500 km/s are this kind of cosmic "orphan".Comment: 7 pages, 2 figure

Are GPs under-investigating older patients presenting with symptoms of ovarian cancer? Observational study using General Practice Research Database

Background: Recent studies suggest that older patients in the United Kingdom are not benefiting as much from improvements in cancer treatments as their younger counterparts. We investigate whether this might be partly due to differential referral rates using ovarian cancer as an example. Methods: From the General Practice Research Database (GPRD), we identified all women aged 40–80 years on 1 June 2002 with a Read code for ovarian cancer between 1 June 2002 and 31 May 2007. Using these records, we compared the GPRD incidence of ovarian cancer with rates compiled from the UK cancer registries and investigated the relationship between age and coded investigations for suspected ovarian cancer. Results: The GPRD rates peaked earlier, at 70–74, and were lower than registry rates for nearly all ages particularly for patients over 59. The proportion investigated or referred by the GP decreased significantly with age and delays between first coded symptom and investigation showed a U-shaped distribution by age. Conclusions: GPs appear to be less likely to recognise and to refer patients presenting with ovarian cancer as they get older. If our findings extend to other cancers, lack of or delays in referral to secondary care may partly explain poor UK cancer mortality rates of older people

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Factors associated with timeliness of post-primary care referral, diagnosis and treatment for lung cancer: population-based, data-linkage study

BACKGROUND: The NHS Cancer Plan for England set waiting time targets for cancer referral (14 days from GP referral to first hospital appointment) and treatment (31 days from diagnosis, 62 days from urgent GP referral). Interim diagnostic intervals can also be calculated. The factors that influence timely post-primary care referral, diagnosis and treatment for lung cancer are not known. METHODS: Northern and Yorkshire Cancer Registry, Hospital Episode Statistics and lung cancer audit data sets were linked. Logistic regression was used to investigate the factors (socioeconomic position, age, sex, histology, co-morbidity, year of diagnosis, stage and performance status (PS)) that may influence the likelihood of referral, diagnosis and treatment within target, for 28 733 lung cancer patients diagnosed in 2006–2010. RESULTS: Late-stage, poor PS and small-cell histology were associated with a higher likelihood of post-primary care referral, diagnosis and treatment within target. Older patients were significantly less likely to receive treatment within the 31-day (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.69–0.91) and 62-day target (OR=0.80, 95% CI 0.67–0.95) compared with younger patients. CONCLUSIONS: Older patients waited longer for treatment and this may be unjustified. Patients who appeared ill were referred, diagnosed and treated more quickly and this ‘sicker quicker’ effect may cancel out system socioeconomic inequalities that might result in longer time intervals for more deprived patients

Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion

This work was supported by a Cancer Research UK Centre Grant to Barts Cancer Institute (C16420/A18066). P.R.C. was funded by BBSRC (BB/M006174/1) and Barts and The London Charity (297/2249). S.A.G. is a fellow of the Lister Institute and is supported by the Medical Research Council (MR/M010414/1)

A qualitative study of unmet needs and interactions with primary care among cancer survivors

INTRODUCTION: Despite increasing numbers, there is little research investigating the long-term needs of cancer survivors. The aim of this study is to explore the experiences of individuals who have survived at least 5 years following a cancer diagnosis, and to describe perceived unmet needs and interactions with primary care. METHODS: Forty long-term survivors of breast, colorectal and prostate cancer were purposively selected for an in-depth qualitative study. We aimed for a maximum variation sample according to cancer site, gender, time since diagnosis, cancer needs, anxiety and depression. Interviews were audio recorded and transcribed verbatim. Transcripts were coded thematically using a grounded theory approach. RESULTS: Analysis of the interview data is presented in four subthemes: the role they perceived for the general practitioner (GP), unmet needs, reasons for not using primary care for needs they perceived as cancer related, and ongoing care for cancer-related issues. The majority of cancer survivors did not see a role for their GP in their long-term care related to their cancer diagnosis as most considered that they did not need active follow-up, but some expressed a need for psychological services and information on possible long-term effects. Cancer survivors cited three main reasons for not using GP services in relation to their cancer diagnosis: GPs were seen as non-experts in cancer; they were perceived as too busy; and a lack of continuity within primary care made it difficult to talk about long-term issues. There was a wide variation in schedules and notification of PSA tests among the prostate cancer survivors. DISCUSSION: The results from this project suggest that some cancer survivors have specific emotional and physical needs that could benefit from input from their primary care team, but not all cancer survivors look to their GP for their long-term cancer-related care. Better information care planning is required from specialists in order to identify those who would benefit mos

Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment

Phase Structure and Compactness

In order to study the influence of compactness on low-energy properties, we compare the phase structures of the compact and non-compact two-dimensional multi-frequency sine-Gordon models. It is shown that the high-energy scaling of the compact and non-compact models coincides, but their low-energy behaviors differ. The critical frequency $\beta^2 = 8\pi$ at which the sine-Gordon model undergoes a topological phase transition is found to be unaffected by the compactness of the field since it is determined by high-energy scaling laws. However, the compact two-frequency sine-Gordon model has first and second order phase transitions determined by the low-energy scaling: we show that these are absent in the non-compact model.Comment: 21 pages, 5 figures, minor changes, final version, accepted for publication in JHE