Malmö University

This paper describes the research process – from planning to presentation, with the emphasis on credibility throughout the whole process – when the methodology of qualitative content analysis is chosen in a qualitative study. The groundwork for the credibility initiates when the planning of the study begins. External and internal resources have to be identified, and the researcher must consider his or her experience of the phenomenon to be studied in order to minimize any bias of his/her own influence. The purpose of content analysis is to organize and elicit meaning from the data collected and to draw realistic conclusions from it. The researcher must choose whether the analysis should be of a broad surface structure (a manifest analysis) or of a deep structure (a latent analysis). Four distinct main stages are described in this paper: the decontextualisation, the recontextualisation, the categorization, and the compilation. This description of qualitative content analysis offers one approach that shows how the general principles of the method can be used.

The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.

Eric Schiffman, DDS, MS/Richard Ohrbach, DDS, PhD/Edmond Truelove, DDS, MSD/John Look, DDS, PhD/Gary Anderson, DDS, MS/Jean-Paul Goulet, DDS, MSD/Thomas List, DDS, Odont Dr/Peter Svensson, DDS, PhD, Dr Odont/Yoly Gonzalez, DDS, MS, MPH/Frank Lobbezoo, DDS, PhD/Ambra Michelotti, DDS/Sharon L. Brooks, DDS, MS/Werner Ceusters, MD/Mark Drangsholt, DDS, PhD/Dominik Ettlin, MD, DDS/Charly Gaul, MD/Louis J. Goldberg, DDS, PhD/Jennifer A. Haythornthwaite, PhD/Lars Hollender, DDS, Odont Dr/Rigmor Jensen, MD, PhD/Mike T. John, DDS, PhD/Antoon De Laat, DDS, PhD/Reny de Leeuw, DDS, PhD/William Maixner, DDS, PhD/Marylee van der Meulen, PhD/Greg M. Murray, MDS, PhD/Donald R. Nixdorf, DDS, MS/Sandro Palla, Dr Med Dent/Arne Petersson, DDS, Odont Dr/Paul Pionchon, DDS, PhD/Barry Smith, PhD/Corine M. Visscher, PT, PhD/Joanna Zakrzewska, MD, FDSRCSI/Samuel F. Dworkin, DDS, PhD: Aims: The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. Methods: Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel’s recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project’s data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project—the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. Results: The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive selfreport instrument sets. The screening instruments’ 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. Conclusion: The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations. J Oral Facial Pain Headache 2014;28:6–27. doi: 10.11607/jop.1151

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. METHODS: We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. RESULTS: In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). CONCLUSIONS: PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)

Abstract Objective : To determine the ability of measurements of bone density in women to predict later fractures. Design : Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Subjects : Eleven separate study populations with about 90000 person years of observation time and over 2000 fractures. Main outcome measures : Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. Results : All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Conclusions : Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density. Key messages Measuring bone mineral density has been suggested as a method of identifying individuals at high risk of fracture in a preventive context Our meta-analysis of prospective studies showed that all studies measuring bone density at any site had similar predictive ability for a decrease of 1 SD in bone density except for measurements at hip and spine, which have better predictive ability for fractures in hip and spine respectively Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease Although bone mineral density measurements can predict fracture risk, they cannot identify individuals who will have a fracture, and a screening programme for osteoporosis cannot be recommended

OBJECTIVE: To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, -4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. INTERVENTIONS: Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. MAIN OUTCOME MEASURES: Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. RESULTS: After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P =.002). CONCLUSIONS: The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.

STUDY OBJECTIVE: In social epidemiology, it is easy to compute and interpret measures of variation in multilevel linear regression, but technical difficulties exist in the case of logistic regression. The aim of this study was to present measures of variation appropriate for the logistic case in a didactic rather than a mathematical way. DESIGN AND PARTICIPANTS: Data were used from the health survey conducted in 2000 in the county of Scania, Sweden, that comprised 10 723 persons aged 18-80 years living in 60 areas. Conducting multilevel logistic regression different techniques were applied to investigate whether the individual propensity to consult private physicians was statistically dependent on the area of residence (that is, intraclass correlation (ICC), median odds ratio (MOR)), the 80% interval odds ratio (IOR-80), and the sorting out index). RESULTS: The MOR provided more interpretable information than the ICC on the relevance of the residential area for understanding the individual propensity of consulting private physicians. The MOR showed that the unexplained heterogeneity between areas was of greater relevance than the individual variables considered in the analysis (age, sex, and education) for understanding the individual propensity of visiting private physicians. Residing in a high education area increased the probability of visiting a private physician. However, the IOR showed that the unexplained variability between areas did not allow to clearly distinguishing low from high propensity areas with the area educational level. The sorting out index was equal to 82%. CONCLUSION: Measures of variation in logistic regression should be promoted in social epidemiological and public health research as efficient means of quantifying the importance of the context of residence for understanding disparities in health and health related behaviour.

AIM: To analyse possible effects of titanium surface topography on bone integration. MATERIALS AND METHODS: Our analyses were centred on a PubMed search that identified 1184 publications of assumed relevance; of those, 1064 had to be disregarded because they did not accurately present in vivo data on bone response to surface topography. The remaining 120 papers were read and analysed, after removal of an additional 20 papers that mainly dealt with CaP-coated and Zr implants; 100 papers remained and formed the basis for this paper. The bone response to differently configurated surfaces was mainly evaluated by histomorphometry (bone-to-implant contact), removal torque and pushout/pullout tests. RESULTS AND DISCUSSION: A huge number of the experimental investigations have demonstrated that the bone response was influenced by the implant surface topography; smooth (S(a)<0.5 microm) and minimally rough (S(a) 0.5-1 mum) surfaces showed less strong bone responses than rougher surfaces. Moderately rough (S(a)>1-2 microm) surfaces showed stronger bone responses than rough (S(a)>2 microm) in some studies. One limitation was that it was difficult to compare many studies because of the varying quality of surface evaluations; a surface termed 'rough' in one study was not uncommonly referred to as 'smooth' in another; many investigators falsely assumed that surface preparation per se identified the roughness of the implant; and many other studies used only qualitative techniques such as SEM. Furthermore, filtering techniques differed or only height parameters (S(a), R(a)) were reported. CONCLUSIONS: * Surface topography influences bone response at the micrometre level. * Some indications exist that surface topography influences bone response at the nanometre level. * The majority of published papers present an inadequate surface characterization. * Measurement and evaluation techniques need to be standardized. * Not only height descriptive parameters but also spatial and hybrid ones should be used.

PURPOSE: A classification for primary and incisional abdominal wall hernias is needed to allow comparison of publications and future studies on these hernias. It is important to know whether the populations described in different studies are comparable. METHODS: Several members of the EHS board and some invitees gathered for 2 days to discuss the development of an EHS classification for primary and incisional abdominal wall hernias. RESULTS: To distinguish primary and incisional abdominal wall hernias, a separate classification based on localisation and size as the major risk factors was proposed. Further data are needed to define the optimal size variable for classification of incisional hernias in order to distinguish subgroups with differences in outcome. CONCLUSIONS: A classification for primary abdominal wall hernias and a division into subgroups for incisional abdominal wall hernias, concerning the localisation of the hernia, was formulated.

Abstract This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library “MaStar”). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).

A new method for extracting seasonality information from time-series of satellite sensor data is presented. The method is based on nonlinear least squares fits of asymmetric Gaussian model functions to the time-series. The smooth model functions are then used for defining key seasonality parameters, such as the number of growing seasons, the beginning and end of the seasons, and the rates of growth and decline. The method is implemented in a computer program TIMESAT and tested on Advanced Very High Resolution Radiometer (AVHRR) normalized difference vegetation index (NDVI) data over Africa. Ancillary cloud data [clouds from AVHRR (CLAVR)] are used as estimates of the uncertainty levels of the data values. Being general in nature, the proposed method can be applied also to new types of satellite-derived time-series data.

OBJECTIVE: The authors synthesize findings of previous studies implicating migration as a risk factor for the development of schizophrenia and provide a quantitative index of the associated effect size. METHOD: MEDLINE was searched for population-based incidence studies concerning migrants in English-language publications appearing between the years 1977 and 2003. Article bibliographies and an Australian database were cross-referenced. Studies were included if incidence reports provided numerators and denominators and if age correction was performed or could be performed by the authors. Relative risks for migrant groups were extracted or calculated for each study. Significant heterogeneity across studies indicated the need for a mixed-effects meta-analytic model. RESULTS: The mean weighted relative risk for developing schizophrenia among first-generation migrants (40 effect sizes) was 2.7 (95% confidence interval [CI]=2.3-3.2). A separate analysis performed for second-generation migrants (seven effect sizes) yielded a relative risk of 4.5 (95% CI=1.5-13.1). An analysis performed for studies concerning both first- and second-generation migrants and studies that did not distinguish between generations (50 effect sizes) yielded a relative risk of 2.9 (95% CI=2.5-3.4). Subgroup comparisons yielded significantly greater effect sizes for migrants from developing versus developed countries (relative risk=3.3, 95% CI=2.8-3.9) and for migrants from areas where the majority of the population is black (relative risk=4.8, 95% CI=3.7-6.2) versus white and neither black nor white. CONCLUSIONS: A personal or family history of migration is an important risk factor for schizophrenia. The differential risk pattern across subgroups suggests a role for psychosocial adversity in the etiology of schizophrenia.

Tissue-based diagnostics and research is incessantly evolving with the development of new molecular tools. It has long been realized that immunohistochemistry can add an important new level of information on top of morphology and that protein expression patterns in a cancer may yield crucial diagnostic and prognostic information. We have generated an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer and cell lines. For each antibody, altogether 708 spots of tissues and cells are analysed and the resulting images and data are presented as freely available in the Human Protein Atlas (www.proteinatlas.org). The new version 4 of the atlas, including more than 5 million images of immunohistochemically stained tissues and cells, is based on 6122 antibodies, representing 5011 human proteins encoded by approximately 25% of the human genome. The gene-centric database includes a putative classification of proteins in various protein classes, both functional classes, such as kinases or transcription factors and project-related classes, such as candidate genes for cancer or cardiovascular diseases. For each of the internally generated antibodies, the exact antigen sequence is presented, together with a visualization of application-specific validation data, including a protein array assay, western blot analysis, immunohistochemistry and, in most cases, immunofluorescent-based confocal microscopy. The updated version also includes new search algorithms to allow complex queries regarding expression profiles, protein classes and chromosome location. Thus, the presented Human Protein Atlas provides a resource for pathology-based biomedical research, including protein science and biomarker discovery.

BACKGROUND: In three families with various forms of venous thrombosis, we observed an apparently inherited poor response to the anticoagulant activated protein C (APC). The condition was due to a deficiency in a previously unrecognized anticoagulant factor that functioned as a cofactor to activated protein C. METHODS: We conducted the present study to determine the prevalence of resistance to APC in patients with venous thrombosis. We compared 104 consecutive patients with venous thrombosis confirmed by objective tests with 130 controls. In addition, 211 members of 34 families of persons with resistance to APC were studied. The anticoagulant response to APC was measured with a modified version of the activated partial-thromboplastin time test; the results were expressed as APC ratios. RESULTS: Forty-five percent of patients had a family history of thrombosis. A significant (P < 0.001) difference in APC ratios was observed between the controls and the patients with thrombosis. For 33 percent of patients, the APC ratio was below the 5th percentile of the control values, although the results of the family studies suggested that the prevalence of APC resistance may be even higher (approximately 40 percent) in the patients with thrombosis. The inherited nature of the defect was confirmed in a majority of cases, and the family studies suggested the mode of inheritance to be autosomal dominant. The thrombosis-free survival of APC-resistant family members was significantly less than that of non-APC-resistant family members. CONCLUSIONS: There was a high prevalence of APC resistance among young persons with a history of venous thrombosis, and this resistance appeared to be inherited as an autosomal dominant trait.

The adipokine resistin is suggested to be an important link between obesity and insulin resistance. In the present study, we assessed the impact of resistin as inflammatogenic cytokine in the setting of arthritis. In vitro experiments on human PBMC were performed to assess cytokine response and transcription pathways of resistin-induced inflammation. Proinflammatory properties of resistin were evaluated in animal model by intra-articular injection of resistin followed by histological evaluation of the joint. Levels of resistin were assessed by ELISA in 74 paired blood and synovial fluid samples of patients with rheumatoid arthritis. Results were compared with the control group comprised blood samples from 34 healthy individuals and 21 synovial fluids from patients with noninflammatory joint diseases. We now show that resistin displays potent proinflammatory properties by 1) strongly up-regulating IL-6 and TNF-alpha, 2) responding to TNF-alpha challenge, 3) enhancing its own activity by a positive feedback, and finally 4) inducing arthritis when injected into healthy mouse joints. Proinflammatory properties of resistin were abrogated by NF-kappaB inhibitor indicating the importance of NF-kappaB signaling pathway for resistin-induced inflammation. Resistin is also shown to specifically accumulate in the inflamed joints of patients with rheumatoid arthritis and its levels correlate with other markers of inflammation. Our results indicate that resistin is a new and important member of the cytokine family with potent regulatory functions. Importantly, the identified properties of resistin make it a novel and interesting therapeutic target in chronic inflammatory diseases such as rheumatoid arthritis.

BACKGROUND: The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. METHODS AND RESULTS: Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2+/-8.4% versus 23.9+/-21.1% of the plaque area, P<0.05), less oxidized LDL immunoreactivity (13.3+/-3.6% versus 22.0+/-6.5%, P<0.001), fewer macrophages (15.0+/-10.2% versus 25.3+/-12.5%, P<0.05), fewer T cells (11.2+/-9.3% versus 24.3+/-13.4%, P<0.05), less matrix metalloproteinase 2 (MMP-2) immunoreactivity (3.6+/-3.9% versus 8.4+/-5.3%, P<0.05), greater tissue inhibitor of metalloproteinase 1 (TIMP-1) immunoreactivity (9.0+/-6.2% versus 3.1+/-3.9%, P<0.05), and a higher collagen content by Sirius red staining (12.4+/-3.1% versus 7.5+/-3.5%, P<0.005). Cell death by TUNEL staining was reduced in the pravastatin group (17.7+/-7.8% versus 32.0+/-12.6%, P<0.05). CONCLUSIONS: -Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans.

We demonstrate the direct involvement of increased collagenase activity in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carboxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepitopes generated by cleavage of native human type II collagen by collagenase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). A secondary cleavage followed the initial cleavage produced by these recombinant collagenases. This generated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C(short) neoepitope in osteoarthritis (OA) compared to adult nonarthritic cartilages as determined by immunoassay of cartilage extracts. A synthetic preferential inhibitor of MMP-13 significantly reduced the unstimulated release in culture of neoepitope COL2-3/4C(short) from human osteoarthritic cartilage explants. These data suggest that collagenase(s) produced by chondrocytes is (are) involved in the cleavage and denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.

In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, the regimens used being 24-40 IU F VIII kg-1 three times weekly in haemophilia-A cases (i.e. greater than 2000 IU kg-1 annually) and 25-40 IU F IX kg-1 twice weekly in haemophilia-B cases. The orthopaedic and radiological joint scores (maximum scores of 90 and 78, respectively) are evaluated as recommended by the World Federation of Haemophilia. Of those subjects aged 3-17 years, 29 out of 35 individuals had joint scores of zero. The oldest group had only minor joint defects. The VIII:C and IX:C concentrations had usually not fallen below 1% of normal. All 60 patients are able to lead normal lives. In conclusion, it appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal.

STUDY OBJECTIVE: To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN: Birth year cohorts of city population separately randomised into study and control groups. SETTING: Screening clinic outside main hospital. PATIENTS: Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS: Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT: Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS: All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS: In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS: Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

BACKGROUND: Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk. High fish intake may be associated with a decreased risk, but the existing evidence is less convincing. METHODS: We prospectively followed 478 040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998. Information on diet and lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329 incident colorectal cancers were documented. We examined the relationship between intakes of red and processed meat, poultry, and fish and colorectal cancer risk using a proportional hazards model adjusted for age, sex, energy (nonfat and fat sources), height, weight, work-related physical activity, smoking status, dietary fiber and folate, and alcohol consumption, stratified by center. A calibration substudy based on 36 994 subjects was used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. All statistical tests were two-sided. RESULTS: Colorectal cancer risk was positively associated with intake of red and processed meat (highest [>160 g/day] versus lowest [<20 g/day] intake, HR = 1.35, 95% CI = 0.96 to 1.88; Ptrend = .03) and inversely associated with intake of fish (>80 g/day versus <10 g/day, HR = 0.69, 95 % CI = 0.54 to 0.88; Ptrend<.001), but was not related to poultry intake. Correcting for measurement error strengthened the associations between colorectal cancer and red and processed meat intake (per 100-g increase HR = 1.25, 95% CI =1.09 to 1.41, Ptrend = .001 and HR = 1.55, 95% CI = 1.19 to 2.02, Ptrend = .001 before and after calibration, respectively) and for fish (per 100 g increase HR = 0.70, 95% CI = 0.57 to 0.87, Ptrend<.001 and HR = 0.46, 95% CI = 0.27 to 0.77, Ptrend = .003; before and after correction, respectively). In this study population, the absolute risk of development of colorectal cancer within 10 years for a study subject aged 50 years was 1.71% for the highest category of red and processed meat intake and 1.28% for the lowest category of intake and was 1.86% for subjects in the lowest category of fish intake and 1.28% for subjects in the highest category of fish intake. CONCLUSIONS: Our data confirm that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake.