Analytical interatomic bond-order potential for simulations of oxygen defects in iron.

We present an analytical bond-order potential for the Fe-O system, capable of reproducing the basic properties of wüstite as well as the energetics of oxygen impurities in [Formula: see text]-iron. The potential predicts binding energies of various small oxygen-vacancy clusters in [Formula: see text]-iron in good agreement with density functional theory results, and is therefore suitable for simulations of oxygen-based defects in iron. We apply the potential in simulations of the stability and structure of Fe/FeO interfaces and FeO precipitates in iron, and observe that the shape of FeO precipitates can change due to formation of well-defined Fe/FeO interfaces. The interface with crystalline Fe also ensures that the precipitates never become fully amorphous, no matter how small they are.

National registry-based case-control study: comorbidity and stroke in young adults.

OBJECTIVES: Stroke is overrepresented in cohorts of young adults with chronic diseases. The prevalence and impact of comorbidity among young stroke patients have not been compared with individuals without stroke. Our aim was to investigate the association between comorbidity and stroke in young adults. MATERIALS AND METHODS: A nationwide cohort of patients (aged 15-44 years), registered in the Swedish Stroke Register, (Riksstroke) 2001-2009, was identified. Age- and sex-matched controls were randomly selected from the Population Register of Sweden. Discharge diagnoses were retrieved from the National Patient Register and grouped by chapter in the International Classification of Diseases 10th revision. Associations between ICD-10 chapters and stroke were stratified (age, sex, and stroke type) and analyzed by multivariable logistic regression. RESULTS: In 2599 stroke patients analyzed, the prevalence of vascular risk factors (hypertension 25.3%, dyslipidemia 13.0%, diabetes 9.7%, heart failure 3.2%, and atrial fibrillation 2.8%), all ICD-10 chapters (except pregnancy) and prestroke hospitalizations were more frequent among cases than controls. Independent associations were found between stroke and eight ICD-10 chapters: neoplasms (odds ratios (OR) 1.53, 95% CI 1.15-2.05), blood (OR 1.61, 1.11-2.34), endocrine (OR 2.28, 1.77-2.93), psychiatric (OR 1.50, 1.24-1.81), nervous (OR 1.91, 1.46-2.50), eye (OR 1.67, 1.05-2.64), circulatory (OR 3.05, 2.45-3.80), and symptoms (OR 1.31, 1.13-1.52). The risk of stroke increased by 26% per ICD-10 chapter diagnosed. CONCLUSIONS: In addition to vascular risk factors, comorbidity (represented by ICD-10 chapters) was associated with increased risk of stroke in young individuals. The risk of stroke was further increased with the number of diagnosed ICD-10 chapters.

A longitudinal study of family structure in Swedish persons with haemophilia.

Haemophilia is an X-linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age- and gender-matched controls. The national Multi-Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.

Atomistic simulations of stainless steels: a many-body potential for the Fe-Cr-C system.

Stainless steels found in real-world applications usually have some C content in the base Fe-Cr alloy, resulting in hard and dislocation-pinning carbides-Fe3C (cementite) and Cr23C6-being present in the finished steel product. The higher complexity of the steel microstructure has implications, for example, for the elastic properties and the evolution of defects such as Frenkel pairs and dislocations. This makes it necessary to re-evaluate the effects of basic radiation phenomena and not simply to rely on results obtained from purely metallic Fe-Cr alloys. In this report, an analytical interatomic potential parameterization in the Abell-Brenner-Tersoff form for the entire Fe-Cr-C system is presented to enable such calculations. The potential reproduces, for example, the lattice parameter(s), formation energies and elastic properties of the principal Fe and Cr carbides (Fe3C, Fe5C2, Fe7C3, Cr3C2, Cr7C3, Cr23C6), the Fe-Cr mixing energy curve, formation energies of simple C point defects in Fe and Cr, and the martensite lattice anisotropy, with fair to excellent agreement with empirical results. Tests of the predictive power of the potential show, for example, that Fe-Cr nanowires and bulk samples become elastically stiffer with increasing Cr and C concentrations. High-concentration nanowires also fracture at shorter relative elongations than wires made of pure Fe. Also, tests with Fe3C inclusions show that these act as obstacles for edge dislocations moving through otherwise pure Fe.

Incidence, mortality rates and causes of deaths in haemophilia patients in Sweden.

Sweden has been a pioneer in the treatment of haemophilia, with the first concentrate available in the 1950s. Treatment has improved over the years to its current state-of-the art. The aim of the current study was to evaluate the long-term outcome of haemophilia in terms of incidence, morbidity and mortality. Patients diagnosed with haemophilia A or B registered at the national haemophilia centres and/or the Patient Registry and born before 2009 and alive in 1968 were enrolled and linked to the Cause of Death-, Migration- and Medical Birth registries. Five age- and sex-matched controls were selected for each patient. A total of 1431 patients with haemophilia A or B were compared with 7150 controls. The 3-year moving average incidence rate per 100,000 population varied between 21 and 36. The hazard ratio for all-cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001 and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates.

A Be-W interatomic potential.

In this work, an interatomic potential for the beryllium-tungsten system is derived. It is the final piece of a potential puzzle, now containing all possible interactions between the fusion reactor materials beryllium, tungsten and carbon as well as the plasma hydrogen isotopes. The potential is suitable for plasma-wall interaction simulations and can describe the intermetallic Be(2)W and Be(12)W phases. The interaction energy between a Be surface and a W atom, and vice versa, agrees qualitatively with ab initio calculations. The potential can also reasonably describe Be(x)W(y) molecules with x, y = 1, 2, 3, 4.

Stroke unit care revisited: who benefits the most? A cohort study of 105,043 patients in Riks-Stroke, the Swedish Stroke Register.

BACKGROUND: Treatment at stroke units is superior to treatment at other types of wards. The objective of the present study is to determine the effect size of stroke unit care in subgroups of patients with stroke. This information might be useful in a formal priority setting. METHODS: All acute strokes reported to the Swedish Stroke Register from 2001 through 2005 were followed until January 2007. The subgroups were age (18-64, 65-74, 75-84, 85+ years and above), sex (male, female), stroke subtype (intracerebral haemorrhage, cerebral infarction and unspecified stroke) and level of consciousness (conscious, reduced, unconscious). Cox proportional hazards and logistic regression analyses were used to estimate the risk for death, institutional living or dependency. RESULTS: 105,043 patients were registered at 86 hospitals. 79,689 patients (76%) were treated in stroke units and 25,354 patients (24%) in other types of wards. Stroke unit care was associated with better long-term survival in all subgroups. The best relative effect was seen among the following subgroups: age 18-64 years (hazard ratio (HR) for death 0.53; 0.49 to 0.58), intracerebral haemorrhage (HR 0.61; 0.58 to 0.65) and unconsciousness (HR 0.70; 0.66 to 0.75). Stroke unit care was also associated with reduced risk for death or institutional living after 3 months. CONCLUSIONS: Stroke unit care was associated with better long-term survival in all subgroups, but younger patients, patients with intracerebral haemorrhage and patients who were unconscious had the best relative effect and may be given the highest priority to this form of care.

Unwanted pregnancy as a risk factor for offspring schizophrenia-spectrum and affective disorders in adulthood: a prospective high-risk study.

BACKGROUND: This study investigated whether 'unwanted pregnancy' (i.e. a negative or ambivalent attitude towards the pregnancy/reproduction) is associated with schizophrenia-spectrum and affective disorders in the offspring in adulthood, and if so, whether other pregnancy, perinatal, childhood or genetic-risk factors account for this association. METHOD: In a prospective study beginning during pregnancy, unwanted pregnancy (in combination with other early life risk factors) was studied in relation to adult mental disorders in 75 genetic high-risk (HR) and 91 normal-risk (NR) offspring, defined through maternal psychosis history. Early life risk factors were studied through personal interviews, observations and medical records, and offspring mental disorders were independently diagnosed through follow-up examination at about 22 years of age. RESULTS: Unwanted pregnancy by itself was significantly related to adult offspring schizophrenia-spectrum disorders in both the total sample and the HR subgroup, but the effect was found to be limited to the HR group and occurred in interaction with genetic risk. Other co-temporaneous pregnancy stressors and later perinatal complications, malformations and early childhood environmental stressors could not explain this relationship. Unwanted pregnancy also interacted with genetic-risk status in relating to affective disorders in the offspring. CONCLUSIONS: Unwanted pregnancy, when occurring together with genetic risk for psychosis, was found to be related to both adult schizophrenia-spectrum and affective mental disorders in the offspring. Although the effect of unwanted pregnancy could be mediated by other yet-unidentified factors, unwanted pregnancy might be a functional, discrete environmental psychosocial factor with its own deleterious impact on offspring mental development, when co-occurring with genetic risk.

Interatomic potentials for the Be-C-H system.

Analytical bond-order potentials for beryllium, beryllium carbide and beryllium hydride are presented. The reactive nature of the formalism makes the potentials suitable for simulations of non-equilibrium processes such as plasma-wall interactions in fusion reactors. The Be and Be-C potentials were fitted to ab initio calculations as well as to experimental data of several different atomic configurations and Be-H molecule and defect data were used in determining the Be-H parameter set. Among other tests, sputtering, melting and quenching simulations were performed in order to check the transferability of the potentials. The antifluorite Be(2)C structure is well described by the Be-C potential and the hydrocarbon interactions are modelled by the established Brenner potentials.

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

A prospective study of offspring of women with psychosis: visual dysfunction in early childhood predicts schizophrenia-spectrum disorders in adulthood.

OBJECTIVE: Children with visual dysfunction have perinatal, neurological, visual-perceptual and cognitive abnormalities, similar to schizophrenia patients. We prospectively investigated whether visual dysfunction in childhood selectively predicts adult schizophrenia-spectrum disorders, and is related to childhood neurological abnormality. METHOD: Offspring of mothers with and without a history of psychosis were prospectively assessed with vision tests at 4 years, neurological examinations at 6 years, and interviews for psychiatric disorders at follow-up (93% effective, n=166) at 22 years. RESULTS: In the total sample and high-risk (HR) offspring, visual dysfunction at 4 years, and its severity, were associated only with schizophrenia-spectrum disorders in adulthood, and with neurological abnormality at 6 years. CONCLUSION: Visual dysfunction at 4 years of age selectively predicts schizophrenia-spectrum disorders in adulthood among HR offspring, this likely reflecting disturbed neurological development.

Craniofacial dysmorphology in Swedish schizophrenia patients.

OBJECTIVE: To perform detailed assessments of craniofacial dysmorphology in individuals with schizophrenia and controls in Sweden, in order to further elucidate the neurodevelopmental origins of schizophrenia. METHOD: We performed detailed, anthropometric assessments of craniofacial dysmorphology in male patients with schizophrenia (n=24), healthy controls (n=16), and patients' siblings with schizophrenia (n=2) in Sweden, while remaining as blind as possible to schizophrenia/control status. RESULTS: Individuals with schizophrenia evidenced significantly more craniofacial dysmorphology than controls, especially in the ears and mouth. At a group level, there was a dose-response type relationship between total dysmorphology score and patient/control status. CONCLUSION: The consistency of results across multiple studies supports the hypothesis that individuals with schizophrenia have increased rates of prenatal developmental disturbances. The presence of a dose-response type relationship between total dysmorphology score and patient/control status supports the importance of neurodevelopmental disturbance as a contributory cause of schizophrenia.

Nucleoside diphosphate kinase A/nm23-H1 promotes metastasis of NB69-derived human neuroblastoma.

Nucleoside diphosphate kinase A (NDPK-A), encoded by the nm23-H1 gene, acts as a metastasis suppressor in certain human tumors such as breast carcinoma. However, evidence also points to NDPK-A functioning as a metastasis promoter in other human tumors including neuroblastoma. In fact, amplification and overexpression of nm23-H1 as well as S120G mutation of NDPK-A (NDPK-A(S120G)) have been detected in 14% to 30% of patients with advanced stages of neuroblastoma. To test whether NDPK-A promotes neuroblastoma metastasis, we established stable transfectants and an orthotopic xenograft animal model from the human neuroblastoma NB69 cell line. We demonstrate that overexpressed NDPK-A or NDPK-A(S120G) increased both incidence and colonization of neuroblastoma metastasis in animal lungs without significantly affecting primary tumor development. In vitro, these metastasis-associated NDPK-A aberrations abrogated retinoic acid-induced neuronal differentiation while increasing cloning efficiency, cell survival, and colony formation of NB69 derivatives. Furthermore, NDPK-A(S120G) reduced cell adhesion and increased cell migration. Compared with its wild-type, NDPK-A(S120G) appears more effective in promoting neuroblastoma metastasis. Our results provide the first evidence that NDPK-A behaves as a metastasis promoter at least in human neuroblastoma derived from NB69 cells. The findings not only suggest a prognostic value of NDPK-A in neuroblastoma patients but also caution NDPK-A-targeted treatment for patients with different tumor types.

A fluorescent orthotopic mouse model for reliable measurement and genetic modulation of human neuroblastoma metastasis.

Neuroblastoma is the most common extra-cranial solid tumor of infancy and childhood, and majority of patients die from the metastatic disease. Orthotopic xenograft mouse models are valuable tools for improving our understanding and control of neuroblastoma metastasis, because they readily represent genetic diversity and allow spontaneous metastasis. Intra-adrenal injection is commonly used for establishing the orthotopic animal models since human neuroblastoma frequently originates in the adrenal gland. However, it is unclear whether the metastatic potential of neuroblastoma can be reliably determined in adrenally-injected mice because their gland size is so small. In this study, we developed and characterized a fluorescent orthotopic xenograft animal model of NB69-derived human neuroblastoma. By comparing animals receiving adrenal injection and adrenal overlay, with the latter mimicking injection spillover, we found that the metastatic potential of neuroblastoma can be reliably determined in animal lungs. Furthermore, the lung metastasis can be genetically modulated in these animals. The results also show that the expression of Renilla green fluorescent protein (GFP) was exceptionally stable in NB69 cells, allowing rapid and sensitive detection of lung metastases at the macroscopic level. Additional features of our model include 100% tumor take, a 1-week tumor latency, resemblance to tumor behaviors in neuroblastoma patients, and the ability to monitor the expression of a gene of interest with GFP. This animal model of human neuroblastoma will be useful for studying genes involved in the metastatic process and for evaluating anti-metastasis agents in pre-clinical trials.

Evaluation of four outpatient educational programmes for patients with longstanding fibromyalgia.

OBJECTIVE: Four programmes based on educational and cognitive principles but with a variation in total length and number of staff/patient contact hours were compared in order to gain further insight into the importance of the format of the programme for the final outcome. DESIGN: A prospective non-randomized intervention study with 191 persons with fibromyalgia. Data were collected before, after and at 1-year follow-up. Participants served as their own controls. Results within and between the programmes were calculated. METHODS: Clinical investigations before and after intervention. Questionnaires were answered before, after and at 1-year follow-up. RESULTS: Most instruments showed no significant improvements after the programme. However, some improvements were found in important variables such as attitudes, self-efficacy, vitality and "days feeling well". Results were unchanged at the 1-year follow-up and 16 persons had started working. Seven had ceased working. Participants reported frequent use of coping strategies in everyday life. No major differences could be found between the programmes. CONCLUSIONS: More comprehensive programmes did not produce better results at group level. Also short and less costly interventions based on educational and cognitive principles were valuable for persons with longstanding fibromyalgia. More attention must be given to evaluating the clinical effect of programmes.

The expression of adhesion molecules in muscle biopsies: the LFA-1/VLA-4 ratio in polymyositis.

OBJECTIVES: The expression of three pairs of adhesion receptors and ligands was examined in 22 consecutive muscle biopsies showing morphological signs of inflammation. MATERIAL AND METHODS: The following groups were studied: patients with polymyositis (PM) (n=7), patients with myositis that did not fulfil criteria for PM, i.e. suspected PM (n=5), patients with other diseases, with no clinical signs of inflammatory myopathy (n=6), and a small group of non-PM inflammatory myopathies (n=4). The endothelial expression of ICAM-1, VCAM-1 and E-selectin was evaluated, as was the cellular expression of LFA-1, VLA-4 and SLex. In addition, the expression of MHC class I and II was studied. RESULTS: The ratio between the number of cells expressing LFA-1 and VLA-4 showed significant differences between the groups, with the lowest values in PM. CONCLUSION: The LFA-1/VLA-4 ratio should be suitable for diagnostic purposes. Our findings also indicate that the VLA-4/VCAM-1 system is important for chronic T cell inflammation in muscle, in line with findings in other "hidden" organs like joints and the central nervous system.

Development of hypertension over 6 years in a birth cohort of young middle-aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS).

OBJECTIVES: To explore the development of hypertension (HT) in a cohort of young middle-aged men. DESIGN: Prospective birth-cohort study of men surveyed over 6 years. SETTING: Helsingborg County Hospital, Sweden, 1990-97. SUBJECTS: A total of 628 men born in 1953-54, all surveyed at 37, 40 and 43 years of age. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), S-cholesterol, body mass index (BMI), alcohol consumption, ethnicity. HT was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg, or ongoing treatment. Using SBP < 130 mmHg and DBP < 85 mmHg as reference, the odds of conversion to HT in men with high normal blood pressure (BP) (SBP 130-139 mmHg and DBP 85-89 mmHg) was investigated. RESULTS: At age 37, 243 men (39%) had reference BP, 167 (26%) had high normal BP and 218 (35%) were hypertensive. Corresponding numbers at age 40 were 265 (42%), 166 (27%) and 197 (31%); and at age 43, 180 (29%), 142 (22%) and 306 (49%), respectively. High normal BP at baseline was associated with the development of HT both at age 40 (odds ratio (OR)=2.45 confidence interval (CI): 1.42-4.22) and at age 43 (OR=2.46, CI: 1.59-3.80), independent of other cardiovascular disease risk factors and ethnicity. The progression to HT was predicted also by S-cholesterol, alcohol consumption, BMI and weight gain. CONCLUSIONS: Over a short-term period, a substantial proportion of young middle-aged men with high normal BP develop HT with overweight and alcohol consumption as important determinants. These findings have implications for the prevention, screening and medical care of HT in this target population.

Associations between body height, body composition and cholesterol levels in middle-aged men. the coronary risk factor study in southern Sweden (CRISS).

BACKGROUND: Short body height is associated with increased risk for coronary heart disease; however, mechanisms are not fully explained. In this study, associations between body height and serum cholesterol, non-high-density lipoprotein (non-HDL cholesterol) and high-density lipoprotein (HDL cholesterol) were investigated. METHODS: Prospective cohort study of middle-aged men from Helsingborg, Sweden starting 1990. Two birth-year cohorts were invited at 37, 40 and 43 years of age; participation at baseline was 991 (68%). Serum and HDL cholesterol, systolic and diastolic blood pressure, weight, height, waist and hip circumferences were measured. Non-HDL cholesterol, body mass index (BMI) and waist/ hip ratio (WHR) were calculated. The participants completed a questionnaire covering lifestyle variables. RESULTS: There were statistically significant inverse correlations between body height and serum cholesterol (-0.11) and non-HDL cholesterol (-0.12). One standard deviation, 6.7 cm, taller body height was associated with a lower serum cholesterol (-0.12 mmol/l) and a lower non-HDL cholesterol (-0.13 m mol/l; p < 0.001). These associations remained when adjusted for BMI and WHR. Men with serum cholesterol equal to or above 6.5 mmol/l were significantly shorter (mean 178.71 cm) than men with serum cholesterol below 6.5 mmol/l (mean 179.71 cm). In addition, BMI and WHR were positively associated with serum and non-HDL cholesterol and inversely associated with HDL cholesterol. The change in cholesterol levels over the six-year follow-up was significantly associated to the change in BMI and WHR. CONCLUSIONS: Body height had an independent and inverse relation to serum cholesterol and non-HDL cholesterol in middle-aged men, and the lipid pattern suggests that the underlying mechanism might be different from the traditional association between lipids and the metabolic syndrome. Although the direct clinical implication is limited, our results may help to explain the association between short height and risk of myocardial infarction.

Research methods courses for GPs: ten years' experience in southern Sweden.

At the Department of Community Medicine at Lund University we have given courses in basic research methodology since 1989. During a ten-year period, 138 (20%) of the 700 general practitioners (GPs) in our region completed the theoretical part of our course, 104 (75%) finished their research projects, and 17 signed up as PhD students at our department. Thus, we have provided a large number of GPs with a fundamental knowledge of research methods and we have recruited new PhD students to the field of general practice.