Full Bayesian identification of linear dynamic systems using stable kernels.

System identification learns mathematical models of dynamic systems starting from input-output data. Despite its long history, such research area is still extremely active. New challenges are posed by identification of complex physical processes given by the interconnection of dynamic systems. Examples arise in biology and industry, e.g., in the study of brain dynamics or sensor networks. In the last years, regularized kernel-based identification, with inspiration from machine learning, has emerged as an interesting alternative to the classical approach commonly adopted in the literature. In the linear setting, it uses the class of stable kernels to include fundamental features of physical dynamical systems, e.g., smooth exponential decay of impulse responses. Such class includes also unknown continuous parameters, called hyperparameters, which play a similar role as the model discrete order in controlling complexity. In this paper, we develop a linear system identification procedure by casting stable kernels in a full Bayesian framework. Our models incorporate hyperparameters uncertainty and consist of a mixture of dynamic systems over a continuum spectrum of dimensions. They are obtained by overcoming drawbacks related to classical Markov chain Monte Carlo schemes that, when applied to stable kernels, are proved to become nearly reducible (i.e., unable to reconstruct posteriors of interest in reasonable time). Numerical experiments show that full Bayes frequently outperforms the state-of-the-art results on typical benchmark problems. Two real applications related to brain dynamics (neural activity) and sensor networks are also included.

Poor long-term prognosis in patients admitted with strong suspicion of acute myocardial infarction but discharged with another diagnosis.

BACKGROUND: Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. OBJECTIVES: To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. METHODS: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. RESULTS: 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. CONCLUSIONS: Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis.

Comparison of agreement between internet-based registration of patient-reported outcomes and clinic-based paper forms within the Swedish Rheumatology Quality Register.

Objective: The Swedish Rheumatology Quality Register has implemented an internet-based method (PER) for registering patient-recorded outcome measures. The aim of this study was to compare the agreement between visual analogue scales (VASs) reported via PER and clinic-based reporting using paper forms. Methods: In a cross-sectional study (70 patients), the results of 79 registrations of VASs for global health, pain, and fatigue from PER were compared with corresponding clinic-based paper registrations. For patients with polyarthritis, 28-joint count Disease Activity Scores (DAS28) were computed. Patients with axial disease also completed Bath Ankylosing Spondylitis Disease Activity Index and Functional Index (BASDAI and BASFI) questionnaires. Mean differences and intraclass correlation coefficients (ICCs) were calculated. Agreement was visualized using Bland-Altman plots. Results: No statistically significant differences in VASs were found comparing PER and paper forms for VAS Global, VAS Pain, and VAS Fatigue (p = 0.295, 0.463, and 0.288, respectively). ICCs for VAS Global, Pain, and Fatigue ranged from 0.889 to 0.952, indicating excellent agreement. Bland-Altman plots for VAS did not show any proportional bias. The mean difference for DAS28 calculated by VASs from paper vs PER was -0.02 (n = 65, p = 0.660), and the mean difference for BASDAI was 0.04 (n = 11, p = 0.742). ICCs for DAS28 and BASDAI were 0.962 and 0.985, respectively. Of the participating patients, 60% preferred PER. Conclusion: Internet-based reporting for patient-reported outcomes in a clinical setting resulted in similar data for VASs and corresponding disease activity scores to clinic-based reporting on paper forms.

Efficacy of primary preventive ICD therapy in an unselected population of patients with reduced left ventricular ejection fraction.

AIMS: International guidelines advocate an implantable cardioverter and defibrillator (ICD) in patients with reduced left ventricular ejection fraction (LVEF) to prevent sudden death (SCD). Previous data suggest that the benefit of ICD therapy in real life may be lower than expected from the results of controlled studies and side-effects are not negligible. It is also unclear whether women benefit from treatment to the same extent as men. The aim of this study was to investigate the balance between benefits and complications of ICD therapy in a real-life population of patients with heart failure. METHODS AND RESULTS: We studied 865 consecutive patients with reduced LVEF treated with ICDs for primary prevention of SCD in 2006-11 in four tertiary care hospitals in Sweden (age 64 ± 11 years, 82% men, 62% ischaemic). The patients' medical records were scrutinized as regards appropriate therapies, complications related to the defibrillator, all-cause mortality, and gender differences. Mean follow-up was 35 ± 18 months. During follow-up 155 patients (18%) received appropriate ICD therapy, 61 patients (7%) had inappropriate shocks, 110 patients (13%) had at least one complication that required reoperation and 213 patients (25%) died. Men were twice as likely to receive ICD treatment compared with women (20 vs. 9%, P < 0.01), but neither total mortality nor complication rates differed. CONCLUSIONS: Ventricular arrhythmias necessitating ICD therapy are common (6% annually). Women are less likely to have correct ICD treatment, but have the same degree of treatment complications, thus reducing the net benefit of their treatment.

Health-related quality of life in advanced non-small cell lung cancer: correlates and comparisons to normative data.

The aim was to describe self-reported health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer and to investigate the associations to stage of disease, age, gender, weight loss and performance status. Further, the study aimed to compare patients' HRQoL with that of the Swedish general population. Data on HRQoL were collected within a multi-centre randomised controlled trial. A total of 334 patients were included between 1998 and 2001. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Lung Cancer Questionnaire (EORTC QLQ-LC13) were used to assess HRQoL. HRQoL data for comparison with the Swedish population were derived from a random sample of the Swedish population. Patients reported a markedly impaired HRQoL compared to the normal population. There were statistically and clinically significant differences with regard to almost all QLQ-C30 functional and symptom scales. Global health status, physical functioning, role functioning and emotional functioning were markedly deteriorated. The most prominent symptoms were dyspnoea, fatigue, coughing, insomnia, appetite loss and pain. A low performance status, younger age, female gender and a more advanced disease were independently associated with a worse HRQoL. Additional studies are required to gain increased insight into this seriously ill group of patients and their need of supportive care.

Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial.

BACKGROUND: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis. METHODS: We undertook a randomised trial in 15 rheumatology units in Sweden. We enrolled patients with early rheumatoid arthritis (symptom duration <1 year) and administered methotrexate (up to 20 mg per week). After 3-4 months, those who had not achieved low disease activity but who could tolerate methotrexate were randomly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab. Primary outcome was achievement of a good response according to European League Against Rheumatism (EULAR) criteria at 12 months. Patients were followed up to 24 months; here, we present findings at 12 months. Analysis was by intention to treat and we used non-responder imputation. The Swefot (Swedish Pharmacotherapy) study is registered in the WHO database at the Karolinska University Hospital, number CT20080004. FINDINGS: 487 patients were initially enrolled. Of 258 who had not achieved low disease activity with methotrexate, 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab. 32 of 130 (25%) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 (39%) assigned infliximab (risk ratio 1.59 [95% CI 1.10-2.30], p=0.0160). Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used. No deaths occurred in either group. INTERPRETATION: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. FUNDING: Swedish Rheumatism Association, Schering-Plough.

Interleukin-1 receptor antagonist is associated with both lipid metabolism and inflammation in rheumatoid arthritis.

BACKGROUND: There is a relationship between cardiovascular morbidity, inflammatory activity, and changes in the lipid profile in rheumatoid arthritis (RA), although the mechanisms are not fully elaborated. Recent know-ledge that white adipose tissue (WAT) is a producer of immunologically and metabolically active substances gives another perspective to study. OBJECTIVE: To evaluate the relationship between interleukin-1 receptor antagonist (IL-1Ra) and variables associated with WAT and inflammation in RA. METHODS: Anthropometric, inflammatory and metabolic variables were assessed in 23 women with RA and 23 matched controls. Spearman, partial correlation and factor analyses were performed. RESULTS: Inflammatory markers were increased in patients. In both groups, IL-1Ra correlated with leptin independent of age and BMI. IL-1Ra also correlated with haptoglobin and apolipoprotein (Apo) B in patients and with soluble TNF receptor (sTNFR) 1 in controls. In factor analysis, three latent factors were identified among patients. The first loaded on IL-1Ra, leptin, BMI, ApoB and body fat content (BF%), the second loaded on IL1-Ra and sTNF-receptors and the third showed inverse loadings on ApoA-I together with loadings on ESR, haptoglobin, orosomucoid, BF% and BMI. CONCLUSION: IL-1Ra was associated with markers of inflammation and with fat-related factors in RA patients, suggesting a dualistic relationship of IL-1Ra in RA. IL-1Ra correlated independently with leptin in both patients and controls, indicating a relationship between inflammation and leptin.

Uptake of porcine rubulavirus (LPMV) by PK-15 cells.

BACKGROUND: The porcine virus denominated La Piedad Michoacan Virus (LPMV) is a member of the family Paramyxoviridae and is the cause of a disease in pigs present only in Mexico. The disease is characterized by meningoencephalitis and respiratory distress in young pigs, epididymitis and orchitis in boars, and reproductive failure and abortion in sows. METHODS: The cytopathology, morphology, and distribution of the hemagglutination neuraminidase (HN) and nucleoprotein (NP) proteins of LPMV were investigated following inoculation into PK-15 cells. The cytopathic effect was characterized by cytoplasmic vacuolation and the formation of syncytia and cytoplasmic inclusion bodies. RESULTS: In immunofluorescence assays using a monoclonal antibody (MAb) against the HN protein at 5-60 min post-infection (early infection), a diffuse immunofluorescence was observed near the cell membrane and adjacent to the nuclear membrane. At 24 h post-infection (late infection), a dust-like immunofluorescence was observed throughout the cytoplasm. LPMV-infected cells incubated with the MAb against the NP protein showed punctate cytoplasmic fluorescence during the early stages of infection. At the late infection stage, these fluorescent particles became larger and were seen predominantly in the cytoplasm of syncytia. This pattern was also apparent by immunohistochemical labeling and immunogold electron microscopy. The latter technique revealed that HN protein was diffusely distributed throughout the cytoplasm. When using the MAb against the NP protein, nucleocapsid organization was the most prominent feature and resulted in the formation of cytoplasmic inclusion bodies visible by light and electron microscopy. Immunogold labeling of purified nucleocapsids was shown by electron microscopy. Virus particles and nucleocapsids were morphologically similar to members of the Paramyxoviridae family. CONCLUSIONS: The morphologic characteristics of the virions and the distribution patterns of the HN and NP proteins in PK-15 infected cells indicate that the mechanisms of LPMV replication are generally similar to those of the members of the Paramyxoviridae family.

Electron microscopy and X-ray microanalyses of uterine epithelium from lead-injected mice in an experimental delay of implantation.

Mice in experimental delay of implantation were injected intravenously with 75 micrograms.g-1 body weight of lead chloride, corresponding to a dose of lead of about 56 micrograms.g-1 body weight. Delay of implantation was obtained by ovariectomy 3 days after mating followed by a depot dose of progesterone every fifth day. Electron microscopy showed that the uterine lumen, which was closed in control mice, was opened in lead-injected mice. This morphology suggested that lead caused an increase in uterine secretion. X-ray microanalysis of pyroantimonate precipitates in the uterine epithelium of injected mice demonstrated lead in the precipitates, suggesting that lead could have a direct effect on the function of the uterine epithelium and that lead also could be secreted into the uterine lumen and affect the blastocysts.

X-ray micro analyses of cations (Na, K, Ca) and anions (S, P, Cl) in uterine secretions during blastocyst implantation in the rat.

The mass changes of sodium, potassium, and calcium ions in the rat uterine secretion at blastocyst delay, activation, and attachment have been estimated with X-ray microanalyses of samples of uterine secretions absorbed by small Sephadex beads. A quantification of the ions was attempted by using a standardized coat of gold on the beads as a reference element for normalization of the ion peaks and by fitting the normalized values into corresponding linear regression equations obtained from measurements of step-wise dilutions of a control rat serum. The concentrations of sodium observed at delay, activation, and attachment were 117, 201, and 203 mEq/l, respectively, and those of potassium were 6, 18, and 19 mEq/l, respectively. Calcium values were about 2 mEq/l and decreased at attachment. Among the anions, only the chloride concentration increased at activation and attachment.