Initial results from the New Horizons exploration of 2014 MU69, a small Kuiper Belt object.

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.

Lower inhaled steroid requirement with a fluticasone/salmeterol combination in family practice patients with asthma or COPD.

BACKGROUND: Previous studies on inhaled steroid and long-acting beta2-agonist combination products may not be representative for the asthma and chronic obstructive pulmonary disease (COPD) patients in family practice. OBJECTIVES: To compare in a group of doctor-diagnosed patients with asthma or COPD, the effects of a lower dose of fluticasone in a combination product with salmeterol with conventional treatment (i.e. a higher dose of fluticasone), both supplemented with as-needed use of a short-acting bronchodilator. METHODS: The study was a 12-week multicentre, randomized controlled, double-blind trial. In all, 41 family practices recruited 137 patients diagnosed with asthma and 40 patients diagnosed with COPD. Primary outcome was the forced expiratory volume in 1 second (FEV1) as percentage of predicted. Morning peak expiratory flow (PEF), symptom-free days, health status [Asthma Quality of Life Questionnaire (AQLQ) and St. George's Respiratory Questionnaire (SGRQ)], exacerbations, use of short-acting bronchodilators and adverse events were secondary outcomes. RESULTS: FEV1% predicted increased 2.6% (SD 8.3) in fluticasone/salmeterol- and 0.01% (SD 6.6) in fluticasone-treated patients (overall: P=0.036, asthma: P=0.025 and COPD: P=0.700). PEF increased in favour of fluticasone/salmeterol in asthma patients only (P=0.016). Fluticasone/salmeterol-treated asthma patients had 1.1 more symptom-free days per week (P=0.044); no such effect was observed for COPD (P=0.769). There were no differences in total AQLQ and SGRQ scores, exacerbations, use of reliever puffs or adverse effects. CONCLUSIONS: In family practice patients diagnosed with asthma, several treatment goals were better achieved with a lower dose of fluticasone and salmeterol in a combination product than with a higher dose of fluticasone. We found no differences between the two approaches for patients with COPD.

Redo- extirpation of a cardiac leiomyosarcoma to avoid transplantation.

Cardiac leiomyosarcoma is a very rare entity that is found in less than 0.2 % of all cardiac tumors. At the time of primary diagnosis, it often shows advanced local invasion or may even be metastasized. Thus, complete resection can not easily be achieved. Cardiac transplantation has been reported as a therapeutic option. Here, we report on a case of a leiomyosarcoma reoccurrence arising 2 years after initial surgery. We performed a radical redo-extirpation without the necessity of transplantation.

Treatment strategy, disease activity, and outcome in four cohorts of patients with early rheumatoid arthritis.

OBJECTIVE: To compare four different inception cohorts of patients with early rheumatoid arthritis (RA) with respect to treatment strategies, disease activity, and outcome during a five year follow up period. METHOD: Data from cohorts of patients with early RA, with a standardised assessment at least every six months for five years from four different centres, were included in one database. Owing to slight differences in the individual study designs, linearly interpolated values were calculated to complete the standard follow up schedule. RESULTS: Despite similar inclusion criteria, significant differences in demographic factors and baseline disease activity were found between the different cohorts. During the follow up an aggressive treatment strategy was followed in the Dutch and Finnish cohort, an intermediate strategy in the British cohort, and a conservative strategy in the Swedish cohort. A significant improvement in disease activity was seen in all cohorts, though the most rapid and striking improvement was seen in those receiving aggressive treatment. This resulted in less radiographic destruction in the long run. CONCLUSION: This observational study of cohorts of patients with early RA confirms that early aggressive treatment results not only in a more rapid reduction of disease activity but also in less radiographic progression in the long term.

Familial vs sporadic rheumatoid arthritis (RA). A prospective study in an early RA inception cohort.

OBJECTIVES: To study potential differences in demographic, process and outcome variables between familial and sporadic rheumatoid arthritis (RA) in an early RA inception cohort. METHODS: In 1998, we ascertained the familial status of all collaborative patients in a large early RA inception cohort at our department. Familial RA was defined by the presence of at least two siblings fulfilling the American College of Rheumatology criteria for RA. Baseline demographic data and prospectively recorded disease activity variables, therapies and radiological damage during the first 6 yr of disease were included in the analysis. A regression analysis was performed to assess whether familial clustering is a prognostic factor. RESULTS: We identified 142 patients with sporadic and 36 with familial RA. The most striking difference between these groups was the larger sibship size in multicase families (8.2 +/- 2.5 vs 5. 5 +/- 2.8; P < 0.0001). Age at onset was similar in both groups, although males with familiar RA were younger at disease onset than those with sporadic RA (median 50 vs 57 yr; P=0.03). No differences were found in gender, presence of rheumatoid factor (RF), antinuclear factor and HLA-DR typing or in disease activity, interventions and outcome over 6 yr of follow-up. Early radiological damage and disease activity, but not familial history of RA were prognostic for X-ray damage. CONCLUSION: We show that sibship size is the only relevant risk factor for familial RA. No differences in genotypic and phenotypic characteristics, disease severity or radiological damage were observed among familial and sporadic RA. Familial history of RA is not a poor prognostic factor. This prospective study confirms previous cross-sectional findings in the Dutch population.

Familial aggregation of rheumatoid arthritis in The Netherlands: a cross-sectional hospital-based survey. European Consortium on Rheumatoid Arthritis families (ECRAF).

OBJECTIVES: To study the familial aggregation of rheumatoid arthritis (RA) in The Netherlands and to analyse the effect of proband characteristics on the concordance rates for RA. Secondary aims were to compare the characteristics of patients in an early RA inception cohort with those of regular patients and to select Dutch families for the genome-wide scan carried out by the European Consortium on RA families (ECRAF). METHODS: A cross-sectional, hospital-based survey aimed to identify affected sibpair (ASP) families among our whole RA population. Familial RA, or an ASP family, was defined by the presence of at least two siblings fulfilling the 1987 ACR criteria for RA. RESULTS: The estimated prevalence for familial RA was 9.8% and similar to that found in previous hospital series. The true-positive reporting rate for RA in sibs was 60%. Sibship size in ASP families (mean +/- S.D. = 7.8+/-3.3) was significantly larger than in the Dutch population. Probands with familial RA were more often rheumatoid factor positive and had a longer follow-up. Male gender and history of joint replacements were associated with higher concordance rates for RA. However, regression analysis showed that, correcting for sibship size, the concordance rate for RA was largely not explained by proband characteristics. Compared to regular RA patients, our inception cohort encompassed more male and/or rheumatoid factor-negative patients, but had similar performance in the study and rate of familial aggregation. CONCLUSIONS: The familial aggregation of RA in The Netherlands is not increased and occurs preferentially in large sibships. Among proband characteristics, sibship size is most clearly related to the recurrence of RA in particular families. Patients' recognition of RA manifestations in relatives is not optimal.

Socio-economic consequences of rheumatoid arthritis in the first years of the disease.

OBJECTIVE: Few data have been presented to document the impact of rheumatoid arthritis (RA) on socio-economic well-being. In this study, exact figures on socio-economic consequences were assessed. METHODS: The socio-economic consequences were studied in an inception cohort (186 early RA patients, mean disease duration 3 yr) by measuring the change in work capability, income, rest during the daytime, leisure time activity, transport mobility, housing and social support occurring in the first years of the disease. RESULTS: For 89% of the patients, RA had an impact on one of the socio-economic items; for 58%, at least three of these items were affected simultaneously. Work disability appeared to be 4-15 times higher than in the general population. After 3 yr, 42% of the patients were registered as work disabled. Nearly a quarter of the patients experienced income reduction. Over 40% of the patients claimed extra rest during the daytime. Leisure activity changed towards activities with a lower joint load. There was a decline in transport mobility for 52% of the patients. Social support increased strongly. CONCLUSIONS: Socio-economic change already presents in the first years of RA and appears to be influenced by age, gender, marital status and work disability. Furthermore, physical limitation appeared to be predictive for work-related income reduction, reduced transport mobility and development of social dependency.

Factors that influence the level of contamination of human milk with poly-chlorinated organic compounds.

Polychlorinated organic compounds (POCs) accumulate in tissues with a high fat content. Nursed babies are exposed to POCs through the fat in human milk. Exposure levels are estimated to exceed those considered acceptable as a lifelong daily dose. Nevertheless, mothers are still positively advised as to breast-feeding. In 1988, a survey on contamination of human milk with POCs was carried out in The Netherlands. Levels of ten different organochlorine pesticides (OCPs), eight polychlorinated biphenyl (PCB) congeners, and seventeen polychlorinated dibenzodioxin (PCDD) and -dibenzofuran (PCDF) congeners were determined by use of gaschromatographic techniques with either electron-capture or mass-spectrometric detection. Information on some factors potentially influencing the level of contamination of human milk was obtained by questionnaires. The estimated response amounted to 71 percent. Regression analysis was used to investigate associations between determining factors and specific contaminants. It appeared that maternal age was positively associated with POC concentrations. Traditional omnivorous diet was associated with lower concentrations of POCs when compared to all other types of diet. The post-pregnancy Quetelet Index [by definition calculated as weight/(length)2] and the cumulated period of previous breast-feeding were negatively associated with POC concentrations. In conclusion, chemical behavior and environmental distribution patterns of the POCs measured in this study, if translated to factors of human exposure, are in accordance with the study results. Exposure levels will decrease if emissions can be further reduced. Still, in the near future, maternal age will probably rise (Vermunt 1992; Netherlands Central Bureau of Statistics 1992), whereas the duration of lactation in expected to decline. Consequently, there might be an increase in average POC-concentrations in human milk in the forthcoming years.

Effect of enzyme inhibitors on profiles of IR-ACTH/beta-endorphin in brain and pituitary.

Processing of pro-opiomelanocortin (POMC) in brain and pituitary results in various proportions of multiple peptides appearing as immunoreactive (IR-) ACTH and IR-beta-endorphin. Because it is desirable that molecular profiles of POMC-related peptides reflect in vivo processing and not isolation artifact, inhibition of proteolytic activity during extraction is critical. Although enzyme inhibitors are frequently used during extraction of POMC-related peptides, their benefit or necessity has not been established. To determine the benefit of using enzyme inhibitors for studying molecular profiles of IR-ACTH and IR-beta-endorphin from rat brain and pituitary, chromatographic profiles were compared to assess the effect of each of several enzyme inhibitors. Results suggested that the enzyme inhibitors studied provided no additional benefit in terms of inhibition of extraction proteolysis over that provided by a strong acid and heat inactivation.