a cephalometric intercentre comparison of patients with unilateral cleft lip and palate at 5 and 10 years of age

SUMMARY The aim of this study was to evaluate any differences between the craniofacial growth of unilateral cleft lip and palate (UCLP) patients who underwent surgery in the Milan CLP centre with those from the Oslo CLP centre at 5 and 10 years of age. The Milan sample comprised 88 UCLP patients (60 males, 28 females) at 5 years of age and 26 patients (17 males, 9 females) at 10 years of age all operated on by the same surgeon. The Oslo sample consisted of 48 UCLP patients (26 males, 22 females) aged 5 years and 29 patients (20 males, 9 females) aged 10 years treated by four different surgeons. Lateral cephalometric radiographs obtained for both samples were analysed and angular measurements and ratios were calculated both for the hard and soft tissues. Statistical analysis was undertaken with an unpaired t -test. At 5 years of age, there were neither sagittal nor vertical hard tissue differences between the two groups. With regard to the soft tissues, only the naso-labial angle showed a statistically signifi cant difference (Milan greater than Oslo by 5 degrees, P 2.6 degrees, P 2.9 degrees, P < 0.001, respectively. At 5 years of age, the Milan UCLP sample had the same maxillary protrusion as the Oslo group, while at 10 years of age, the Milan sample were slightly less protruded than the Oslo group

Psoriatic arthritis, axial spondyloarthritis and rheumatoid arthritis in Norway : nationwide prevalence and use of biologic agents

Objective To estimate the prevalence of psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA) and the use of biologic agents in these diseases in Norway. Methods From the Norwegian Patient Registry (NPR), we identified as PsA, axSpA and RA patients >= 18 years those with >= 2 recorded episodes with diagnostic coding for index disease (L40.5, M07.0-M07.3 for PsA; M45, M46.0, M46.1, M46.8 and M46.9 for axSpA; M05-M06 for RA). We calculated the point prevalence of PsA, axSpA and RA as per the 1(st) of January 2017 in the Norwegian adult population (age >= 18). Dispensed disease-modifying antirheumatic drug (DMARD) prescriptions were obtained from the Norwegian Prescription Database and biologic DMARDs given in hospitals from the NPR. Results The point prevalence of PsA, axSpA, RA, and any of these diseases in total was 0.46%, 0.41%, 0.78%, and 1.56%, respectively. Among women, the prevalence of PsA, axSpA, and RA was 0.50%, 0.37%, and 1.10%, and among men 0.43%, 0.45%, and 0.46%, respectively. In 2017, 27.3% of RA patients, 25.7% of PsA patients and 35.1% of axSpA patients used biologic DMARDs. Treatment with biologics was more frequent in younger age groups in all three diseases, and became more infrequent especially after age >= 55 years. Conclusion In Norway, the combined prevalence of PsA, axSpA, and RA was over 1.5%. Reflecting the good overall access to highly effective but costly biologic treatments, more than a fourth of these patients used biologic agents, which corresponds to over 0.4% of Norwegian adult population.Peer reviewe

Nitrate stable isotopes and major ions in snow and ice samples from four Svalbard sites

Increasing reactive nitrogen (N-r) deposition in the Arctic may adversely impact N-limited ecosystems. To investigate atmospheric transport of N-r to Svalbard, Norwegian Arctic, snow and firn samples were collected from glaciers and analysed to define spatial and temporal variations (1 10 years) in major ion concentrations and the stable isotope composition (delta N-15 and delta O-18) of nitrate (NO3-) across the archipelago. The delta N-15(NO3-) and delta O-18(NO3-) averaged -4 parts per thousand and 67 parts per thousand in seasonal snow (2010-11) and -9 parts per thousand and 74 parts per thousand in firn accumulated over the decade 2001-2011. East-west zonal gradients were observed across the archipelago for some major ions (non-sea salt sulphate and magnesium) and also for delta N-15(NO3-) and delta O-18(NO3-) in snow, which suggests a different origin for air masses arriving in different sectors of Svalbard. We propose that snowfall associated with long-distance air mass transport over the Arctic Ocean inherits relatively low delta N-15(NO3-) due to in-transport N isotope fractionation. In contrast, faster air mass transport from the north-west Atlantic or northern Europe results in snowfall with higher delta N-15(NO3-) because in-transport fractionation of N is then time-limited

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid, diabetes, and antithrombotic trials.

This review article aims to explain the important issues that data safety monitoring boards (DSMB) face when considering early termination of a trial and is specifically addressed to the needs of clinical and research cardiologists. We give an insight into the overall background and then focus on the three principal reasons for stopping trials, i.e. efficacy, futility, and harm. The statistical essentials are also addressed to familiarize clinicians with the key principles. The topic is further highlighted by numerous examples from lipid trials and antithrombotic trials. This is followed by an overview of regulatory aspects, including an insight into industry–investigator interactions. To conclude, we summarize the key elements that are the basis for a decision to stop a randomized clinical trial (RCT)

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Diagnosis and management of drug-associated interstitial lung disease

Symptoms of drug-associated interstitial lung disease (ILD) are nonspecific and can be difficult to distinguish from a number of illnesses that commonly occur in patients with non-small-cell lung cancer (NSCLC) on therapy. Identification of drug involvement and differentiation from other illnesses is problematic, although radiological manifestations and clinical tests enable many of the alternative causes of symptoms in advanced NSCLC to be excluded. In lung cancer patients, high-resolution computed tomography (HRCT) is more sensitive than a chest radiograph in evaluating the severity and progression of parenchymal lung disease. Indeed, the use of HRCT imaging has led to the recognition of many distinct patterns of lung involvement and, along with clinical signs and symptoms, helps to predict both outcome and response to treatment. This manuscript outlines the radiology of drug-associated ILD and its differential diagnosis in NSCLC. An algorithm that uses clinical tests to exclude alternative diagnoses is also described

Quantitative Comparison of Constitutive Promoters in Human ES cells

BACKGROUND: Constitutive promoters that ensure sustained and high level gene expression are basic research tools that have a wide range of applications, including studies of human embryology and drug discovery in human embryonic stem cells (hESCs). Numerous cellular/viral promoters that ensure sustained gene expression in various cell types have been identified but systematic comparison of their activities in hESCs is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have quantitatively compared promoter activities of five commonly used constitutive promoters, including the human β-actin promoter (ACTB), cytomegalovirus (CMV), elongation factor-1α, (EF1α), phosphoglycerate kinase (PGK) and ubiquitinC (UbC) in hESCs. Lentiviral gene transfer was used to ensure stable integration of promoter-eGFP constructs into the hESCs genome. Promoter activities were quantitatively compared in long term culture of undifferentiated hESCs and in their differentiated progenies. CONCLUSION/SIGNIFICANCE: The ACTB, EF1α and PGK promoters showed stable activities during long term culture of undifferentiated hESCs. The ACTB promoter was superior by maintaining expression in 75-80% of the cells after 50 days in culture. During embryoid body (EB) differentiation, promoter activities of all five promoters decreased. Although the EF1α promoter was downregulated in approximately 50% of the cells, it was the most stable promoter during differentiation. Gene expression analysis of differentiated eGFP+ and eGFP- cells indicate that promoter activities might be restricted to specific cell lineages, suggesting the need to carefully select optimal promoters for constitutive gene expression in differentiated hESCs

Ploidy elicits a whole-genome dosage effect: growth of triploid Atlantic salmon is linked to the genetic origin of the second maternal chromosome set

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Update on management of hypokalemia and goals for the lower potassium level in patients with cardiovascular disease: A review in collaboration with the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Hypokalaemia is common in patients with cardiovascular disease. In this review, we emphasize the importance of tight potassium regulation in patients with cardiovascular disease based on findings from observational studies. To enhance the understanding, we also describe the mechanisms of potassium homeostasis maintenance, the most common causes of hypokalaemia and present strategies for monitoring and management of low potassium levels. We propose elevation of potassium in asymptomatic patients with lower normal concentrations and concurrent cardiovascular disease. These proposals are intended to assist clinicians until more evidence is available