Lars Bruun Larsen

Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection

BACKGROUND little is known about inflammatory mediators (IM); like cytokines, chemokines and receptors; in respiratory secretion as possible indicators of the severity of respiratory syncytial virus (RSV) disease. Nor have systematic studies been published on the ratios between IM as such indicators. OBJECTIVE to define the role of IM ratios as possible indicators of the severity of RSV disease. STUDY DESIGN about 46 infants aged 0-9 months with acute RSV infections were studied. Prematurity (PM) and/or underlying disease (UD) were present in 11 of them. The concentrations of seven different IM were measured by ELISA in samples of nasopharyngeal secretions (NPS), four cytokines; IL-1, IL-6, IL-10 and TNF-alpha; the cytokine receptor TNF-R1 and the chemokines; IL-8 and RANTES. 21 IM ratios were calculated from these concentrations. The patients were assigned a clinical score (CS) ranging from 0 to 3 according to the severity of disease. RESULTS when 25 patients with severe disease (CS 2-3) and 21 patients with mild disease (CS 0-1) were compared with respect to different IM ratios, three ratios were related to severity of disease: IL-1/RANTES, IL-8/RANTES and TNF-R1/RANTES. When 12 patients with mild disease were compared with 16 patients with severe disease, omitting patients more than 5 months of age and patients with PM and/or UD, the following IM ratios were related to severity of disease: TNF-R1/RANTES, IL-8/RANTES and RANTES/IL-10. CONCLUSION of 21 IM ratios studied, TNF-R1/RANTES was related to severity of disease with greatest consistency.

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions

BACKGROUND Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.

Wideband measurements of ice sheet attenuation and basal scattering

We are developing a multifrequency multistatic synthetic aperture radar (SAR) for determining polar ice sheet basal conditions. To obtain data for designing and optimizing radar performance, we performed field measurements with a network-analyzer-based system during the 2003 field season at the North Greenland Ice Core Project camp (75.1 N and 42.3 W). From the measurements, we determine the ice sheet complex transfer function over the frequency range from 110-500 MHz by deconvolving out the system transfer function. Over this frequency range, we observe an increase in total loss of 8/spl plusmn/2.5 dB using a linear regression to the log-scale data. With the ice sheet transfer function and an ice extinction model, we estimate the return loss from the basal surface to be approximately 37 dB. These measurements have broad applicability to interpreting radar-sounding data, which are widely used in glaciological studies of the polar ice sheets. These data have also been used in the link budget for the design considerations of the multifrequency multistatic SAR system.

The fluctuating pattern of various genome types of respiratory syncytial virus in Copenhagen and some other locations in Denmark

A semi‐nested RT‐PCR method based on a region of the F and G glycoprotein genes was established, allowing the simultaneous detection and differentiation of group A and group B isolates of respiratory syncytial virus (RSV). The PCR products were subjected to digestion with restriction endonucleases to further differentiate the isolates. Using, in addition, previously reported studies the prevalence of various genome types in the Copenhagen region over a period of 6 years was established. Furthermore, the prevalence of genome types was determined in a distant region in Denmark during the winters of 1996/97 and 1997/98, and in yet another distant region during the winter of 1997/98. It was shown that the different regions in Denmark to a large extent share the same pool of genome types of RSV. Yet, while the fluctuating patterns of the two groups and various genome types were almost identical at different hospitals in the Copenhagen region, they varied between the different regions. This suggests that epidemics in local communities primarily rely on region‐specific herd immunity parameters and emerge from strains endemically circulating in these local communities. Group B strains in Copenhagen showed an overall predominance, being predominant in three of the six epidemic seasons studied, and of almost equal predominance in one season.

High-resolution radar mapping of internal layers at NGRIP

A major goal of NASAs Office of Earth Science Polar Program is to determine the mass balance of the Greenland and Antarctic ice sheets. A key variable in assessing the mass balance of an ice sheet is accumulation rate. Currently, accumulation rate is determined from ice cores and pits. There are large uncertainties in existing accumulation rate maps derived from sparely distributed ice cores and pits. There is an urgent need for developing remote sensing techniques for determining the accumulation rate. A prototype Frequency Modulated Continuous Wave (FMCW) radar system has been developed for mapping internal layers from known volcanic events in the ice. The prototype system has been designed and developed using the latest RF technologies. The system was operated from 100 to 2000 MHz, for imaging the top 200 meters of ice with high resolution. We tested this system during the 1998 and 1999 surface experiments at the North GReenland Ice core Project (NGRIP) ice camp. Our results show that internal layers were successfully mapped with high resolution down to 200 m.

A novel approach to population-based risk stratification, comprising individualized lifestyle intervention in Danish general practice to prevent chronic diseases: Results from a feasibility study.

Early detection of patients at risk seems to be effective for reducing the prevalence of lifestyle-related chronic diseases. We aim to test the feasibility of a novel intervention for early detection of lifestyle-related chronic diseases based on a population-based stratification using a combination of questionnaire and electronic patient record data. The intervention comprises four elements: (1) collection of information on lifestyle risk factors using a short 15-item questionnaire, (2) electronic transfer of questionnaire data to the general practitioners’ electronic patient records, (3) identification of patients already diagnosed with a lifestyle-related chronic disease, and (4) risk estimation and stratification of apparently healthy patients using questionnaire and electronic patient record data on validated risk estimation models. We show that it is feasible to implement a novel intervention that identifies and stratifies patients for further examinations in general practice or behaviour change interventions at the municipal level without any additional workload for the general practitioner.

Targeted prevention in primary care aimed at lifestyle-related diseases: a study protocol for a non-randomised pilot study

BackgroundThe consequences of lifestyle-related disease represent a major burden for the individual as well as for society at large. Individual preventive health checks to the general population have been suggested as a mean to reduce the burden of lifestyle-related diseases, though with mixed evidence on effectiveness. Several systematic reviews, on the other hand, suggest that health checks targeting people at high risk of chronic lifestyle-related diseases may be more effective. The evidence is however very limited. To effectively target people at high risk of lifestyle-related disease, there is a substantial need to advance and implement evidence-based health strategies and interventions that facilitate the identification and management of people at high risk. This paper reports on a non-randomized pilot study carried out to test the acceptability, feasibility and short-term effects of a healthcare intervention in primary care designed to systematically identify persons at risk of developing lifestyle-related disease or who engage in health-risk behavior, and provide targeted and coherent preventive services to these individuals.MethodsThe intervention took place over a three-month period from September 2016 to December 2016. Taking a two-pronged approach, the design included both a joint and a targeted intervention. The former was directed at the entire population, while the latter specifically focused on patients at high risk of a lifestyle-related disease and/or who engage in health-risk behavior. The intervention was facilitated by a digital support system. The evaluation of the pilot will comprise both quantitative and qualitative research methods. All outcome measures are based on validated instruments and aim to provide results pertaining to intervention acceptability, feasibility, and short-term effects.DiscussionThis pilot study will provide a solid empirical base from which to plan and implement a full-scale randomized study with the central aim of determining the efficacy of a preventive health intervention.Trial registrationRegistered at Clinical Trial Gov (Unique Protocol ID: TOFpilot2016). Registered 29 April 2016. The study adheres to the SPIRIT guidelines.

High-resolution monitoring of internal layers over the Greenland ice sheet

The global sea level rise has been attributed to the melting of mountain glaciers among other causes. The mass balance of the glacial ice plays an important role in the rise of the Earths sea level. A key variable in assessing the mass balance of an ice sheet is accumulation rate, which is currently determined from ice cores and pits. Accumulation data are sparse, and there are large uncertainties in existing accumulation rate maps derived from sparely distributed ice cores and pits. The accumulation rate can be estimated more accurately if we are able to obtain a continuous profile of the dated layers in the ice sheet. The authors describe the development of a high-resolution radar system to map the layers in the ice sheet and present the results obtained at the North GReenland Ice core Project (NGRIP) ice camp with their prototype system.

High-resolution monitoring of internal layers at NGRIP

A key variable in assessing the mass balance of an ice sheet is accumulation rate. Currently, accumulation rate is determined from sparsely distributed ice cores and pits. There are uncertainties in existing accumulation rates derived from these cores and pits. The authors developed an ultra wideband frequency modulated continuous wave (FMCW) radar for mapping internal layers, from known volcanic events, in the ice for estimating accumulation rate from high-resolution radar data. The authors tested the radar system during the 1998 surface experiment at the North Greenland Ice core Project (NGRIP) ice camp. Their results show that internal layers were mapped with high resolution down to 200 m. In this paper, they present the results of the 1998 NGRIP surface experiment.

A third perspective on the effects of general health checks may provide a less biased estimate (letter commenting J Clin Epidemiol 2016;71:120–2)

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