Per Jönsson

TIMESAT - a program for analyzing time-series of satellite sensor data

Three different least-squares methods for processing time-series of satellite sensor data are presented. The first method uses local polynomial functions and can be classified as an adaptive Savitzky-Golay filter. The other two methods are more clear cut least-squares methods, where data are fit to a basis of harmonic functions and asymmetric Gaussian functions, respectively. The methods incorporate qualitative information on cloud contamination from ancillary datasets. The resulting smooth curves are used for extracting seasonal parameters related to the growing seasons. The methods are implemented in a computer program, TIMESAT, and applied to NASA/NOAA Pathfinder AVHRR Land Normalized Difference Vegetation Index data over Africa, giving spatially coherent images of seasonal parameters such as beginnings and ends of growing seasons, seasonally integrated NDVI and seasonal amplitudes. Based on general principles, the TIMESAT program can be used also for other types of satellite-derived time-series data.

Seasonality extraction by function fitting to time-series of satellite sensor data

A new method for extracting seasonality information from time-series of satellite sensor data is presented. The method is based on nonlinear least squares fits of asymmetric Gaussian model functions to the time-series. The smooth model functions are then used for defining key seasonality parameters, such as the number of growing seasons, the beginning and end of the seasons, and the rates of growth and decline. The method is implemented in a computer program TIMESAT and tested on Advanced Very High Resolution Radiometer (AVHRR) normalized difference vegetation index (NDVI) data over Africa. Ancillary cloud data [clouds from AVHRR (CLAVR)] are used as estimates of the uncertainty levels of the data values. Being general in nature, the proposed method can be applied also to new types of satellite-derived time-series data.

The grasp2K relativistic atomic structure package

This paper describes grasp2K, a general-purpose relativistic atomic structure package. It is a modification and extension of the GRASP92 package by [F.A. Parpia, C. Froese Fischer, I.P. Grant, Comput. Phys. Comm. 94 (1996) 249]. For the sake of continuity, two versions are included. Version 1 retains the GRASP92 formats for wave functions and expansion coefficients, but no longer requires preprocessing and more default options have been introduced. Modifications have eliminated some errors, improved the stability, and simplified interactive use. The transition code has been extended to cases where the initial and final states have different orbital sets. Several utility programs have been added. Whereas Version 1 constructs a single interaction matrix for all the Js and parities, Version 2 treats each J and parity as a separate matrix. This block structure results in a reduction of memory use and considerably shorter eigenvectors. Additional tools have been developed for this format. The CPU intensive parts of Version 2 have been parallelized using MPI. The package includes a “make” facility that relies on environment variables. These make it easier to port the application to different platforms. The present version supports the 32-bit Linux and ibmSP environments where the former is compatible with many Unix systems. Descriptions of the features and the program/data flow of the package will be given in some detail in this report.

High Progesterone Receptor Expression Correlates to the Effect of Adjuvant Tamoxifen in Premenopausal Breast Cancer Patients

Purpose: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor–positive breast cancer, and it still remains important due to its well-documented beneficial effect. Hormone receptor status is often reported as “positive” or “negative” using 10% positive nuclei as a cutoff. In this study, we aimed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value. Experimental Design: The immunohistochemical expression of estrogen receptor (ER) and progesterone receptor (PR) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a randomized trial of adjuvant tamoxifen compared with an untreated control group. Results: Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER-positive nuclei. However, when analyzing tamoxifen response according to various PR fractions, we found that it was primarily patients with tumors showing >75% PR-positive nuclei that responded to tamoxifen treatment, with an improved recurrence-free [relative risk, 0.42 (0.25-0.70); P = 0.001] as well as overall [relative risk, 0.49 (0.28-0.84); P = 0.010] survival. Conclusions: Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing >75% PR-positive nuclei. No effect could be shown in tumors with fewer PR-positive nuclei. The PR was a stronger predictor of treatment response than the ER. Based on these findings, we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice, possibly with greater emphasis on the PR than the ER.

Tumor-Specific Expression of Vascular Endothelial Growth Factor Receptor 2 but Not Vascular Endothelial Growth Factor or Human Epidermal Growth Factor Receptor 2 Is Associated With Impaired Response to Adjuvant Tamoxifen in Premenopausal Breast Cancer

PURPOSE Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance. PATIENTS AND METHODS Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors. RESULTS VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER-positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor-positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status. CONCLUSION Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor-positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.

A ground-validated NDVI dataset for monitoring vegetation dynamics and mapping phenology in Fennoscandia and the Kola peninsula

An NDVI dataset covering Fennoscandia and the Kola peninsula was created for vegetation and climate studies, using Moderate Resolution Imaging Spectroradiometer 16‐day maximum value composite data from 2000 to 2005. To create the dataset, (1) the influence of the polar night and snow on the NDVI values was removed by replacing NDVI values in winter with a pixel‐specific NDVI value representing the NDVI outside the growing season when the pixel is free of snow; and (2) yearly NDVI time series were modelled for each pixel using a double logistic function defined by six parameters. Estimates of the onset of spring and the end of autumn were then mapped using the modelled dataset and compared with ground observations of the onset of leafing and the end of leaf fall in birch, respectively. Missing and poor‐quality data prevented estimates from being produced for all pixels in the study area. Applying a 5 km×5 km mean filter increased the number of modelled pixels without decreasing the accuracy of the predictions. The comparison shows good agreement between the modelled and observed dates (root mean square error = 12 days, n = 108 for spring; root mean square error = 10 days, n = 26, for autumn). Fennoscandia shows a range in the onset of spring of more than 2 months within a single year and locally the onset of spring varies with up to one month between years. The end of autumn varies by one and a half months across the region. While continued validation with ground data is needed, this new dataset facilitates the detailed monitoring of vegetation activity in Fennoscandia and the Kola peninsula.

Forkhead box F1 regulates tumor-promoting properties of cancer-associated fibroblasts in lung cancer.

Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability to stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing the tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target of hedgehog signaling, known to regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain- and loss-of-function fibroblasts revealed that FoxF1 regulates the contractility of fibroblasts, their production of hepatocyte growth factor and fibroblast growth factor-2, and their stimulation of lung cancer cell migration. FoxF1 status of fibroblasts was also shown to control the ability of fibroblasts to stimulate xenografted tumor growth. FoxF1 was expressed in CAFs of human lung cancer and associated with activation of hedgehog signaling. These observations suggest that hedgehog-dependent FoxF1 is a clinically relevant lung CAF-inducing factor, and support experimentally the general concept that CAF properties can be induced by activation of developmentally important transcription factors.

Early Surgical Results After Pneumonectomy for Non-Small Cell Lung Cancer are not Affected by Preoperative Radiotherapy and Chemotherapy

BACKGROUND Higher operative risks after pneumonectomy for non-small cell lung cancer (NSCLC) have been reported after neoadjuvant chemotherapy or radiotherapy, or both. Patients who underwent pneumonectomy for NSCLC were evaluated for effect of neoadjuvant treatment on mortality and morbidity, especially bronchopleural fistula. METHODS Between 1996 and 2003, 130 consecutive patients underwent pneumonectomy: 35 received preoperative radiotherapy and chemotherapy (the neoadjuvant group), and 95 patients did not (the first-surgery group). Operative mortality and postoperative complications were compared between the groups. RESULTS Minor postoperative complications were comparable in both groups (p > 0.10). Five patients in the neoadjuvant group and 10 in the first-surgery group had serious complications (p = 0.55). Eight had bronchopleural fistulas (7 right and 1 left, p < 0.01); 3 were in the neoadjuvant group (p = 0.49). Three fistulas required reoperation. One patient in the first-surgery group died within 30 days postoperatively. Duration of symptoms (hazard ratio, 6.6; p = 0.01) and right-sided pneumonectomy (hazard ratio, 2.4; p = 0.05) were associated with an increased risk of bronchopleural fistula. Induction treatment, postoperative radiotherapy, or coverage of the bronchial stump did not increase the risk of bronchopleural fistulation. Survival at 1 and 5 years was comparable for the neoadjuvant and first-surgery groups: 74% and 46% vs 72% and 34%, respectively (p > 0.2). CONCLUSIONS Pneumonectomy is a safe procedure with low operative mortality. Postoperative morbidity is significant, especially bronchopleural fistulas after right-sided pneumonectomy (11%). However, neither operative mortality nor morbidity appears to be directly associated with preoperative radiotherapy or chemotherapy.

Mapping fractional forest cover across the highlands of mainland Southeast Asia using MODIS data and regression tree modelling

Data from the moderate‐resolution imaging spectroradiometer (MODIS) sensor, in combination with new mapping techniques, has the potential to improve regional research on tropical forest resources and land use dynamics. In this study, a supervised regression tree model was used to map fractions of (1) mature forest, (2) secondary forest, and (3) non‐forest, using multi‐temporal MODIS 250‐m data as explanatory variables, and land cover information derived from high‐spatial resolution image data as the response variables. From independent validation data, the overall mean absolute deviation of the resulting maps are estimated at 14.6% for mature forest, 21.6% for secondary forest, and 17.1% for non‐forest cover. This study shows the increased potential of this new mapping technique to infer human imprints on forest cover across the highlands of mainland Southeast Asia, compared to other existing map sources.

Esophageal perforation in South of Sweden: Results of surgical treatment in 125 consecutive patients

BackgroundFor many years there has been a debate as to which is the method of choice in treating patients with esophageal perforation. The literature consists mainly of small case series. Strategies for aiding patients struck with this disease is changing as new and less traumatic treatment options are developing. We studied a relatively large consecutive material of esophageal perforations in an effort to evaluate prognostic factors, diagnostic efforts and treatment strategy in these patients.Methods125 consecutive patients treated at the University Hospital of Lund from 1970 to 2006 were studied retrospectively. Prognostic factors were evaluated using the Cox proportional hazards model.ResultsPre-operative ASA score was the only factor that significantly influenced outcome. Neck incision for cervical perforation (n = 8) and treatment with a covered stent with or without open drainage for a thoracic perforation (n = 6) had the lowest mortality. Esophageal resection (n = 8) had the highest mortality. A CAT scan or an oesophageal X-ray with oral contrast were the most efficient diagnostic tools. The preferred treatment strategy changed over the course of the study period, from a more aggressive surgical approach towards using covered stents to seal the perforation.ConclusionPre-operative ASA score was the only factor that significantly influenced outcome in this study. Treatment strategies are changing as less traumatic options have become available. Sealing an esophageal perforation with a covered stent, in combination with open or closed drainage when necessary, is a promising treatment strategy.