Catalog of 199 register-based definitions of chronic conditions

Introduction: The aim of the current study was to present and discuss a broad range of register-based definitions of chronic conditions for use in register research, as well as the challenges and pitfalls when defining chronic conditions by the use of registers. Materials and methods: The definitions were defined based on information from nationwide Danish public healthcare registers. Medical and epidemiological specialists identified and grouped relevant diagnosis codes that covered chronic conditions, using the International Classification System version 10 (ICD-10). Where relevant, prescription and other healthcare data were also used to define the chronic conditions. Results: We identified 199 chronic conditions and subgroups, which were divided into four groups according to a medical judgment of the expected duration of the conditions, as follows. Category I: Stationary to progressive conditions (maximum register inclusion time of diagnosis since the start of the register in 1994). Category II: Stationary to diminishing conditions (10 years of register inclusion after time of diagnosis). Category III: Diminishing conditions (5 years of register inclusion after time of diagnosis). Category IV: Borderline conditions (2 years of register inclusion time following diagnosis). The conditions were primarily defined using hospital discharge diagnoses; however, for 35 conditions, including common conditions such as diabetes, chronic obstructive lung disease and allergy, more complex definitions were proposed based on record linkage between multiple registers, including registers of prescribed drugs and use of general practitioners’ services. Conclusions: This study provided a catalog of register-based definitions for chronic conditions for use in healthcare planning and research, which is, to the authors’ knowledge, the largest currently compiled in a single study

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy

PURPOSE To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings

Modular 5′-UTR hexamers for context-independent tuning of protein expression in eukaryotes

Functional characterization of regulatory DNA elements in broad genetic contexts is a prerequisite for forward engineering of biological systems. Translation initiation site (TIS) sequences are attractive to use for regulating gene activity and metabolic pathway fluxes because the genetic changes are minimal. However, limited knowledge is available on tuning gene outputs by varying TISs in different genetic and environmental contexts. Here, we created TIS hexamer libraries in baker's yeast Saccharomyces cerevisiae directly 5' end of a reporter gene in various promoter contexts and measured gene activity distributions for each library. Next, selected TIS sequences, resulted in almost 10-fold changes in reporter outputs, were experimentally characterized in various environmental and genetic contexts in both yeast and mammalian cells. From our analyses, we observed strong linear correlations (R2 = 0.75-0.98) between all pairwise combinations of TIS order and gene activity. Finally, our analysis enabled the identification of a TIS with almost 50% stronger output than a commonly used TIS for protein expression in mammalian cells, and selected TISs were also used to tune gene activities in yeast at a metabolic branch point in order to prototype fitness and carotenoid production landscapes. Taken together, the characterized TISs support reliable context-independent forward engineering of translation initiation in eukaryotes

Classification of death causes after transplantation (CLASS):Evaluation of methodology and initial results

Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry

Global Research Alliance N2 O chamber methodology guidelines:Introduction, with health and safety considerations

Non-steady-state (NSS) chamber techniques have been used for decades to measure nitrous oxide (N₂O) fluxes from agricultural soils. These techniques are widely used because they are relatively inexpensive, easy to adopt, versatile, and adaptable to varying conditions. Much of our current understanding of the drivers of N₂O emissions is based on studies using NSS chambers. These chamber techniques require decisions regarding multiple methodological aspects (e.g., chamber materials and geometry, deployment, sample analysis, and data and statistical analysis), each of which may significantly affect the results. Variation in methodological details can lead to challenges in comparing results between studies and assessment of reliability and uncertainty. Therefore, the New Zealand Government, in support of the objectives of the Livestock Research Group of the Global Research Alliance on Agricultural Greenhouse Gases (GRA), funded two international projects to, first, develop standardized guidelines on the use of NSS chamber techniques and, second, refine them based on the most up to date knowledge and methods. This introductory paper summarizes a collection of papers that represent the revised guidelines. Each article summarizes existing knowledge and provides guidance and minimum requirements on chamber design, deployment, sample collection, storage and analysis, automated chambers, flux calculations, statistical analysis, emission factor estimation and data reporting, modeling, and “gap-filling” approaches. The minimum requirements are not meant to be highly prescriptive but instead provide researchers with clear direction on best practices and factors that need to be considered. Health and safety considerations of NSS chamber techniques are also provided with this introductory paper