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Martian gullies are landforms consisting of an erosional alcove, a channel, and a depositional apron. A significant proportion of Martian gullies at the mid-latitudes is active today. The seasonal sublimation of CO2 ice has been suggested as a driver behind present-day gully activity. However, due to a lack of in situ observations, the actual processes causing the observed changes remain unresolved. Here, we present results from flume experiments in environmental chambers in which we created CO2-driven granular flows under Martian atmospheric conditions. Our experiments show that under Martian atmospheric pressure, large amounts of granular material can be fluidized by the sublimation of small quantities of CO2 ice in the granular mixture (only 0.5% of the volume fraction of the flow) under slope angles as low as 10°. Dimensionless scaling of the CO2-driven granular flows shows that they are dynamically similar to terrestrial two-phase granular flows, that is, debris flows and pyroclastic flows. The similarity in flow dynamics explains the similarity in deposit morphology with levees and lobes, supporting the hypothesis that CO2-driven granular flows on Mars are not merely modifying older landforms, but they are actively forming them. This has far-reaching implications for the processes thought to have formed these gullies over time. For other planetary bodies in our solar system, our experimental results suggest that the existence of gully like landforms is not necessarily evidence for flowing liquids but that they could also be formed or modified by sublimation-driven flow processes.

BACKGROUND: The regulation of Factor X (FX) is critical to maintain the balance between blood coagulation and fluidity.OBJECTIVES: To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX.METHODS: We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. The activity and inhibition of recombinant FX variants was quantified in pure component assays. The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma.RESULTS: The Factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. Prothrombin activation was, however, recovered in presence of cofactor Factor Va (FVa) despite a reduced prothrombinase assembly. The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, while ATIII inhibition in the presence of the heparin-analogue Fondaparinux was modestly increased by 2- to 15-fold compared to wild type. When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants.CONCLUSION: The autolysis loop participate in all aspects of FX regulation. In plasma-based assays, a modest decrease in FX-activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced.

Obesity is associated with increased risk for fragility fractures. However, the cellular mechanisms are unknown. Using a translational approach combining RNA sequencing and cellular analyses, we investigated bone marrow stromal stem cells (BM-MSCs) of 54 men divided into lean, overweight, and obese groups on the basis of BMI. Compared with BM-MSCs obtained from lean, obese BM-MSCs exhibited a shift of molecular phenotype toward committed adipocytic progenitors and increased expression of metabolic genes involved in glycolytic and oxidoreductase activity. Interestingly, compared with paired samples of peripheral adipose tissue-derived stromal cells (AT-MSCs), insulin signaling of obese BM-MSCs was enhanced and accompanied by increased abundance of insulin receptor positive (IR+) and leptin receptor positive (LEPR+) cells in BM-MSC cultures. Their hyper-activated metabolic state was accompanied by an accelerated senescence phenotype. Our data provide a plausible explanation for the bone fragility in obesity caused by enhanced insulin signaling leading to accelerated metabolic senescence of BM-MSCs. Tencerova et al. show that in human obesity, BM-MSCs exhibit a hypermetabolic state defined by upregulation of insulin signaling with enhanced adipogenesis and increased intracellular reactive oxygen species (ROS), leading to a senescence bone microenvironment contributing to bone fragility. Moreover, increased abundance of IR+ and LEPR+ BM-MSCs is characteristic of this phenotype, with an activated metabolic rate in obese subjects.

Obesity is associated with increased risk for fragility fractures. However, the cellular mechanisms are unknown. Using a translational approach combining RNA sequencing and cellular analyses, we investigated bone marrow stromal stem cells (BM-MSCs) of 54 men divided into lean, overweight, and obese groups on the basis of BMI. Compared with BM-MSCs obtained from lean, obese BM-MSCs exhibited a shift of molecular phenotype toward committed adipocytic progenitors and increased expression of metabolic genes involved in glycolytic and oxidoreductase activity. Interestingly, compared with paired samples of peripheral adipose tissue-derived stromal cells (AT-MSCs), insulin signaling of obese BM-MSCs was enhanced and accompanied by increased abundance of insulin receptor positive (IR+) and leptin receptor positive (LEPR+) cells in BM-MSC cultures. Their hyper-activated metabolic state was accompanied by an accelerated senescence phenotype. Our data provide a plausible explanation for the bone fragility in obesity caused by enhanced insulin signaling leading to accelerated metabolic senescence of BM-MSCs. Tencerova et al. show that in human obesity, BM-MSCs exhibit a hypermetabolic state defined by upregulation of insulin signaling with enhanced adipogenesis and increased intracellular reactive oxygen species (ROS), leading to a senescence bone microenvironment contributing to bone fragility. Moreover, increased abundance of IR+ and LEPR+ BM-MSCs is characteristic of this phenotype, with an activated metabolic rate in obese subjects.

Obesity is associated with increased risk for fragility fractures. However, the cellular mechanisms are unknown. Using a translational approach combining RNA sequencing and cellular analyses, we investigated bone marrow stromal stem cells (BM-MSCs) of 54 men divided into lean, overweight, and obese groups on the basis of BMI. Compared with BM-MSCs obtained from lean, obese BM-MSCs exhibited a shift of molecular phenotype toward committed adipocytic progenitors and increased expression of metabolic genes involved in glycolytic and oxidoreductase activity. Interestingly, compared with paired samples of peripheral adipose tissue-derived stromal cells (AT-MSCs), insulin signaling of obese BM-MSCs was enhanced and accompanied by increased abundance of insulin receptor positive (IR+) and leptin receptor positive (LEPR+) cells in BM-MSC cultures. Their hyper-activated metabolic state was accompanied by an accelerated senescence phenotype. Our data provide a plausible explanation for the bone fragility in obesity caused by enhanced insulin signaling leading to accelerated metabolic senescence of BM-MSCs. Tencerova et al. show that in human obesity, BM-MSCs exhibit a hypermetabolic state defined by upregulation of insulin signaling with enhanced adipogenesis and increased intracellular reactive oxygen species (ROS), leading to a senescence bone microenvironment contributing to bone fragility. Moreover, increased abundance of IR+ and LEPR+ BM-MSCs is characteristic of this phenotype, with an activated metabolic rate in obese subjects.

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

Background: The Triple Aim posits that health care should strive to improve patient experience, improve population health, and maintain or lower costs. However, most organizations are not organized to achieve the Triple Aim. Attempts to improve the ability of health care organizations to deliver increased value through the introduction of management concepts, most recently Value-based Health Care (VBHC), have led to the emergence of a pattern of pseudoinnovation, where concepts are frequently replaced with similar content, but in new “packaging”. This suggests that organizations and their ability to adapt to their environment and integrate new management concepts could potentially be explored by looking at how the concepts themselves are understood and at how organizations deliver care. In management terms, the latter can be described as the business model (i.e., how an organization creates, delivers, and captures value). Aim: The overall aim of this thesis is to understand how management concepts about value are understood and to explore how health care organizations in a publicly financed health care system are organized so that they create, deliver, and capture value. Methodology: In Study I, citation registry data and literature were sequentially analyzed qualitatively and quantitatively to assess diffusion and understanding of VBHC as a nascent management concept in the literature. Study II, a systematic review, employed an explanatory synthesis approach to understand how business model frameworks have been applied in health care. Studies III and IV apply the Business Model Canvas (BMC) framework in a deductive content analysis of interviews with top managers (Study III) and with multiple data sources (Study IV) to conceptualize a hospital business model and to compare perinatal clinics’ business models in a publicly financed, Swedish health care setting. Findings: VBHC and business model frameworks are commonly and increasingly used to improve value in health

The study assesses to what extent the production and use of advanced sustainable jet fuel may contribute to GHG reduction and mitigation, and identifies the commercial potential for initiating and scaling up advanced sustainable jet fuel production at a Nordic level. The report explores as well on how to most efficiently use the available Nordic know-how, feedstock and production facilities. The report draws on the latest available reports and statistics, as well as interviews with stakeholders and experts across the Nordic countries, concludes on identifying the most matured technologies, the Nordic opportunities and challenges, and ideas to mitigate the barriers within the Nordic private and public sectors.

The study assesses to what extent the production and use of advanced sustainable jet fuel may contribute to GHG reduction and mitigation, and identifies the commercial potential for initiating and scaling up advanced sustainable jet fuel production at a Nordic level. The report explores as well on how to most efficiently use the available Nordic know-how, feedstock and production facilities. The report draws on the latest available reports and statistics, as well as interviews with stakeholders and experts across the Nordic countries, concludes on identifying the most matured technologies, the Nordic opportunities and challenges, and ideas to mitigate the barriers within the Nordic private and public sectors.

The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55 ± 5 and 35 ± 5 min) were significantly different to the buccal anaesthetised groups (120 ± 0 and 165 ± 15 min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7 ± 4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.

The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55 ± 5 and 35 ± 5 min) were significantly different to the buccal anaesthetised groups (120 ± 0 and 165 ± 15 min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7 ± 4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.

This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7.4, 8.5, 9.0 and 9.5. Permeability studies showed a correlation (r(2)=0.92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber. A higher apparent permeability was observed at higher pH values, i.e. the more compound that was unionised the higher the permeability. In vivo studies were conducted in anaesthetised Göttingen mini-pigs. A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively. Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks. A very clear level C in vitro in vivo correlation (r(2)=0.98) was obtained between the observed in vitro permeabilities and the bioavailability observed in vivo, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.

This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7.4, 8.5, 9.0 and 9.5. Permeability studies showed a correlation (r(2)=0.92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber. A higher apparent permeability was observed at higher pH values, i.e. the more compound that was unionised the higher the permeability. In vivo studies were conducted in anaesthetised Göttingen mini-pigs. A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively. Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks. A very clear level C in vitro in vivo correlation (r(2)=0.98) was obtained between the observed in vitro permeabilities and the bioavailability observed in vivo, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.

Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable in the diagnosis of hereditary canine FVII deficiency.

OBJECTIVE: The inflammatory biomarker YKL-40 is elevated and associated with mortality in patients with stable coronary artery disease (CAD). The aim was to investigate the influence of statin treatment and lipid status on serum YKL-40 and Hs-CRP in patients with stable CAD. DESIGN: Serum YKL-40, HsCRP, total cholesterol, HDL-c, LDL-c and triglycerides levels were measured in 404 statin treated and in 404 matched non-statin treated patients with stable CAD. RESULTS: YKL-40 was significantly higher in non-statin treated 110 µg/l (median) compared with 65 µg/l in statin treated (p

Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable in the diagnosis of hereditary canine FVII deficiency.

OBJECTIVE: The inflammatory biomarker YKL-40 is elevated and associated with mortality in patients with stable coronary artery disease (CAD). The aim was to investigate the influence of statin treatment and lipid status on serum YKL-40 and Hs-CRP in patients with stable CAD. DESIGN: Serum YKL-40, HsCRP, total cholesterol, HDL-c, LDL-c and triglycerides levels were measured in 404 statin treated and in 404 matched non-statin treated patients with stable CAD. RESULTS: YKL-40 was significantly higher in non-statin treated 110 µg/l (median) compared with 65 µg/l in statin treated (p

Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable in the diagnosis of hereditary canine FVII deficiency.

OBJECTIVE: The inflammatory biomarker YKL-40 is elevated and associated with mortality in patients with stable coronary artery disease (CAD). The aim was to investigate the influence of statin treatment and lipid status on serum YKL-40 and Hs-CRP in patients with stable CAD. DESIGN: Serum YKL-40, HsCRP, total cholesterol, HDL-c, LDL-c and triglycerides levels were measured in 404 statin treated and in 404 matched non-statin treated patients with stable CAD. RESULTS: YKL-40 was significantly higher in non-statin treated 110 µg/l (median) compared with 65 µg/l in statin treated (p

Udgivelsesdato: 2009, OBJECTIVE: The aim of this study was to evaluate the analytical performance of a new portable haemoglobinometer, Hemo_Control (EKF-diagnostic, GmbH, Germany), which measures haemoglobin concentration in venous and capillary samples. METHOD: The within series and between series imprecision of the Hemo_Control instrument were calculated after measuring the concentration of venous samples under standardized conditions; by experienced laboratory technicians in a hospital laboratory, and venous and capillary samples under conditions similar to where the instrument is intended for use; by personnel at two primary health care centres. The bias of the Hemo_Control instrument was calculated as the difference between its results and results obtained with a Coulter LH 750 instrument traceable to the ICSH reference method. RESULTS: The uncertainty of the Hemo_Control instrument for venous samples was lower than the quality goal of +/- 5% considered acceptable for patient care. High within series imprecision (5.5%) was observed for measurements of capillary blood samples in one of the primary care centres, whereas adequate analytical performance was obtained at the other centre. The Hemo_Control instrument showed negligible bias of +0.8 g/L for both venous and capillary samples in primary health care. CONCLUSION: The observed uncertainty indicates that Hemo_Control is appropriate for near patient testing using venous samples. Capillary samples may be used if sampling skills are adequate.

Udgivelsesdato: 2009, OBJECTIVE: The aim of this study was to evaluate the analytical performance of a new portable haemoglobinometer, Hemo_Control (EKF-diagnostic, GmbH, Germany), which measures haemoglobin concentration in venous and capillary samples. METHOD: The within series and between series imprecision of the Hemo_Control instrument were calculated after measuring the concentration of venous samples under standardized conditions; by experienced laboratory technicians in a hospital laboratory, and venous and capillary samples under conditions similar to where the instrument is intended for use; by personnel at two primary health care centres. The bias of the Hemo_Control instrument was calculated as the difference between its results and results obtained with a Coulter LH 750 instrument traceable to the ICSH reference method. RESULTS: The uncertainty of the Hemo_Control instrument for venous samples was lower than the quality goal of +/- 5% considered acceptable for patient care. High within series imprecision (5.5%) was observed for measurements of capillary blood samples in one of the primary care centres, whereas adequate analytical performance was obtained at the other centre. The Hemo_Control instrument showed negligible bias of +0.8 g/L for both venous and capillary samples in primary health care. CONCLUSION: The observed uncertainty indicates that Hemo_Control is appropriate for near patient testing using venous samples. Capillary samples may be used if sampling skills are adequate.

Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.

Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.

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Martian gullies are landforms consisting of an erosional alcove, a channel, and a depositional apron. A significant proportion of Martian gullies at the mid‐latitudes is active today. The seasonal sublimation of CO2 ice has been suggested as a driver behind present‐day gully activity. However, due to a lack of in situ observations, the actual processes causing the observed changes remain unresolved. Here, we present results from flume experiments in environmental chambers in which we created CO2‐driven granular flows under Martian atmospheric conditions. Our experiments show that under Martian atmospheric pressure, large amounts of granular material can be fluidized by the sublimation of small quantities of CO2 ice in the granular mixture (only 0.5% of the volume fraction of the flow) under slope angles as low as 10°. Dimensionless scaling of the CO2‐driven granular flows shows that they are dynamically similar to terrestrial two‐phase granular flows, that is, debris flows and pyroclastic flows. The similarity in flow dynamics explains the similarity in deposit morphology with levees and lobes, supporting the hypothesis that CO2‐driven granular flows on Mars are not merely modifying older landforms, but they are actively forming them. This has far‐reaching implications for the processes thought to have formed these gullies over time. For other planetary bodies in our solar system, our experimental results suggest that the existence of gully like landforms is not necessarily evidence for flowing liquids but that they could also be formed or modified by sublimation‐driven flow processes.

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