Age-specific and diurnal patterns of locomotory activity, can be considered as biomarkers of agin... more Age-specific and diurnal patterns of locomotory activity, can be considered as biomarkers of aging in model organisms and vary across the lifetime of individuals. Τhe Mediterranean fruit fly (medfly), Ceratitis capitata, is a commonly used model-species in studies regarding demography and aging. In the present study, we introduce a modification of the automated locomotory activity electronic device LAM25system (Locomotory Activity Monitor)–Trikinetics, commonly used in short time studies, to record the daily locomotory activity patterns of adult medflies throughout the life. Additionally, fecundity rates and survival of adult medflies were recorded. Male and female medflies were kept in the system tubes and had access to an agar-based gel diet, which provided water and nutrients. The locomotory activity was recorded at every minute by three monitors in the electronic device. The locomotory activity of females was higher than that of males across the different ages. For both sexes lo...
FruiTemp is an open-source prototype developed to study the response of endophytic insect species... more FruiTemp is an open-source prototype developed to study the response of endophytic insect species such as fruit flies (Diptera: Tephrtidae) to variable temperature conditions including the controlled laboratory and fluctuating field settings. The system is a three-channel temperature sensor that consists of two precision thermistors that measure the temperature in the core and the surface of a fruit on a tree and a Harsh Environment thermistor that measures the air temperature surrounding the host at a rate of one measurement per 15 min. The sample rate can be adjusted according to the researcher’s needs. The system was successfully tested in field and laboratory experimental conditions using apples as the fruit model. The measurements on apples on trees lasted five consecutive days and produced a range of reliable data. After assessing statistical agreement and precision, the results revealed a differential bias of 0.331 °C and a proportional bias of a magnitude of 0.982. This work...
The overlap coefficient ([Formula: see text]) measures the similarity between two distributions t... more The overlap coefficient ([Formula: see text]) measures the similarity between two distributions through the overlapping area of their distribution functions. Given its intuitive description and ease of visual representation by the straightforward depiction of the amount of overlap between the two corresponding histograms based on samples of measurements from each one of the two distributions, the development of accurate methods for confidence interval construction can be useful for applied researchers. The overlap coefficient has received scant attention in the literature since it lacks readily available software for its implementation, while inferential procedures that can cover the whole range of distributional scenarios for the two underlying distributions are missing. Such methods, both parametric and non-parametric are developed in this article, while R-code is provided for their implementation. Parametric approaches based on the binormal model show better performance and are a...
BackgroundRadiomic features calculated from routine medical images show great potential for perso... more BackgroundRadiomic features calculated from routine medical images show great potential for personalized medicine in cancer. Patients with systemic sclerosis (SSc), a rare, multi-organ autoimmune disorder, have a similarly poor prognosis due to interstitial lung disease (ILD).ObjectivesTo explore computed tomography (CT)-based high-dimensional image analysis (radiomics) for disease characterisation, risk stratification, and relaying information on lung pathophysiology in SSc-ILD.MethodsWe investigated two independent, prospectively followed SSc-ILD cohorts (Zurich, derivation cohort, n=90; Oslo, validation cohort, n=66). For every subject, we defined 1′355 robust radiomic features from standard-of-care CT images. We performed unsupervised clustering to identify and characterize imaging-based patient clusters. A clinically applicable prognostic quantitative radiomic risk score (qRISSc) for progression-free survival was derived from radiomic profiles using supervised analysis. The bio...
Background: There is conflicting evidence on the effect of exercise on systemic insulin concentra... more Background: There is conflicting evidence on the effect of exercise on systemic insulin concentrations in adults with type 1 diabetes. Methods: This prospective single-arm study examined the effect of exercise on systemic insulin degludec (IDeg) concentrations. The study involved 15 male adults with type 1 diabetes (age 30.7 ± 8.0 years, HbA1c 6.9 ± 0.7%) on stable IDeg regimen. Blood samples were collected every 15 minutes at rest, during 60 minutes of cycling (66% VO2max) and until 90 minutes after exercise termination. IDeg concentrations were quantified using high-resolution mass-spectrometry and analyzed applying generalized estimation equations. Results: Compared to baseline, systemic IDeg increased during exercise over time ( P
Aims Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular... more Aims Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients. Methods and results For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adj...
IntroductionThis study sought to compare the metabolomic, hormonal and physiological responses to... more IntroductionThis study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D).Research design and methodsThirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05.ResultsCardio...
BACKGROUND Variations in patient demand increase the challenge of balancing high-quality nursing ... more BACKGROUND Variations in patient demand increase the challenge of balancing high-quality nursing skill mixes against budgetary constraints. Developing staffing guidelines that will allow high quality care at minimal cost requires first exploring the dynamic changes in nursing workload over the course of a day. OBJECTIVE Accordingly, this longitudinal study analyzed nursing care supply and demand in 30-minute increments over a period of three years. We assessed five care factors: 1) patient count (care demand); 2) nurse count (care supply); 3) patient-to-nurse ratio for each nurse group; 4) extreme supply-demand mismatches; and 5) patient turnover, i.e., number of admissions, discharges, and transfers. METHODS Our retrospective analysis of data from the Inselspital University Hospital Bern, Switzerland included all inpatients and nurses working on their units from 1 January 2015 to 31 December 2017. Two data sources were used: 1) The nurse staffing system (tacs®) (including informati...
BACKGROUND Quantification of dietary intake is key to the prevention and management of numerous m... more BACKGROUND Quantification of dietary intake is key to the prevention and management of numerous metabolic disorders. Conventional approaches are challenging, laborious, and, suffer from lack of accuracy. The recent advent of depth-sensing smartphones in conjunction with computer vision has the potential to facilitate reliable quantification of food intake. OBJECTIVE To evaluate the accuracy of a novel smartphone application combining depth-sensing hardware with computer vision to quantify meal macronutrient content. METHODS The application ran on a smartphone with built-in depth sensor applying structured light (iPhone X) and estimated weight, macronutrient (carbohydrate, protein, fat) and energy content of 48 randomly chosen meals (type of meals: breakfast, cooked meals, snacks) encompassing 128 food items. Reference weight was generated by weighing individual food items using a precision scale. The study endpoints were fourfold: i) error of estimated meal weight; ii) error of esti...
Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic cur... more Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic curve analysis frequently involves a limit of detection imposed by the laboratory analytical system precision. As a consequence, measurements below a certain level are undetectable and ignoring these is known to lead to negatively biased estimates of the area under the receiver operating characteristic curve. In this article, we introduce two receiver operating characteristic curve-based parametric approaches that tackle the issue of correct assessment of diagnostic markers in the presence of a limit of detection. Proposed approaches are simulation-based utilising bootstrap methodology. Non-parametric alternatives that are naively used in the literature do not solve the inherent problem of limit of detection values which are treated as censored observations. However, the latter seems to perform adequately well in our simulation study. Nonparametric bootstrap was consistently used throughout...
Nonadherence to standard operating procedures (SOPs) during handling and processing of whole bloo... more Nonadherence to standard operating procedures (SOPs) during handling and processing of whole blood is one of the most frequent causes affecting the quality of serum and plasma. Yet, the quality of blood samples is of the utmost importance for reliable, conclusive research findings, valid diagnostics, and appropriate therapeutic decisions. UHPLC-MS-driven nontargeted metabolomics was applied to identify biomarkers that reflected time to processing of blood samples, and a targeted UHPLC-MS analysis was used to quantify and validate these biomarkers. We found that (4E,14Z)-sphingadienine-C18-1-phosphate (S1P-d18:2) was suitable for the reliable assessment of the pronounced changes in the quality of serum and plasma caused by errors in the phase between collection and centrifugation of whole blood samples. We rigorously validated S1P-d18:2, which included the use of practicality tests on >1400 randomly selected serum and plasma samples that were originally collected during single- an...
Age-specific and diurnal patterns of locomotory activity, can be considered as biomarkers of agin... more Age-specific and diurnal patterns of locomotory activity, can be considered as biomarkers of aging in model organisms and vary across the lifetime of individuals. Τhe Mediterranean fruit fly (medfly), Ceratitis capitata, is a commonly used model-species in studies regarding demography and aging. In the present study, we introduce a modification of the automated locomotory activity electronic device LAM25system (Locomotory Activity Monitor)–Trikinetics, commonly used in short time studies, to record the daily locomotory activity patterns of adult medflies throughout the life. Additionally, fecundity rates and survival of adult medflies were recorded. Male and female medflies were kept in the system tubes and had access to an agar-based gel diet, which provided water and nutrients. The locomotory activity was recorded at every minute by three monitors in the electronic device. The locomotory activity of females was higher than that of males across the different ages. For both sexes lo...
FruiTemp is an open-source prototype developed to study the response of endophytic insect species... more FruiTemp is an open-source prototype developed to study the response of endophytic insect species such as fruit flies (Diptera: Tephrtidae) to variable temperature conditions including the controlled laboratory and fluctuating field settings. The system is a three-channel temperature sensor that consists of two precision thermistors that measure the temperature in the core and the surface of a fruit on a tree and a Harsh Environment thermistor that measures the air temperature surrounding the host at a rate of one measurement per 15 min. The sample rate can be adjusted according to the researcher’s needs. The system was successfully tested in field and laboratory experimental conditions using apples as the fruit model. The measurements on apples on trees lasted five consecutive days and produced a range of reliable data. After assessing statistical agreement and precision, the results revealed a differential bias of 0.331 °C and a proportional bias of a magnitude of 0.982. This work...
The overlap coefficient ([Formula: see text]) measures the similarity between two distributions t... more The overlap coefficient ([Formula: see text]) measures the similarity between two distributions through the overlapping area of their distribution functions. Given its intuitive description and ease of visual representation by the straightforward depiction of the amount of overlap between the two corresponding histograms based on samples of measurements from each one of the two distributions, the development of accurate methods for confidence interval construction can be useful for applied researchers. The overlap coefficient has received scant attention in the literature since it lacks readily available software for its implementation, while inferential procedures that can cover the whole range of distributional scenarios for the two underlying distributions are missing. Such methods, both parametric and non-parametric are developed in this article, while R-code is provided for their implementation. Parametric approaches based on the binormal model show better performance and are a...
BackgroundRadiomic features calculated from routine medical images show great potential for perso... more BackgroundRadiomic features calculated from routine medical images show great potential for personalized medicine in cancer. Patients with systemic sclerosis (SSc), a rare, multi-organ autoimmune disorder, have a similarly poor prognosis due to interstitial lung disease (ILD).ObjectivesTo explore computed tomography (CT)-based high-dimensional image analysis (radiomics) for disease characterisation, risk stratification, and relaying information on lung pathophysiology in SSc-ILD.MethodsWe investigated two independent, prospectively followed SSc-ILD cohorts (Zurich, derivation cohort, n=90; Oslo, validation cohort, n=66). For every subject, we defined 1′355 robust radiomic features from standard-of-care CT images. We performed unsupervised clustering to identify and characterize imaging-based patient clusters. A clinically applicable prognostic quantitative radiomic risk score (qRISSc) for progression-free survival was derived from radiomic profiles using supervised analysis. The bio...
Background: There is conflicting evidence on the effect of exercise on systemic insulin concentra... more Background: There is conflicting evidence on the effect of exercise on systemic insulin concentrations in adults with type 1 diabetes. Methods: This prospective single-arm study examined the effect of exercise on systemic insulin degludec (IDeg) concentrations. The study involved 15 male adults with type 1 diabetes (age 30.7 ± 8.0 years, HbA1c 6.9 ± 0.7%) on stable IDeg regimen. Blood samples were collected every 15 minutes at rest, during 60 minutes of cycling (66% VO2max) and until 90 minutes after exercise termination. IDeg concentrations were quantified using high-resolution mass-spectrometry and analyzed applying generalized estimation equations. Results: Compared to baseline, systemic IDeg increased during exercise over time ( P
Aims Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular... more Aims Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients. Methods and results For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adj...
IntroductionThis study sought to compare the metabolomic, hormonal and physiological responses to... more IntroductionThis study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D).Research design and methodsThirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05.ResultsCardio...
BACKGROUND Variations in patient demand increase the challenge of balancing high-quality nursing ... more BACKGROUND Variations in patient demand increase the challenge of balancing high-quality nursing skill mixes against budgetary constraints. Developing staffing guidelines that will allow high quality care at minimal cost requires first exploring the dynamic changes in nursing workload over the course of a day. OBJECTIVE Accordingly, this longitudinal study analyzed nursing care supply and demand in 30-minute increments over a period of three years. We assessed five care factors: 1) patient count (care demand); 2) nurse count (care supply); 3) patient-to-nurse ratio for each nurse group; 4) extreme supply-demand mismatches; and 5) patient turnover, i.e., number of admissions, discharges, and transfers. METHODS Our retrospective analysis of data from the Inselspital University Hospital Bern, Switzerland included all inpatients and nurses working on their units from 1 January 2015 to 31 December 2017. Two data sources were used: 1) The nurse staffing system (tacs®) (including informati...
BACKGROUND Quantification of dietary intake is key to the prevention and management of numerous m... more BACKGROUND Quantification of dietary intake is key to the prevention and management of numerous metabolic disorders. Conventional approaches are challenging, laborious, and, suffer from lack of accuracy. The recent advent of depth-sensing smartphones in conjunction with computer vision has the potential to facilitate reliable quantification of food intake. OBJECTIVE To evaluate the accuracy of a novel smartphone application combining depth-sensing hardware with computer vision to quantify meal macronutrient content. METHODS The application ran on a smartphone with built-in depth sensor applying structured light (iPhone X) and estimated weight, macronutrient (carbohydrate, protein, fat) and energy content of 48 randomly chosen meals (type of meals: breakfast, cooked meals, snacks) encompassing 128 food items. Reference weight was generated by weighing individual food items using a precision scale. The study endpoints were fourfold: i) error of estimated meal weight; ii) error of esti...
Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic cur... more Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic curve analysis frequently involves a limit of detection imposed by the laboratory analytical system precision. As a consequence, measurements below a certain level are undetectable and ignoring these is known to lead to negatively biased estimates of the area under the receiver operating characteristic curve. In this article, we introduce two receiver operating characteristic curve-based parametric approaches that tackle the issue of correct assessment of diagnostic markers in the presence of a limit of detection. Proposed approaches are simulation-based utilising bootstrap methodology. Non-parametric alternatives that are naively used in the literature do not solve the inherent problem of limit of detection values which are treated as censored observations. However, the latter seems to perform adequately well in our simulation study. Nonparametric bootstrap was consistently used throughout...
Nonadherence to standard operating procedures (SOPs) during handling and processing of whole bloo... more Nonadherence to standard operating procedures (SOPs) during handling and processing of whole blood is one of the most frequent causes affecting the quality of serum and plasma. Yet, the quality of blood samples is of the utmost importance for reliable, conclusive research findings, valid diagnostics, and appropriate therapeutic decisions. UHPLC-MS-driven nontargeted metabolomics was applied to identify biomarkers that reflected time to processing of blood samples, and a targeted UHPLC-MS analysis was used to quantify and validate these biomarkers. We found that (4E,14Z)-sphingadienine-C18-1-phosphate (S1P-d18:2) was suitable for the reliable assessment of the pronounced changes in the quality of serum and plasma caused by errors in the phase between collection and centrifugation of whole blood samples. We rigorously validated S1P-d18:2, which included the use of practicality tests on >1400 randomly selected serum and plasma samples that were originally collected during single- an...
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Papers by Christos T Nakas