Computer-based Eye-tracking Analysis of King-Devick Test Differentiates Persons with Idiopathic Normal Pressure Hydrocephalus from Cognitively Unimpaired

Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.Background: Functional defects in eye movements and reduced reading speed in neurodegenerative diseases represent a potential new biomarker to support clinical diagnosis. We investigated whether computer-based eye-tracking (ET) analysis of the King-Devick (KD) test differentiates persons with idiopathic normal pressure hydrocephalus (iNPH) from cognitively unimpaired [control (CO)] and persons with Alzheimer's disease (AD). Methods: We recruited 68 participants (37 CO, 10 iNPH, and 21 AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating interview. The KD reading test was performed using computer-based ET. We analyzed the total time used for the reading test, number of errors, durations of fixation and saccade, and saccade amplitudes. Results: The iNPH group significantly differed from the CO group in the KD test mean total time (CO 69.3 s, iNPH 87.3 s; P≤0.009) and eye-tracking recording of the mean saccade amplitude (CO 3.6 degree, iNPH 3.2 degree; P≤0.001). The AD group significantly differed from the CO group in each tested parameter. No significant differences were detected between the iNPH and AD groups. Conclusion: For the first time, we demonstrated altered reading ability and saccade amplitudes in patients with iNPH.Peer reviewe

Shortening of Saccades as a Possible Easy-to-Use Biomarker to Detect Risk of Alzheimer's Disease

Background: Wide-ranging functional defects in eye movements have been reported in Alzheimer's disease (AD) dementia. The detection of abnormal eye movements and reading problems may identify persons at risk of AD when clear clinical symptoms are lacking. Objective: To examine whether computer-based eye-tracking (ET) analysis of King-Devick (KD) test results differentiates cognitively healthy persons from persons with minor problems in cognitive testing or diagnosed mild AD. Methods: We recruited 78 participants (57 non-demented, 21 with mild AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating (CDR) interview. The non-demented participants were further divided into control (normal CERAD subtests, mean MMSE= 28) and objective mild cognitive impairment (MCI; decline in at least one CERAD memory score, mean MMSE= 27) groups. The KD reading test was performed using computer-based ET. The total time used for the reading test, errors made, fixation and saccade durations, and saccade amplitudes were analyzed. Results: We found significant differences between the control, objective MCI, and AD groups in regard to the mean saccade amplitude (3.58, 3.33, and 3.21 ms, respectively, p < 0.03) and duration (27.1, 25.3, and 24.8 ms, respectively, p < 0.05). The KD error scores in the AD group differed significantly (p < 0.01) from the other groups. Conclusion: Computed ET analysis of the KD test may help detect persons with objective MCI early when clear clinical symptoms are lacking. The portable device for ET is easy to use in primary health care memory clinics.Peer reviewe

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

Background Studies have shown altered vitamin D metabolism in obesity. We assessed differences between obese and normal-weight subjects in total, free, and bioavailable 25-hydroxyvitamin D (25(OH) D, 25(OH) D-Free, and 25(OH) D-Bio, respectively), vitamin D binding protein (DBP), parathyroid hormone (PTH) and bone traits. Methods 595 37-47-year-old healthy Finnish men and women stratified by BMI were examined in this cross-sectional study. Background characteristic and intakes of vitamin D and calcium were collected. The concentrations of 25(OH) D, PTH, DBP, albumin and bone turnover markers were determined from blood. 25(OH) D-Free and 25(OH) D-Bio were calculated. pQCT was performed at radius and tibia. Results Mean +/- SE (ANCOVA) 25(OH) D-Free (10.8 +/- 0.6 vs 12.9 +/- 0.4 nmol/L; P = 0.008) and 25(OH) DBio (4.1 +/- 0.3 vs 5.1 +/- 0.1 nmol/L; P = 0.003) were lower in obese than in normal-weight women. In men, 25(OH) D (48.0 +/- 2.4 vs 56.4 +/- 2.0 nmol/L, P = 0.003), 25(OH) D-Free (10.3 +/- 0.7 vs 12.5 +/- 0.6 pmol/L; P = 0.044) and 25(OH) D-Bio (4.2 +/- 0.3 vs 5.1 +/- 0.2 nmol/L; P = 0.032) were lower in obese. Similarly in all subjects, 25(OH) D, 25(OH) D-Free and 25(OH) D-Bio were lower in obese (P Conclusions The associations between BMI and 25(OH) D, 25(OH) D-Free, and 25(OH) D-Bio, DBP, and PTH suggest that obese subjects may differ from normal-weight subjects in vitamin D metabolism. BMI associated positively with trabecular bone traits and CSI in our study, and slightly negatively with cortical bone traits. Surprisingly, there was a negative association of free and bioavailable 25(OH) D and some of the bone traits in obese women.Peer reviewe

Tilaus-toimitusketjun toiminnallista erinomaisuutta arvioivan kypsyysmallin kehittäminen ja testaus

Diplomityö on ollut osa Oulun Eteläisen seutukunnissa toteutettavaa TUTOES -hanketta. Diplomityön tavoitteena on ollut kehittää tuotannollisen toiminnan erinomaisuutta arvioiva kypsyysmalli ja mittaristo projektialueen valmistavan teollisuuden ja yrityskehittäjien käyttöön. Kypsyysmallit juontavat laatujohtamisesta. Ne kuvaavat millä kehitystasolla organisaatio tai prosessi on, ja mitä seuraavalle tasolle pääseminen vaatii. Tuotannollista erinomaisuutta arvioiva malli 2.1 on Excel-pohjainen kypsyysmalli, jossa kypsyystasot sekä prosessifaktorit muodostavat 30-soluisen matriisin. Jokaisessa solussa on kutakin prosessifaktoria kuvaava että ohjaava määritelmä. Tuotannollisen toiminnan erinomaisuudessa prosessit ja niiden suorituskyky on yksi tärkeimmistä elementeistä. Tuotannollisen toiminnan erinomaisuutta arvioiva malli mittaa prosessien erinomaisuuteen vaikuttavia tekijöitä kuten prosessien määrittämistä, prosessien johtamista, prosessin suorituskyvyn monitorointia ja optimointia, prosessiomistajien sekä työntekijöiden taitoja sekä prosessiin integroituneiden osastojen välistä tiedonsiirtoa. Tuotannollisen toiminnan erinomaisuutta määrittäessä yrityksen on arvioitava heidän tilaus-toimitusketjuun kuuluvat prosessit. Malli on jakanut nämä prosessit karkeasti neljään eri ydinprosessiin: myynnin-, hankinnan-, tuotannon- ja tuotekehityksen prosesseihin. Tuotannollisen toiminnan erinomaisuutta arvioivaa mallilla testattiin kymmenen yrityksen tuotannollista toimintaa samalla optimoiden mallia ja testauskäytäntöä. Tässä työssä esitettään mallista versiot 1.0 ja 2.1, josta versio 2.1 toimii hyvin suurten ja keskisuurten yritysten tilaus-toimitusketjun nykytilan arviointiin, kehitystarpeiden määritykseen sekä työkaluksi prosesseista vastaaville johtamisen tueksi. TUTOES-projektin yritysarviointeja jatketaan versiolla 2.1, jossa ei ole mukana tuotekehityksen arviointikehikkoa.This master’s thesis was done as a part of TUTOES project accomplished in the subregions of Oulu Southern. The aim of the thesis was to develop an effective maturity model with reliable metrics to evaluate the operational excellence of order-delivery processes in the companies located in project area. The maturity model of operational excellence 2.1 will provide comparable information on current state of SMEs’ operation excellence and guidelines to improve the order-delivery processes. Maturity models and approaches have their roots in the field of quality management. They describe the typical behavior exhibited by an organization at five levels of maturity. Maturity models typically include a sequence of levels (or stages) that form an anticipated, desired, or logical path from an initial state to maturity. The maturity model evaluating operational excellence of order-delivery processes is three dimensional Excel-based model including five stages of maturity and six process factors forming together 30-cells matrix. The model provides descriptive and prescriptive information about maturity of each stage. Assessing processes and the performance of processes is one of the most important elements in operational excellence. The model 2.1 assesses the factors affecting processes excellence such as defining processes, process management, process performance metrics and monitoring, process optimization, the skills and expertise of process owner and process performers. It assesses also IT-structure and information flows. All processes of supply chain should be evaluated when assessing operational excellence. The processes of supply chain are categorized into four main processes where each of them is assessed separately: Sales, supply, production and R&D. In this study of master’s thesis the model 1.0 was tested and iterate into version 2.1. The order-delivery processes of five companies were assessed using the improved version 2.1 lacking framework for evaluation of R&D. In this thesis the model 1.0 and 2.1 are introduced. The model 2.1 fits well for evaluating the currents states of supply chain processes in companies over 10 employees and also giving guidelines for improving practices

Are risk predicting models useful for estimating survival of patients with rheumatoid arthritis-associated interstitial lung disease?

Abstract Background: Risk predicting models have been applied in idiopathic pulmonary fibrosis (IPF), but still not validated in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The purpose of this study was to test the suitability of three prediction models as well as individual lung function and demographic factors for evaluating the prognosis of RA-ILD patients. Methods: Clinical and radiological data of 59 RA-ILD patients was re-assessed. GAP (gender, age, physiologic variables) and the modified interstitial lung disease (ILD)-GAP as well as the composite physiologic indexes (CPI) were tested for predicting mortality using the goodness-of-fit test and Cox model. Potential predictors of mortality were also sought from single lung function parameters and clinical characteristics

Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis

Abstract Background: Cigarette smoking has been associated with the risk of idiopathic pulmonary fibrosis (IPF). Certain comorbidities have been associated with reduced survival although some studies have indicated that current smokers have a longer survival than ex-smokers. Comorbidities in relation to smoking history have not been previously analyzed. Methods: Retrospective data was collected and patients were categorized according to gender and smoking habits. Comorbidities and medications were collected. Predictive values for mortality were identified by COX proportional hazard analyses. Results: We examined 45 non-smokers (53.3% female), 66 ex-smokers (9.1% female) and 17 current smokers (17.6% female) with IPF. Current smokers were younger at baseline (58.1 ± 8.74 years) compared to non-smokers (71.4 ± 8.74, p &lt; 0.001) and ex-smokers (72.5 ±7.95, p &lt;0.001). Median survival of non-smokers and current smokers was longer (55.0 and 52.0 months, respectively) than that of ex-smokers (36.0 months) (p=0.028 and 0.034, respectively). In age and severity adjusted analyses, smoking was not related to survival. Cardiovascular diseases (CVD) (72.7 %) were the most common comorbidities, current smokers had more chronic obstructive pulmonary disease (COPD) and lung cancer compared to ex-smokers (p&lt;0.001). CVD, COPD and use of insulin were related to poorer survival in adjusted analyses. Conclusions: Smoking seems to influence the course of disease in IPF since current smokers developed the disease at a younger age in comparison to non-smokers and ex-smokers. No significant differences in the major comorbidities were detected between IPF patients with different smoking histories. The mechanism through which smoking influences IPF progression requires further investigation

Comparison of disease progression subgroups in idiopathic pulmonary fibrosis

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia with an unpredictable course. The aims of this study were to retrospectively re-evaluate a cohort of patients with IPF according to the 2011 international IPF guidelines and 1) to characterize the subgroups of patients when classified according to their observed survival times and 2) to evaluate whether Composite Physiologic Index (CPI), Gender-Age-Physiology (GAP) Index or clinical variables could predict mortality. Methods: Retrospective data was collected and patients were classified into subgroups according to their observed lifespans. Differences in clinical variables, CPI and GAP stages as well as in comorbidities were investigated between the subgroups. Predictors of mortality were identified by COX proportional hazard analyses. Results: A total of 132 patients were included in this study. The disease course was rapid (≤ 2 years) in 30.0%, moderate (2—5 years) in 28.0% and slow (≥ 5 years) in 29.0% of the patients. Pulmonary function tests (PFT) and CPI at baseline differentiated significantly between the rapid disease course group and those patients with longer survival times. However, the predictive accuracy of the investigated clinical variables was mainly less than 0.80. The proportions of patients with comorbidities did not differ between the subgroups, but more patients with a rapid disease course were diagnosed with heart failure after the diagnosis of IPF. Most patients with a rapid disease course were categorized in GAP stages I and II, but all patients in GAP stage III had a rapid disease course. The best predictive multivariable model included age, gender and CPI. GAP staging had slightly better accuracy (0.67) than CPI (0.64) in predicting 2-year mortality. Conclusions: Although the patients with a rapid disease course could be differentiated at baseline in terms of PFT and CPI, the predictive accuracy of any single clinical variable as well as CPI and GAP remained low. GAP staging was unable to identify the majority of patients with a rapid disease progression. It is challenging to predict disease progression and mortality in IPF even with risk prediction models

Underlying and immediate causes of death in patients with idiopathic pulmonary fibrosis

Abstract Background: The most common cause of death of patients with idiopathic pulmonary fibrosis (IPF) has been reported to be the lung disease itself and mortality from IPF appears to be increasing. However, the causes of death in patients with IPF taking into account differences between genders and smoking histories as well as disease progression, have not been previously explored. Methods: Retrospective data from hospital register and death certificates from national database of IPF patients treated in Kuopio University Hospital (KUH) from 2002 to 2012 were collected. Mortality was also explored from the death registry database via ICD-10 code J84 revealing the numbers of deaths from pulmonary fibrosis in Finland from 1998 to 2015. Results: Out of 117 deaths, 26.5% were females and 73.5% males in KUH. The most common underlying causes of death were IPF 67.5% and ischemic heart diseases 14.8%. More males died for reasons other than IPF (39.5%) compared to females (12.9%) (p = 0.007). Pneumonia as the immediate cause of death was more common in males (27.9%) than in females (3.2%) (p = 0.004) and in ex-smokers (32.7%) compared to non-smokers (9.3%) (p = 0.007). Death register based mortality from pulmonary fibrosis is increasing in Finland. Conclusions: Even though the overall mortality was higher in males with IPF, the disease-specific mortality for IPF was higher in females i.e. in males, comorbidities were more often the underlying causes of death. Pneumonia-triggered acute exacerbations of IPF may be associated with smoking and gender since females and non-smokers were less likely to succumb to pneumonia. We conclude that disease progression at the end of life may vary depending on smoking habits and gender

Dietary phosphorus intake is negatively associated with bone formation among women and positively associated with some bone traits among men-a cross-sectional study in middle-aged Caucasians

High dietary phosphorus (P) intake has acute negative effects on calcium (Ca) and bone metabolism, but long-term clinical data are contradictory. We hypothesized that high P intake is associated with impaired bone health as suggested by earlier short-term studies on bone metabolism. In this cross-sectional study, we investigated associations between dietary P intake, bone traits in the radius and tibia, and bone turnover in a population-based sample of 37- to 47-year-old Caucasian premenopausal women (n = 333) and men (n = 179) living in Southern Finland (60 degrees N). We used various regression models in an "elaboration approach" to elucidate the role of P intake in bone traits and turnover. The addition of relevant covariates to the models mainly removed the significance of P intake as a determinant of bone traits. In the final regression model (P intake, weight, height, age, Ca intake, serum 25-hydroxyvitamin D, physical activity, smoking, contraceptive use in women), P intake was slightly positively associated only with bone mineral content and cross-sectional cortical bone area in the tibia of men. Among women, inclusion of Ca removed all existing significance in the crude models for any bone trait. In women P intake was negatively associated with the bone formation marker serum intact pro-collagen type I amino-terminal propeptide, whereas no association was present between P intake and bone turnover in men. In conclusion, these findings disagree with the hypothesis; P intake was not deleteriously associated with bone traits; however, P intake may negatively contribute to bone formation among women. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Several specific high-resolution computed tomography patterns correlate with survival in patients with idiopathic pulmonary fibrosis

Abstract Background: Evidence of honeycombing in high-resolution computed tomography (HRCT) is a recognized risk factor for shortened survival in patients with idiopathic pulmonary fibrosis (IPF), but few studies have evaluated the feasibility of exploiting other specific patterns for predicting survival. The aim of this study was to examine the extent of specific HRCT patterns in IPF and determine whether they correlate with clinical features, pulmonary function tests (PFT), and survival. Methods: Both the presence and extent of specific HRCT patterns, such as traction bronchiectasis, honeycombing, architectural distortion, reticulation, emphysema, and ground glass opacity, in 129 HRCT examinations were scored semi-quantitatively in three zones of each lung. HRCT examinations were also re-classified according to the 2011 and 2018 international statements. Correlations were calculated between the scores of specific HRCT patterns, clinical features, PFT, and patient survival. Results: The extent of traction bronchiectasis was found to be an independent risk factor of shortened survival (HR 1.227, P=0.001). Patients with a possible usual interstitial pneumonia (UIP) pattern had a better median survival than the patients with a definite UIP pattern (61 vs. 37 months, P=0.026). The extents of traction bronchiectasis, honeycombing, and architectural distortion displayed an inverse correlation with all PFT values at the time of diagnosis. There were few differences between the radiological classifications of the 2011 and 2018 international statements