Formal Definition of Traceability Graph

Data-centric workflows focus on how the data is transferred between processes and how it is logically stored. In addition to traditional workflow analysis, these can be applied to monitoring, tracing, and analyzing data in processes and their mutual relationships. In many applications, e.g. manufacturing, the tracing of products thorough entire lifecycle is becoming more and more important. In the present paper we define the traceability graph that involves a framework for data that adapts to different levels of precision of tracing. Advanced analyzing requires modeling of data in processes and methods for accumulating resources and emissions thorough the lifecycle of products. The traceability graph enables tracing and accumulation of resources, emissions and other information associated with products. The traceability graph is formally defined by set theory that is an established and exact specification method

Formal Definition of Traceability Graph

Data-centric workflows focus on how the data is transferred between processes and how it is logically stored. In addition to traditional workflow analysis, these can be applied to monitoring, tracing, and analyzing data in processes and their mutual relationships. In many applications, e.g. manufacturing, the tracing of products thorough entire lifecycle is becoming more and more important. In the present paper we define the traceability graph that involves a framework for data that adapts to different levels of precision of tracing. Advanced analyzing requires modeling of data in processes and methods for accumulating resources and emissions thorough the lifecycle of products. The traceability graph enables tracing and accumulation of resources, emissions and other information associated with products. The traceability graph is formally defined by set theory that is an established and exact specification method

Diabetes is associated with familial idiopathic normal pressure hydrocephalus : a case-control comparison with family members

Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their >= 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.Peer reviewe

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

Objective To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. Methods Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. Results The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p <0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. Conclusions This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.Peer reviewe

Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus

Background: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. Objective: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-beta (A beta) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. Methods: L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed A beta plaques in frontal cortical brain biopsy and 13 iNPH patients without A beta pathology. CSF Amyloid-beta(42) (A beta(42)), total tau (T-tau), phosphorylated tau (P-tau(181)), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. Results: All biomarkers but A beta(42) increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. A beta(42) instead showed divergent longitudinal decrease between A beta-positive and -negative patients in L-CSF, and thereafter increase in A beta-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (A beta(42) R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (A beta(42) 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only A beta(42) showed higher concentration in non-carriers of allele epsilon 4. Conclusion: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy A beta pathology, while NFL normalized toward its pre-shunt levels. A beta(42) as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V-than L-CSF yet showing strong correlations.Peer reviewe

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case-control comparison with family members

Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their >= 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.</div

Prevalence of Schizophrenia in Idiopathic Normal Pressure Hydrocephalus

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and potentially treatable neurodegenerative disease affecting elderly people, characterized by gait impairment and ventricular enlargement in brain imaging. Similar findings are seen in some patients with schizophrenia (SCZ).OBJECTIVE: To determine the prevalence of SCZ among patients suffering from probable or possible iNPH and the specific effects of comorbid SCZ on the outcome of the cerebrospinal fluid (CSF) shunting.METHODS: All medical records of the 521 iNPH patients in the NPH registry were retrospectively analyzed from 1991 until 2017. The prevalence of comorbidity of SCZ was determined and compared to that of general aged (≥65 yr) population in Finland.RESULTS: We identified a total of 16 (3.1%) iNPH patients suffering from comorbid SCZ. The prevalence of SCZ among the iNPH patients was significantly higher compared to the general population (3.1% vs 0.9%, P CONCLUSION: SCZ seems to occur 3 times more frequently among iNPH patients compared to the general aged population in Finland. The outcome of the treatment was not affected by comorbid SCZ and therefore iNPH patients suffering from comorbid SCZ should not be left untreated. These results merit validation in other populations. In addition, further research towards the potential connection between these chronic conditions is warranted.</p

Why Does the Health-Related Quality of Life in Idiopathic Normal-Pressure Hydrocephalus Fail to Improve Despite the Favorable Clinical Outcome?

OBJECTIVE: Occasionally, a favorable clinical diseasespecific outcome does not reflect into improved generic health-related quality of life (HRQoL) in patients with idiopathic normal-pressure hydrocephalus (iNPH) at 1 year after the installation of a cerebrospinal fluid shunt. Our aim was to identify factors causing this discrepancy. METHODS: The 1-year HRQoL outcomes of 141 patients with iNPH were evaluated with the generic 15D instrument, in which the minimum clinically important change/difference on the 0-1 scale has been estimated to be +/- 0.015.A 12-point iNPH grading scale (iNPHGS) was used as a clinical disease-specific outcome measure, in which a 1-point decrease is considered to be clinically important. We identified 29 (21%) patients with iNPH from our prospective study whose HRQoL deteriorated or remained the same despite of a favorable iNPHGS outcome. We analyzed this discrepancy using patients' clinical variables and characteristics. RESULTS: Multivariate binary logistic regression analysis indicated that a greater (worse) iNPHGS score at baseline (adjusted odds ratio [OR], 1.7; 95% confidence interval [CI] 1.3-2.3; P <0.001), comorbid chronic pulmonary disease (40% vs. 20%; adjusted OR 17.8; 95% CI 3.6-89.9; P <0.001), and any comorbid nonmetastatic tumor (62% vs. 17%; adjusted OR 11.5; 95% CI 1.5-85.3; P [0.017) predicted discrepancy between iNPHGS and 15D outcomes. - CONCLUSIONS: Frail patients suffering from certain preexisting comorbidities may not experience improvement in generic HRQoL despite of a favorable clinical diseasespecific response. Acknowledging the comorbidity burden of the patient may help clinicians and the patients to understand the conflict between patient-reported and clinical outcomes.Peer reviewe

Lasten haimatulehdusten etiologia, hoito ja lopputulema

Viimeaikaisten tutkimusten perusteella lasten akuutin pankreatiitin (AP) insidenssi on nousussa. Tutkimuksessamme kävimme systemaattisesti läpi akuutin tai akuutin toistuvan pankreatiitin vuoksi entisellä Lastenklinikalla hoidetut lapsipotilaat vuosilta 1999-2018. Akuutti toistuva pankreatiitti (ARP) määriteltiin kahdeksi tai useammaksi akuutin pankreatiitin episodiksi elinajan aikana. Potilastietojärjestelmästä ja potilastietoarkistosta kerättiin tietoja kliinisistä löydöksistä, sairaalahoidon aikaisista laboratoriokokeista, geenitutkimuksista, kuvantamistutkimuksista, endoskooppisesta ja kirurgisesta hoidosta, sairaalahoidon kestosta, haimatulehdusepisodien määrästä sekä lopputulemasta. Löysimme 34 tutkimusasetelmaan sopivaa potilasta [n=22 (64%) AP; n=12 (35%) ARP; n=17 (50%) naispuolisia]. Yksikään potilaista ei menehtynyt haimatulehduksen seurauksena. Yleisimmät etiologiat olivat haiman ja sappiteiden anatomiset poikkeavuudet (26%), haimatoksiset lääkeaineet (21%), perinnölliset tekijät (18%), autoimmuunitulehdus (9%) sekä idiopaattinen pankreatiitti (21%). Haimatulehduksen taustalta löytyi SPINK1-mutaatio neljältä ja PRSS1-mutaatio viideltä potilaalta. Mediaani-ikä ensimmäisen haimatulehdusdiagnoosin asettamisen hetkellä oli 9.8 (8.2-11) vuotta. Potilaat, joilla haimatulehduksen etiologia oli haiman ja sappiteiden anatominen poikkeavuus sairastuivat muita potilaita nuorempina [4.3 (2.5-9.8) vs. 10 (8.5-12) vuotta, p=0.025]. Lisäksi he joutuivat muita useammin sekä ERCP tutkimuksiin (n=7/9 vs. 8/25, p=0.025), että kirurgisten tai endoskooppisten interventioiden kohteeksi kohortin muihin potilaisiin verrattuna (n= 8/9 vs. 8/25 p=0.006). Yleisimmät pitkäaikaiskomplikaatiot haimatulehduksen jälkeen olivat ripuli ja krooninen kipu ylävatsalla. Näistä kärsi yhteensä 29% potilaista, kummastakin yksittäisestä oireesta kolme potilasta. Neljä potilasta saivat seuranta-ajan päättyessä entsyymikorvaushoitoa. Kellekään ei kehittynyt diabetesta. Tutkimuksemme perusteella lasten haimatulehdusten taustatekijät ovat varsin moninaisia myös Suomessa.Objective. Recent studies have reported an increasing incidence of acute pancreatitis (AP) in children. The etiology of AP in children is more diverse compared to adults. All patients treated for acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in Helsinki University Children’s hospital during 1999-2018 were reviewed. Methods. ARP was considered as two or more episodes of AP over a lifetime. Demographics, clinical findings, laboratory test results, genetic assessment, imaging findings, endoscopic and surgical treatment, duration of hospital stay, number of pancreatitis episodes, and outcome were analyzed. Results. Of a total of 34 identified patients [n=22 (64%) AP; n=12 (35%) ARP; n=17 (50%) females] none died. The most frequent etiologies were pancreaticobiliary (26%), drug-induced (21%), hereditary (18%), autoimmune (9%) and idiopathic (21%) pancreatitis. An underlying SPINK1 (n=4) and PRSS1 mutation was found in five (15%) patients. Median age at diagnosis was 9.8 (8.2-11) years. Patients with pancreaticobiliary pancreatitis were younger at presentation [4.3 (2.5-9.8) vs. 10 (8.5-12) years, p=0.025] and underwent ERCP (n=7/9 vs. 8/25, p=0.025), and surgical or endoscopic interventions (n= 8/9 vs. 8/25 p=0.006) more frequently compared to the rest of the cohort. The most common long-term complications affecting 29% of patients were chronic upper abdominal pain and diarrhea, occurring each in three patients (8.8%), respectively. Four patients received pancreatic enzyme substitution, while none developed diabetes. Conclusions. Our study highlights the diverse etiology of pediatric pancreatitis necessitating comprehensive diagnostic work-up and management options with relatively low long-term morbidity

Normaalipaineisen hydrokefaluksen kliininen kuva, diagnostiset tutkimukset ja hoito

Abstract Acute hydrocephalus is a life-threatening emergency. Primary diagnosis and suspected shunt malfunction requires immediate CT or MR imaging and neurosurgical consultation. Normal pressure hydrocephalus (NPH) is a chronic degenerative disease but requires prompt diagnosis and treatment due to progressive nature. Recent studies indicate apparent specific disease mechanisms of idiopathic NPH including potential genetic risk factors. CSF shunt may significantly improve gait, urinary incontinence and cognitive symptoms in selected patients. Noteworthy, iNPH seems to progress frequently despite of shunt emphasizing the need for active follow-up. Recognition and appropriate treatment of potential comorbid neurodegenerative diseases like vascular dementia and Alzheimer’s disease are needed in case of cognitive deterioration.Tiivistelmä Akuutti hydrokefalia on henkeä uhkaava tila kaikenikäisillä. Mikäli sunttiriippuvaisella potilaalla epäillään suntin toimintahäiriötä, on pään TT (tai MK) tehtävä viipymättä ja tarvitessa konsultoitava päivystävää neurokirurgista yksikköä välittömästi. Normaalipaineinen hydrokefalia (NPH) on harvoin päivystyksellinen ongelma, mutta tauti on selkeästi etenevä ja hoidon viivästyminen heikentää ennustetta. Tuoreet tutkimukset avaavat idiopaattisen NPH-taudin (iNPH) etiologiaa ja patofysiologisia mekanismeja sekä ennustetta. Osalla potilaista likvorisuntti voi merkittävästi lievittää oireita, erityisesti liikkumisvaikeuksia mutta myös inkontinenssia ja tiedonkäsittelyn ongelmia. Suntista huolimatta tauti pyrkii vuosien myötä etenemään, korostaen seurannan merkitystä. iNPH potilailla on usein myös samanaikainen vaskulaarinen kognitiivinen heikkenemä, Alzheimerin tauti tai muu aivorappeumasairaus, joka on myös diagnosoitava ja hoidettava