Markers of nephropathy in young Fabry disease patients; role of kidney biopsies and functional measurements

Backgound: Fabry disease is an X-linked disease affecting glycosphingolipid metabolism due to deficiency of the lysosomal enzyme α-galactosidase. The natural course of the disease is related to progressive accumulation of globotriaocylceramide (GL3) in various cell types and causes premature death from stroke, renal failure or cardiac disease. Modern therapies in many common kidney diseases, as well as in a rapidly increasing number of rare diseases, include potentially toxic and expensive drug interventions. As a consequence, it becomes important to use accurate methods for investigation of kidney disease. Aims: The aims of this thesis were to evaluate early Fabry nephropathy by means of morphologic and exact functional methods in children and young adults and to validate the safety of kidney biopsies in general. Materials and methods: Renal biopsies from thirteen young patients with Fabry disease (mean age 17.3 ± 7.5, range 7-33 years) were examined before and after longterm (5 years) enzyme replacement therapy (ERT). Comparisons of different formulas for estimation of GFR (eGFR) and measured GFR (mGFR) were performed in 42 children with Fabry disease (mean age 12.3 ± 3.6, range 2-17 years). Safety evaluation of kidney biopsies was done in 715 paediatric (mean age 12.0 ± 4.9, range 0.04-17.9 years) and 8573 adult (mean age 50.6 ± 17.7, range 18.0-94.4) cases registered from 1988 to 2010 in The Norwegian Kidney Biopsy Registry. Results: The baseline biopsies of Fabry disease patients showed disease specific potentially progressive morphologic changes in glomerular, tubulointerstitial and vascular compartments. In the follow-up biopsies complete clearance of glomerular endothelial and mesangial GL3 deposits was found in all patients and linear regression analysis showed a significant correlation between podocyte GL3-clearance and cumulative agalsidase dose (r=0.804, p=0.002). Simultaneous eGFR and mGFR analysis showed that the widely used original Schwartz formula overestimated mGFR by an average of 50.6 ml/min/1.73 m2 in our cohort with normal mGFR. Nationwide renal biopsy registry data showed that major complications after kidney biopsy were rare both in children and adults (blood transfusion 0.9 % and surgery/angiographic embolization 0.2 %), the most important risk factors for major complications were lower GFR and smaller centre size. Conclusions and consequences: Long-term ERT clears glomerular endothelial and mesangial GL3 deposits across all dosing regimens of agalsidase. The reduction of Fabry disease specific damage in podocytes is dose-dependent, suggesting that podocyte damage may be a promising biomarker in Fabry nephropathy. Kidney biopsy is a low risk procedure and we recommend a baseline biopsy in the assessment of early renal damage in Fabry disease. A follow-up biopsy after 5 years ERT is valuable in the evaluation of progression and reversibility of kidney damage. Several GFR formulas show low accuracy in the normal GFR-range. The new abbreviated Schwartz formula (2009) has the better performance and is recommended in the routine follow-up of children with Fabry disease. Additional mGFR is recommended when exact measurements are needed; e.g. when ERT is initiated

SecureScale: Exploring Synergies between Security and Scalability in Software Development and Operation

Security and scalability are core software qualities, which as non-functional aspects share certain characteristics and challenges in how they are approached during software development and operation. Based on expert interviews, this paper explores interactions and dependencies between security and scalability, as well as similarities and differences in their challenges. It concludes that the current understanding of the relationship between security and scalability is not yet mature. Further, it points to future research needs to better understand the relationship between these two quality aspects and better support practitioners in addressing security and scalability in a more integrated fashion.publishedVersio

Cardiovascular changes in young renal failure patients

Progresses in medical care of severe kidney disease and congenital anomalies of kidney and urinary tract make it possible for a higher percentage of young renal failure patients to survive and enter adulthood. There is thus an increasing need to focus on the long-term effects of severely reduced kidney function early in life. Cardiovascular changes are known to contribute considerably in adulthood to the severe complications of renal failure. In young chronic kidney disease patients, there is limited knowledge of subclinical cardiovascular disease. In this issue of Clinical Kidney Journal, Lalayiannis et al. describe significant structural and functional cardiovascular changes in a young cohort of kidney failure patients with glomerular filtration rate <30 mL/min/1.73 m2. Among the 100 patients between 5 and 30 years of age included in the study, 84 presented with signs of cardiovascular disease. There is a need for long-term follow-up data on cardiovascular consequences of renal failure early in life and evaluation of prophylactic and therapeutic measures that can ameliorate the overall prognosis for these patients. We look forward to planned future long-term data from this cohort as well as increased focus in general on cardiovascular changes in young renal failure patients.publishedVersio

Current overview and way forward for the use of machine learning in the field of petroleum gas hydrates

Gas hydrates represent one of the main flow assurance challenges in the oil and gas industry as they can lead to plugging of pipelines and process equipment. In this paper we present a literature study performed to evaluate the current state of the use of machine learning methods within the field of gas hydrates with specific focus on the oil chemistry. A common analysis technique for crude oils is Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) which could be a good approach to achieving a better understanding of the chemical composition of hydrates, and the use of machine learning in the field of FT-ICR MS was therefore also examined. Several machine learning methods were identified as promising, their use in the literature was reviewed and a text analysis study was performed to identify the main topics within the publications. The literature search revealed that the publications on the combination of FT-ICR MS, machine learning and gas hydrates is limited to one. Most of the work on gas hydrates is related to thermodynamics, while FT-ICR MS is mostly used for chemical analysis of oils. However, with the combination of FT-ICR MS and machine learning to evaluate samples related to gas hydrates, it could be possible to improve the understanding of the composition of hydrates and thereby identify hydrate active compounds responsible for the differences between oils forming plugging hydrates and oils forming transportable hydrates.Current overview and way forward for the use of machine learning in the field of petroleum gas hydratespublishedVersio

GENERATOR DENAH MEJA UJIAN DENGAN IMPLEMENTASI ALGORITMA BACKTRACKING

Beberapa penelitian mengidentifikasikan bahwa teknik menyontek yang paling umum digunakan adalah bertukar jawaban dengan peserta didik yang berada pada posisi terdekat atau melihat jawaban tanpa sepengetahuan orang yang bersangkutan. (Davis, et al, 1998). Pada penelitian ini dibangun sebuah sistem generator denah meja ujian agar setiap meja ujian memiliki kode soal yang berbeda dari meja tetangganya baik secara vertikal, horizontal dan diagonal dengan mengimplementasikan algoritma backtracking. Pengujian kemudian dilakukan pada matriks dengan berbagai dimensi dimulai dari jumlah kode soal 1 hingga 9. Dari hasil pengujian disimpulkan bahwa untuk kode soal < 4, persoalan dinyatakan tidak akan memiliki solusi kecuali jumlah baris atau kolom pada matriks juga < 4. Untuk jumlah kode soal ≥ 4, persoalan pastilah memiliki solusi berapapun dimensi matriksnya. Kata Kunci: menyontek, algoritma backtracking, generator denah meja ujian, matriks, pembagian kode soal ujian. Some research have identified that the most commonly cheating technique used while exam are exchanging the exam answers with other classmates who sit at the closest range then copying their answer sheet without being noticed (Davis, et al, 1998). In this paper, exam class generator was built by implementing backtracking algorithm in order to arrange exam sheets, so each cell has different code with the cell around. The testing of system then performed on some matrix variety which have sum of exams code within 1 to 9. The results shows, for sum of code < 4, each case will never has any solution unless row or column of the matrix is also < 4. And for sum of code ≥ 4, every case will have solution regardless of the matrix dimension. Keyword: cheat in exam, backtracking algorithm, exam class generator, matrix, distribution of exams sheets

Using machine learning-based variable selection to identify hydrate related components from FT-ICR MS spectra

The blockages of pipelines caused by agglomeration of gas hydrates is a major flow assurance issue in the oil and gas industry. Some crude oils form gas hydrates that remain as transportable particles in a slurry. It is commonly believed that naturally occurring components in those crude oils alter the surface properties of gas hydrate particles when formed. The exact structure of the crude oil components responsible for this surface modification remains unknown. In this study, a successive accumulation and spiking of hydrate-active crude oil fractions was performed to increase the concentration of hydrate related compounds. Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) was then utilised to analyse extracted oil samples for each spiking generation. Machine learning-based variable selection was used on the FT-ICR MS spectra to identify the components related to hydrate formation. Among six different methods, Partial Least Squares Discriminant Analysis (PLS-DA) was selected as the best performing model and the 23 most important variables were determined. The FT-ICR MS mass spectra for each spiking level was compared to samples extracted before the successive accumulation, to identify changes in the composition. Principal Component Analysis (PCA) exhibited differences between the oils and spiking levels, indicating an accumulation of hydrate active components. Molecular formulas, double bond equivalents (DBE) and hydrogen-carbon (H/C) ratios were determined for each of the selected variables and evaluated. Some variables were identified as possibly asphaltenes and naphthenic acids which could be related to the positive wetting index (WI) for the oils.publishedVersio

Measurement of renal functional response using iohexol clearance—a study of different outpatient procedures

Background: Glomerular filtration rate (GFR) increases after a heavy protein load; an increase termed renal functional response (RFR). Decreased RFR could be a marker of early kidney damage, but published methods are cumbersome in the outpatient setting. The present study investigates the use of iohexol clearance to measure RFR in outpatients using both one- and two-sample methods. Methods: Fourteen healthy volunteers with a mean ± SD age of 42 ± 12 years were included (six males and eight females). GFR was measured using plasma iohexol clearance with one- and two-sample methodologies. Four measurements in each individual were performed: one baseline test and three protein loading tests containing 80 g protein (commercially available protein supplementations from Myo Nutrition and Proteinfabrikken and 350 g chicken breast). RFR was calculated as percentage increase in GFR from the baseline test. Results: Mean RFR was 11.4 ± 5.4% and 12.1 ± 6.4% using one- and two-sample methods, respectively. The three different protein loads resulted in similar mean RFR but there was considerable intra-individual variability. One- and two-sample methods for measurement of RFR showed similar results with near-identical means, but there was some intra-individual variation that was similar for different protein loads. The overall 95% limit of agreement between one- and two-sample methods for calculating RFR was −8.7 to 7.3. Conclusions: RFR can be investigated using plasma iohexol clearance in an outpatient setting. Protocols using commercially available protein supplementation showed a mean RFR of about 12%. One- and two-sample methods for measuring RFR yield similar results.publishedVersio

Antibiotikaforskrivning ved samfunnservervet pneumoni og KOLS-eksaserbasjon ved Universitetssykehuset Nord-Norge

Bakgrunn: Rasjonell antibiotikaforskrivning, som i denne sammenheng vil si i henhold til Nasjonal faglig retningslinje for antibiotikabruk i sykehus, er et av de viktigste tiltakene vi har for å motvirke resistensutvikling. Forskrivning i henhold til retningslinjer er også assosiert med gunstige pasientutfall. Samfunnservervet pneumoni (community-acquired pneumonia; CAP) og kronisk obstruktiv lungesykdom (KOLS)-eksaserbasjon er blant de vanligste tilstandene som behandles med antibiotika i sykehus. Ved å rette tiltak mot forskrivning ved slike tilstander kan man bidra til å optimalisere antibiotikabehandlingen til store pasientgrupper. Utvikling av effektive tiltak på sykehus- og avdelingsnivå må baseres på kunnskap om hvordan antibiotika forskrives. Formål: Formålet er todelt. I del 1 undersøker vi etterlevelse av nasjonal faglig retningslinje for antibiotikaforskrivning ved CAP og KOLS eksaserbasjon, samt undersøker om det er forskjeller i forskrivning mellom UNN Tromsø, Harstad og Narvik. I del 2 evaluerer vi om en intervensjonsstudie utført i 2014 ved Lungemedisinsk avdeling UNN Tromsø har hatt vedvarende effekt på forskrivning ved CAP og KOLS-eksaserbasjon, med fokus empirisk antibiotikavalg, total behandlingslengde og dosering av benzylpenicillin Metode: Del 1 var en retrospektiv, deskriptiv journalstudie. Vi inkluderte pasienter utskrevet fra UNN Tromsø, Harstad og Narvik i perioden juli-desember 2017 med diagnosekoder for pneumoni og/eller KOLS-eksaserbasjon, og ekskluderte pasienter < 18 år samt pasienter med aspirasjonspneumoni, nosokomial pneumoni, cystisk fibrose eller koinfeksjon ved utskrivelse. Valg av empirisk antibiotika, dose av benzylpenicillin, intravenøs- og total behandlingstid samt revurdering av antibiotikaforskrivning ble undersøkt, og forskrivningspraksis ved de tre sykehusene ble sammenlignet statistisk. I del 2 ble data fra en publisert intervensjonsstudie, i tillegg til nye data samlet inn i forbindelse med del 1 fra UNN Tromsø brukt for å evaluere effekten av intervensjonen tre år etter. Effekten ble vurdert ved hjelp av før-etter-analyse og interrupted time series-analyse. Resultater: I del 1 ble totalt 262 pasienter fra UNN Tromsø, Harstad og Narvik inkludert, og blant disse hadde 185 (71%) pasienter CAP og 77 (29%) KOLS-eksaserbasjon. Ved CAP fikk 68% av pasientene empirisk antibiotika i henhold til retningslinjene. Ved UNN Tromsø ble det imidlertid forskrevet cefalosporiner oftere enn i Harstad og Narvik. Blant pasienter behandlet med benzylpenicillin, fikk 64% høydose (3 g x 4). Gjennomsnittlig behandlingstid intravenøst og totalt var henholdsvis 3,7 dager og 9,7 dager. I snitt ble pasienter behandlet lengre ved UNN Tromsø. Kun 51% av pasientene fikk revurdering av antibiotikabehandlingen dokumentert i pasientjournalen innen 48-72 timer. UNN Harstad var betydelig bedre på dokumentasjon enn Tromsø og Narvik. Kun 38% av pasientene med KOLS-eksaserbasjon fikk empirisk antibiotika i henhold til retningslinjene. Høydose benzylpenicillin ble forskrevet til 46%. Gjennomsnittlig intravenøs og total behandlingstid var henholdsvis 2,2 og 9 dager. Kun 27% av pasientene fikk revurdering av antibiotikabehandlingen dokumentert i pasientjournalen innen 48-72 timer. I del 2 observerte vi at effekten på forskrivningen av foretrukne empiriske antibiotika var opprettholdt, tre år etter at intervensjonen ble utført. Intervensjonen hadde ikke vedvarende effekt på total behandlingstid og dosering av benzylpenicillin, selv om total behandlingstid var lavere enn før intervensjonen. Konklusjon: Valg av empirisk antibiotika i behandlingen av CAP og KOLS-eksaserbasjon ved de tre sykehusene ser stort sett fordelaktig ut. Det bør imidlertid rettes fokus mot lang total behandlingslengde og utstrakt bruk av høydose benzylpenicillin. Det bør også være et mål å implementere revurdering av antibiotikabehandling innen 48-72 timer for alle pasienter. Tre år etter at en intervensjonsstudie ble utført, ser vi at effekten på forskrivning av foretrukne empiriske antibiotika er opprettholdt. Intervensjonen hadde ikke vedvarende effekt på total behandlingstid og dosering av benzylpenicillin. Våre funn tyder på at for å opprettholde mest mulig rasjonell forskrivning er det nødvendig med kontinuerlig innsats og muligens bør lignende intervensjoner utføres med jevne mellomrom

What Could Possibly Go Wrong? Smart Grid Misuse Case Scenarios

The modernisation of the power grid is ongoing, and the level of digitalisation of the power grid in, say, ten years may be quite different than today. Cyber security needs will change correspondingly. In this paper we utilise a qualitative research approach to explore misuse cases related to three main areas of modernisation that we envision for the next ten year period: 1) managing flexibility in the TSO-DSO relation, 2) smart distribution grids, and 3) microgrids. The misuse cases represent potential security challenges to be considered when working on modernising the grid, however they are not exhaustive. The misuse cases presented in this paper can contribute to identifying security requirements, thus reducing associated cyber risks, and assist in development of new cyber security mechanisms for the next-generation power grid employing digitally-connected, self-healing, and automation characteristics.acceptedVersio