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In this paper, the high-temperature constitutive behaviour of an additively manufactured ductile nickel-based superalloy is investigated and modelled, with application to thermomechanical fatigue, low-cycle fatigue and creep conditions at temperatures up to 800∘800∘C. Thermomechanical fatigue tests have been performed on smooth specimens in both in-phase and out-of-phase conditions at a temperature range of 100−800∘100−800∘C, and creep tests at 625∘625∘C, 700∘700∘C, 750∘750∘C and 800∘800∘C. Additionally, low-cycle fatigue tests at different strain ranges and load ratios have been performed at 700∘700, Funding Agencies|Linkoping University and Siemens Energy AB

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe., SCOPUS: ar.j, info:eu-repo/semantics/published

The steel company SSAB in Borlänge will, in the near future, replace its protective relays in one of their substations due to the condition and age of the relays. In connection with the change, SSAB intended to switch the current communication protocol IEC 60870-5-103 (IEC 103) to IEC 61850. They were thus interested in knowing what differences there were between these protocols and what were the technical and economical pros and cons for the change. To answer SSAB's questions, this bachelor thesis project was initiated with the aim of a feasibility study regarding the relays change and the protocol switching. To this purpose, the relevant parts of the substation and its functions were first examined to have an overall picture and the understanding of how they worked and interacted. After that, the communication protocols IEC 103 and IEC 61850 were investigated separately and comparatively. After a few weeks a visit was paid to SSAB to visually see what was to be done and to obtain a better understanding. During the visit, the substation that would receive new protection relays were shown and how their parts in the system were connected and interacted. Besides, other electrical devices were also shown, for example, large step-down transformers and a capacitor bank. After this, further study of the protocols, the relays as well as the associated parts were conducted and the information collected. Finally, the collected information was analysed, compared and documented in this thesis to generate a result and a comparison. From this feasibility study, it is clear that the new protocol had many advantages technically and some economically, which in particular include: 1) communication where IEC 103 uses master/slave at speeds up to 10 Mbit/s and IEC 61850 uses client/server and peer to peer at speeds between 100 Mbit/s to 1 Gbit/s; 2) connection where IEC 103 was point to point and with IEC 61850 it will be connected in ring formation for better redundancy; 3) interoper

Introduktion: Smärta är vanligt förekommande i livets slutskede och är en av de faktorer inom palliativ vård som skapar mest oro och ångest hos patienten men även närstående. Cancer är ofta associerat med smärta, men smärta förekommer även vid en rad andra sjukdomar i livets slutskede såsom vid hjärtsvikt, njursvikt och kronisk obstruktiv lungsjukdom. Förekomsten av smärta ökar ju närmare livets slutskede en patient befinner sig och 25 % av patienterna upplever en otillräcklig smärtlindring under sista veckan i livet. Användning av intratekalbedövning kan ha en avgörande betydelse som smärtlindringsmetod i livets slutskede för att minska smärta, förbättra patientens autonomi och på så vis öka livskvalitén. Syfte: Att beskriva patienters och sjuksköterskors upplevelse av intratekal som smärtlindringsmetod i livets slutskede. Metod: En fallstudie med kvalitativ metod och induktiv ansats användes, där semistrukturerade intervjuer analyserades med kvalitativ innehållsanalys. Resultat: Totalt erhölls fem kategorier ur dataanalysen, vilka var: Bristande information och erfarenhet av intratekal blockad, Intratekal blockad som en sista utväg, Varierande effekt av intratekal blockad, komplikationer med intratekal blockad och Att uppleva självständighet och livskvalité. Slutsats: Denna studie visar på varierande effekter av intratekal blockad som smärtlindring till patienter i livets slutskede. För de patienter där det fungerar väl är det en god smärtlindringsmetod som ger en ökad självständighet och livskvalité. Smärta är mångdimensionellt och bör behandlas med flera komponenter, där patienten är i centrum och ett holistiskt synsätt ses över hela patienten. Intratekal smärtlindring bör vara ett alternativ i tidig planering för långvarig smärtproblematik och det behövs utbildning för vårdpersonal inom området.

The steel company SSAB in Borlänge will, in the near future, replace its protective relays in one of their substations due to the condition and age of the relays. In connection with the change, SSAB intended to switch the current communication protocol IEC 60870-5-103 (IEC 103) to IEC 61850. They were thus interested in knowing what differences there were between these protocols and what were the technical and economical pros and cons for the change. To answer SSAB's questions, this bachelor thesis project was initiated with the aim of a feasibility study regarding the relays change and the protocol switching. To this purpose, the relevant parts of the substation and its functions were first examined to have an overall picture and the understanding of how they worked and interacted. After that, the communication protocols IEC 103 and IEC 61850 were investigated separately and comparatively. After a few weeks a visit was paid to SSAB to visually see what was to be done and to obtain a better understanding. During the visit, the substation that would receive new protection relays were shown and how their parts in the system were connected and interacted. Besides, other electrical devices were also shown, for example, large step-down transformers and a capacitor bank. After this, further study of the protocols, the relays as well as the associated parts were conducted and the information collected. Finally, the collected information was analysed, compared and documented in this thesis to generate a result and a comparison. From this feasibility study, it is clear that the new protocol had many advantages technically and some economically, which in particular include: 1) communication where IEC 103 uses master/slave at speeds up to 10 Mbit/s and IEC 61850 uses client/server and peer to peer at speeds between 100 Mbit/s to 1 Gbit/s; 2) connection where IEC 103 was point to point and with IEC 61850 it will be connected in ring formation for better redundancy; 3) interoper

Sweden's Animal Welfare Act of 1988 stated that regulations and directives within the law should be in favor of animals' wellbeing, protect them against unnecessary harm, allow them to express their natural behavior, and prevent behavioral disorders. However, ethological studies present several welfare problems found in animals held legally in factory farming settings. By using one of Sweden's most commonly slaughtered animals-the pig-this paper scrutinizes how politicians consider different interests while debating animal living conditions in factory farms. The results demonstrate an overall absence of discussions addressing welfare problems in Swedish pig farming. When such welfare issues are addressed, they are often overlooked in favor of interests that cannot directly be associated with animal welfare. Political claims of having the best animal welfare legislation in the world are used when arguing for decreasing as well as enhancing the living conditions.

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at > 1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though similar to 0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (< 0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at > 1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though similar to 0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (< 0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.

Bacterial spores are problematic in agriculture, the food industry, and healthcare, with the fallout costs from spore-related contamination being very high. Spores are difficult to detect since they are resistant to many of the bacterial disruption techniques used to bring out the biomarkers necessary for detection. Because of this, effective and practical spore disruption methods are desirable. In this study, we demonstrate the efficiency of a compact microfluidic lab-on-chip built around a coplanar waveguide (CPW) operating at 2.45 GHz. We show that the CPW generates an electric field hotspot of ∼10 kV/m, comparable to that of a commercial microwave oven, while using only 1.2 W of input power and thus resulting in negligible sample heating. Spores passing through the microfluidic channel are disrupted by the electric field and release calcium dipicolic acid (CaDPA), a biomarker molecule present alongside DNA in the spore core. We show that it is possible to detect this disruption in a bulk spore suspension using fluorescence spectroscopy. We then use laser tweezers Raman spectroscopy (LTRS) to show the loss of CaDPA on an individual spore level and that the loss increases with irradiation power. Only 22% of the spores contain CaDPA after exposure to 1.2 W input power, compared to 71% of the untreated control spores. Additionally, spores exposed to microwaves appear visibly disrupted when imaged using scanning electron microscopy (SEM). Overall, this study shows the advantages of using a CPW for disrupting spores for biomarker release and detection.

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at > 1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though similar to 0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (< 0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.

Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can thereby provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.

Bacterial spores are problematic in agriculture, the food industry, and healthcare, with the fallout costs from spore-related contamination being very high. Spores are difficult to detect since they are resistant to many of the bacterial disruption techniques used to bring out the biomarkers necessary for detection. Because of this, effective and practical spore disruption methods are desirable. In this study, we demonstrate the efficiency of a compact microfluidic lab-on-chip built around a coplanar waveguide (CPW) operating at 2.45 GHz. We show that the CPW generates an electric field hotspot of ∼10 kV/m, comparable to that of a commercial microwave oven, while using only 1.2 W of input power and thus resulting in negligible sample heating. Spores passing through the microfluidic channel are disrupted by the electric field and release calcium dipicolic acid (CaDPA), a biomarker molecule present alongside DNA in the spore core. We show that it is possible to detect this disruption in a bulk spore suspension using fluorescence spectroscopy. We then use laser tweezers Raman spectroscopy (LTRS) to show the loss of CaDPA on an individual spore level and that the loss increases with irradiation power. Only 22% of the spores contain CaDPA after exposure to 1.2 W input power, compared to 71% of the untreated control spores. Additionally, spores exposed to microwaves appear visibly disrupted when imaged using scanning electron microscopy (SEM). Overall, this study shows the advantages of using a CPW for disrupting spores for biomarker release and detection.

Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can thereby provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.

Bacterial spores are problematic in agriculture, the food industry, and healthcare, with the fallout costs from spore-related contamination being very high. Spores are difficult to detect since they are resistant to many of the bacterial disruption techniques used to bring out the biomarkers necessary for detection. Because of this, effective and practical spore disruption methods are desirable. In this study, we demonstrate the efficiency of a compact microfluidic lab-on-chip built around a coplanar waveguide (CPW) operating at 2.45 GHz. We show that the CPW generates an electric field hotspot of ∼10 kV/m, comparable to that of a commercial microwave oven, while using only 1.2 W of input power and thus resulting in negligible sample heating. Spores passing through the microfluidic channel are disrupted by the electric field and release calcium dipicolic acid (CaDPA), a biomarker molecule present alongside DNA in the spore core. We show that it is possible to detect this disruption in a bulk spore suspension using fluorescence spectroscopy. We then use laser tweezers Raman spectroscopy (LTRS) to show the loss of CaDPA on an individual spore level and that the loss increases with irradiation power. Only 22% of the spores contain CaDPA after exposure to 1.2 W input power, compared to 71% of the untreated control spores. Additionally, spores exposed to microwaves appear visibly disrupted when imaged using scanning electron microscopy (SEM). Overall, this study shows the advantages of using a CPW for disrupting spores for biomarker release and detection.

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at > 1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though similar to 0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (< 0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.

Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can thereby provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.

The Swampland program is way of sorting effective field theories based on conjectures of how an effective field theory consistent with quantum gravity should look like. In this thesis we take a closer look at the No Global Symmetries Conjecture, the Weak Gravity Conjecture, the de Sitter Conjecture and the Trans-Planckian Censorship Conjecture. The Weak Gravity Conjecture generalized to arbitrary dimensions and p-forms is tested under dimensional reduction and its sharpened version is used to discuss how under this conjecture non-supersymmetric AdS geometries are unstable. The de Sitter Conjecture and the Trans-Planckian Censorship Conjecture are compared to show that they give similar predictions based on different assumptions. Lastly we provide an example of a theory emerging from the swampland that utilizes the instability of AdS geometries to model our universe as the boundary of a higher dimensional expanding bubble., Swampland-programmet är ett sätt att sortera effektiva fältteorier baserat på antaganden om hur en effektiv fältteori förenlig med kvantgravitation bör se ut. I den här avhandlingen tittar vi närmare på No Global Symmetries-antagandet, Weak Gravity-antagandet, de Sitter-antagandet och Trans-Planckian Censorship-antagandet. Weak gravity-antagandet generaliserat till godtyckliga dimensioner och p-former testas under dimensionsreduktion och dess skärpta version används för att diskutera hur man via detta antagande finner en instabilitet i icke-supersymmetriska AdS-geometrier. De sitter-antagandet och Trans-Planckian Censorship-antagandet jämförs för att visa att de ger liknande förutsägelser baserat på olika frågeställningar. Slutligen ger vi ett exempel på en teori som växer fram ur programmet som använder instabiliteten hos AdS-geometrier genom att modellera vårt universum som randen på en expanderande bubbla i högre dimensioner.

Introduktion: Smärta är vanligt förekommande i livets slutskede och är en av de faktorer inom palliativ vård som skapar mest oro och ångest hos patienten men även närstående. Cancer är ofta associerat med smärta, men smärta förekommer även vid en rad andra sjukdomar i livets slutskede såsom vid hjärtsvikt, njursvikt och kronisk obstruktiv lungsjukdom. Förekomsten av smärta ökar ju närmare livets slutskede en patient befinner sig och 25 % av patienterna upplever en otillräcklig smärtlindring under sista veckan i livet. Användning av intratekalbedövning kan ha en avgörande betydelse som smärtlindringsmetod i livets slutskede för att minska smärta, förbättra patientens autonomi och på så vis öka livskvalitén. Syfte: Att beskriva patienters och sjuksköterskors upplevelse av intratekal som smärtlindringsmetod i livets slutskede. Metod: En fallstudie med kvalitativ metod och induktiv ansats användes, där semistrukturerade intervjuer analyserades med kvalitativ innehållsanalys. Resultat: Totalt erhölls fem kategorier ur dataanalysen, vilka var: Bristande information och erfarenhet av intratekal blockad, Intratekal blockad som en sista utväg, Varierande effekt av intratekal blockad, komplikationer med intratekal blockad och Att uppleva självständighet och livskvalité. Slutsats: Denna studie visar på varierande effekter av intratekal blockad som smärtlindring till patienter i livets slutskede. För de patienter där det fungerar väl är det en god smärtlindringsmetod som ger en ökad självständighet och livskvalité. Smärta är mångdimensionellt och bör behandlas med flera komponenter, där patienten är i centrum och ett holistiskt synsätt ses över hela patienten. Intratekal smärtlindring bör vara ett alternativ i tidig planering för långvarig smärtproblematik och det behövs utbildning för vårdpersonal inom området.

The crack initiation life of a ductile additively manufactured nickel-based superalloy is studied and modeled for low-cycle fatigue and thermomechanical fatigue conditions up to 600 degrees C. Isothermal experiments were performed on smooth specimens at temperatures up to 600 degrees C with different applied strain ranges. Additionally, thermomechanical fatigue experiments at 100-450 degrees C and 100-600 degrees C were performed on smooth specimens under in-phase and out-of-phase conditions. A life prediction model accounting for the anisotropy was developed, where the temperature cycle is accounted with a Delta T$$ \Delta T $$-functionality, generating good agreements with the experiments. The model was also validated on notched specimens undergoing thermomechanical fatigue conditions at 100-500 degrees C using simplified notch correction methods., Funding Agencies|Linkoping University; Siemens Energy AB

The crack initiation life of a ductile additively manufactured nickel-based superalloy is studied and modeled for low-cycle fatigue and thermomechanical fatigue conditions up to 600 degrees C. Isothermal experiments were performed on smooth specimens at temperatures up to 600 degrees C with different applied strain ranges. Additionally, thermomechanical fatigue experiments at 100-450 degrees C and 100-600 degrees C were performed on smooth specimens under in-phase and out-of-phase conditions. A life prediction model accounting for the anisotropy was developed, where the temperature cycle is accounted with a Delta T$$ \Delta T $$-functionality, generating good agreements with the experiments. The model was also validated on notched specimens undergoing thermomechanical fatigue conditions at 100-500 degrees C using simplified notch correction methods., Funding Agencies|Linkoping University; Siemens Energy AB

Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can thereby provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.

Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can thereby provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.

The Swampland program is way of sorting effective field theories based on conjectures of how an effective field theory consistent with quantum gravity should look like. In this thesis we take a closer look at the No Global Symmetries Conjecture, the Weak Gravity Conjecture, the de Sitter Conjecture and the Trans-Planckian Censorship Conjecture. The Weak Gravity Conjecture generalized to arbitrary dimensions and p-forms is tested under dimensional reduction and its sharpened version is used to discuss how under this conjecture non-supersymmetric AdS geometries are unstable. The de Sitter Conjecture and the Trans-Planckian Censorship Conjecture are compared to show that they give similar predictions based on different assumptions. Lastly we provide an example of a theory emerging from the swampland that utilizes the instability of AdS geometries to model our universe as the boundary of a higher dimensional expanding bubble., Swampland-programmet är ett sätt att sortera effektiva fältteorier baserat på antaganden om hur en effektiv fältteori förenlig med kvantgravitation bör se ut. I den här avhandlingen tittar vi närmare på No Global Symmetries-antagandet, Weak Gravity-antagandet, de Sitter-antagandet och Trans-Planckian Censorship-antagandet. Weak gravity-antagandet generaliserat till godtyckliga dimensioner och p-former testas under dimensionsreduktion och dess skärpta version används för att diskutera hur man via detta antagande finner en instabilitet i icke-supersymmetriska AdS-geometrier. De sitter-antagandet och Trans-Planckian Censorship-antagandet jämförs för att visa att de ger liknande förutsägelser baserat på olika frågeställningar. Slutligen ger vi ett exempel på en teori som växer fram ur programmet som använder instabiliteten hos AdS-geometrier genom att modellera vårt universum som randen på en expanderande bubbla i högre dimensioner.

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at > 1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though similar to 0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (< 0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.

The main objective of this study is to examine whether monetary policy and lockdown of the Covid-19 pandemic together with social distancing, have had a significant impact on the economy. In terms of monetary policy, this study primarily focuses on the use of quantitative easing by the Swedish Riksbanken and European Central Bank. The purpose is to observe to what extent Sweden has managed to moderate the economic costs of the pandemic, relative to the countries of the eurozone. Estimates of several regressions of monetary policy chocks, indices of lockdown policies and social distancing on the real economy have been conducted. The panel data between 2010-2022 includes various economic variables such as real GDP, HICP inflation, housing prices, quantitative easing, interest rates, in addition indices of lockdown policies and social distancing. We find in our analysis evidence for both Sweden and the Euro area that quantitative easing has suppressed the negative economic impact. The effect on HICP inflation is significant however for some time periods, the long-run effect is negative. Regarding the housing market, the estimated regression had a positive significant effect only for the Euro area during the period 2010-22. Lockdown policies only had a significant negative economic effect in Sweden and not the Euro area. However, one part of our study suggests that the use of voluntary social distancing has had limited negative economic impact compared to lockdown policies, but only for Sweden in the time period 2015-2022 and not in the Euro area. Nonetheless one has to take the robustness into consideration since our society is still in an early phase after the pandemic. Further research in the future is necessary in order to estimate the long term economic effects.

Bacterial spores are problematic in agriculture, the food industry, and healthcare, with the fallout costs from spore-related contamination being very high. Spores are difficult to detect since they are resistant to many of the bacterial disruption techniques used to bring out the biomarkers necessary for detection. Because of this, effective and practical spore disruption methods are desirable. In this study, we demonstrate the efficiency of a compact microfluidic lab-on-chip built around a coplanar waveguide (CPW) operating at 2.45 GHz. We show that the CPW generates an electric field hotspot of ∼10 kV/m, comparable to that of a commercial microwave oven, while using only 1.2 W of input power and thus resulting in negligible sample heating. Spores passing through the microfluidic channel are disrupted by the electric field and release calcium dipicolic acid (CaDPA), a biomarker molecule present alongside DNA in the spore core. We show that it is possible to detect this disruption in a bulk spore suspension using fluorescence spectroscopy. We then use laser tweezers Raman spectroscopy (LTRS) to show the loss of CaDPA on an individual spore level and that the loss increases with irradiation power. Only 22% of the spores contain CaDPA after exposure to 1.2 W input power, compared to 71% of the untreated control spores. Additionally, spores exposed to microwaves appear visibly disrupted when imaged using scanning electron microscopy (SEM). Overall, this study shows the advantages of using a CPW for disrupting spores for biomarker release and detection.

Bacterial spores are problematic in agriculture, the food industry, and healthcare, with the fallout costs from spore-related contamination being very high. Spores are difficult to detect since they are resistant to many of the bacterial disruption techniques used to bring out the biomarkers necessary for detection. Because of this, effective and practical spore disruption methods are desirable. In this study, we demonstrate the efficiency of a compact microfluidic lab-on-chip built around a coplanar waveguide (CPW) operating at 2.45 GHz. We show that the CPW generates an electric field hotspot of ∼10 kV/m, comparable to that of a commercial microwave oven, while using only 1.2 W of input power and thus resulting in negligible sample heating. Spores passing through the microfluidic channel are disrupted by the electric field and release calcium dipicolic acid (CaDPA), a biomarker molecule present alongside DNA in the spore core. We show that it is possible to detect this disruption in a bulk spore suspension using fluorescence spectroscopy. We then use laser tweezers Raman spectroscopy (LTRS) to show the loss of CaDPA on an individual spore level and that the loss increases with irradiation power. Only 22% of the spores contain CaDPA after exposure to 1.2 W input power, compared to 71% of the untreated control spores. Additionally, spores exposed to microwaves appear visibly disrupted when imaged using scanning electron microscopy (SEM). Overall, this study shows the advantages of using a CPW for disrupting spores for biomarker release and detection.

Real-time forecasting of travel demand during wildfire evacuations is crucial for emergency managers and transportation planners to make timely and better-informed decisions. However, few studies focus on accurate travel demand forecasting in large-scale emergency evacuations. Therefore, this study develops and tests a new methodological framework for modeling trip generation in wildfire evacuations by using (a) large-scale GPS data generated by mobile devices and (b) state-of-the-art AI technologies. The proposed methodology aims at forecasting evacuation trips and other types of trips. Based on the travel demand inferred from the GPS data, we develop a new deep learning model, i.e., Situational-Aware Multi-Graph Convolutional Recurrent Network (SA-MGCRN), along with a model updating scheme to achieve real-time forecasting of travel demand during wildfire evacuations. The proposed methodological framework is tested in this study for a real-world case study: the 2019 Kincade Fire in Sonoma County, CA. The results show that SA-MGCRN significantly outperforms all the selected state-of-the-art benchmarks in terms of prediction performance. Our finding suggests that the most important model components of SA-MGCRN are evacuation order/warning information, proximity to fire, and population change, which are consistent with behavioral theories and empirical findings.

The crack initiation life of a ductile additively manufactured nickel-based superalloy is studied and modeled for low-cycle fatigue and thermomechanical fatigue conditions up to 600 degrees C. Isothermal experiments were performed on smooth specimens at temperatures up to 600 degrees C with different applied strain ranges. Additionally, thermomechanical fatigue experiments at 100-450 degrees C and 100-600 degrees C were performed on smooth specimens under in-phase and out-of-phase conditions. A life prediction model accounting for the anisotropy was developed, where the temperature cycle is accounted with a Delta T$$ \Delta T $$-functionality, generating good agreements with the experiments. The model was also validated on notched specimens undergoing thermomechanical fatigue conditions at 100-500 degrees C using simplified notch correction methods., Funding Agencies|Linkoping University; Siemens Energy AB

In an age where e-commerce can provide a huge variety of different products online, customers still face the issue of the last mile challenge. The purpose of this paper is to find out if the last-mile delivery of products is efficient and explore the possible improvement to this service. This research shows that home delivery is the preferred method of last-mile delivery. A significant gap was disclosed between the available options for delivery on e-commerce websites and consumer preferences of last-mile delivery. Time of delivery and accuracy are the greatest barriers in the delivery chain. The research also shows that there is a lack of home delivery services provided in the market. The research is limited by the usage of non-probability sampling and equal distribution of respondents of all ages. The research identifies a clear gap between customers’ demands in the last mile and the firms’ offerings. © 2021 Informa UK Limited, trading as Taylor & Francis Group

Barnneurokirurgi är en subspecialitet inom neurokir­urgin. Barnens neurokirurgiska sjukdomar skiljer sig från de vuxnas med andra diagnoser, patofysiologiska mekanismer, tumörtyper och inte minst annan prognos. I denna artikel belyser vi de tre vanligaste barnneurokirurgiska tillstånden: hjärntumörer, hydrocefalus samt neuralrörsdefekter inklusive ryggmärgsbråck. Vi sammanfattar bakgrund, symtombild och initial handläggning samt ger en översikt av neurokirurgisk behandling av sjukdomarna. Prognosen är oftast god, men samtliga tillstånd är allvarliga och både sjukdom och behandling riskerar att ge livslånga konsekvenser för individen och dess anhöriga.

Virtual reality allows creating highly immersive visual and auditory experiences, making users feel physically present in the environment. This makes it an ideal platform to simulate dangerous scenarios, including fire evacuation, and study human behaviour without exposing users to harmful elements. However, human perception of the surroundings is based on the integration of multiple sensory cues (visual, auditory, tactile, or/and olfactory) present in the environment. When some of the sensory stimuli are missing in the virtual experience, it can break the illusion of being there in the environment and could lead to actions that deviate from normal behaviour. In this work, we added an olfactory cue in a well-documented historic hotel fire scenario that was recreated in VR, and examined the effects of the olfactory cue on human behaviour. We conducted a between subject study on 40 naive participants. Our results show that the addition of the olfactory cue could increase behavioural realism. We found that 80% of the studied actions for the VR with olfactory cue condition matched the ones performed by the survivors. In comparison, only 40% of the participants' actions for VR only condition were similar to the survivors., Comment: Accepted at IEEE International Symposium on Mixed and Augmented Reality (ISMAR) 2023, 9 pages

In this study, the mechanical response of an additively manufactured nickel-based combustor alloy, subjected to thermomechanical fatigue (TMF) loadings has been investigated and modelled. TMF tests were performed in both in-phase and out-of-phase conditions with different strain ranges and temperature ranges of 100 degrees C-450 degrees C and 100 degrees C-600 degrees C, respectively. The smooth specimens were manufactured in two different orientations to study the influence of anisotropy, and the specimens were machined to final dimensions with conventional techniques. A constitutive model with focus on describing the mid-life behaviour was developed where the total inelastic strain was divided into one plastic (rate-independent) and one creep (rate-dependent) part, to be able to describe both the rate-dependent effects from TMF conditions as well as rate-independent responses. A cycle jumping procedure was used, which enables to simulate the mid-life response of the material for TMF as well as low-cycle fatigue conditions within three simulated loading cycles., Funding Agencies|Swedish Energy Agency; Siemens Energy AB through Turbines for Future Energy Systems (Turbiner foer framtidens energisystem) [44112-1]

Visualizing medical images from patients as physical 3D models (phantom models) have many roles in the medical field, from education to preclinical preparation and clinical research. However, current phantom models are generally generic, expensive, and time-consuming to fabricate. Thus, there is a need for a cost- and time-efficient pipeline from medical imaging to patient-specific phantom models. In this work, we present a method for creating complex 3D sacrificial molds using an off-the-shelf water-soluble resin and a low-cost desktop 3D printer. This enables us to recreate parts of the cerebral arterial tree as a full-scale phantom model (10×6×410×6×4 cm) in transparent silicone rubber (polydimethylsiloxane, PDMS) from computed tomography angiography images (CTA). We analyzed the model with magnetic resonance imaging (MRI) and compared it with the patient data. The results show good agreement and smooth surfaces for the arteries. We also evaluate our method by looking at its capability to reproduce 1 mm channels and sharp corners. We found that round shapes are well reproduced, whereas sharp features show some divergence. Our method can fabricate a patient-specific phantom model with less than 2 h of total labor time and at a low fabrication cost.

Visualizing medical images from patients as physical 3D models (phantom models) have many roles in the medical field, from education to preclinical preparation and clinical research. However, current phantom models are generally generic, expensive, and time-consuming to fabricate. Thus, there is a need for a cost- and time-efficient pipeline from medical imaging to patient-specific phantom models. In this work, we present a method for creating complex 3D sacrificial molds using an off-the-shelf water-soluble resin and a low-cost desktop 3D printer. This enables us to recreate parts of the cerebral arterial tree as a full-scale phantom model (10×6×410×6×4 cm) in transparent silicone rubber (polydimethylsiloxane, PDMS) from computed tomography angiography images (CTA). We analyzed the model with magnetic resonance imaging (MRI) and compared it with the patient data. The results show good agreement and smooth surfaces for the arteries. We also evaluate our method by looking at its capability to reproduce 1 mm channels and sharp corners. We found that round shapes are well reproduced, whereas sharp features show some divergence. Our method can fabricate a patient-specific phantom model with less than 2 h of total labor time and at a low fabrication cost.

In this study, the mechanical response of an additively manufactured nickel-based combustor alloy, subjected to thermomechanical fatigue (TMF) loadings has been investigated and modelled. TMF tests were performed in both in-phase and out-of-phase conditions with different strain ranges and temperature ranges of 100 degrees C-450 degrees C and 100 degrees C-600 degrees C, respectively. The smooth specimens were manufactured in two different orientations to study the influence of anisotropy, and the specimens were machined to final dimensions with conventional techniques. A constitutive model with focus on describing the mid-life behaviour was developed where the total inelastic strain was divided into one plastic (rate-independent) and one creep (rate-dependent) part, to be able to describe both the rate-dependent effects from TMF conditions as well as rate-independent responses. A cycle jumping procedure was used, which enables to simulate the mid-life response of the material for TMF as well as low-cycle fatigue conditions within three simulated loading cycles., Funding Agencies|Swedish Energy Agency; Siemens Energy AB through Turbines for Future Energy Systems (Turbiner foer framtidens energisystem) [44112-1]

Enterprise social networks are closed social networks with the purpose of increasingcommunication within the company. However, a current estimate is that up to 80% of theimplementations of an enterprise social network fails due to low usage. Previous studies havelisted several important influencing factors that will impact the usage of this platform. Sinceidentifying these factors however, the field has mainly moved away from studying this andbecause of that there are few studies confirming the factors that have been discovered and fewindependent research teams that have worked on this topic.This work aims to observe actual historical usage of an enterprise social network to observe ifthe previously identified influencing factors provide a good indication about its usage. Thework will be able to provide an indication to the scientific community that there are stillunknown parameters relating to the usage of enterprise social networks.The purpose of the thesis is hence to test the existing theories and the research question of thework is: How well can known influencing factors predict the usage of an enterprise socialnetwork in a global manufacturing company?During the work, seven factors were studied. Of these seven, one of the factors could beconfirmed. For three of the factors there were insufficient data to draw any reliableconclusions and for three of the factors no or only a weak correlation between the usage of theenterprise social network and the influencing factor was observed. As such, the knowninfluencing factors do not appear to be able to predict the usage of an enterprise socialnetwork in this setting.Hence, this work indicates that further studies are needed within this area and that theinfluencing factors as listed today are inadequate in predicting the usage of an enterprisesocial network. The answer to the research question is thus that the quality of any predicationmade of these influencing factors appears to be weak at best and the scientific cont

Massa- och pappersindustrin är stora energiförbrukare och står för 6 % av världens totala industriella energiförbrukning. I Sverige ligger andelen än högre, 50 % av den svenska industrins energiförbrukningen används av massa- och pappersindustrin. Anledningen till denna stora energiförbrukning är att det krävs stora mängder värme vid framställning av massan samt vid torkningsprocesser för papperstillverkning. Värmebehovet möts genom att producera ånga. Den höga energiförbrukningen gör att arbetet gällande energieffektiviseringar ständigt är pågående, både med hjälp av ny teknik och optimering av befintlig teknik.BillerudKorsnäs Karlsborg är ett massa- och pappersbruk med idag 400 anställda och en produktionskapacitet på 350 000 ton/år. Bruket har utmaningar med trycksvängningar som uppstår i ångnätet, vilket till stor del orsakas av Karlsborgs typ av kokprocess som består av åtta batchkokare. Batch innebär att ångförbrukningen i kokeriet inte är konstant utan är beroende av kokcykeln för samtliga kokare. Syftet med arbetet var att få en bättre förståelse för de svängningar som uppstår i ångnätet genom att kartlägga uttagningsmönster för de olika ångförbrukarna, samt identifiera möjligheter till minimering av svängningar i ångnätet. Ångnätet är den del av ångsystemet som kopplar samman ångproduktion med ångförbrukarna. Olika trycknivåer hålls i nätet beroende på vilka behov ångförbrukarna har, högtrycksånga från pannorna tryckreduceras via en mottrycksturbin eller via direktreducörer.Kartläggningen visar på tydliga samband mellan de kraftiga flödesvariationerna av ånga till kokeriet och trycksvängningar i ångnätet. Det totala ångbehovet i kokeriet är större under kallare perioder, dock sker stora flödesvariationer under alla förhållanden vilket medför att en viss typ av svängningar finns under hela året. Dessa svängningar har en amplitud på cirka två bar och uppstår vid ``normal drift´´ av fabriken, vilket innebär att de inte går att koppla till någon driftstörning i

It is desirable to be able to distinguish between Bluetooth Low Energy (BLE) devices purely based on individual hardware imperfections because such imperfections are often prohibitly expensive to imitate. Other works have been done on this topic in the past, which utilized signal transients requiring a multi-GHz sampling rate recorded with costly special equipment to be satisfactorily captured. This work explores an alternative approach which avoids these requirements, with new features tailor-made for the Bluetooth Low Energy protocol that allow us to achieve a micro-recall of 99% with the full test set of 58 motes. The lessons learned during this work bring us one step closer to pervasive deployment where regular BLE-enabled hardware could be configured to use radiometric fingerprinting in order to distinguish between devices in receiver range.

Induced pluripotent stem cells (iPSCs) from patients are an attractive disease model to study tissues with poor accessibility such as the brain. Using this approach, we and others have shown that trisomy 21 results in genome-wide transcriptional dysregulations. The effects of loss of genes on chromosome 21 is much less characterized. Here, we use patient-derived neural cells from an individual with neurodevelopmental delay and a ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, containing 60 protein-coding genes. To investigate the molecular perturbations of the partial monosomy on neural cells, we established patient-derived iPSCs from fibroblasts retaining the ring chromosome 21, and we then induced iPSCs into neuroepithelial stem cells. RNA-Seq analysis of NESCs with the ring chromosome revealed downregulation of 18 genes within the deleted region together with global transcriptomic dysregulations when compared to euploid NESCs. Since the deletions on chromosome 21 represent a genetic "contrary" to trisomy of the corresponding region, we further compared the dysregulated transcriptomic profile in with that of two NESC lines with trisomy 21. The analysis revealed opposed expression changes for 23 genes on chromosome 21 as well as 149 non-chromosome 21 genes. Taken together, our results bring insights into the effects on the global and chromosome 21 specific gene expression from a partial monosomy of chromosome 21qter during early neuronal differentiation.

Induced pluripotent stem cells (iPSCs) from patients are an attractive disease model to study tissues with poor accessibility such as the brain. Using this approach, we and others have shown that trisomy 21 results in genome-wide transcriptional dysregulations. The effects of loss of genes on chromosome 21 is much less characterized. Here, we use patient-derived neural cells from an individual with neurodevelopmental delay and a ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, containing 60 protein-coding genes. To investigate the molecular perturbations of the partial monosomy on neural cells, we established patient-derived iPSCs from fibroblasts retaining the ring chromosome 21, and we then induced iPSCs into neuroepithelial stem cells. RNA-Seq analysis of NESCs with the ring chromosome revealed downregulation of 18 genes within the deleted region together with global transcriptomic dysregulations when compared to euploid NESCs. Since the deletions on chromosome 21 represent a genetic "contrary" to trisomy of the corresponding region, we further compared the dysregulated transcriptomic profile in with that of two NESC lines with trisomy 21. The analysis revealed opposed expression changes for 23 genes on chromosome 21 as well as 149 non-chromosome 21 genes. Taken together, our results bring insights into the effects on the global and chromosome 21 specific gene expression from a partial monosomy of chromosome 21qter during early neuronal differentiation.

Induced pluripotent stem cells (iPSCs) from patients are an attractive disease model to study tissues with poor accessibility such as the brain. Using this approach, we and others have shown that trisomy 21 results in genome-wide transcriptional dysregulations. The effects of loss of genes on chromosome 21 is much less characterized. Here, we use patient-derived neural cells from an individual with neurodevelopmental delay and a ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, containing 60 protein-coding genes. To investigate the molecular perturbations of the partial monosomy on neural cells, we established patient-derived iPSCs from fibroblasts retaining the ring chromosome 21, and we then induced iPSCs into neuroepithelial stem cells. RNA-Seq analysis of NESCs with the ring chromosome revealed downregulation of 18 genes within the deleted region together with global transcriptomic dysregulations when compared to euploid NESCs. Since the deletions on chromosome 21 represent a genetic "contrary" to trisomy of the corresponding region, we further compared the dysregulated transcriptomic profile in with that of two NESC lines with trisomy 21. The analysis revealed opposed expression changes for 23 genes on chromosome 21 as well as 149 non-chromosome 21 genes. Taken together, our results bring insights into the effects on the global and chromosome 21 specific gene expression from a partial monosomy of chromosome 21qter during early neuronal differentiation.

Massa- och pappersindustrin är stora energiförbrukare och står för 6 % av världens totala industriella energiförbrukning. I Sverige ligger andelen än högre, 50 % av den svenska industrins energiförbrukningen används av massa- och pappersindustrin. Anledningen till denna stora energiförbrukning är att det krävs stora mängder värme vid framställning av massan samt vid torkningsprocesser för papperstillverkning. Värmebehovet möts genom att producera ånga. Den höga energiförbrukningen gör att arbetet gällande energieffektiviseringar ständigt är pågående, både med hjälp av ny teknik och optimering av befintlig teknik.BillerudKorsnäs Karlsborg är ett massa- och pappersbruk med idag 400 anställda och en produktionskapacitet på 350 000 ton/år. Bruket har utmaningar med trycksvängningar som uppstår i ångnätet, vilket till stor del orsakas av Karlsborgs typ av kokprocess som består av åtta batchkokare. Batch innebär att ångförbrukningen i kokeriet inte är konstant utan är beroende av kokcykeln för samtliga kokare. Syftet med arbetet var att få en bättre förståelse för de svängningar som uppstår i ångnätet genom att kartlägga uttagningsmönster för de olika ångförbrukarna, samt identifiera möjligheter till minimering av svängningar i ångnätet. Ångnätet är den del av ångsystemet som kopplar samman ångproduktion med ångförbrukarna. Olika trycknivåer hålls i nätet beroende på vilka behov ångförbrukarna har, högtrycksånga från pannorna tryckreduceras via en mottrycksturbin eller via direktreducörer.Kartläggningen visar på tydliga samband mellan de kraftiga flödesvariationerna av ånga till kokeriet och trycksvängningar i ångnätet. Det totala ångbehovet i kokeriet är större under kallare perioder, dock sker stora flödesvariationer under alla förhållanden vilket medför att en viss typ av svängningar finns under hela året. Dessa svängningar har en amplitud på cirka två bar och uppstår vid ``normal drift´´ av fabriken, vilket innebär att de inte går att koppla till någon driftstörning i

The amount of data available from genomic medicine has revolutionized the approach to identify the determinants underlying many rare diseases. The task of confirming a genotype–phenotype causality for a patient affected with a rare genetic disease is often challenging. In this context, the establishment of the Matchmaker Exchange (MME) network has assumed a pivotal role in bridging heterogeneous patient information stored on different medical and research servers. MME has made it possible to solve rare disease cases by “matching” the genotypic and phenotypic characteristics of a patient of interest with patient data available at other clinical facilities participating in the network. Here, we present PatientMatcher (https://github.com/Clinical-Genomics/patientMatcher), an open-source Python and MongoDB-based software solution developed by Clinical Genomics facility at the Science for Life Laboratory in Stockholm. PatientMatcher is designed as a standalone MME server, but can easily communicate via REST API with external applications managing genetic analyses and patient data. The MME node is being implemented in clinical routine in collaboration with the Genomic Medicine Center Karolinska at the Karolinska University Hospital. PatientMatcher is written to implement the MME API and provides several customizable settings, including a custom-fit similarity score algorithm and adjustable matching results notifications., QC 20221125

Purpose: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. Methods: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). Results: The diagnostic yield was 35% (GS -first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. Conclusion: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time-and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The crack initiation life of a ductile additively manufactured nickel-based superalloy is studied and modeled for low-cycle fatigue and thermomechanical fatigue conditions up to 600 degrees C. Isothermal experiments were performed on smooth specimens at temperatures up to 600 degrees C with different applied strain ranges. Additionally, thermomechanical fatigue experiments at 100-450 degrees C and 100-600 degrees C were performed on smooth specimens under in-phase and out-of-phase conditions. A life prediction model accounting for the anisotropy was developed, where the temperature cycle is accounted with a Delta T$$ \Delta T $$-functionality, generating good agreements with the experiments. The model was also validated on notched specimens undergoing thermomechanical fatigue conditions at 100-500 degrees C using simplified notch correction methods., Funding Agencies|Linkoping University; Siemens Energy AB