The design of mixture experiments in the presence of covariates

Over the past three decades, the design and analysis of mixture experiments has been an active area of research, often driven by industrial applications. However, the construction of block designs for mixture experiments and trend-free orderings of the mixtures are problems that have been largely ignored until recently. These two problems form the principal subjects of this dissertation after presenting some key concepts in the design and analysis of mixture experiments;Block designs are constructed using combinatorial structures called symbolic and integral mixture mates of strength t. Certain pairs of Latin squares are a special case of symbolic mixture mates. One flexible method of constructing integral mixture mates of strength t uses the theory of trade-off for m-ary designs. In addition to mixture mates, block designs may be constructed via other methods. When the region of interest is a constrained subregion of the simplex, confounding in fractional factorial designs or asymmetrical orthogonal arrays may be used to produce orthogonal block designs. Methods for constructing non-orthogonal block designs utilizing factorial designs or orthogonal arrays in another manner are given. Finally, we formulate algorithms that allocate a given set of mixtures to blocks in such a way that an objective function is maximized;Trend-free mixture orderings allow uncorrelated estimators of mixture model parameters and deterministic trend parameters to be obtained. Deterministic trends may be induced by time effects or other lurking variables. Given a trend-free ordering of a factorial design in p - 1 factors, we illustrate how a trend-free order of mixtures can be found by transforming the p - 1 factors into p mixture variables, using one of the many transformations available, see Cornell (1991) for example. If the experimental region is a constrained subregion of the simplex, trend-free run orders are constructed using trend-free factorial designs in p - 1 factors as a template and incorporating a p-th factor by adjusting the levels of the other p - 1 components for each row. Nearly trend-free mixture orders are also found by ordering the mixtures according to an objective function

Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial

Objective: Reports of cardiac arrhythmias and cardiac pathology at postmortem examination of patients with epilepsy suggest a possible cardiac component of risk for sudden unexpected death in epilepsy (SUDEP). T-wave alternans (TWA) is an established marker of cardiac electrical instability and risk for sudden death in patients with cardiovascular disease. We determined the TWA level before vagus nerve stimulation (VNS) system implantation and subsequently the effect of VNS on TWA in patients with drug-resistant epilepsy. Methods: Patients (n = 28) from the Seizure Detection and Automatic Magnet Mode Performance Study (E-36), a clinical trial of the AspireSR (R) VNS Therapy System (R) (NCT01325623), were monitored with ambulatory electrocardiograms (ECGs) similar to 2 weeks before de novo VNS system implantation and following 2- to 4-week VNS titration during a protocol-specified 3- to 5-day epilepsy monitoring unit stay with concurrent EEG/ECG recordings. The TWA level was assessed interictally by the Modified Moving Average (MMA) method. Results: At preimplantation baseline, TWA was elevated above the 47-mu V abnormality cutpoint in 23 (82%) patients with drug-resistant epilepsy. In 16 (70%) patients, TWA level was reduced during VNS treatment to <47 mu V, thereby converting positive TWA test results to negative. Peak TWA level in all 28 patients improved (group mean, 43%, from 72 +/- 4.3 to 41 +/- 2.3 mu V; p < 0.0001). Vagus nerve stimulation was not associated with reduced heart rate (77 +/- 1.4 to 75 +/- 1.4 beats/min; p = 0.18). Heart rate variability was unchanged. Significance: These findings suggest significant interictal cardiac electrical instability in this population of patients with drug-resistant epilepsy and suggest that VNS may be a novel approach to reducing risk

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The design of mixture experiments in the presence of covariates

Over the past three decades, the design and analysis of mixture experiments has been an active area of research, often driven by industrial applications. However, the construction of block designs for mixture experiments and trend-free orderings of the mixtures are problems that have been largely ignored until recently. These two problems form the principal subjects of this dissertation after presenting some key concepts in the design and analysis of mixture experiments;Block designs are constructed using combinatorial structures called symbolic and integral mixture mates of strength t. Certain pairs of Latin squares are a special case of symbolic mixture mates. One flexible method of constructing integral mixture mates of strength t uses the theory of trade-off for m-ary designs. In addition to mixture mates, block designs may be constructed via other methods. When the region of interest is a constrained subregion of the simplex, confounding in fractional factorial designs or asymmetrical orthogonal arrays may be used to produce orthogonal block designs. Methods for constructing non-orthogonal block designs utilizing factorial designs or orthogonal arrays in another manner are given. Finally, we formulate algorithms that allocate a given set of mixtures to blocks in such a way that an objective function is maximized;Trend-free mixture orderings allow uncorrelated estimators of mixture model parameters and deterministic trend parameters to be obtained. Deterministic trends may be induced by time effects or other lurking variables. Given a trend-free ordering of a factorial design in p - 1 factors, we illustrate how a trend-free order of mixtures can be found by transforming the p - 1 factors into p mixture variables, using one of the many transformations available, see Cornell (1991) for example. If the experimental region is a constrained subregion of the simplex, trend-free run orders are constructed using trend-free factorial designs in p - 1 factors as a template and incorporating a p-th factor by adjusting the levels of the other p - 1 components for each row. Nearly trend-free mixture orders are also found by ordering the mixtures according to an objective function.</p

An interface for easier use : A qualitative study of a mobile tracking application's interface and the elements that need to be developed

I takt med att ägandet av smartphones ökat samt att tekniken utvecklats så har det blivit allt mer förekommande med spårning av GPS-enheter. Användningen innefattar flera områden som exempelvis berör spårning av djur, fordon och människor. Tidigare forskning har främst fokuserat på de tekniska aspekterna med GPS och i flera av dessa källor nämns kortfattat att de mobila gränssnitten har fått kritik från studiernas deltagare och ansetts vara svåra att använda. Syftet med studien var att öka förståelsen för hur spårningsapplikationers gränssnitt kan utformas för att bli mer användarvänliga. Att genom ett användarcentrerat arbete kartlägga vilka element i nuvarande gränssnitt som kan förbättras för att underlätta användares kognitiva belastning vid användning. Studien hade en kvalitativ ansats och data samlades in genom intervjuer med erfarna användare av spårningsapplikationen Go. Det var Go-applikationens gränssnitt som undersöktes i studien. För att kunna besvara forskningsfrågan användes Foggs beteendemodell, UX och informationsarkitektur för att skapa intervjufrågor samt för att analysera och diskutera resultaten. Studiens resultat är inte generaliserbart eftersom urvalet var för litet och ej slumpmässigt framtaget. Därmed gav studiens resultat endast en första inblick av vilka element i gränssnittet som var i behov av att utvecklas för att förbättra spårningsapplikationens gränssnitt. Studien visade att informanterna var tillräckligt motiverade och att det framför allt var förmågan som behövde ökas och att det i vissa fall behövdes triggers. De element i gränssnittet som behövde utvecklas var historiken, larm, platsmarkörer, inställningar, informationssidan och livespårning. Tillvägagångssätten för att utveckla dessa element berör oftast ett grafiskt tydliggörande eller förklarande.As the usage of smartphones has increased and the technology also has developed, it has become increasingly common with tracking of GPS devices. The usage includes multiple areas such as tracking of animals, vehicles, and people. Early research has mainly focused on the technical aspects with GPS and in a few of these sources it is briefly mentioned that mobile interfaces have been criticized by the study participants and are considered difficult to use. The purpose of this research was to increase the understanding on how tracking applications interface can be designed to be more user friendly. Through a User-Centered work to map how elements and functions in a current interface can improve to ease the users cognitive load during usage. The research had a qualitative approach and the data that was collected through interviews with experienced users of the tracking application Go. It was the interface of Go that was being studied during the research. To answer our research question, Fogg's behavior model was used together with UX and information architecture to create questions for the interviews and to analyze the results. Results of this research are not generalizable since the sample was small and not randomly selected. Hence, the results of the research provided a first insight of which elements in the interface that need development to improve the interface of tracking applications. The research showed that the informants are motivated enough and that it was primarily their ability that needed to be increased and, in some cases, triggers were needed. The elements on the interface that needed to be developed were, the history, the alarm, placemarks, settings, information page and live tracking. The approach to develop the elements often touches on a graphical clarity or explanatory note

An interface for easier use : A qualitative study of a mobile tracking application's interface and the elements that need to be developed

I takt med att ägandet av smartphones ökat samt att tekniken utvecklats så har det blivit allt mer förekommande med spårning av GPS-enheter. Användningen innefattar flera områden som exempelvis berör spårning av djur, fordon och människor. Tidigare forskning har främst fokuserat på de tekniska aspekterna med GPS och i flera av dessa källor nämns kortfattat att de mobila gränssnitten har fått kritik från studiernas deltagare och ansetts vara svåra att använda. Syftet med studien var att öka förståelsen för hur spårningsapplikationers gränssnitt kan utformas för att bli mer användarvänliga. Att genom ett användarcentrerat arbete kartlägga vilka element i nuvarande gränssnitt som kan förbättras för att underlätta användares kognitiva belastning vid användning. Studien hade en kvalitativ ansats och data samlades in genom intervjuer med erfarna användare av spårningsapplikationen Go. Det var Go-applikationens gränssnitt som undersöktes i studien. För att kunna besvara forskningsfrågan användes Foggs beteendemodell, UX och informationsarkitektur för att skapa intervjufrågor samt för att analysera och diskutera resultaten. Studiens resultat är inte generaliserbart eftersom urvalet var för litet och ej slumpmässigt framtaget. Därmed gav studiens resultat endast en första inblick av vilka element i gränssnittet som var i behov av att utvecklas för att förbättra spårningsapplikationens gränssnitt. Studien visade att informanterna var tillräckligt motiverade och att det framför allt var förmågan som behövde ökas och att det i vissa fall behövdes triggers. De element i gränssnittet som behövde utvecklas var historiken, larm, platsmarkörer, inställningar, informationssidan och livespårning. Tillvägagångssätten för att utveckla dessa element berör oftast ett grafiskt tydliggörande eller förklarande.As the usage of smartphones has increased and the technology also has developed, it has become increasingly common with tracking of GPS devices. The usage includes multiple areas such as tracking of animals, vehicles, and people. Early research has mainly focused on the technical aspects with GPS and in a few of these sources it is briefly mentioned that mobile interfaces have been criticized by the study participants and are considered difficult to use. The purpose of this research was to increase the understanding on how tracking applications interface can be designed to be more user friendly. Through a User-Centered work to map how elements and functions in a current interface can improve to ease the users cognitive load during usage. The research had a qualitative approach and the data that was collected through interviews with experienced users of the tracking application Go. It was the interface of Go that was being studied during the research. To answer our research question, Fogg's behavior model was used together with UX and information architecture to create questions for the interviews and to analyze the results. Results of this research are not generalizable since the sample was small and not randomly selected. Hence, the results of the research provided a first insight of which elements in the interface that need development to improve the interface of tracking applications. The research showed that the informants are motivated enough and that it was primarily their ability that needed to be increased and, in some cases, triggers were needed. The elements on the interface that needed to be developed were, the history, the alarm, placemarks, settings, information page and live tracking. The approach to develop the elements often touches on a graphical clarity or explanatory note

Fine-scale assessment of home ranges and activity patterns for resident black vultures (\u3ci\u3eCoragyps atratus\u3c/i\u3e) and turkey vultures (\u3ci\u3eCathartes aura\u3c/i\u3e)

Knowledge of black vulture (Coragyps atratus) and turkey vulture (Cathartes aura) spatial ecology is surprisingly limited despite their vital ecological roles. Fine-scale assessments of space use patterns and resource selection are particularly lacking, although development of tracking technologies has allowed data collection at finer temporal and spatial resolution. Objectives of this study were to conduct the first assessment of monthly home range and core area sizes of resident black and turkey vultures with consideration to sex, as well as elucidate differences in monthly, seasonal, and annual activity patterns based on fine-scale movement data analyses. We collected 2.8-million locations for 9 black and 9 turkey vultures from June 2013 - August 2015 using solar-powered GSM/GPS transmitters. We quantified home ranges and core areas using the dynamic Brownian bridge movement model and evaluated differences as a function of species, sex, and month. Mean monthly home ranges for turkey vultures were ~50% larger than those of black vultures, although mean core area sizes did not differ between species. Turkey vulture home ranges varied little across months, with exception to a notable reduction in space-use in May, which corresponds with timing of chick-rearing activities. Black vulture home ranges and core areas as well as turkey vulture core areas were larger in breeding season months (January - April). Comparison of space use between male and female vultures was only possible for black vultures, and space use was only slightly larger for females during breeding months (February - May). Analysis of activity patterns revealed turkey vultures spend more time in flight and switch motion states (between flight and stationary) more frequently than black vultures across temporal scales. This study reveals substantive variability in space use and activity rates between sympatric black and turkey vultures, providing insights into potential behavioral mechanisms contributing to niche differentiation between these species

The Flux OSKit: A Substrate for Kernel and Language Research

Implementing new operating systems is tedious, costly, and often impractical except for large projects. The Flux OSKit addresses this problem in a novel way by providing clean, well-documented OS components designed to be reused in a wide variety of other environments, rather than defining a new OS structure. The OSKit uses unconventional techniques to maximize its usefulness, such as intentionally exposing implementation details and platform-specific facilities. Further, the OSKit demonstrates a technique that allows unmodified code from existing mature operating systems to be incorporated quickly and updated regularly, by wrapping it with a small amount of carefully designed &quot;glue&quot; code to isolate its dependencies and export well-defined interfaces. The OSKit uses this technique to incorporate over 230,000 lines of stable code including device drivers, file systems, and network protocols. Our experience demonstrates that this approach to component software structure and reuse has a surprisingly large impact in the OS implementation domain. Four real-world examples show how the OSKit is catalyzing research and development in operating systems and programming languages