Mathematische Optimierung von Wasserversorgungsnetzwerken für informelle Siedlungen in Mega Cities

Der Zugang zu sicherem und sauberem Trinkwasser ist ein Menschenrecht und fehlt dennoch hunderten Millionen von Menschen auf der Welt. Viele dieser Menschen leben in informellen Siedlungen, eine meist unterversorgte aber in Städten häufig vorkommende Siedlungsform, insbesondere im globalen Süden. Im Angesicht dieser Missstände stellt diese Arbeit ein ganzheitliches Konzept vor, um die Wasserversorgung von Slums optimal zu gestalten. Dabei werden die folgenden drei Forschungsfragen gestellt und im Rahmen der Arbeit beantwortet: 1. Wie kann die Wasserversorgung von Slums durch ein ganzheitliches Konzept verbessert werden? 2. Wie kann die Optimierung der Versorgungsnetzwerkplanung als mathematisches Optimierungsproblem modelliert werden? 3. Wie kann das Optimierungsproblem, in einer angemessenen Zeit, gelöst werden? Das entwickelte Konzept für die Optimierung der Wasserversorgung von Slums besteht aus fünf Schritten: (I) Es nutzt Fernerkundungsdaten als Informationsgrundlage zur geografischen Lage und Größe der zu versorgenden Slums in den betrachteten Städten. (II) Diese Satellitendaten werden analysiert, um die Slumflächen zu klassifizieren. (III) In einem Kostenmodell werden die Versorgungsmöglichkeiten genauer detailliert und eine Berechnungsgrundlage für die spätere Optimierung geschaffen. Das Kostenmodell wird in ein mathematisches Optimierungsproblem überführt. (IV) Die Lösung des Optimierungsproblems liefert das beste, in diesem Fall kostengünstigste oder emissionsärmste, Wasserversorgungsnetzwerk für die klassifizierten Slums. Zur Lösung werden MIP-Solver verwendet sowie weitere problemspezifische Lösungsverfahren entwickelt und diese verglichen. (V) Im letzten Konzeptschritt werden die Ergebnisse aus der Optimierung in eine anschauliche Darstellung übersetzt

Optimal Parameters for XMSS^MT

We introduce Multi Tree XMSS (XMSS^MT), a hash-based signature scheme that can be used to sign a virtually unlimited number of messages. It is provably forward and hence EU-CMA secure in the standard model and improves key and signature generation times compared to previous schemes. XMSS^MT has --- like all practical hash-based signature schemes --- a lot of parameters that control different trade-offs between security, runtimes and sizes. Using linear optimization, we show how to select provably optimal parameter sets for different use cases

Applicability of exercise and education programmes for knee osteoarthritis management to Switzerland

Objectives: The aim of this study was to assess the applicability of six OARSI (Osteoarthritis Research Society International) approved exercise and education programmes for the conservative management of knee osteoarthritis to the Swiss health care system. Methods: The RE-AIM framework was used in this cross-sectional survey study to analyse the characteristics of the six exercise and education programmes. A survey was developed based on the RE-AIM dimensions, “Reach, Effectiveness, Adoption, Implementation, and Maintenance,” for rating the applicability of the programmes (on a scale of 1 = “least applicable” to 10 = “most applicable”). Programme scores of ≥7 indicated applicability to the Swiss health care system. Nine selected physiotherapy experts for knee OA management in Switzerland were invited for the rating. Results: The six programmes were rated by six of the nine invited research experts with mean scores of between 5.9 and 9.45. Four programmes scored 7 or more. These four programmes all included supervised exercise sessions and education with the goal that the participants understand the diagnosis and the management of OA. The two lower rated programmes focused on exercise counselling or weight reduction. Conclusion: The programme with the highest scores consists of exercise and education and scored higher than 7 in all RE-AIM dimensions. Therefore, this programme is most applicable to the Swiss health care system as only a few adaptations would be needed for its successful implementation

Evaluation of the strategy for implementing the GLA:D programme in Switzerland : protocol for an implementation-effectiveness hybrid type 3 design study with a mixed-method approach

Introduction: International guidelines recommend the use of exercise, education and weight reduction, when appropriate, as first-line treatment for the conservative management of knee osteoarthritis (OA). These guidelines have not been applied systematically in Switzerland, resulting in an evidence-performance gap. After an analysis of available programmes, the Good Life with osteoArthritis Denmark (GLA:D) programme was determined as the most applicable exercise and education programme for its implementation in Switzerland. The implementation of GLA:D Switzerland OA was initiated to encourage the wider implementation of the clinical guideline recommendations and to improve conservative management of knee OA. The aim of this study protocol is to describe the evaluation of the implementation strategy and its impact on implementation, service and clinical outcomes; as well as to identify contributing barriers and facilitators. Methods and analysis: The Implementation Research Logic Model will be used to evaluate the strategy and analyse its impact on the implementation outcomes by means of a mixed methods approach. This protocol outlines the proposed measures, data sources and strategies for the evaluation. Predefined implementation outcomes will help to identify the implementation impact and analyse barriers and facilitators systematically. The study population will be the healthcare professionals who are involved in the conservative management of knee OA in Switzerland, that is, physiotherapists and medical doctors, and their patients. Ethics and dissemination: The use of the registry data containing data of patients participating in the GLA:D Switzerland OA programme does not fall within the scope of the Swiss Human Research Act (BASEC-Nr. Req-2019-00274). However, all participants involved in the evaluation will be asked to give informed written consent and all measures are taken to protect data and privacy of participants. Research findings will be submitted to journals relevant for the topic

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario

Molecular targets of alcohol action: translational research for pharmacotherapy development and screening.

Alcohol abuse and dependence are multifaceted disorders with neurobiological, psychological, and environmental components. Research on other complex neuropsychiatric diseases suggests that genetically influenced intermediate characteristics affect the risk for heavy alcohol consumption and its consequences. Diverse therapeutic interventions can be developed through identification of reliable biomarkers for this disorder and new pharmacological targets for its treatment. Advances in the fields of genomics and proteomics offer a number of possible targets for the development of new therapeutic approaches. This brain-focused review highlights studies identifying neurobiological systems associated with these targets and possible pharmacotherapies, summarizing evidence from clinically relevant animal and human studies, as well as sketching improvements and challenges facing the fields of proteomics and genomics. Concluding thoughts on using results from these profiling technologies for medication development are also presented

A Holistic Concept to Design Optimal Water Supply Infrastructures for Informal Settlements Using Remote Sensing Data

Ensuring access to water and sanitation for all is Goal No. 6 of the 17 UN Sustainability Development Goals to transform our world. As one step towards this goal, we present an approach that leverages remote sensing data to plan optimal water supply networks for informal urban settlements. The concept focuses on slums within large urban areas, which are often characterized by a lack of an appropriate water supply. We apply methods of mathematical optimization aiming to find a network describing the optimal supply infrastructure. Hereby, we choose between different decentral and central approaches combining supply by motorized vehicles with supply by pipe systems. For the purposes of illustration, we apply the approach to two small slum clusters in Dhaka and Dar es Salaam. We show our optimization results, which represent the lowest cost water supply systems possible. Additionally, we compare the optimal solutions of the two clusters (also for varying input parameters, such as population densities and slum size development over time) and describe how the result of the optimization depends on the entered remote sensing data

A Holistic Concept to Design Optimal Water Supply Infrastructures for Informal Settlements Using Remote Sensing Data

Ensuring access to water and sanitation for all is Goal No. 6 of the 17 UN Sustainability Development Goals to transform our world. As one step towards this goal, we present an approach that leverages remote sensing data to plan optimal water supply networks for informal urban settlements. The concept focuses on slums within large urban areas, which are often characterized by a lack of an appropriate water supply. We apply methods of mathematical optimization aiming to find a network describing the optimal supply infrastructure. Hereby, we choose between different decentral and central approaches combining supply by motorized vehicles with supply by pipe systems. For the purposes of illustration, we apply the approach to two small slum clusters in Dhaka and Dar es Salaam. We show our optimization results, which represent the lowest cost water supply systems possible. Additionally, we compare the optimal solutions of the two clusters (also for varying input parameters, such as population densities and slum size development over time) and describe how the result of the optimization depends on the entered remote sensing data

A Late Miocene – Early Pliocene Paratethyan type ostracod fauna from the Denizli Basin (SW Anatolia) and its palaeogeographic implications

The upper Miocene – lower Pliocene sedimentary succession of the Denizli Basin (SW Anatolia) displays a unique record of undisturbed stratigraphy and provides an excellent opportunity to study long-term palaeoecological changes. This paper documents the ostracod assemblages of two sections of the Neogene Kolankaya Formation, resulting in the following taxonomic, palaeobiogeographic and ecological interpretations. The ostracod assemblages from the two sections consist of a mixture of oligohaline to mesohaline tolerant taxa but expose fundamental differences in their composition. This is reflected by the fact that out of 32 determined species, both sections only have 3 in common. In the stratigraphic older succession, the diverse ostracod fauna resembles taxa known from the Paratethys. Faunal relations to the brackish lake habitats of the Euxinic and Pannonian basins are apparent and the palaeobiogeographic significance of the fauna is discussed. The ostracod association of the younger section indicates a low brackish water habitat with fluctuating salinities, most likely in the oligohaline range. The ostracod assemblage of the Kolankaya Formation only permits a broad age assignment to the late Miocene – early Pliocene

Optimal Parameters for XMSSMT

Part 2: Security EngineeringInternational audienceWe introduce Multi Tree XMSS (XMSSMT), a hash-based signature scheme that can be used to sign a virtually unlimited number of messages. It is provably forward and hence EU-CMA secure in the standard model and improves key and signature generation times compared to previous schemes. XMSSMT has — like all practical hash-based signature schemes — a lot of parameters that control different trade-offs between security, runtimes and sizes. Using linear optimization, we show how to select provably optimal parameter sets for different use cases