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Since the early 2000s, effectuation has gained substantial interest in literature. Whereas Sarasvathy in her seminal 2001 article distinguished effectuation from causal decision-making, still effectuation seems to get confused with ad hoc decision-making or strategy absence. On the basis of a qualitative study with 12 managers from 10 Swiss small-to-medium enterprises (SMEs), this manuscript analyzes their decision-making approaches and distinguishes between causal, effectual, and absence-of-strategy reasoning. Whereas principles for effectuation and causation are well established, this study reveals new categories on which strategy absence can be mapped. The three decision approaches and their interplay are then investigated in four business contexts (founding, takeover, new artifact creation, and existing artifacts). Whereas causal reasoning is found in all four, signs of strategy absence are apparent in three. Effectual logic dominates all four contexts. Further, this manuscript finds that choice of the strategic decision approach does not depend on company size but rather on decision context. Also, firms demonstrate the ability to switch between effectual and causal decision models according to the specific decision context.

Diese Dissertationsschrift beschäftigt sich einerseits mit der Aktivierung von Elementen der Gruppe 15 mittels niedervalenter metallorganischer Vorstufen. Im Fokus steht hierbei die Aktivierung von nanopartikulärem Arsen mit mono- und divalenten Aluminiumverbindungen sowie nicht-klassischen, divalenten Lanthanoidkomplexen zur Darstellung von 4f-Element Polyarseniden. Darüber hinaus wird über die Aktivierung von weißem Phosphor mit verschiedenen Lanthanoid-Vorstufen berichtet, welche zur Darstellung von 4f-Element-Polyphosphiden dient. Ein zweites Themengebiet dieser Dissertation behandelt die Synthese und Charakterisierung von Lanthanoid-Sandwichverbindungen. Dabei wird zum einen die Synthese von Lanthanoid-Koordinationspolymeren auf Basis eines disilylsubstituierten Cyclooctatetraendiid-Liganden beschrieben, zum anderen wird das Cycloheptatrienyl-Trianion als verbrückender Ligand in der Synthese von heteroleptischen Lanthanoid-Multideckerkomplexen eingesetzt. Neben den strukturellen Eigenschaften dieser neuen metallorganischen Verbindungen, wurden diese auf ihr Verhalten als Einzelmolekülmagnet (SMM) sowie auf ihre lumineszente Eigenschaften untersucht.

Nuclear magnetic resonance (NMR) spectroscopy is one of the most promising methods for use in metabolomics studies as it is able to perform non targeted measurement of metabolites in a quantitative and non-destructive way. Sample preparation of liquid samples like urine or blood serum is comparatively easy in NMR metabolomics, because mainly buffer and chemical shift reference substance are added. For solid samples like feces suitable extraction protocols need to be defined as initial step, where the exact protocol depends on sample type and features. Focusing on short chain fatty acids (SCFAs) in mice feces, we describe here a set of extraction protocols developed with the aim to suppress changes in metabolite composition within 24 h after extraction. Feces are obtained from mice fed on either standard rodent diet or high fat diet. The protocols presented in this manuscript are straightforward for application, and successfully minimize residual bacterial and enzymatic activities. Additionally, they are able to minimize the lipid background originating from the high fat diet.

Cyclic nanometre-scale sandwich complexes assembled from individual building blocks were synthesized. Sandwich complexes, in which a metal ion is π-coordinated by two planar aromatic organic rings belong to the foundations of organometallic chemistry. They have been successfully used in a wide variety of applications ranging from catalysis, synthesis and electrochemistry to nanotechnology, materials science and medicine 1 , 2 . Extending the sandwich structural motif leads to linear multidecker compounds, in which aromatic organic rings and metal atoms are arranged in an alternating fashion. However, the extension to a cyclic multidecker scaffold is unprecedented. Here we show the design, synthesis and characterization of an isomorphous series of circular sandwich compounds, for which the term ‘cyclocenes’ is suggested. These cyclocenes consist of 18 repeating units, forming almost ideally circular, closed rings in the solid state, that can be described by the general formula [ cyclo -M II ( μ - η 8 :η 8 -Cot TIPS )] 18 (M = Sr, Sm, Eu; Cot TIPS  = 1,4-( i Pr 3 Si) 2 C 8 H 6 2− ). Quantum chemical calculations lead to the conclusion that a unique interplay between the ionic metal-to-ligand bonds, the bulkiness of the ligand system and the energy gain on ring closure, which is crucially influenced by dispersion interactions, facilitate the formation of these cyclic systems. Up to now, only linear one-dimensional multidecker sandwich compounds have been investigated for possible applications such as nanowires 3 – 10 . This textbook example of cyclic sandwich compounds is expected to open the door for further innovations towards new functional organometallic materials. The design, synthesis and characterization of a series of circular sandwich compounds, cyclocenes, is described, and these cyclic sandwich compounds are expected to lead to further innovations in new functional organometallic materials.

Background There is evidence that in older adults the combination of strength training (ST) and endurance training (ET) (i.e., concurrent training [CT]) has similar effects on measures of muscle strength and cardiorespiratory endurance (CRE) compared with single-mode ST or ET, respectively. Therefore, CT seems to be an effective method to target broad aspects of physical fitness in older adults. Objectives The aim was to examine the effects of CT on measures of physical fitness (i.e., muscle strength, power, balance and CRE) in healthy middle-aged and older adults aged between 50 and 73 years. We also aimed to identify key moderating variables to guide training prescription. Study Design We conducted a systematic review with meta-analysis of randomized controlled trials. Data Sources The electronic databases PubMed, Web of Science Core Collection, MEDLINE and Google Scholar were systematically searched until February 2022. Eligibility Criteria for Selecting Studies We included randomized controlled trials that examined the effects of CT versus passive controls on measures of physical fitness in healthy middle-aged and older adults aged between 50 and 73 years. Results Fifteen studies were eligible, including a total of 566 participants. CT induced moderate positive effects on muscle strength (standardized mean difference [SMD] = 0.74) and power (SMD = 0.50), with a small effect on CRE (SMD = 0.48). However, no significant effects were detected for balance ( p  > 0.05). Older adults > 65 years (SMD = 1.04) and females (SMD = 1.05) displayed larger improvements in muscle strength compared with adults ≤ 65 years old (SMD = 0.60) and males (SMD = 0.38), respectively. For CRE, moderate positive effects (SMD = 0.52) were reported in those ≤ 65 years old only, with relatively larger gains in females (SMD = 0.55) compared with males (SMD = 0.45). However, no significant differences between all subgroups were detected. Independent single training factor analysis indicated larger positive effects of 12 weeks (SMD = 0.87 and 0.88) compared with 21 weeks (SMD = 0.47 and 0.29) of CT on muscle strength and power, respectively, while for CRE, 21 weeks of CT resulted in larger gains (SMD = 0.62) than 12 weeks (SMD = 0.40). For CT frequency, three sessions per week produced larger beneficial effects (SMD = 0.91) on muscle strength compared with four sessions (SMD = 0.55), whereas for CRE, moderate positive effects were only noted after four sessions per week (SMD = 0.58). A session duration of > 30–60 min generated larger improvements in muscle strength (SMD = 0.99) and power (SMD = 0.88) compared with > 60–90 min (SMD = 0.40 and 0.29, respectively). However, for CRE, longer session durations (i.e., > 60–90 min) seem to be more effective (SMD = 0.61) than shorter ones (i.e., > 30–60 min) (SMD = 0.34). ET at moderate-to-near maximal intensities produced moderate (SMD = 0.64) and small positive effects (SMD = 0.49) on muscle strength and CRE, respectively, with no effects at low intensity ET ( p  > 0.05). Finally, intra-session ST before ET produced larger gains in muscle strength (SMD = 1.00) compared with separate sessions (SMD = 0.55), whereas ET and ST carried out separately induced larger improvements in CRE (SMD = 0.58) compared with intra-session ET before ST (SMD = 0.49). Conclusions CT is an effective method to improve measures of physical fitness (i.e., muscle strength, power, and CRE) in healthy middle-aged and older adults aged between 50 and 73 years, regardless of sex. Results of independent single training factor analysis indicated that the largest effects on muscle strength were observed after 12 weeks of training, > 30–60 min per session, three sessions per week, higher ET intensities and when ST preceded ET within the same session. For CRE, the largest effects were noted after 21 weeks of training, four sessions per week, > 60–90 min per session, higher ET intensities and when ET and ST sessions were performed separately. Regarding muscle power, the largest effects were observed after 12 weeks of training and > 30–60 min per session.

Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate ‘enhancer hijacking’ as an efficient mechanism driving oncogene activation in a childhood cancer. Focusing on two ill-characterized subtypes of medulloblastoma (group 3 and group 4), this study identifies prevalent genomic structural variants that are restricted to these two subtypes and independently bring together coding regions of GFI1 family proto-oncogenes with active enhancer elements, leading to their mutually exclusive oncogenic activation. Oncogenesis through enhancer hijacking Medulloblastoma is a highly malignant paediatric brain tumour. Here the authors focus on two ill-characterized subtypes — group 3 and group 4 — which account for the majority of paediatric cases. They identify prevalent genomic structural variants, which are restricted to these two subtypes, and bring together coding regions of proto-oncogenes, GFI1 and GFI1B , and active enhancer elements leading to oncogene activation. This work identifies 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.

Background Concurrent training can be an effective and time-efficient method to improve both muscle strength and aerobic capacity. A major challenge with concurrent training is how to adequately combine and sequence strength exercise and aerobic exercise to avoid interference effects. This is particularly relevant for athletes. Objective We aimed to examine the acute effects of aerobic exercise on subsequent measures of muscle strength and power in trained male individuals. Design We performed a systematic review with meta-analysis. Data Sources Systematic literature searches in the electronic databases PubMed, Web of Science, and Google Scholar were conducted up to July 2021. Eligibility Criteria for Selecting Studies Studies were included that applied a within-group repeated-measures design and examined the acute effects of aerobic exercise (i.e., running, cycling exercise) on subsequent measures of lower limb muscle strength (e.g., maximal isometric force of the knee extensors) and/or proxies of lower limb muscle power (e.g., countermovement jump height) in trained individuals. Results Fifteen studies met the inclusion criteria. Aerobic exercise resulted in moderate declines in muscle strength (standardized mean difference [SMD] = 0.79; p  = 0.003). Low-intensity aerobic exercise did not moderate effects on muscle strength (SMD = 0.65; p  = 0.157) while moderate-to-high intensity aerobic exercise resulted in moderate declines in muscle strength (SMD = 0.65; p  = 0.020). However, the difference between subgroups was not statistically significant ( p  = 0.979). Regarding aerobic exercise duration, large declines in muscle strength were found after > 30 min (SMD = 1.02; p  = 0.049) while ≤ 30 min of aerobic exercise induced moderate declines in muscle strength (SMD = 0.59; p  = 0.013). The subgroup difference was not statistically significant ( p  = 0.204). Cycling exercise resulted in significantly larger decrements in muscle strength (SMD = 0.79; p  = 0.002) compared with running (SMD = 0.28; p  = 0.035). The difference between subgroups was statistically significant ( p  < 0.0001). For muscle power, aerobic exercise did not result in any statistically significant changes (SMD = 0.04; p  = 0.846). Conclusions Aerobic exercise induced moderate declines in measures of muscle strength with no statistically significant effects on proxies of muscle power in trained male individuals. It appears that higher compared with lower intensity as well as longer compared with shorter aerobic exercise duration exacerbate acute declines in muscle strength. Our results provide evidence for acute interference effects when aerobic exercies is performed before strength exercises. These findings may help practitioners to better prescribe single training sessions, particularly if environmental and/or infrastructural reasons (e.g., availability of training facilities) do not allow the application of strength training before aerobic exercise.

Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report \"allelic heterogeneity\" at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels.