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Sökning: WFRF:(Jakob Robert) > (2020-2022) > (2020)

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1.
  • De Rezende, Susanna F., et al. (författare)
  • KRW composition theorems via lifting
  • 2020
  • Ingår i: Proceedings - 2020 IEEE 61st Annual Symposium on Foundations of Computer Science, FOCS 2020. - 0272-5428. - 9781728196220 - 9781728196213 ; 2020-November, s. 43-49
  • Konferensbidrag (refereegranskat)abstract
    • One of the major open problems in complexity theory is proving super-logarithmic lower bounds on the depth of circuits (i.e., mathrm{P} nsubseteq text{NC}{1}). Karchmer, Raz, and Wigderson [13] suggested to approach this problem by proving that depth complexity behaves'as expected' with respect to the composition of functions f diamond g. They showed that the validity of this conjecture would imply that mathrm{P} nsubseteq text{NC}{1}. Several works have made progress toward resolving this conjecture by proving special cases. In particular, these works proved the KRW conjecture for every outer function, but only for few inner functions. Thus, it is an important challenge to prove the KRW conjecture for a wider range of inner functions. In this work, we extend significantly the range of inner functions that can be handled. First, we consider the monotone version of the KRW conjecture. We prove it for every monotone inner function whose depth complexity can be lower bounded via a query-to-communication lifting theorem. This allows us to handle several new and well-studied functions such as the s-t-connectivity, clique, and generation functions. In order to carry this progress back to the non-monotone setting, we introduce a new notion of semi-monotone composition, which combines the non-monotone complexity of the outer function with the monotone complexity of the inner function. In this setting, we prove the KRW conjecture for a similar selection of inner functions, but only for a specific choice of the outer function f.
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2.
  • De Rezende, Susanna, et al. (författare)
  • Lifting with simple gadgets and applications to circuit and proof complexity
  • 2020
  • Ingår i: Proceedings - 2020 IEEE 61st Annual Symposium on Foundations of Computer Science, FOCS 2020. - 0272-5428. - 9781728196220 - 9781728196213 ; 2020-November, s. 24-30
  • Konferensbidrag (refereegranskat)abstract
    • We significantly strengthen and generalize the theorem lifting Nullstellensatz degree to monotone span program size by Pitassi and Robere (2018) so that it works for any gadget with high enough rank, in particular, for useful gadgets such as equality and greater-than. We apply our generalized theorem to solve three open problems: •We present the first result that demonstrates a separation in proof power for cutting planes with unbounded versus polynomially bounded coefficients. Specifically, we exhibit CNF formulas that can be refuted in quadratic length and constant line space in cutting planes with unbounded coefficients, but for which there are no refutations in subexponential length and subpolynomial line space if coefficients are restricted to be of polynomial magnitude. •We give the first explicit separation between monotone Boolean formulas and monotone real formulas. Specifically, we give an explicit family of functions that can be computed with monotone real formulas of nearly linear size but require monotone Boolean formulas of exponential size. Previously only a non-explicit separation was known. •We give the strongest separation to-date between monotone Boolean formulas and monotone Boolean circuits. Namely, we show that the classical GEN problem, which has polynomial-size monotone Boolean circuits, requires monotone Boolean formulas of size 2{Omega(n text{polylog}(n))}. An important technical ingredient, which may be of independent interest, is that we show that the Nullstellensatz degree of refuting the pebbling formula over a DAG G over any field coincides exactly with the reversible pebbling price of G. In particular, this implies that the standard decision tree complexity and the parity decision tree complexity of the corresponding falsified clause search problem are equal. This is an extended abstract. The full version of the paper is available at https://arxiv.org/abs/2001.02144.
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3.
  • Ji, Xuemei, et al. (författare)
  • Protein-altering germline mutations implicate novel genes related to lung cancer development
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
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4.
  • Lindqvist, Karin, et al. (författare)
  • Affect-Focused Psychodynamic Internet-Based Therapy for Adolescent Depression : Randomized Controlled Trial
  • 2020
  • Ingår i: Journal of Medical Internet Research. - Toronto, ON, Canada : JMIR Publications Inc.. - 1438-8871. ; 22:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adolescent depression is one of the largest health issues in the world and there is a pressing need for effective and accessible treatments.Objective: This trial examines whether affect-focused internet-based psychodynamic therapy (IPDT) with therapist support is more effective than an internet-based supportive control condition on reducing depression in adolescents.Methods: The trial included 76 adolescents (61/76, 80% female; mean age 16.6 years), self-referred via an open access website and fulfilling criteria for major depressive disorder. Adolescents were randomized to 8 weeks of IPDT (38/76, 50%) or supportive control (38/76, 50%). The primary outcome was self-reported depressive symptoms, measured with the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR). Secondary outcomes were anxiety severity, emotion regulation, self-compassion, and an additional depression measure. Assessments were made at baseline, postassessment, and at 6 months follow-up, in addition to weekly assessments of the primary outcome measure as well as emotion regulation during treatment.Results: IPDT was significantly more effective than the control condition in reducing depression (d=0.82, P=.01), the result of which was corroborated by the second depression measure (d=0.80, P<.001). IPDT was also significantly more effective in reducing anxiety (d=0.78, P<.001) and increasing emotion regulation (d=0.97, P<.001) and self-compassion (d=0.65, P=.003). Significantly more patients in the IPDT group compared to the control group met criteria for response (56% vs 21%, respectively) and remission (35% vs 8%, respectively). Results on depression and anxiety symptoms were stable at 6 months follow-up. On average, participants completed 5.8 (SD 2.4) of the 8 modules.Conclusions: IPDT may be an effective intervention to reduce adolescent depression. Further research is needed, including comparisons with other treatments.Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 16206254; http://www.isrctn.com/ISRCTN16206254
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5.
  • Mechler, Jakob, et al. (författare)
  • Internet-based psychodynamic versus cognitive behaviour therapy for adolescents with depression : study protocol for a non-inferiority randomized controlled trial (the ERiCA study)
  • 2020
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adolescent depression is a common mental health problem and there is an urgent need for effective and accessible treatments. Internet-based interventions solve many obstacles for seeking and receiving treatment, thus increasing access to effective treatments. Internet-based cognitive behavioural therapy (ICBT) for adolescent depression has demonstrated efficacy in previous trials. In order to broaden the range of evidence-based treatments for young people, we evaluated a newly developed affect-focused Internet-based psychodynamic treatment (IPDT) in a previous study with promising results. The purpose of the planned study is to evaluate the efficacy of IPDT for adolescent depression in a non-inferiority trial, comparing it to ICBT.Methods: The study will employ a parallel randomized non-inferiority design (ratio 1:1; n = 270). Eligible participants are adolescents 15–19 years suffering from depression. The primary hypothesis is that IPDT will be non-inferior to ICBT in reducing depressive symptoms from pre-treatment to end of treatment. Secondary research questions include comparing outcomes of IPDT and ICBT regarding anxiety symptoms, emotion regulation and self-compassion. Additional data will be collected to evaluate cost-effectiveness as well as investigating predictors, moderators and mediators of outcome. In addition, we will examine long-term outcome up to 1 year after end of treatment. Diagnostic interviews with MINI 7.0 will be used to establish primary diagnosis of depression as well as ruling out any exclusion criteria. Both treatments consist of eight modules over 10 weeks, complemented with therapist support through text messages and weekly chat sessions. Primary outcome measure is the Quick Inventory of Depressive Symptomatology in Adolescents Self-Rated (QIDS-A17-SR). Primary outcome will be analysed using data from all participants entering the study using a multilevel growth curve strategy based on the weekly measurements of QIDS-A17-SR. The non-inferiority margin is defined as d = 0.30.Discussion: This trial will demonstrate whether IPDT is non-inferior to ICBT in the treatment of adolescent depression. The study might therefore broaden the range of evidence-based treatment alternatives for young people struggling with depression. Further analyses of data from this trial may increase our knowledge about “what works for whom” and the pathways of change for two distinct types of interventions.Trial registration: ISRCTN12552584, Registered on 13 August 2019.
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6.
  • Myers-Smith, Isla H., et al. (författare)
  • Complexity revealed in the greening of the Arctic
  • 2020
  • Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 10:2, s. 106-117
  • Tidskriftsartikel (refereegranskat)abstract
    • As the Arctic warms, vegetation is responding, and satellite measures indicate widespread greening at high latitudes. This ‘greening of the Arctic’ is among the world’s most important large-scale ecological responses to global climate change. However, a consensus is emerging that the underlying causes and future dynamics of so-called Arctic greening and browning trends are more complex, variable and inherently scale-dependent than previously thought. Here we summarize the complexities of observing and interpreting high-latitude greening to identify priorities for future research. Incorporating satellite and proximal remote sensing with in-situ data, while accounting for uncertainties and scale issues, will advance the study of past, present and future Arctic vegetation change.
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7.
  • Trolle Lagerros, Ylva, et al. (författare)
  • Risk of Delayed Discharge and Reoperation of Gastric Bypass Patients with Psychiatric Comorbidity : a Nationwide Cohort Study
  • 2020
  • Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 30:7, s. 2511-2518
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGastric bypass (GBP) surgery is considered a safe and effective treatment for obesity. However, there is uncertainty regarding the impact of preexisting psychiatric comorbidity on GBP complications. We have investigated whether a psychiatric diagnosis before GBP surgery is associated with delayed discharge (the odds of being in the 90th percentile of length of stay) and rate of reoperation in a nationwide Swedish cohort.MethodsPatients undergoing GBP surgery during 2008–2012 were identified and followed up through the National Patient Register and the Prescribed Drug Register. Logistic regression models were fitted to the studied outcomes.ResultsAmong the 22,539 patients identified, a prior diagnosis of bipolar disorder, schizophrenia, depression, neurotic disorders, ADHD (attention deficit hyperactivity disorder), substance use disorder, eating disorder, personality disorder, or self-harm since 1997 (n = 9480) was found to be associated with delayed discharge after GBP surgery (odds ratio [OR] = 1.47, confidence interval [CI] 1.34–1.62), especially in patients with psychiatric hospitalization exceeding 1 week in the 2 years preceding GBP surgery (OR = 2.06, CI 1.30–3.28), compared with those not hospitalized within psychiatry. Likewise, patients with a prior psychiatric diagnosis were more likely to be reoperated within 30 days (OR = 1.25, CI 1.11–1.41), with twice the likelihood OR 2.23 (CI 1.26–3.92) for patients with psychiatric hospitalization of up to a week in the 2 years preceding GBP surgery, compared with patients who had not been hospitalized within psychiatry.ConclusionsA psychiatric diagnosis before GBP surgery was associated with delayed discharge and increased likelihood of reoperation within 30 days. Patients with a prior psychiatric diagnosis may, therefore, need additional attention and support.
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8.
  • Vogelezang, Suzanne, et al. (författare)
  • Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
  • 2020
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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9.
  • Wagner, Nils, et al. (författare)
  • Deep learning-enhanced light-field imaging with continuous validation
  • 2020
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Light field microscopy (LFM) has emerged as a powerful tool for fast volumetric image acquisition in biology, but its effective throughput and widespread use has been hampered by a computationally demanding and artefact-prone image reconstruction process. Here, we present a novel framework consisting of a hybrid light-field light-sheet microscope and deep learning-based volume reconstruction, where single light-sheet acquisitions continuously serve as training data and validation for the convolutional neural network reconstructing the LFM volume. Our network delivers high-quality reconstructions at video-rate throughput and we demonstrate the capabilities of our approach by imaging medaka heart dynamics and zebrafish neural activity.
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10.
  • Wallgren, Jakob, 1987-, et al. (författare)
  • Structure elucidation of urinary metabolites of fentanyl and five fentanyl analogues using LC-QTOF-MS, hepatocyte incubations and synthesized reference standards
  • 2020
  • Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Fentanyl analogues constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism and studies utilizing LC-QTOF-MS analysis of hepatocyte incubations and/or authentic urine samples does not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogues, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC-QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogues, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogues where nothing is known about the metabolism.
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