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Brigitte Holzinger,1,2 Franziska Nierwetberg,1 Frances Chung,3 Courtney J Bolstad,4 Bjørn Bjorvatn,5 Ngan Yin Chan,6 Yves Dauvilliers,7 Colin A Espie,8 Fang Han,9 Yuichi Inoue,10 Damien Leger,11 Tainá Macêdo,12 Kentaro Matsui,13,14 Ilona Merikanto,15,16 Charles M Morin,17 Sérgio A Mota-Rolim,18 Markku Partinen,19 Giuseppe Plazzi,20,21 Thomas Penzel,22 Mariusz Sieminski,23 Yun Kwok Wing,6 Serena Scarpelli,24 Michael R Nadorff,4,25 Luigi De Gennaro24,26 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Medical University Vienna, Postgraduate Master ULG Sleep Coaching, Vienna, Austria; 3Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 4Mississippi State University, Mississippi State, MS, USA; 5Department of Global Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People’s Republic of China; 7Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 8Sir Jules Thorn Sleep & Circadian Neuroscience Institute (SCNi), University of Oxford, Oxford, UK; 9Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 10Tokyo Medical University, Tokyo, Japan; 11Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 12Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 13Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 14Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 15SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 16Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 17École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, QC, Canada; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 23Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 24Department of Psychology, Sapienza University of Rome, Rome, Italy; 25Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Brigitte Holzinger, Tel +43 699 101 99 042, Email brigitte.holzinger@meduniwien.ac.atPurpose: The COVID-19 pandemic affects mental health and sleep, resulting in frequent nightmares. Therefore, identifying factors associated with nightmare frequency is important, as it can indicate mental health issues. The study aimed to investigate increases in nightmare frequency comparing the pre-pandemic and pandemic period, and identify its risk factors. Further, the mediating role of post-traumatic stress disorder symptoms between the pandemic and nightmares is explored.Patients and Methods: For this cross-sectional survey data were obtained via self-rating online survey (ICOSS: details in Partinen et al, 2021), which was open to anyone older than 18 years. The final volunteer sample consisted of 15,292 participants, divided according to their nightmare frequency (high: ≥ 1– 2 nights/week; low: < 1– 2 nights/week). A total of 9100 participants were excluded if answers on variables of interest were missing or receiving rewards for participation. Chi-square tests identified changes of nightmare frequency. Predictors of high nightmare frequency were assessed using logistic regression and presented as Odds Ratios. Post-hoc mediation models were used to investigate the role of post-traumatic stress symptoms (PTSS).Results: The mean age was 41.63 (SD=16.55) with 64.05% females. High nightmare frequency increased significantly from 13.24% to 22.35% during the pandemic. Factors associated with it included self-reported PTSS (OR=2.11), other mental disorders and various sleep disorders or problems. Financial burden due to the pandemic, confinement, having had COVID-19, and work situation during the pandemic were associated with nightmare frequency, those relations were partly mediated through PTSS.Conclusion: Our results display the pandemic influence on nightmare frequency, which in turn connects to multiple mental health and sleep factors. These relations were partly mediated through PTSS. The COVID-19 pandemic appears to have caused traumatization of a substantial proportion of society. Health care workers should consider nightmares in their screening routines, as it might indicate PTSS and/or other mental and sleep disorders.Keywords: COVID-19, nightmares, mental health, sleep, post-traumatic stress disorder, collective trauma

Serena Scarpelli,1 Michael R Nadorff,2,3 Bjørn Bjorvatn,4 Frances Chung,5 Yves Dauvilliers,6 Colin A Espie,7 Yuichi Inoue,8 Kentaro Matsui,9,10 Ilona Merikanto,11,12 Charles M Morin,13 Thomas Penzel,14 Mariusz Sieminski,15 Han Fang,16 Tainá Macêdo,17 Sérgio A Mota-Rolim,18 Damien Leger,19 Giuseppe Plazzi,20,21 Ngan Yin Chan,22 Markku Partinen,23 Courtney J Bolstad,2 Brigitte Holzinger,24,25 Luigi De Gennaro1,26 1Department of Psychology, Sapienza University of Rome, Rome, Italy; 2Mississippi State University, Mississippi State, MS, USA; 3Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 4Department of Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 5Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, Canada; 6Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 7Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 8Tokyo Medical University, Tokyo, Japan; 9Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 10Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 11SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 12Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 13École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 14Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 15Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 16Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 17Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Regions, People’s Republic of China; 23Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 24Institute for Consciousness and Dream Research, Vienna, Austria; 25Medical University Vienna, Postgraduate Master Program Medical Sleep Coaching, ZK-Schlafcoaching, Vienna, Austria; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Luigi De Gennaro, Tel +39-06-49917647, Fax +39-06-49917711, Email luigi.degennaro@uniroma1.itIntroduction: A growing number of studies have demonstrated that the coronavirus disease-19 (COVID-19) pandemic has severely affected sleep and dream activity in healthy people. To date, no investigation has examined dream activity specifically in COVID-19 patients.Methods: As part of the International COVID-19 Sleep Study (ICOSS), we compared 544 COVID-19 participants with 544 matched-controls. A within-subjects comparison between pre-pandemic and pandemic periods computed separately for controls and COVID-19 participants were performed on dream recall and nightmare frequency (DRF; NF). Also, non-parametric comparisons between controls and COVID-19 participants were carried out. Further, we compared psychological measures between the groups collected during pandemic. Ordinal logistic regression to detect the best predictors of NF was performed.Results: We found that people reported greater dream activity during the pandemic. Comparisons between controls and COVID-19 participants revealed a) no difference between groups concerning DRF in the pre-pandemic period and during the pandemic; b) no difference between groups concerning nightmare frequency in the pre-pandemic period; and c) COVID-19 participants reported significantly higher NF than controls during pandemic (p = 0.003). Additionally, we showed that a) anxiety, depression, post-traumatic stress-disorder (PTSD) symptom scores were higher in COVID-19 participants than controls; and b) quality of life and health as well as wellbeing (WHO-5) scores were significantly higher in controls than COVID-19 participants. Finally, ordinal logistic regression indicates that DRF (p < 0.001), PTSD (p < 0.001), anxiety (p = 0.018), insomnia (p = 0.039), COVID-19 severity (p = 0.014), sleep duration (p = 0.003) and age (p = 0.001) predicted NF.Discussion: Our work shows strong associations between increased nightmares in those reporting having had COVID-19. This suggests that the more that people were affected by COVID-19, the greater the impact upon dream activity and quality of life.Keywords: dreaming, pandemic, sleep, PTSD, anxiety, COVID-19 severity

Luiz Eduardo Mateus Brandão,1 Teemu Martikainen,1 Ilona Merikanto,2– 4 Brigitte Holzinger,5,6 Charles M Morin,7– 9 Colin A Espie,10,11 Courtney J Bolstad,12 Damien Leger,13 Frances Chung,14 Giuseppe Plazzi,15 Yves Dauvilliers,16 Kentaro Matsui,17,18 Luigi De Gennaro,19– 21 Mariusz Sieminski,22 Michael R Nadorff,12,23 Ngan Yin Chan,24 Yun Kwok Wing,24 Sérgio Arthuro Mota-Rolim,25– 27 Yuichi Inoue,28 Markku Partinen,29,30 Christian Benedict,31 Bjorn Bjorvatn,32,33 Jonathan Cedernaes1,34 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 2Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 3Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; 4Orton Orthopaedic Hospital, Helsinki, Finland; 5ZK-Schlafcoaching, Medical University Vienna, Vienna, Austria; 6Institute for Consciousness and Dream Research, Vienna, Austria; 7École de Psychologie, Université Laval, Québec, Canada; 8Centre d’étude des troubles du sommeil, Université Laval, Québec, Canada; 9Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 10Sleep & Circadian Institute, University of Oxford, Oxford, UK; 11Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 12Department of Psychology, Mississippi State University, Starkville, MS, USA; 13APHP, VIFASOM, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Université de Paris, Paris, France; 14Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; 15Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, Modena, Italy; 16Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Institute for Neurosciences of Montpellier INM, INSERM, University of Montpellier, Montpellier, France; 17National Center of Neurology and Psychiatry National Institute of Mental Health, Department of Clinical Laboratory and Department of Sleep-Wake Disorders, Tokyo, Japan; 18Tokyo Women’s Medical University, Department of Psychiatry, Tokyo, Japan; 19Department of Psychology, Sapienza University of Rome, Rome, Italy; 20IRCCS Fondazione Santa Lucia, Rome, Italy; 21IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 22Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 23Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 24Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 25Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 26Physiology and Behaviour Department, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 27Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 28Department of Somnology, Tokyo Medical University, Tokyo, Japan; 29Helsinki Sleep Clinic, Vitalmed Research Center, Terveystalo Biobank and Research, Helsinki, Finland; 30Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 31Sleep Science Laboratory, Department of Neuroscience, Uppsala University, Uppsala, Sweden; 32Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 33Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 34Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Jonathan Cedernaes Email jonathan.cedernaes@medsci.uu.sePurpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) – ie, the difference between sleep timing on working vs free days – and 2) symptoms of insomnia.Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example.Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23– 54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL.Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms – even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.Keywords: BNSQ, ISI, midsleep, MSFsc, PHQ-4, psychological distress

Eirin Fränkl,1 Serena Scarpelli,2 Michael R Nadorff,3,4 Bjørn Bjorvatn,5 Courtney J Bolstad,3 Ngan Yin Chan,6 Frances Chung,7 Yves Dauvilliers,8 Colin A Espie,9 Yuichi Inoue,10,11 Damien Leger,12,13 Tainá Macêdo,14 Kentaro Matsui,15,16 Ilona Merikanto,17– 19 Charles M Morin,20 Sérgio Mota-Rolim,21 Markku Partinen,22,23 Thomas Penzel,24 Giuseppe Plazzi,25,26 Mariusz Sieminski,27 Yun Kwok Wing,6 Luigi De Gennaro,2,28 Brigitte Holzinger1,29 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Department of Psychology, Sapienza University of Rome, Rome, Italy; 3Mississippi State University, Mississippi State, MS, USA; 4Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 5Department of Global Public Health and Primary Care, University of Bergen, and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 7Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, Canada; 8Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Institute for Neurosciences of Montpellier INM, INSERM, University of Montpellier, Montpellier, France; 9Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 10Department of Somnology, Tokyo Medical University, Tokyo, Japan; 11Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan; 12Université de Paris, VIFASOM (EA 7331 Vigilance Fatigue, Sommeil et Santé Publique), Paris, France; 13APHP, Hotel-Dieu de Paris, Centre du Sommeil et de la Vigilance, Paris, France; 14Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 15Department of Clinical Laboratory and Department of Sleep-Wake Disorders, National Center of Neurology and Psychiatry National Institute of Mental Health, Kodaira, Japan; 16Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 17Sleep Well Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 18Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 19Orton Orthopaedics Hospital, Helsinki, Finland; 20École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 21Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal, Brazil; 22Helsinki Sleep Clinic, Terveystalo Healthcare, Helsinki, Finland; 23Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 24Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 25IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 26Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 27Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 28IRCCS Fondazione Santa Lucia, Rome, Italy; 29Medical University Vienna, ZK-Schlafcoaching, Vienna, AustriaCorrespondence: Brigitte HolzingerInstitute for Consciousness and Dream Research, Canongasse 13/1, Vienna, 1180, AustriaTel +43699-101 99 042Fax +4301-25330334600Email brigitte.holzinger@meduniwien.ac.atObjective: Many have reported odd dreams during the pandemic. Given that dreams are associated with mental health, understanding these changes could provide crucial information about wellbeing during the pandemic. This study explored associations between COVID-19 and dream recall frequency (DRF), and related social, health, and mental health factors.Methods: We conducted a cross-sectional web survey of 19,355 individuals in 14 countries from May to July 2020. We collected data on COVID-19, mental health, sleep and DRF during the pandemic. We performed McNemar Tests to compare low (< 3 nights per week) and high DRF (≥ 3 nights per week) before and during COVID-19 and to evaluate changes in sleep variables segmented by DRF. Chi-square tests were conducted to compare characteristics between low and high DRF. Logistic regression analyses were conducted to examine associations between various independent variables and DRF.Results: Reports of high DRF during the pandemic were higher than before the pandemic (P< 0.001). Female gender (aOR=1.25, 95% CI 1.10– 1.41), nightmares (aOR=4.22, 95% CI 3.45– 5.17), sleep talking (aOR= 2.36, 1.73– 3.23), sleep maintenance problems (aOR=1.34, 95% CI 1.15– 1.56), symptoms of REM sleep behavior disorder (RBD; aOR=1.24, 95% CI 1.09– 1.41) and repeated disturbing thoughts (posttraumatic stress disorder (PTSD) symptoms) were associated with high DRF. Age group 55– 64 years (aOR=0.69, 95% CI 0.58– 0.83) reported less high DRF than younger participants. Unadjusted OR showed associations between depression, anxiety, and DRF; however, in adjusted regression depression (aOR= 0.71, 0.59– 0.86) and anxiety (aOR=0.79, 95% CI 0.66– 0.94) were negatively associated with high DRF.Conclusion and Relevance: DRF was higher than pre-pandemic levels across four continents. DRF was associated with gender and parasomnias like nightmares and RBD symptoms, sleep maintenance problems, PTSD symptoms and negatively associated with depression and anxiety. The results implicate that COVID-19 is reflected in our dreams as an expression of the emotional intensity of the pandemic.Keywords: sleep, sleep disorder, mental health, parasomnia, collective threat

A new program, ECEP2D, for simulating the one-dimensional (1D) and two-dimensional (2D) patterns of the gel electrophoresis of a protein after it has been digested by one or more enzymes is introduced. With ECEP2D, students can gain deeper insights into gel electrophoresis by performing hands-on simulations. For example, students can visualize how 2D gel electrophoresis can improve resolution over 1D by comparing them side-by-side. Students can watch how different enzymes cut a protein into different fragments, giving rise to different gel patterns; some patterns are less congested than the others. Students can recognize how enzyme digestion can enhance gel electrophoresis to distinguish proteins. For students not having the chance to take biochemistry laboratories, ECEP2D provides a useful simulated learning environment. Instructors can also complement wet-lab experiments with simulations by ECEP2D to introduce more concepts with fewer laboratory hours. ECEP2D is available for free at http://www.umsl.edu/~wongch/software.html.

A series of drought simulations were performed using the California Department of Water Resources codes and historical datasets representing a range of droughts from mild to severe for time periods lasting up to 60 years. Land use, agricultural cropping patterns, and water demand were held fixed at the 1973-2003 mean and water supply decreased by effective amounts ranging between 25 and 50 percent for the Central Valley, representing light to severe drought types. An examination of the impacts include four sub-basins, the Sacramento Basin, the San Joaquin Basin, the Tulare Basin, and the Eastside Drainage. Model output results suggest the greatest impacts are at the San Joaquin and Tulare Basins, regions that are heavily irrigated. Surface diversions decrease by as much as 42 percent in these regions. Stream-to-aquifer flows reversed and aquifer storage dropped. Most significant was the decline in groundwater head for the severe drought cases, where results suggest the water table is unlikely to recovery within the foreseeable future. However, the overall response to such droughts is not as severe as anticipated and the northern Central Valley may act as groundwater insurance to sustain California during extended dry periods.

Spectral graph theoretic methods have recently shown great promise for the problem of image segmentation. However, due to the computational demands of these approaches, applications to large problems such as spatiotemporal data and high resolution imagery have been slow to appear. The contribution of this paper is a method that substantially reduces the computational requirements of grouping algorithms based on spectral partitioning making it feasible to apply them to very large grouping problems. Our approach is based on a technique for the numerical solution of eigenfunction problems known as the Nystrom method. This method allows one to extrapolate the complete grouping solution using only a small number of samples. In doing so, we leverage the fact that there are far fewer coherent groups in a scene than pixels.

Most early-stage drug discovery projects focus on equilibrium binding affinity to the target alongside selectivity and other pharmaceutical properties. Since many approved drugs have nonequilibrium binding characteristics, there has been increasing interest in optimizing binding kinetics early in the drug discovery process. As focal adhesion kinase (FAK) is an important drug target, we examine whether steered molecular dynamics (SMD) can be useful for identifying drug candidates with the desired drug-binding kinetics. In simulating the dissociation of 14 ligands from FAK, we find an empirical power–law relationship between the simulated time needed for ligand unbinding and the experimental rate constant for dissociation, with a strong correlation depending on the SMD force used. To improve predictions, we further develop regression models connecting experimental dissociation rate with various structural and energetic quantities derived from the simulations. These models can be used to predict dissociation rates from FAK for related compounds.