Long-term course and outcome of obsessive-compulsive patientsafter cognitive-behavioral therapy in combination with eitherfluvoxamine or placebo: A 7-year follow-up of a randomized double-blind trial

Longitudinal studies with very long follow-up periods of patients with obsessive-compulsive disorder (OCD) who have received adequate treatment are rare. In the current study, 30 of 37 inpatients (81%) with severe OCD were followed up 6-8 years after treatment with cognitive-behavioral therapy (CBT) in combination with either fluvoxamine or placebo in a randomized design. The significant improvements (with large effectsizes) in obsessive-compulsive symptoms from pre- to post-treatment (41% reduction on the Y-BOCS) remained stable at follow-up (45 %). Responder rates, defined as ≥35% reduction on the Y-BOCS, were 67% and 60%, respectively. Depressive symptoms decreased significantly not only from pre- to post-treatment but also during follow-up. Re-hospitalization, which occurred in 11 patients (37 %), was associated with more severe depressive symptoms at pre-treatment and living without a partner. Full symptom remission at follow-up, defined as both Y-BOCS total score ≤ 7 and no longer meeting diagnostic criteria for OCD, was achieved by 8 patients (27 %). Patients without full remission at follow-up had a significantly longer history of OCD, assessed at pretreatment, compared to remitted patients. The shortterm treatment outcome had no predictive value for the long-term course. Throughout the naturalistic follow-up, nearly all patients (29 patients) received additional psychotherapy and/or medication. This might indicate that such chronic OCD patients usually need additional therapeutic support after effective inpatient treatment to maintain their improvements over long period

Redshift-weighted constraints on primordial non-Gaussianity from the clustering of the eBOSS DR14 quasars in Fourier space

We present constraints on local primordial non-Gaussianity (PNG), parametrized through $f^{\rm loc}_{\rm NL}$, using the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey Data Release 14 quasar sample. We measure and analyze the anisotropic clustering of the quasars in Fourier space, testing for the scale-dependent bias introduced by primordial non-Gaussianity on large scales. We derive and employ a power spectrum estimator using optimal weights that account for the redshift evolution of the PNG signal. We find constraints of $-51<f^{\rm loc}_{\rm NL}<21$ at 95% confidence level. These are amont the tightest constraints from Large Scale Structure (LSS) data. Our redshift weighting improves the error bar by 15% in comparison to the unweighted case. If quasars have lower response to PNG, the constraint degrades to $-81<f^{\rm loc}_{\rm NL}<26$, with a 40% improvement over the standard approach. We forecast that the full eBOSS dataset could reach $\sigma_{f^{\rm loc}_{\rm NL}}\simeq 5\text{-}8$ using optimal methods and full range of scales.Comment: 28 pages, 12 figures. Comments welcome

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

ROC curves in cost space

The final publication is available at Springer via http://dx.doi.org/10.1007/s10994-013-5328-9ROC curves and cost curves are two popular ways of visualising classifier performance, finding appropriate thresholds according to the operating condition, and deriving useful aggregated measures such as the area under the ROC curve (AUC) or the area under the optimal cost curve. In this paper we present new findings and connections between ROC space and cost space. In particular, we show that ROC curves can be transferred to cost space by means of a very natural threshold choice method, which sets the decision threshold such that the proportion of positive predictions equals the operating condition. We call these new curves rate-driven curves, and we demonstrate that the expected loss as measured by the area under these curves is linearly related to AUC. We show that the rate-driven curves are the genuine equivalent of ROC curves in cost space, establishing a point-point rather than a point-line correspondence. Furthermore, a decomposition of the rate-driven curves is introduced which separates the loss due to the threshold choice method from the ranking loss (Kendall τ distance). We also derive the corresponding curve to the ROC convex hull in cost space; this curve is different from the lower envelope of the cost lines, as the latter assumes only optimal thresholds are chosen.We would like to thank the anonymous referees for their helpful comments. This work was supported by the MEC/MINECO projects CONSOLIDER-INGENIO CSD2007-00022 and TIN 2010-21062-C02-02, GVA project PROMETEO/2008/051, the COST-European Cooperation in the field of Scientific and Technical Research IC0801 AT, and the REFRAME project granted by the European Coordinated Research on Long-term Challenges in Information and Communication Sciences & Technologies ERA-Net (CHIST-ERA), and funded by the Engineering and Physical Sciences Research Council in the UK and the Ministerio de Economia y Competitividad in Spain.Hernández Orallo, J.; Flach ., P.; Ferri Ramírez, C. (2013). ROC curves in cost space. Machine Learning. 93(1):71-91. https://doi.org/10.1007/s10994-013-5328-9S7191931Adams, N., & Hand, D. (1999). Comparing classifiers when the misallocation costs are uncertain. Pattern Recognition, 32(7), 1139–1147.Chang, J., & Yap, C. (1986). A polynomial solution for the potato-peeling problem. Discrete & Computational Geometry, 1(1), 155–182.Drummond, C., & Holte, R. (2000). Explicitly representing expected cost: an alternative to ROC representation. In Knowl. discovery & data mining (pp. 198–207).Drummond, C., & Holte, R. (2006). Cost curves: an improved method for visualizing classifier performance. Machine Learning, 65, 95–130.Elkan, C. (2001). The foundations of cost-sensitive learning. In B. Nebel (Ed.), Proc. of the 17th intl. conf. on artificial intelligence (IJCAI-01) (pp. 973–978).Fawcett, T. (2006). An introduction to ROC analysis. Pattern Recognition Letters, 27(8), 861–874.Fawcett, T., & Niculescu-Mizil, A. (2007). PAV and the ROC convex hull. Machine Learning, 68(1), 97–106.Flach, P. (2003). The geometry of ROC space: understanding machine learning metrics through ROC isometrics. In Machine learning, proceedings of the twentieth international conference (ICML 2003) (pp. 194–201).Flach, P., Hernández-Orallo, J., & Ferri, C. (2011). A coherent interpretation of AUC as a measure of aggregated classification performance. In Proc. of the 28th intl. conference on machine learning, ICML2011.Frank, A., & Asuncion, A. (2010). UCI machine learning repository. http://archive.ics.uci.edu/ml .Hand, D. (2009). Measuring classifier performance: a coherent alternative to the area under the ROC curve. Machine Learning, 77(1), 103–123.Hernández-Orallo, J., Flach, P., & Ferri, C. (2011). Brier curves: a new cost-based visualisation of classifier performance. In Proceedings of the 28th international conference on machine learning, ICML2011.Hernández-Orallo, J., Flach, P., & Ferri, C. (2012). A unified view of performance metrics: translating threshold choice into expected classification loss. Journal of Machine Learning Research, 13, 2813–2869.Kendall, M. G. (1938). A new measure of rank correlation. Biometrika, 30(1/2), 81–93. doi: 10.2307/2332226 .Swets, J., Dawes, R., & Monahan, J. (2000). Better decisions through science. Scientific American, 283(4), 82–87

Addressing the threat of climate change to agriculture requires improving crop resilience to short-term abiotic stress

Climate change represents a serious threat to global agriculture, necessitating the development of more environmentally resilient crops to safeguard the future of food production. The effects of climate change are appearing to include a higher frequency of extreme weather events and increased day-to-day weather variability. As such, crops which are able to cope with short-term environmental stress, in addition to those that are tolerant to longer term stress conditions are required . It is becoming apparent that the hitherto relatively little studied process of post-stress plant recovery could be key to optimizing growth and production under fluctuating conditions with intermittent transient stress events. Developing more durable crops requires the provision of genetic resources to identify useful traits through the development of screening protocols. Such traits can then become the objective of crop breeding programmes. In this study, we discuss these issues and outline example research in leafy vegetables that is investigating resilience to short-term abiotic stress

Driving and Parkinson’s Disease: A Survey of the Patient’s Perspective

Background: Parkinson’s disease (PD) is a multi-system disorder that can impact on driving ability. Little is known about how these changes in driving ability affect people with PD, making it difficult for clinicians and carers to offer appropriate support. Objective: To assess patient views concerning the effect of PD on their driving ability, the impact of these changes and how they manage them. Method: An online survey was created by a team of clinicians, people with PD, their carers, and representatives from Parkinson’s UK. People with PD throughout the United Kingdom were invited to participate through Parkinson’s UK’s website, newsletter and Parkinson’s Excellence Network email list. Results: 805 people with PD took part in the survey. We found that the loss of a driving licence had an adverse impact on employment, socialisation, travel costs and spontaneous lifestyle choices. Multiple changes in driving ability related to PD were described, including that impulse control disorders can have an adverse impact on driving. Changes in driving ability caused people to change their driving practices including taking shorter journeys and being less likely to drive at night. Participants advised managing changes in driving ability through planning, vehicle adaptions, maintaining skills and self-assessment. Conclusion: This study demonstrates the impact that changes in driving ability can have on the lifestyle of people with PD and reveals the strategies that individuals adopt to manage these changes

Assembly and characterisation of a unique onion diversity set identifies resistance to Fusarium basal rot and improved seedling vigour

Conserving biodiversity is critical for safeguarding future crop production. Onion (Allium cepa L.) is a globally important crop with a very large (16 Gb per 1C) genome which has not been sequenced. While onions are self-fertile, they suffer from severe inbreeding depression and as such are highly heterozygous as a result of out-crossing. Bulb formation is driven by daylength, and accessions are adapted to the local photoperiod. Onion seed is often directly sown in the field, and hence seedling establishment is a critical trait for production. Furthermore, onion yield losses regularly occur worldwide due to Fusarium basal rot caused by Fusarium oxysporum f. sp. cepae. A globally relevant onion diversity set, consisting of 10 half-sib families for each of 95 accessions, was assembled and genotyping carried out using 892 SNP markers. A moderate level of heterozygosity (30–35%) was observed, reflecting the outbreeding nature of the crop. Using inferred phylogenies, population structure and principal component analyses, most accessions grouped according to local daylength. A high level of intra-accession diversity was observed, but this was less than inter-accession diversity. Accessions with strong basal rot resistance and increased seedling vigour were identified along with associated markers, confirming the utility of the diversity set for discovering beneficial traits. The onion diversity set and associated trait data therefore provide a valuable resource for future germplasm selection and onion breeding

LibrettOS: A Dynamically Adaptable Multiserver-Library OS

We present LibrettOS, an OS design that fuses two paradigms to simultaneously address issues of isolation, performance, compatibility, failure recoverability, and run-time upgrades. LibrettOS acts as a microkernel OS that runs servers in an isolated manner. LibrettOS can also act as a library OS when, for better performance, selected applications are granted exclusive access to virtual hardware resources such as storage and networking. Furthermore, applications can switch between the two OS modes with no interruption at run-time. LibrettOS has a uniquely distinguishing advantage in that, the two paradigms seamlessly coexist in the same OS, enabling users to simultaneously exploit their respective strengths (i.e., greater isolation, high performance). Systems code, such as device drivers, network stacks, and file systems remain identical in the two modes, enabling dynamic mode switching and reducing development and maintenance costs. To illustrate these design principles, we implemented a prototype of LibrettOS using rump kernels, allowing us to reuse existent, hardened NetBSD device drivers and a large ecosystem of POSIX/BSD-compatible applications. We use hardware (VM) virtualization to strongly isolate different rump kernel instances from each other. Because the original rumprun unikernel targeted a much simpler model for uniprocessor systems, we redesigned it to support multicore systems. Unlike kernel-bypass libraries such as DPDK, applications need not be modified to benefit from direct hardware access. LibrettOS also supports indirect access through a network server that we have developed. Applications remain uninterrupted even when network components fail or need to be upgraded. Finally, to efficiently use hardware resources, applications can dynamically switch between the indirect and direct modes based on their I/O load at run-time. [full abstract is in the paper]Comment: 16th ACM SIGPLAN/SIGOPS International Conference on Virtual Execution Environments (VEE '20), March 17, 2020, Lausanne, Switzerlan

Climate Change Meets the Law of the Horse

The climate change policy debate has only recently turned its full attention to adaptation - how to address the impacts of climate change we have already begun to experience and that will likely increase over time. Legal scholars have in turn begun to explore how the many different fields of law will and should respond. During this nascent period, one overarching question has gone unexamined: how will the legal system as a whole organize around climate change adaptation? Will a new distinct field of climate change adaptation law and policy emerge, or will legal institutions simply work away at the problem through unrelated, duly self-contained fields, as in the famous Law of the Horse? This Article is the first to examine that question comprehensively, to move beyond thinking about the law and climate change adaptation to consider the law of climate change adaptation. Part I of the Article lays out our methodological premises and approach. Using a model we call Stationarity Assessment, Part I explores how legal fields are structured and sustained based on assumptions about the variability of natural, social, and economic conditions, and how disruptions to that regime of variability can lead to the emergence of new fields of law and policy. Case studies of environmental law and environmental justice demonstrate the model’s predictive power for the formation of new distinct legal regimes. Part II applies the Stationarity Assessment model to the topic of climate change adaptation, using a case study of a hypothetical coastal region and the potential for climate change impacts to disrupt relevant legal doctrines and institutions. We find that most fields of law appear capable of adapting effectively to climate change. In other words, without some active intervention, we expect the law and policy of climate change adaptation to follow the path of the Law of the Horse - a collection of fields independently adapting to climate change - rather than organically coalescing into a new distinct field. Part III explores why, notwithstanding this conclusion, it may still be desirable to seek a different trajectory. Focusing on the likelihood of systemic adaptation decisions with perverse, harmful results, we identify the potential benefits offered by intervening to shape a new and distinct field of climate change adaptation law and policy. Part IV then identifies the contours of such a field, exploring the distinct purposes of reducing vulnerability, ensuring resiliency, and safeguarding equity. These features provide the normative policy components for a law of climate change adaptation that would be more than just a Law of the Horse. This new field would not replace or supplant any existing field, however, as environmental law did with regard to nuisance law, and it would not be dominated by substantive doctrine. Rather, like the field of environmental justice, this new legal regime would serve as a holistic overlay across other fields to ensure more efficient, effective, and just climate change adaptation solutions

Bacterial Symbiosis Maintenance in the Asexually Reproducing and Regenerating Flatworm Paracatenula galateia

Bacteriocytes set the stage for some of the most intimate interactions between animal and bacterial cells. In all bacteriocyte possessing systems studied so far, de novo formation of bacteriocytes occurs only once in the host development, at the time of symbiosis establishment. Here, we present the free-living symbiotic flatworm Paracatenula galateia and its intracellular, sulfur-oxidizing bacteria as a system with previously undescribed strategies of bacteriocyte formation and bacterial symbiont transmission. Using thymidine analogue S-phase labeling and immunohistochemistry, we show that all somatic cells in adult worms – including bacteriocytes – originate exclusively from aposymbiotic stem cells (neoblasts). The continued bacteriocyte formation from aposymbiotic stem cells in adult animals represents a previously undescribed strategy of symbiosis maintenance and makes P. galateia a unique system to study bacteriocyte differentiation and development. We also provide morphological and immunohistochemical evidence that P. galateia reproduces by asexual fragmentation and regeneration (paratomy) and, thereby, vertically transmits numerous symbiont-containing bacteriocytes to its asexual progeny. Our data support the earlier reported hypothesis that the symbiont population is subjected to reduced bottleneck effects. This would justify both the codiversification between Paracatenula hosts and their Candidatus Riegeria symbionts, and the slow evolutionary rates observed for several symbiont genes