The Complexity of Routing with Few Collisions

We study the computational complexity of routing multiple objects through a network in such a way that only few collisions occur: Given a graph $G$ with two distinct terminal vertices and two positive integers $p$ and $k$, the question is whether one can connect the terminals by at least $p$ routes (e.g. paths) such that at most $k$ edges are time-wise shared among them. We study three types of routes: traverse each vertex at most once (paths), each edge at most once (trails), or no such restrictions (walks). We prove that for paths and trails the problem is NP-complete on undirected and directed graphs even if $k$ is constant or the maximum vertex degree in the input graph is constant. For walks, however, it is solvable in polynomial time on undirected graphs for arbitrary $k$ and on directed graphs if $k$ is constant. We additionally study for all route types a variant of the problem where the maximum length of a route is restricted by some given upper bound. We prove that this length-restricted variant has the same complexity classification with respect to paths and trails, but for walks it becomes NP-complete on undirected graphs

Clinical predictors of antipsychotic use in children and adolescents with autism spectrum disorders: a historical open cohort study using electronic health records.

JOURNAL ARTICLEThe final publication is available at Springer via http://dx.doi.org/ 10.1007/s00787-015-0780-7Children with autism spectrum disorders (ASD) are more likely to receive antipsychotics than any other psychopharmacological medication, yet the psychiatric disorders and symptoms associated with treatment are unclear. We aimed to determine the predictors of antipsychotic use in children with ASD receiving psychiatric care. The sample consisted of 3482 children aged 3-17 with an ICD-10 diagnosis of ASD referred to mental health services between 2008 and 2013. Antipsychotic use outcome, comorbid diagnoses, and other clinical covariates, including challenging behaviours were extracted from anonymised patient records. Of the 3482 children (79 % male) with ASD, 348 (10 %) received antipsychotic medication. The fully adjusted model indicated that comorbid diagnoses including hyperkinetic (OR 1.44, 95 %CI 1.01-2.06), psychotic (5.71, 3.3-10.6), depressive (2.36, 1.37-4.09), obsessive-compulsive (2.31, 1.16-4.61) and tic disorders (2.76, 1.09-6.95) were associated with antipsychotic use. In addition, clinician-rated levels of aggression, self-injurious behaviours, reduced adaptive function, and overall parental concern for their child's presenting symptoms were significant risk factors for later antipsychotic use. In ASD, a number of comorbid psychiatric disorders are independent predictors for antipsychotic treatment, even after adjustment for familial, socio-demographic and individual factors. As current trial evidence excludes children with comorbidity, more pragmatic randomised controlled trials with long-term drug monitoring are needed.NIHRBiomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College LondonGuy’s and St. Thomas’ CharityMaudsley CharityMR

Lightfastness assessment of Levantine rock art by means of microfading spectrometry

This is the peer reviewed version of the following article: del Hoyo-Meléndez JM, Carrión-Ruiz B, Riutort-Mayol G, Lerma JL. Lightfastness assessment of Levantine rock art by means of microfading spectrometry. Color Res Appl. 2019;44:547 555, which has been published in final form at https://doi.org/10.1002/col.22372. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] The documentation of archeological sites requires the adoption of non-destructive techniques to safeguard the unique legacy coming from prehistoric periods. This article tackles the assessment of lightfastness properties on a rock art site to deter- mine the behavior of motif's color deterioration over time in Remi¿gia Cave, Castello¿n (Spain), which is considered part of a UNESCO World Heritage Site. The measurements were performed using a microfade testing device to analyze the spectral characteristics and the aging properties of the colorant system and various substrates on site. Two scenarios have been identified depending on whether the lightness (L*) parameter of the rocky substrate changes or not in relation with the painted motifs. If the substrate remains stable without any change, red motifs con- taining iron oxide pigments will become more visible. If the substrate becomes lighter, the pigments will experience similar changes. Therefore, the contrast between paintings and support will be considerably enhanced.The authors also would like to thank the Generalitat Valenciana for providing access to the site during the measurement campaigns. Fruitful comments from the Spanish archeologists Prof. Valentín Villaverde and Dra. Esther López-Montalvo are also gratefully acknowledged. The authors acknowledge the research project HAR2014-59873-R from the Spanish Ministerio de Economía y Competitividad for providing financial support.Del Hoyo-Meléndez, JM.; Carrión-Ruiz, B.; Riutort-Mayol, G.; Lerma, JL. (2019). Lightfastness assessment of Levantine rock art by means of microfading spectrometry. Color Research & Application. 44(4):547-555. https://doi.org/10.1002/col.22372S547555444Vileikis, O., Cesaro, G., Santana Quintero, M., van Balen, K., Paolini, A., & Vafadari, A. (2012). Documentation in World Heritage conservation. Journal of Cultural Heritage Management and Sustainable Development, 2(2), 130-152. doi:10.1108/20441261211273635Management Planning for Archaelogical Sites 2002 The Getty Conservation Institute Los Angeles G Palumbo Threats and challenges to the archaeological heritage in the Mediterranean 3 12ICOMOS. ICOMOS World Report 2000 on Monuments and Sites in Danger; 2000.https://www.icomos.org/risk/world_report/2000/risk2000.htm. Accessed October 25 2017.Giesen, M. J., Ung, A., Warke, P. A., Christgen, B., Mazel, A. D., & Graham, D. W. (2014). Condition assessment and preservation of open-air rock art panels during environmental change. Journal of Cultural Heritage, 15(1), 49-56. doi:10.1016/j.culher.2013.01.013Díez-Herrero, A., Gutiérrez-Pérez, I., Lario, J., Cañaveras, J. C., Benavente, D., Sánchez-Moral, S., & Alonso-Azcárate, J. (2009). Analysis of potential direct insolation as a degradation factor of cave paintings in Villar del Humo, Cuenca, Central Spain. Geoarchaeology, 24(4), 450-465. doi:10.1002/gea.20274López-Montalvo, E., Villaverde, V., Roldán, C., Murcia, S., & Badal, E. (2014). An approximation to the study of black pigments in Cova Remigia (Castellón, Spain). Technical and cultural assessments of the use of carbon-based black pigments in Spanish Levantine Rock Art. Journal of Archaeological Science, 52, 535-545. doi:10.1016/j.jas.2014.09.017Hernanz, A., Ruiz-López, J. F., Gavira-Vallejo, J. M., Martin, S., & Gavrilenko, E. (2010). Raman microscopy of prehistoric rock paintings from the Hoz de Vicente, Minglanilla, Cuenca, Spain. Journal of Raman Spectroscopy, 41(11), 1394-1399. doi:10.1002/jrs.2582Domingo, I., Villaverde, V., López-Montalvo, E., Lerma, J. L., & Cabrelles, M. (2013). Latest developments in rock art recording: towards an integral documentation of Levantine rock art sites combining 2D and 3D recording techniques. Journal of Archaeological Science, 40(4), 1879-1889. doi:10.1016/j.jas.2012.11.024Iturbe, A., Cachero, R., Cañal, D., & Martos, A. (2018). Digitalización de cuevas con arte paleolítico parietal de Bizkaia. Análisis científico y divulgación mediante nuevas técnicas de visualización. Virtual Archaeology Review, 9(18), 57. doi:10.4995/var.2018.7579Carrión-Ruiz, B., Blanco-Pons, S., & Lerma, J. L. (2016). DIGITAL IMAGE ANALYSIS OF THE VISIBLE REGION THROUGH SIMULATION OF ROCK ART PAINTINGS. Proceedings of the ARQUEOLÓGICA 2.0 8th International Congress on Archaeology, Computer Graphics, Cultural Heritage and Innovation. doi:10.4995/arqueologica8.2016.3560Fredlund, G., & Sundstrom, L. (2007). Digital infra-red photography for recording painted rock art. Antiquity, 81(313), 733-742. doi:10.1017/s0003598x00095697Cerrillo-Cuenca, E., & Sepúlveda, M. (2015). An assessment of methods for the digital enhancement of rock paintings: the rock art from the precordillera of Arica (Chile) as a case study. Journal of Archaeological Science, 55, 197-208. doi:10.1016/j.jas.2015.01.006Robert, E., Petrognani, S., & Lesvignes, E. (2016). Applications of digital photography in the study of Paleolithic cave art. Journal of Archaeological Science: Reports, 10, 847-858. doi:10.1016/j.jasrep.2016.07.026López-Menchero Bendicho, V. M., Marchante Ortega, Á., Vincent, M., Cárdenas Martín-Buitrago, Á. J., & Onrubia Pintado, J. (2017). Uso combinado de la fotografía digital nocturna y de la fotogrametría en los procesos de documentación de petroglifos: el caso de Alcázar de San Juan (Ciudad Real, España). Virtual Archaeology Review, 8(17), 64. doi:10.4995/var.2017.6820Molada-Tebar, A., Lerma, J. L., & Marqués-Mateu, Á. (2017). Camera characterization for improving color archaeological documentation. Color Research & Application, 43(1), 47-57. doi:10.1002/col.22152Del Hoyo-Meléndez, J. M., Lerma, J. L., López-Montalvo, E., & Villaverde, V. (2015). Documenting the light sensitivity of Spanish Levantine rock art paintings. ISPRS Annals of Photogrammetry, Remote Sensing and Spatial Information Sciences, II-5/W3, 53-59. doi:10.5194/isprsannals-ii-5-w3-53-2015Whitmore, P. M., Bailie, C., & Connors, S. A. (2000). Micro-fading tests to predict the result of exhibition: progress and prospects. Studies in Conservation, 45(sup1), 200-205. doi:10.1179/sic.2000.45.supplement-1.200Whitmore, P. M., Pan, X., & Bailie, C. (1999). Predicting the Fading of Objects: Identification of Fugitive Colorants through Direct Nondestructive Lightfastness Measurements. Journal of the American Institute for Conservation, 38(3), 395. doi:10.2307/3179999Ford, B. (2011). Non-destructive microfade testing at the National Museum of Australia. AICCM Bulletin, 32(1), 54-64. doi:10.1179/bac.2011.32.1.008Del Hoyo-Meléndez, J. M., & Mecklenburg, M. F. (2010). A survey on the light-fastness properties of organic-based Alaska Native artifacts. Journal of Cultural Heritage, 11(4), 493-499. doi:10.1016/j.culher.2010.01.004Conservation of Ancient Sites on the Silk Road 2010 The Getty Conservation Institute The Getty. Los Angeles JR Druzik Evaluating the light sensitivity of paints in selected wall paintings at the Mogao Grottoes: caves 217 98 and 85 457 463López-Montalvo, E., Roldán, C., Badal, E., Murcia-Mascarós, S., & Villaverde, V. (2017). Identification of plant cells in black pigments of prehistoric Spanish Levantine rock art by means of a multi-analytical approach. A new method for social identity materialization using chaîne opératoire. PLOS ONE, 12(2), e0172225. doi:10.1371/journal.pone.0172225Roldán, C., Murcia-Mascarós, S., Ferrero, J., Villaverde, V., López, E., Domingo, I., … Guillem, P. M. (2010). Application of field portable EDXRF spectrometry to analysis of pigments of Levantine rock art. X-Ray Spectrometry, 39(3), 243-250. doi:10.1002/xrs.1254Roldán García, C., Villaverde Bonilla, V., Ródenas Marín, I., & Murcia Mascarós, S. (2016). A Unique Collection of Palaeolithic Painted Portable Art: Characterization of Red and Yellow Pigments from the Parpalló Cave (Spain). PLOS ONE, 11(10), e0163565. doi:10.1371/journal.pone.0163565Łojewski, T., Thomas, J., Gołąb, R., Kawałko, J., & Łojewska, J. (2011). Note: Light ageing with simultaneous colorimetry via fibre optics reflection spectrometry. Review of Scientific Instruments, 82(7), 076102. doi:10.1063/1.3606645Ruppert, D., Wand, M. P., & Carroll, R. J. (2009). Semiparametric regression during 2003–2007. Electronic Journal of Statistics, 3(0), 1193-1256. doi:10.1214/09-ejs525ISO11664‐2:2007(E)/CIE S 014‐2/E:2006 Colorimetry—Part 2: Standard Illuminants for Colorimetry.http://cie.co.at/index.php?i_ca_id=484. Accessed October 25 2017.ISO11664‐1:2007(E)/CIE S 014‐1/E:2006 CIE Colorimetry—Part 1: Standard Colorimetric Observers.http://cie.co.at/index.php?i_ca_id=483. Accessed October 25 2017.Arkivprodukter. The Blue Wool Standards.www.arkivprodukter.no. Accessed November 23 2017.Bacci, M., Cucci, C., Mencaglia, A. A., Mignani, A. G., & Porcinai, S. (2004). Calibration and Use of Photosensitive Materials for Light Monitoring in Museums. Studies in Conservation, 49(2), 85-98. doi:10.1179/sic.2004.49.2.85ISO 12647‐2. International Standard for the Production of Half‐Tone Colour.2004;2004

The Evolutionary Status of Clusters of Galaxies at z ~ 1

Combined HST, X-ray, and ground-based optical studies show that clusters of galaxies are largely "in place" by $z \sim 1$, an epoch when the Universe was less than half its present age. High resolution images show that elliptical, S0, and spiral galaxies are present in clusters at redshifts up to $z \sim 1.3$. Analysis of the CMDs suggest that the cluster ellipticals formed their stars several Gyr earlier, near redshift 3. The morphology--density relation is well established at $z\sim1$, with star-forming spirals and irregulars residing mostly in the outer parts of the clusters and E/S0s concentrated in dense clumps. The intracluster medium has already reached the metallicity of present-day clusters. The distributions of the hot gas and early-type galaxies are similar in $z\sim1$ clusters, indicating both have largely virialized in the deepest potentials wells. In spite of the many similarities between $z\sim1$ and present-day clusters, there are significant differences. The morphologies revealed by the hot gas, and particularly the early-type galaxies, are elongated rather than spherical. We appear to be observing the clusters at an epoch when the sub-clusters and groups are still assembling into a single regular cluster. Support for this picture comes from CL0152 where the gas appears to be lagging behind the luminous and dark mass in two merging sub-components. Moreover, the luminosity difference between the first and second brightest cluster galaxies at $z\sim1$ is smaller than in 93% of present-day Abell clusters, which suggests that considerable luminosity evolution through merging has occurred since that epoch. Evolution is also seen in the bolometric X-ray luminosity function.Comment: 18 pages, 12 figures, to appear in Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuing Fork Strikes a New Note, eds. D.L. Block, K.C. Freeman, I. Puerari & R. Groess. Figures degraded to meet astroph size limit; a version with higher resolution figures may be downloaded from: http://acs.pha.jhu.edu/~jpb/z1clusters/ford_clusters.pd

Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease The PRESERVE Randomized Clinical Trial

Importance: Blood pressure lowering is considered neuroprotective in patients with cerebral small vessel disease, however more “intensive” regimens may increase cerebral hypoperfusion. We examined the effect of intensive vs. standard blood pressure treatment on cerebral perfusion in severe small vessel disease patients. Objective: To determine whether intensive vs. standard blood pressure lowering over 3 months causes decreased cerebral perfusion. Design, Setting and Participants: This randomised, parallel, controlled, blinded-outcomes clinical trial took place in 2 English university medical centres. A central, online randomisation system (1:1 ratio) allocated grouping. 70 hypertensive patients with MRI confirmed symptomatic lacunar infarct and confluent white matter hyperintensities were recruited between 2012 and 2015, and randomised (36/34 in standard/intensive arms). Analysable data were available in 62 patients, 33/29 in the standard/intensive groups respectively, for intention to treat analysis. This experiment examines the 3 month follow-up period. Intervention: Patients were randomised to “standard” (systolic=130-140mmHg) or “intensive” (systolic=<125mmHg) blood pressure targets, to be achieved through medication regimen changes. Main Outcome and Measure: Cerebral perfusion was determined using arterial spin labelling; the primary end point was change in global perfusion between baseline and 3 months, compared between treatment groups by ANOVA. Linear regression compared change in perfusion against change in blood pressure. MR scan analysis was blinded to treatment arm. Results: Patients were 69.3 years old (mean) and 59.7% male. Mean(SD) systolic blood pressure reduced by 8(12) and 27(17)mmHg in the standard/intensive groups, respectively (p<0.001), with achieved pressures of 141(13) and 126(10) mmHg respectively. Change in global perfusion did not differ between treatment arms: standard, mean(SD) (ml/min/100g)= -0.5(9.4); intensive, 0.7(8.6), partial ETA2= 0.004, 95% CI= -3.6–5.8, p= 0.63. No differences were observed when analysis examined grey/white matter only, or was confined to those achieving target blood pressure. The number of adverse events did not differ between treatment groups (standard/intensive mean(SD)= .21(.65)/.32(.75), p=.44). Conclusions and Relevance: Intensive blood pressure lowering did not reduce cerebral perfusion in severe small vessel disease.This study was funded by a joint Stroke Association/British Heart Foundation program grant (TSA BHF 2010/01). The study received additional support from the Newcastle Biomedical Research Centre, which is funded by the National Institute for Health Research (NIHR). Drs O’Brien, Ford, and Markus are supported by NIHR Senior Investigator awards. Drs O’Brien and Markus are also supported by the Cambridge University Hospitals NIHR Comprehensive Biomedical Research Centre

Measurement of the antineutrino neutral-current elastic differential cross section

arXiv:1309.7257v1 [hep-ex

Impact of the Specific Mutation in KRAS Codon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy. Copyright (C) 2012 S. Karger AG, Base

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Distinguishing the Impacts of Inadequate Prey and Vessel Traffic on an Endangered Killer Whale (Orcinus orca) Population

Managing endangered species often involves evaluating the relative impacts of multiple anthropogenic and ecological pressures. This challenge is particularly formidable for cetaceans, which spend the majority of their time underwater. Noninvasive physiological approaches can be especially informative in this regard. We used a combination of fecal thyroid (T3) and glucocorticoid (GC) hormone measures to assess two threats influencing the endangered southern resident killer whales (SRKW; Orcinus orca) that frequent the inland waters of British Columbia, Canada and Washington, U.S.A. Glucocorticoids increase in response to nutritional and psychological stress, whereas thyroid hormone declines in response to nutritional stress but is unaffected by psychological stress. The inadequate prey hypothesis argues that the killer whales have become prey limited due to reductions of their dominant prey, Chinook salmon (Oncorhynchus tshawytscha). The vessel impact hypothesis argues that high numbers of vessels in close proximity to the whales cause disturbance via psychological stress and/or impaired foraging ability. The GC and T3 measures supported the inadequate prey hypothesis. In particular, GC concentrations were negatively correlated with short-term changes in prey availability. Whereas, T3 concentrations varied by date and year in a manner that corresponded with more long-term prey availability. Physiological correlations with prey overshadowed any impacts of vessels since GCs were lowest during the peak in vessel abundance, which also coincided with the peak in salmon availability. Our results suggest that identification and recovery of strategic salmon populations in the SRKW diet are important to effectively promote SRKW recovery

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding