Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD

Statistically derived contributions of diverse human influences to twentieth-century temperature changes

The warming of the climate system is unequivocal as evidenced by an increase in global temperatures by 0.8 °C over the past century. However, the attribution of the observed warming to human activities remains less clear, particularly because of the apparent slow-down in warming since the late 1990s. Here we analyse radiative forcing and temperature time series with state-of-the-art statistical methods to address this question without climate model simulations. We show that long-term trends in total radiative forcing and temperatures have largely been determined by atmospheric greenhouse gas concentrations, and modulated by other radiative factors. We identify a pronounced increase in the growth rates of both temperatures and radiative forcing around 1960, which marks the onset of sustained global warming. Our analyses also reveal a contribution of human interventions to two periods when global warming slowed down. Our statistical analysis suggests that the reduction in the emissions of ozone-depleting substances under the Montreal Protocol, as well as a reduction in methane emissions, contributed to the lower rate of warming since the 1990s. Furthermore, we identify a contribution from the two world wars and the Great Depression to the documented cooling in the mid-twentieth century, through lower carbon dioxide emissions. We conclude that reductions in greenhouse gas emissions are effective in slowing the rate of warming in the short term.F.E. acknowledges financial support from the Consejo Nacional de Ciencia y Tecnologia (http://www.conacyt.gob.mx) under grant CONACYT-310026, as well as from PASPA DGAPA of the Universidad Nacional Autonoma de Mexico. (CONACYT-310026 - Consejo Nacional de Ciencia y Tecnologia; PASPA DGAPA of the Universidad Nacional Autonoma de Mexico

Formation of gutingimycin: analytical investigation of trioxacarcin A-mediated alkylation of dsDNA

Formation and fragmentation of recognition complexes between trioxacarcin A and various DNA sequences were examined by temperature-dependent UV and CD spectroscopy, HPLC analysis, and ESI mass spectrometry with regard to reaction conditions, intermediates, products, mechanism, and sequence specificity. Cleavage of the trioxacarcin–DNA complexes provided the natural product gutingimycin by guanine abstraction. The resulting DNA with an abasic site was further cleaved into a DNA fragment with a furanyl unit at the 3′-end and an oligonucleotide with a phosphorylated 5′-end

Update to the study protocol, including statistical analysis plan for a randomized clinical trial comparing comprehensive cardiac rehabilitation after heart valve surgery with control: the CopenHeartVR trial

Comparative StudyRandomized Controlled TrialThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. METHODS: This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. CONCLUSION: This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). TRIAL REGISTRATION: Trial registered 16 March 2012; ClinicalTrials.gov ( NCT01558765 ).This work is supported by the Strategic Research Council, The Heart Centre Research Foundation Rigshospitalet, Familien Hede Nielsens Fond, The Regional Research Council of Region Sealand (Denmark), The National Institute of Public Health, and the University of Southern Denmark

Measuring Complex Morphological Traits with 3D Photogrammetry: A Case Study with Deer Antlers

The increasing availability of 3D-imaging technology provides new opportunities for measuring morphology. Photogrammetry enables easy 3D-data acquisition compared to conventional methods and here we assess its accuracy for measuring the size of deer antlers, a complex morphological structure. Using a proprietary photogrammetry software, we generated 3D images of antlers for 92 individuals from 29 species of cervids that vary widely in antler size and shape and used these to measure antler volume. By repeating the process, we found that the relative error averaged 8.5% of object size. Errors in converting arbitrary voxel units into real volumetric units accounted for 70% of the measurement variance and can therefore be reduced by replicating the conversion. We applied the method to clay models of known volume and found no indication of bias. The estimation was robust against variation in imaging device, distance and operator, but approximately 40 images per specimen were necessary to achieve good precision. We used the method to show that conventional measures of main-beam length are relatively poor estimators of antler volume. Using loose antlers of known weight, we also showed that the volume may be a relatively poor predictor of antler weight due to variation in bone density across species. We conclude that photogrammetry can be an efficient and accurate tool for measuring antlers, and likely many other complex morphological traits

PainDroid: An android-based virtual reality application for pain assessment

Earlier studies in the field of pain research suggest that little efficient intervention currently exists in response to the exponential increase in the prevalence of pain. In this paper, we present an Android application (PainDroid) with multimodal functionality that could be enhanced with Virtual Reality (VR) technology, which has been designed for the purpose of improving the assessment of this notoriously difficult medical concern. Pain- Droid has been evaluated for its usability and acceptability with a pilot group of potential users and clinicians, with initial results suggesting that it can be an effective and usable tool for improving the assessment of pain. Participant experiences indicated that the application was easy to use and the potential of the application was similarly appreciated by the clinicians involved in the evaluation. Our findings may be of considerable interest to healthcare providers, policy makers, and other parties that might be actively involved in the area of pain and VR research

A mixed methods approach to evaluating community drug distributor performance in the control of neglected tropical diseases

BACKGROUND: Trusted literate, or semi-literate, community drug distributors (CDDs) are the primary implementers in integrated preventive chemotherapy (IPC) programmes for Neglected Tropical Disease (NTD) control. The CDDs are responsible for safely distributing drugs and for galvanising communities to repeatedly, often over many years, receive annual treatment, create and update treatment registers, monitor for side-effects and compile treatment coverage reports. These individuals are 'volunteers' for the programmes and do not receive remuneration for their annual work commitment. METHODS: A mixed methods approach, which included pictorial diaries to prospectively record CDD use of time, structured interviews and focus group discussions, was used to triangulate data on how 58 CDDs allocated their time towards their routine family activities and to NTD Programme activities in Uganda. The opportunity costs of CDD time were valued, performance assessed by determining the relationship between time and programme coverage, and CDD motivation for participating in the programme was explored. RESULTS: Key findings showed approximately 2.5 working weeks (range 0.6-11.4 working weeks) were spent on NTD Programme activities per year. The amount of time on NTD control activities significantly increased between the one and three deliveries that were required within an IPC campaign. CDD time spent on NTD Programme activities significantly reduced time available for subsistence and income generating engagements. As CDDs took more time to complete NTD Programme activities, their treatment performance, in terms of validated coverage, significantly decreased. Motivation for the programme was reported as low and CDDs felt undervalued. CONCLUSIONS: CDDs contribute a considerable amount of opportunity cost to the overall economic cost of the NTD Programme in Uganda due to the commitment of their time. Nevertheless, programme coverage of at least 75 %, as required by the World Health Organisation, is not being achieved and vulnerable individuals may not have access to treatment as a consequence of sub-optimal performance by the CDDs due to workload and programmatic factors