Insights into the decontamination of cocaine-positive hair samples

A highly discussed step in hair sample preparation for forensic analytics is the applied decontamination. The here presented investigations aim to gain insight and give recommendations on how to conduct this decontamination for the analysis of cocaine consumption in hair. Key insights were gained from the investigation of cocaine consumer hair, which was artificially contaminated in a humid atmosphere with 13C6 labelled cocaine and from cocaine powder contaminated hair. Several decontamination protocols were investigated, whereby the usage of a decontamination protocol consisting of multiple short repetitive washes allowed to visualize the wash-out of (13C6-) cocaine. Multiple methanol washes proved to be an efficient and simple decontamination approach. Our findings showed that decontamination protocols can successfully wash-out recent cocaine contaminations. They were observed to be rather quickly washed-out, whereas cocaine from consumption or “older” cocaine contaminations were shown to eliminate both at a constant rate (from inner hair compartments). Thus, the usage of decontamination protocols to differentiate between consumption and contamination was shown to be limited. As contamination can happen any time at any level, only the application of elaborated decision trees, based on cocaine metabolite ratios and thresholds, can provide the distinction between consumption and contamination. Thus, the authors highly recommend the usage of such tools on all hair samples analyzed for cocaine consumption

Circumstellar Structure around Evolved Stars in the Cygnus-X Star Formation Region

We present observations of newly discovered 24 micron circumstellar structures detected with the Multiband Imaging Photometer for Spitzer (MIPS) around three evolved stars in the Cygnus-X star forming region. One of the objects, BD+43 3710, has a bipolar nebula, possibly due to an outflow or a torus of material. A second, HBHA 4202-22, a Wolf-Rayet candidate, shows a circular shell of 24 micron emission suggestive of either a limb-brightened shell or disk seen face-on. No diffuse emission was detected around either of these two objects in the Spitzer 3.6-8 micron Infrared Array Camera (IRAC) bands. The third object is the luminous blue variable candidate G79.29+0.46. We resolved the previously known inner ring in all four IRAC bands. The 24 micron emission from the inner ring extends ~1.2 arcmin beyond the shorter wavelength emission, well beyond what can be attributed to the difference in resolutions between MIPS and IRAC. Additionally, we have discovered an outer ring of 24 micron emission, possibly due to an earlier episode of mass loss. For the two shell stars, we present the results of radiative transfer models, constraining the stellar and dust shell parameters. The shells are composed of amorphous carbon grains, plus polycyclic aromatic hydrocarbons in the case of G79.29+0.46. Both G79.29+0.46 and HBHA 4202-22 lie behind the main Cygnus-X cloud. Although G79.29+0.46 may simply be on the far side of the cloud, HBHA 4202-22 is unrelated to the Cygnus-X star formation region.Comment: Accepted by A

Exercise medicine for cancer cachexia: Targeted exercise to counteract mechanisms and treatment side-effects

Purpose: Cancer-induced muscle wasting (i.e., cancer cachexia, CC) is a common and devastating syndrome that results in the death of more than 1 in 5 patients. Although primarily a result of elevated inflammation, there are multiple mechanisms that complement and amplify one another. Research on the use of exercise to manage CC is still limited, while exercise for CC management has been recently discouraged. Moreover, there is a lack of understanding that exercise is not a single medicine, but mode, type, dosage, and timing (exercise prescription) have distinct health outcomes. The purpose of this review was to examine the effects of these modes and subtypes to identify the most optimal form and dosage of exercise therapy specific to each underlying mechanism of CC. Methods: The relevant literatures from MEDLINE and Scopus databases were examined. Results: Exercise can counteract the most prominent mechanisms and signs of CC including muscle wasting, increased protein turnover, systemic inflammation, reduced appetite and anorexia, increased energy expenditure and fat wasting, insulin resistance, metabolic dysregulation, gut dysbiosis, hypogonadism, impaired oxidative capacity, mitochondrial dysfunction, and cancer treatments side-effects. There are different modes of exercise, and each mode has different sub-types that induce vastly diverse changes when performed over multiple sessions. Choosing suboptimal exercise modes, types, or dosages can be counterproductive and could further contribute to the mechanisms of CC without impacting muscle growth. Conclusion: Available evidence shows that patients with CC can safely undertake higher-intensity resistance exercise programs, and benefit from increases in body mass and muscle mass

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies

How Much Does Self- Talk Influence Fatigue? A Comparison of Performance, Perceived Exertion, and Neuromuscular Patterns during High-Intensity Power Cleans

Experienced athletes use self-talk (ST) when challenged to monitor distress, to continue effort, and battle fatigue. The power clean, a training modality for power sports, challenges athletes to develop cognitive strategies to maintain performance, technique, and persist. A problem has been that ST studies have not measured perception of effort and muscle firing when ST is purposefully withheld. The purpose of this study was to compare the effects of ST to a control group during a session of power clean to fatigue. Also, multiple parameters were assessed and included perceptual, neural, and performance standards. The method of randomly assigned ST and control (CON) groups compared 24 experienced Olympic lifting men (age range 18 to 28 years). The groups completed continuous sets of power cleans for three repetitions at 85% of maximum effort with a three-minute rest in between sets until failure. The ST group was instructed to engage in organic, goal-directed self-talk (ST group) during exercise. The CON group focused on a neutral attentional focus. The results demonstrated that the ST group achieved more sets, reps, and total weight lifted (p < 0.05). Both groups had comparable increases in perceived exertion prior to fatigue (p < 0.001). Persistence (numbers of sets and repetitions) after reaching the perceptual breakpoint (RPE of “8”) was higher for the ST group (p <0.01) by 8.5 repetitions. Pain tolerance was slightly higher in the ST group as well. The ST group demonstrated lower activation in two muscle groups despite performing more work. In conclusion, ST enhanced performance by 43% once an RPE of eight was reached, resulted in 63% more repetitions, and demonstrated more efficient muscle activation patterns.

[Letter] A distinct genotype of XP complementation group A: surprisingly mild phenotype highly prevalent in Northern India/ Pakistan/ Afghanistan

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The personalized advantage index: Translating research on prediction into individualized treatment recommendations. A demonstration

Background: Advances in personalized medicine require the identification of variables that predict differential response to treatments as well as the development and refinement of methods to transform predictive information into actionable recommendations. Objective: To illustrate and test a new method for integrating predictive information to aid in treatment selection, using data from a randomized treatment comparison. Method: Data from a trial of antidepressant medications (N = 104) versus cognitive behavioral therapy (N = 50) for Major Depressive Disorder were used to produce predictions of post-treatment scores on the Hamilton Rating Scale for Depression (HRSD) in each of the two treatments for each of the 154 patients. The patient's own data were not used in the models that yielded these predictions. Five pre-randomization variables that predicted differential response (marital status, employment status, life events, comorbid personality disorder, and prior medication trials) were included in regression models, permitting the calculation of each patient's Personalized Advantage Index (PAI), in HRSD units. Results: For 60% of the sample a clinically meaningful advantage (PAI≥3) was predicted for one of the treatments, relative to the other. When these patients were divided into those randomly assigned to their "Optimal" treatment versus those assigned to their "Non-optimal" treatment, outcomes in the former group were superior (d = 0.58, 95% CI .17-1.01). Conclusions: This approach to treatment selection, implemented in the context of two equally effective treatments, yielded effects that, if obtained prospectively, would rival those routinely observed in comparisons of active versus control treatments. © 2014 DeRubeis et al

Misuse of “Power” and other mechanical terms in sport and exercise science research

In spite of the Système International d’Unitès (SI) that was published in 1960, there continues to be widespread misuse of the terms and nomenclature of mechanics in descriptions of exercise performance. Misuse applies principally to failure to distinguish between mass and weight, velocity and speed, and especially the terms "work" and "power." These terms are incorrectly applied across the spectrum from high-intensity short-duration to long-duration endurance exercise. This review identifies these misapplications and proposes solutions. Solutions include adoption of the term "intensity" in descriptions and categorisations of challenge imposed on an individual as they perform exercise, followed by correct use of SI terms and units appropriate to the specific kind of exercise performed. Such adoption must occur by authors and reviewers of sport and exercise research reports to satisfy the principles and practices of science and for the field to advance

Moderators, Mediators, and Other Predictors of Risperidone Response in Children with Autistic Disorder and Irritability

Objective/Background: The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritabilityin autistic disorder. This paper explores moderators and mediators of this effect. Method: Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the evaluation of the results. Results: Only baseline severity moderated treatment response: Higher severity showed greater improvement for risperidone but not for placebo. Weight gain mediated treatment response negatively: Those who gained more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity negatively predicted outcome. Risperidone moderated the effect of change in 5'-nucleotidase, a marker of zinc status, for which decrease was associated with improvement only with risperidone, not with placebo. Conclusion: The benefit–risk ratio of risperidone is better with greater symptom severity. Risperidone can be individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and absence of co-morbid problems non-specifically predict better outcome. Mineral interactions with risperidone deserve further study

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine