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A recent DNA barcoding study of Australian microgastrines (Hymenoptera: Braconidae) sought to use next‐generation sequencing of the cytochrome c oxidase subunit 1 (COI) barcoding gene region, the wingless (WG) gene and the internal transcribed spacer 2 (ITS2) to delimit molecular species in a highly diverse group of parasitic wasps. Large intragenomic distances between ITS2 variants, often larger than the average interspecific variation, caused difficulties in using ITS2 for species delimitation in both threshold and tree‐based approaches, and the gene was not included in the reported results of the previous DNA barcoding study. We here report on the intragenomic, and the intra‐ and interspecies, variation in ITS2in the microgastrine genus Diolcogasterto further investigate the value of ITS2as a marker for species delimitation and phylogenetics of the Microgastrinae. Distinctive intragenomic variant patterns were found in different species of Diolcogaster, with some species possessing a single major variant, and others possessing many divergent variants. Characterizing intragenomic variation of ITS2is critical as it is a widely used marker in hymenopteran phylogenetics and species delimitation, and large intragenomic distances such as those found in this study may obscure phylogenetic signal. [ABSTRACT FROM AUTHOR]

Effective use of biological control agents (BCAs) is a potentially important component of sustainable agriculture. Recently, there has been an increasing interest among researchers in using combinations of BCAs to exploit potential synergistic effects among them. The methodology for investigating such synergistic effects was reviewed first and published results were then assessed for available evidence for synergy. Correct formulation of hypotheses based on the theoretical definition of independence (Bliss independence or Loewe additivity) and the subsequent and statistical testing for the independence-synergistic-antagonistic interactions have rarely been carried out thus far in studies on biocontrol of plant diseases. Thus, caution must be taken when interpreting reported "synergistic" effects without assessing the original publications. Recent theoretical modeling work suggested that disease suppression from combined use of two BCAs was. in general, very similar to that achieved by the more efficacious one, indicating no synergistic but more likely antagonistic interactions. Only in 2% of the total 465 published treatments was there evidence for synergistic effects among BCAs. In the majority of the cases, antagonistic interactions among BCAs were indicated. Thus. both theoretical and experimental studies suggest that, in combined use of BCAs, antagonistic interactions among BCAs are more likely to occur than synergistic interactions. Several research strategies, including formulation of synergy hypotheses in relation to biocontrol mechanisms, are outlined to exploit microbial mixtures for uses in biocontrol of plant diseases. Additional keywords: hypothesis testing. [ABSTRACT FROM AUTHOR]

The goal of this study was to develop a method for examining children's expectations about the short-term consequences of defensive interpersonal behaviour. We employed the theory of interpersonal defence (Dahmen & Westerman, in press; Westerman, 1998, 2005; Westerman & Prieto, 2006), an interpersonal reconceptualization of defence processes, as the framework for this method. We developed a two-part procedure for eliciting children's responses to closed-ended and open-ended questions about interpersonal vignettes presented in storyboard format, and we employed this method in a preliminary investigation with a sample of 62 intellectually gifted boys and girls aged 7-8 and 10-11. The results showed that the participants understood that defensive interpersonal behaviours affect the likelihood that feared and wished-for short-term outcomes will occur. Participants demonstrated that they understood that people behave defensively in order to avoid feared consequences and nondefensively in order to pursue wished-for outcomes. Findings also indicated that older participants understood that a person is more likely to behave defensively in highly conflict-ridden situations. The results suggest that our method provides the basis for research that complements previous studies of children's understanding of how intrapsychic defence mechanisms regulate a person's affective experience. Future research using this method could investigate the role of beliefs about defensive behaviour in the development of behaviour problems. [ABSTRACT FROM AUTHOR]

Stoma care nurses aim to meet the physical, psychological, social and spiritual needs of patients. Development of stoma care nursing services has varied, as it has been the responsibility of each nurse, resulting in differences in the mode of delivery. This qualitative and quantitative study involved stoma care nurses from six areas in Essex, to assess patient perception of the service they received. Overall, the satisfaction level was high despite differences in delivery of care especially timing and frequency of visits at home. [ABSTRACT FROM AUTHOR]

A previously published generic mathematic model has been used in a numerical study to understand the dynamics of foliar pathogens in relation to mechanisms, and timing and coverage of biocontrol agent (BCA) applications. With the model parameter values used, it was demonstrated that a BCA possessing either competition or induced resistance as the main mechanism of biological control was more effective in reducing disease development than a BCA with either mycoparasitism or antibiosis as its mechanism. Application coverage, ranging from 50 to 90%, had little effect on biocontrol efficacy, particularly for a BCA with competition and induced resistance as the main mechanism of biocontrol Conversely, delayed application of BCA had more profound effects on biocontrol efficacy for those with competition or induced resistance as their main mechanism than those with mycoparasitism and antibiosis. Biocontrol efficacy was greatest for a single BCA combining competition with mycoparasitism or antibiosis. The efficacy for a single BCA combining induced resistance with competition critically depended on application time; the efficacy was greatly reduced lot delayed applications. The present study suggests that development of an effective strategy for BCA application is critically dependent upon our quantitative understanding of several key biocontrol processes and their interactions. Without reliable quantitative estimation of these processes, it is impossible to make quantitative predictions about biological control and hence Io optimize BCA application strategies [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, wastewater surveillance was widely used to monitor temporal and geographical infection trends. Using this as a foundation, a statewide program for routine wastewater monitoring of gastrointestinal pathogens was established in Oklahoma. The results from 18 months of surveillance showed that wastewater concentrations of Salmonella , Campylobacter, and norovirus exhibit similar seasonal patterns to those observed in reported human cases (F = 4-29, p < 0.05) and that wastewater can serve as an early warning tool for increases in cases, offering between one- and two-weeks lead time. Approximately one third of outbreak alerts in wastewater correlated in time with confirmed outbreaks of Salmonella or Campylobacter and our results further indicated that several outbreaks are likely to go undetected through the traditional surveillance approach currently in place. Better understanding of the true distribution and burden of gastrointestinal infections ultimately facilitates better disease prevention and control and reduces the overall socioeconomic and healthcare related impact of these pathogens. In this respect, wastewater represents a unique opportunity for monitoring infections in real-time, without the need for individual human testing. With increasing demands for sustainable and low-cost disease surveillance, the usefulness of wastewater as a long-term method for tracking infectious disease transmission is likely to become even more pronounced.

SARS-CoV-2 was discovered among humans in late 2019 and rapidly spread across the world. Although the virus is transmitted by respiratory droplets, most infected persons also excrete viral particles in their feces. This fact prompted a range of studies assessing the usefulness of wastewater surveillance to determine levels of infection and transmission and produce early warnings of outbreaks in local communities, independently of human testing. In this study, we collected samples of wastewater from 13 locations across Oklahoma City, representing different population types, twice per week from November 2020 to end of March 2021. Wastewater samples were collected and analyzed for the presence and concentration of SARS-CoV-2 RNA using RT-qPCR. The concentration of SARS-CoV-2 in the wastewater showed notable peaks, preceding the number of reported COVID-19 cases by an average of one week (ranging between 4 and 10 days). The early warning lead-time for an outbreak or increase in cases was significantly higher in areas with larger Hispanic populations and lower in areas with a higher household income or higher proportion of persons aged 65 years or older. Using this relationship, we predicted the number of cases with an accuracy of 81-92% compared to reported cases. These results confirm the validity and timeliness of using wastewater surveillance for monitoring local disease transmission and highlight the importance of differences in population structures when interpreting surveillance outputs and planning preventive action., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To qualitatively explore perceptions of pain/suffering, disability, and coping by race among pregnant women facing the threat of a periviable delivery (22 0/7-24 6/7 weeks)., Study Design: Interviews were conducted in-hospital prior to delivery. Transcripts were coded verbatim and responses were stratified by race (white vs non-white). Conventional content analysis was conducted using NVivo 12., Results: We recruited 30 women (50% white, 50% non-white). Most women expressed love and acceptance of their babies and described pain as a "means to an end." Non-white women focused almost exclusively on immediate survival and perseverance, while white women expressed concerns about quality of life beyond the NICU. The majority of non-white women were unable to recall any discussions with their doctors about their baby's comfort, pain, or suffering., Conclusions: These findings may suggest that culturally tailored approaches to counseling and decision-support may be beneficial for patients from marginalized or minoritized groups.

Background: Values clarification can assist families facing the threat of periviable delivery in navigating the complexity of competing values related to death, disability, and quality of life (QOL)., Objective: We piloted values clarification exercises to inform resuscitation decision making and qualitatively assess perceptions of QOL., Methods: We conducted a mixed-method study of women with threatened periviable delivery (22 0/7-24 6/7 weeks) and their important others (IOs). Participants engaged in three values clarification activities as part of a semi-structured interview-(a) Card sorting nine conditions as an acceptable/unacceptable QOL for a child; (b) Rating/ranking seven common concerns in periviable decision making (scale 0-10, not at all to extremely important); and (c) "Agreed/disagreed" with six statements regarding end-of-life treatment, disability, and QOL. Participants were also asked to define "QOL" and describe their perceptions of a good and poor QOL for their child. Analysis was conducted using SAS version 9.4 and NVivo 12., Results: All mild disabilities were an acceptable QOL, while two-thirds of participants considered long-term mechanical ventilation unacceptable. Although pregnant women rated "Impact on Your Physical/Mental Health" (average 5.6) and IOs rated "Financial Concerns" the highest (average 6.6), both groups ranked "Financial Concerns" as the most important concern (median 5.0 and 6.0, respectively). Most participants agreed that "Any amount of life is better than no life at all" (pregnant women 62.1%; IOs 75.0%) and disagreed that resuscitation would cause "Too much suffering" for their child (pregnant women 71.4%; IOs 80.0%). Half were familiar with the phrase "QOL". Although the majority described a good QOL in terms of emotional well-being (eg "loved", "happy", "supported"), a poor QOL was described in terms of functionality (eg "dependent" and "confined"). Additionally, financial stability emerged as a distinctive theme when IOs discussed poor QOL., Conclusion: The study offers important insights on parental perspectives in periviable decision making and potential values clarification tools for decision support., (© 2019 John Wiley & Sons Ltd.)

During periviable deliveries, parents are confronted with overwhelming and challenging decisions. This study aimed to qualitatively explore the language that pregnant women and important others utilize when discussing palliation, or "comfort care," as a treatment option in the context of periviability. We prospectively recruited women admitted for a threatened periviable delivery (22-25 weeks) at 2 hospitals between September 2016 and January 2018. Using a semistructured interview guide, we investigated participants' perceptions of neonatal treatment options, asking items such as "How was the choice of resuscitation presented to you?" and "What were the options presented?" Conventional content analysis was used and matrices were created to facilitate using a within- and across-case approach to identify and describe patterns. Thirty women and 16 important others were recruited in total. Participants' descriptions of treatment options included resuscitating at birth or not resuscitating. Participants further described the option to not resuscitate as "comfort care," "implicit" comfort care, "doing nothing," and "withdrawal of care." This study revealed that many parents facing periviable delivery may lack an understanding of comfort care as a neonatal treatment option, highlighting the need to improve counseling efforts in order to maximize parents' informed decision-making.

The bio-integrated electronics industry is booming and becoming more integrated with biological tissues. To successfully integrate with the soft tissues of the body (eg. skin), the material must possess many of the same properties including compliance, toughness, elasticity, and tear resistance. In this work, we prepare mechanically and biologically skin-like materials (PSeD-U elastomers) by designing a unique physical and covalent hybrid crosslinking structure. The introduction of an optimal amount of hydrogen bonds significantly strengthens the resultant elastomers with 11 times the toughness and 3 times the strength of covalent crosslinked PSeD elastomers, while maintaining a low modulus. Besides, the PSeD-U elastomers show nonlinear mechanical behavior similar to skins. Furthermore, PSeD-U elastomers demonstrate the cytocompatibility and biodegradability to achieve better integration with tissues. Finally, piezocapacitive pressure sensors are fabricated with high pressure sensitivity and rapid response to demonstrate the potential use of PSeD-U elastomers in bio-integrated electronics.

Purpose: To assess the relationship between decision quality and mental health outcomes for women and their important others (IO) 3 months following periviable birth., Method: Mental health outcomes were assessed prior to delivery and at 3 months postpartum using depression (PHQ-9), anxiety (GAD-7), and post-traumatic stress disorder (PTSD) (IES-22) scales. Decision quality was measured in terms of Decisional Conflict, Control, Regret, and Satisfaction with Decision. Descriptive analyses and linear regression modeling were conducted using SAS version 9.4., Result: We recruited 30 eligible women and 16 IOs. Participants had mild anxiety and depression, and symptoms of PTSD were among bereaved parents. Participants with lower decision control had higher levels of depression (women: p = 0.014; IOs: p = 0.059) and anxiety (women: p = 0.053; IOs: p = 0.032). Depression was also associated with higher decisional regret (women: p = 0.073; IOs: p = 0.023)., Conclusion: Our findings suggest that decision quality is associated with mental health outcomes for families who experience periviable delivery.

Background: Shared decision-making (SDM) is optimal in the context of periviable delivery, where the decision to pursue life-support measures or palliation is both preference sensitive and value laden. We sought to develop a decision support tool (DST) prototype to facilitate SDM by utilizing a user-centered design research approach., Methods: We convened four patient and provider advisory boards with women and their partners who had experienced a surviving or non-surviving periviable delivery, pregnant women who had not experienced a prior preterm birth, and obstetric providers. Each 2-h session involved design research activities to generate ideas and facilitate sharing of values, goals, and attitudes. Participant feedback shaped the design of three prototypes (a tablet application, family story videos, and a virtual reality experience) to be tested in a final session., Results: Ninety-five individuals (48 mothers/partners; 47 providers) from two hospitals participated. Most participants agreed that the prototypes should include factual, unbiased outcomes and probabilities. Mothers and support partners also desired comprehensive explanations of delivery and care options, while providers wanted a tool to ease communication, help elicit values, and share patient experiences. Participants ultimately favored the tablet application and suggested that it include family testimonial videos., Conclusion: Our results suggest that a DST that combines unbiased information and understandable outcomes with family testimonials would be meaningful for periviable SDM. User-centered design was found to be a useful method for creating a DST prototype that may lead to improved effectiveness, usability, uptake, and dissemination in the future, by leveraging the expertise of a wide range of stakeholders.

Background and Objectives: Synthetic cannabinoid use is associated with severe problems, including psychosis, kidney failure, and death. Given that young adults are especially vulnerable to using synthetic cannabinoids, the current study sought to identify factors and consequences related to use within this population., Methods: 1140 undergraduates completed an online survey of synthetic cannabinoid use, consequences, and related constructs., Results: The prevalence of lifetime synthetic cannabinoid use was 7.9% (n = 90), 15.6% (n = 13) of which were regular users, meaning they used once a year or more often. Synthetic cannabinoid users reported multiple adverse effects (e.g., anxiety, paranoia, tachycardia, lightheadedness) and 16.7% (n = 15) of users said they considered or did go to the Emergency Room while using synthetic cannabinoids. In the entire sample, participants believed their friends (t = 18.3, p < .001) and students in general (t = 46.0, p < .001) use synthetic cannabinoids more than they do. Natural cannabis users were associated with increased odds of having tried synthetic cannabinoids than those who had never used natural cannabis, OR = 7.63 (4.44 to 13.14) p < .0001, and 92.2% (n = 83) of synthetic cannabinoid users reported lifetime use of natural cannabis. Common reasons for use were legality, not appearing on drug tests, and availability, not that students enjoyed using synthetic cannabinoids or thought they were safe to use., Discussion and Conclusions: Synthetic cannabinoid use is associated with a variety of negative consequences. The data also supports a strong link between natural cannabis use and synthetic cannabinoid use., Scientific Significance: Natural cannabis users appear to be a high-risk group for using synthetic cannabinoids. There are multiple negative effects associated with synthetic cannabinoid use and reasons for use relate to convenience vs. enjoyment. Data have important implications for prevention and treatment efforts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background. Because failed trial of labor after cesarean (TOLAC) is associated with greater morbidity than planned cesarean, it is important to distinguish women with a high likelihood of successful vaginal birth after cesarean (VBAC) from those likely to fail. The VBAC Calculator may help make this distinction but little is known about how often providers use it; nor whether use improves risk estimation and/or influences TOLAC counseling. Methods. In a cross-sectional survey, a convenience sample of obstetrical providers reported their likelihood (4-point Likert-type scale) to "Recommend,""Offer," or "Agree to" TOLAC for patients presented first through five clinical vignettes; then, in different order, by corresponding VBAC calculator estimates. Results. Of the 85 (of 101, 84% response rate) participants, 88% routinely performed TOLAC, but only 21% used the Calculator. The majority (67.1% to 89.3%) overestimated the likelihood of success for all but one vignette (which had the highest estimate of success). Most providers (42% to 89%) recommended TOLAC for all five vignettes. Given calculated estimates, the majority of providers (67% to 95%) recommended TOLAC for success estimates exceeding 40%. For estimates between 20% and 40%, most providers offered (58%) or agreed (68%) to TOLAC; and even below 20%, over half still agreed to TOLAC. The vignette with the lowest estimate of success (18.7%) had the weakest intraprovider agreement (kappa = 0.116; confidence interval [CI] = 0.045-0.187), whereas the strongest agreement was found in the two vignettes with highest success estimates: 77.9% (kappa = 0.549; CI = 0.382-0.716) and 96.6% (kappa = 0.527; CI = 0.284-0.770). Limitations. Survey responses may not reflect actual practice patterns. Conclusion. Providers are overly optimistic in their clinical estimation of VBAC success. Wider use of decision support could aid in risk stratification and TOLAC counseling to reduce patient morbidity., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams., Objective: This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep., Methods: A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight., Results: Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery, particularly in the TMJ field, by proposing a rigorous design in black Merino sheep. The authors also intend to test the feasibility of pilot outcomes. The authors expect to increase the quality of further studies in this field and to progress in future treatment options for patients undergoing surgery for TMJ disk replacement., Conclusions: The study has commenced, but it is too early to provide results or conclusions., (©David Faustino Ângelo, Florencio Gil Monje, Raúl González-García, Christopher B Little, Lisete Mónico, Mário Pinho, Fábio Abade Santos, Belmira Carrapiço, Sandra Cavaco Gonçalves, Pedro Morouço, Nuno Alves, Carla Moura, Yadong Wang, Eric Jeffries, Jin Gao, Rita Sousa, Lia Lucas Neto, Daniel Caldeira, Francisco Salvado. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.03.2017.)

Successful regeneration of nerves can benefit from biomaterials that provide a supportive biochemical and mechanical environment while also degrading with controlled inflammation and minimal scar formation. Herein, we report a neuroactive polymer functionalized by covalent attachment of the neurotransmitter acetylcholine (Ach). The polymer was readily synthesized in two steps from poly(sebacoyl diglyceride) (PSeD), which previously demonstrated biocompatibility and biodegradation in vivo. Distinct from prior acetylcholine-biomimetic polymers, PSeD-Ach contains both quaternary ammonium and free acetyl moieties, closely resembling native acetylcholine structure. The polymer structure was confirmed via (1)H nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Hydrophilicity, charge, and thermal properties of PSeD-Ach were determined by tensiometer, zetasizer, differential scanning calorimetry, and thermal gravimetric analysis, respectively. PC12 cells exhibited the greatest proliferation and neurite outgrowth on PSeD-Ach and laminin substrates, with no significant difference between these groups. PSeD-Ach yielded much longer neurite outgrowth than the control polymer containing ammonium but no the acetyl group, confirming the importance of the entire acetylcholine-like moiety. Furthermore, PSeD-Ach supports adhesion of primary rat dorsal root ganglions and subsequent neurite sprouting and extension. The sprouting rate is comparable to the best conditions from previous report. Our findings are significant in that they were obtained with acetylcholine-like functionalities in 100% repeating units, a condition shown to yield significant toxicity in prior publications. Moreover, PSeD-Ach exhibited favorable mechanical and degradation properties for nerve tissue engineering application. Humidified PSeD-Ach had an elastic modulus of 76.9 kPa, close to native neural tissue, and could well recover from cyclic dynamic compression. PSeD-Ach showed a gradual in vitro degradation under physiologic conditions with a mass loss of 60% within 4 weeks. Overall, this simple and versatile synthesis provides a useful tool to produce biomaterials for creating the appropriate stimulatory environment for nerve regeneration.

Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4., (© The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Aims: This proof-of-concept study was designed to determine if functional, pharmacodynamic profiles relevant to targeted therapy could be derived from live human melanoma samples using a novel automated platform., Methods: A series of 13 melanoma cell lines was briefly exposed to a BRAF inhibitor (PLX-4720) on a platform employing automated fluidics for sample processing. Levels of the phosphoprotein p-ERK in the mitogen-activated protein kinase (MAPK) pathway from treated and untreated sample aliquots were determined using a bead-based immunoassay. Comparison of these levels provided a determination of the pharmacodynamic effect of the drug on the MAPK pathway. A similar ex vivo analysis was performed on fine needle aspiration (FNA) biopsy samples from four murine xenograft models of metastatic melanoma, as well as 12 FNA samples from patients with metastatic melanoma., Results: Melanoma cell lines with known sensitivity to BRAF inhibitors displayed marked suppression of the MAPK pathway in this system, while most BRAF inhibitor-resistant cell lines showed intact MAPK pathway activity despite exposure to a BRAF inhibitor (PLX-4720). FNA samples from melanoma xenografts showed comparable ex vivo MAPK activity as their respective cell lines in this system. FNA samples from patients with metastatic melanoma successfully yielded three categories of functional profiles including: MAPK pathway suppression; MAPK pathway reactivation; MAPK pathway stimulation. These profiles correlated with the anticipated MAPK activity, based on the known BRAF mutation status, as well as observed clinical responses to BRAF inhibitor therapy., Conclusion: Pharmacodynamic information regarding the ex vivo effect of BRAF inhibitors on the MAPK pathway in live human melanoma samples can be reproducibly determined using a novel automated platform. Such information may be useful in preclinical and clinical drug development, as well as predicting response to targeted therapy in individual patients.