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Parasitoid wasps are one of the most species‐rich groups of animals on Earth, due to their ability to successfully develop as parasites of nearly all types of insects. Unlike most known parasitoid wasps that specialize towards one or a few host species, Diachasmimorpha longicaudata is a generalist that can survive within multiple genera of tephritid fruit fly hosts, including many globally important pest species. Diachasmimorpha longicaudata has therefore been widely released to suppress pest populations as part of biological control efforts in tropical and subtropical agricultural ecosystems. In this study, we investigated the role of a mutualistic poxvirus in shaping the host range of D. longicaudata across three genera of agricultural pest species: two of which are permissive hosts for D. longicaudata parasitism and one that is a nonpermissive host. We found that permissive hosts Ceratitis capitata and Bactrocera dorsalis were highly susceptible to manual virus injection, displaying rapid virus replication and abundant fly mortality. However, the nonpermissive host Zeugodacus cucurbitae largely overcame virus infection, exhibiting substantially lower mortality and no virus replication. Investigation of transcriptional dynamics during virus infection demonstrated hindered viral gene expression and limited changes in fly gene expression within the nonpermissive host compared with the permissive species, indicating that the host range of the viral symbiont may influence the host range of D. longicaudata wasps. These findings also reveal that viral symbiont activity may be a major contributor to the success of D. longicaudata as a generalist parasitoid species and a globally successful biological control agent. [ABSTRACT FROM AUTHOR]

In experiments on the Belousov–Zhabotinskii reaction in a flow reactor we have observed dynamical behavior that is described well by one-dimensional maps with a single maximum. A sequence of period doubling bifurcations was observed as a parameter was varied, and beyond the accumulation point for the period doubling sequence there was a sequence of periodic states that has the same symbolic dynamics as the states of the U (universal) sequence of Metropolis, Stein, and Stein (1973). However, in another experiment with malonic acid from a different vendor, we found that some states with particular symbol sequences occurred in three different parameter ranges rather than in one range as in the U sequence. Analysis of the effect of impurities in the reagents showed that some impurities (e.g., Fe3+ and esters of malonic acid) at concentrations of only a few ppm produced dramatic changes in the dynamics; such impurities are contained in commercially available malonic acid. Experiments with purified malonic acid indicate that the Fe2+/Fe3+ and Cu+/Cu2+ redox couples act as co-catalysts of the Belousov–Zhabotinskii reaction; their effect can be explained by a free radical mechanism. Other metal ions (e.g., Ni2+ and Co2+) at low concentrations have negligible effect on the dynamics. Finally, both the sequences with universal ordering and the sequences with multiplicity are described well by indented trapezoid maps of the type analyzed by Beyer, Mauldin, and Stein (1986). [ABSTRACT FROM AUTHOR]

Angiostatin is a potent inhibitor of angiogenesis generated in cancer-bearing hosts by tumor-derived proteases. Because the naturally occurring bone and prostate cancers of pet dogs provide unique model systems to study factors that regulate cancer progression and tumor dormancy, we investigated the capacity of these tumors to generate angiostatin. We determined that angiostatin fragments are present in urine of dogs with bone cancer. The identity of these fragments was confirmed by comparison of the experimentally determined protein sequence to that of a clone of canine angiostatin. Importantly, these fragments were absent in urine collected from the same dogs after complete surgical removal of the primary tumor. We also demonstrate that canine prostate cancer cells are capable of processing plasminogen to angiostatin in vitro. These findings provide rationale for using spontaneous canine tumor models to isolate endogenous angiogenesis inhibitors and to investigate their therapeutic use against cancer. [Copyright &y& Elsevier]

The avidity of breast milk IgA antibody was studied with the aid of thiocyanate elution of antibody from solid-phase bound E.coli polysaccharides and diphtheria toxoid. The relative avidity index for each sample was determined by the molarity of thiocyanate required to elute 50% of the bound IgA antibody under conditions or antigen excess. Milk samples collected from Pakistani mothers during early lactation (2–4 weeks after delivery; n=12) had a significantly lower median relative avidity index of IgA antibody to E.coli antigens than did early lactation samples from Swedish mothers (n=11; avidity indices 1.78 M and 2.65 M: P<0.02). Samples collected from Pakistani mothers in mid-lactation showed a significant rise in the relative avidity index to a median of 2.50 m (P<0.01), with a subsequent fall in late lactation (28–36 weeks after delivery) to 1.75 m (P<0.01). Milk samples from Pakistani mothers in mid-lactation (n= 12) also had a lower median relative avidity index of IgA antibody to diphtheria toxoid than did samples from Swedish mothers (n= 14; avidity indices 2.35 M and 4.30 m: P <0.002). The lower avidity of breast milk IgA in Pakistani mothers in comparison with Swedish mothers may arise from differences in antigen exposure or nutritional status or could possibly be genetically determined. [ABSTRACT FROM AUTHOR]

Objective: To improve mechanistic understanding, this randomized controlled trial examined anxiety, mood, emotional support, and pain-related self-efficacy as mediators of music therapy for pain management in people with advanced cancer., Methods: People with advanced cancer who had chronic pain were randomized (1:1) to 6 weekly individual music therapy or social attention control sessions. We measured mediators and pain outcomes (pain interference and pain intensity) using self-report measures at baseline, session 4, and post-intervention. We included outcome expectancy/treatment credibility, music reward, adult playfulness, and baseline pain interference and pain intensity as moderators., Results: Participants (n = 92) had a mean age of 56 years. Most were female (71.7%), white (47.8%) or Black (39.1%), and had stage IV cancer (75%). Self-efficacy was found to be a significant mediator of music therapy for pain intensity (indirect effect ab = 0.79, 95% CI 0.01-1.82) and pain interference (indirect effect ab = 1.16, 95% CI 0.02-2.51), while anxiety, mood, and emotional support were not. The mediating effect of pain-related self-efficacy was significantly moderated by baseline pain interference but not by the other moderators., Conclusions: The findings suggest that the impact of music therapy on chronic pain is mediated by self-efficacy. This knowledge can help optimize music therapy interventions for chronic pain management for people with advanced cancer by capitalizing on teaching music-based self-management strategies., Trial Registration: ClinicalTrials.gov identifier: NCT03432247., (© 2024 John Wiley & Sons Ltd.)

Diacylglycerol O-acyltransferase 2 (DGAT2) inhibitors have been shown to lower liver triglyceride content and are being explored clinically as a treatment for non-alcoholic steatohepatitis (NASH). This work details efforts to find an extended-half-life DGAT2 inhibitor. A basic moiety was added to a known inhibitor template, and the basicity and lipophilicity were fine-tuned by the addition of electrophilic fluorines. A weakly basic profile was required to find an appropriate balance of potency, clearance, and permeability. This work culminated in the discovery of PF-07202954 ( 12 ), a weakly basic DGAT2 inhibitor that has advanced to clinical studies. This molecule displays a higher volume of distribution and longer half-life in preclinical species, in keeping with its physicochemical profile, and lowers liver triglyceride content in a Western-diet-fed rat model., Competing Interests: The authors declare the following competing financial interest(s): All authors were employees of Pfizer, Inc. at the time that work was done and may own Pfizer stock. This work was financially supported by Pfizer, Inc., (© 2023 American Chemical Society.)

Diabetes (DM) is a common comorbidity in transplant patients with known effects on gastrointestinal (GI) motility and absorption; however, DM's impact on immediate release (IR) tacrolimus to LCP-tacrolimus (LCP) conversion ratios has not been studied. This multivariable analysis of a retrospective longitudinal cohort study included kidney transplant recipients converted from IR to LCP between 2019 and 2020. The primary outcome was IR to LCP conversion ratio based on DM status. Other outcomes included tacrolimus variability, rejection, graft loss, and death. Of the 292 patients included, 172 patients had DM and 120 did not. The IR:LCP conversion ratio was significantly higher with DM (67.5% ± 21.1% no DM vs. 79.8% ± 28.7% in DM; P < .001). In multivariable modeling, DM was the only variable significantly and independently associated with IR:LCP conversion ratios. No difference was observed in rejection rates. Graft (97.5% no DM vs. 92.4% in DM; P = .062) and patient survival (100% no DM vs. 94.8% in DM; P = .011) were lower with DM. The presence of DM significantly increased the IR:LCP conversion ratio by 13%-14%, compared to patients without DM. On multivariable analysis, DM was the only significant predictor of conversion ratios, potentially related to GI motility or absorption differences., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The melanocortin-4 receptor (MC4R) is a centrally expressed, class A GPCR that plays a key role in the regulation of appetite and food intake. Deficiencies in MC4R signaling result in hyperphagia and increased body mass in humans. Antagonism of MC4R signaling has the potential to mitigate decreased appetite and body weight loss in the setting of anorexia or cachexia due to underlying disease. Herein, we report on the identification of a series of orally bioavailable, small-molecule MC4R antagonists using a focused hit identification effort and the optimization of these antagonists to provide clinical candidate 23 . Introduction of a spirocyclic conformational constraint allowed for simultaneous optimization of MC4R potency and ADME attributes while avoiding the production of hERG active metabolites observed in early series leads. Compound 23 is a potent and selective MC4R antagonist with robust efficacy in an aged rat model of cachexia and has progressed into clinical trials.

Daratumumab, a CD38-directed monoclonal antibody indicated for multiple myeloma treatment in adult patients, is associated with a high incidence of infusion-related reactions (IRRs). Due to CD38 receptor presence in the lungs, many reactions present similarly to asthma or allergic rhinitis. Montelukast, a leukotriene receptor antagonist, has been hypothesized to reduce daratumumab IRRs due to its efficacy in treating allergic rhinitis and asthma and the presence of leukotriene receptors in the lungs. Recently published data reported daratumumab can be safely administered via rapid rate protocol that reduces infusion time from 195 min to 90 min after completion of two doses. This retrospective, observational cohort study examined 73 patients who received daratumumab in the outpatient setting between December 2015 and April 2020. Patients were included if they were 18 years or older, had an International Classification of Disease (ICD)-10 diagnosis code for multiple myeloma, and received daratumumab intravenously. The primary outcome was a comparison of IRRs between those who did and did not receive montelukast. Secondary outcomes included IRR symptoms, rescue medications utilized for IRRs, and rapid rate administration outcomes. Montelukast use was associated with a lower rate of IRRs (44.4% vs. 65.2%, p = 0.044). Pulmonary IRR symptoms were more common in those who did not receive montelukast. Rapid rate administration of daratumumab did not lead to any IRRs. Adding montelukast as a pre-medication for daratumumab infusions led to a reduction in IRRs, and rapid rate administration was found to be safe after completion of two full doses of daratumumab.

Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson's disease (PD), and pharmacological blockade of LRRK2 represents a new opportunity for therapeutical treatment of PD and other related neurodegenerative conditions. The development of an LRRK2-specific positron emission tomography (PET) ligand would enable a target occupancy study in vivo and greatly facilitate LRRK2 drug discovery and clinical translation as well as provide a molecular imaging tool for studying physiopathological changes in neurodegenerative diseases. In this work, we present the design and development of compound 8 (PF-06455943) as a promising PET radioligand through a PET-specific structure-activity relationship optimization, followed by comprehensive pharmacology and ADME/neuroPK characterization. Following an efficient 18 F-labeling method, we have confirmed high brain penetration of [ 18 F] 8 in nonhuman primates (NHPs) and validated its specific binding in vitro by autoradiography in postmortem NHP brain tissues and in vivo by PET imaging studies.

Background: Oncolytic immunotherapy represents a unique therapeutic platform for the treatment of cancer. Here, we evaluated the safety and efficacy of the combination of pexastimogene devacirepvec (PexaVec) plus durvalumab (anti-programmed death ligand 1) with and without tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4) in patients with standard chemotherapy refractory mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) in a phase I/II trial., Methods: Adult patients with histologically confirmed advanced pMMR mCRC, who had progressed on at least two prior lines of systemic chemotherapy were studied in four cohorts. Patients received four doses of PexaVec IV at a dose of 3×10 8 plaque forming units (pfu) (dose level 1) or 1×10 9  pfu (dose level 2) every 2 weeks. Twelve days after the first PexaVec administration, patients received either 1500 mg of durvalumab every 28 days alone or an additional single dose of 300 mg tremelimumab on day 1. Responses were assessed every 8 weeks by CT or MRI. AEs were recorded. The primary endpoints were safety and feasibility. Secondary endpoints included progression-free survival (PFS) and overall survival. Paired tumor samples and peripheral blood were collected to perform immune monitoring., Results: Thirty-four patients with mCRC enrolled on to the study: 16 patients in the PexaVec/durvalumab cohorts and 18 patients in the PexaVec/durvalumab/tremelimumab cohorts. Overall, the combination of PexaVec plus immune checkpoint inhibitors did not result in any unexpected toxicities. Most common toxicities observed were fever and chills after PexaVec infusion. Two cases of grade 3 colitis, one case of a grade 2 myositis and one case of grade 3 hypotension resulted in discontinuation of immune checkpoint inhibitor and PexaVec treatment, respectively. The median PFS in the PexaVec/durvalumab/tremelimumab cohorts was 2.3 months (95% CI: 2.2 to 3.2 months) vs 2.1 months (95% CI: 1.7 to 2.8 months; p=0.57) in the PexaVec/durvalumab cohorts. Flow cytometry analysis of peripheral blood mononuclear cells revealed an increase in Ki67 + CD8 + T cells on treatment., Conclusion: PexaVec in combination with durvalumab and tremelimumab is safe and tolerable. No unexpected toxicities were observed. The combination of PexaVec/durvalumab/tremelimumab demonstrated potential clinical activity in patients with pMMR mCRC, but further studies are needed to identify the predictive biomarkers., Trial Registration Number: NCT03206073., Competing Interests: Competing interests: AD reports participation of Advisory Boards from AstraZeneca, outside the submitted work. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent studies suggest that the prevalence of cardiac involvement in young competitive athletes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears to be low., Aim: This study aimed to determine the prevalence of cardiovascular involvement in young competitive athletes., Methods: In this single-center retrospective cohort study from one Division I university; we assessed the prevalence of cardiovascular involvement among collegiate athletes who tested positive for SARS-CoV-2 by polymerase chain reaction testing. Data were collected from June 25, 2020, to May 15, 2021. The primary outcome was the prevalence of cardiac involvement based on a comparison of pre- and post-infection electrocardiogram (ECGs). The secondary outcome was to evaluate for any association between ethnicity and the presence or absence of symptoms., Results: Among 99 athletes who tested positive for the SARS-CoV-2 virus (mean age 19.9 years [standard deviation 1.7 years]; 31% female), baseline ECG changes suggestive of cardiovascular involvement post-infection were detected in two athletes (2/99; 2%). There was a statistically significant association between ethnicity and the presence or absence of symptoms, χ 2 (3, n = 99) = 10.61, P = 0.01., Conclusions: The prevalence of cardiovascular involvement among collegiate athletes following SARS-CoV-2 infection in this cohort is low. Afro-American and Caucasian athletes are more likely to experience symptoms following SARS-CoV-2 infection in comparison to Hispanic and Pacific Islander athletes; however, there is no association between ethnicity and symptom severity., Relevance for Patients: These data add to the growing body of the literature and agree with larger cohorts that the risk of cardiac involvement post-infection appears to be low among elite athletic and semi-professional athletic populations., Competing Interests: Dr. Murray received payments during the project from NIH grant: P20GM103650. All other authors declare no conflict of interest., (Copyright: © Whioce Publishing Pte. Ltd.)

Introduction: Lutetium-177 (177Lu)-DOTATATE received FDA approval in 2018 to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs). Little data are available on response and outcomes for well-differentiated (WD) high-grade (HG) NETs treated with 177Lu-DOTATATE., Materials and Methods: Patients with WD HG NETs treated with 177Lu-DOTATATE at MSK from 2018 to 2020 were identified. Demographics, response (RECIST 1.1), and progression-free survival (PFS) were determined. Next-generation sequencing (NGS) was performed in the archival tumor., Results: Nineteen patients, all with progressive, heavily treated disease, were identified. Sites of tumor origin were: pancreas (74%), small bowel (11%), rectum (11%), and lung (5%); median Ki-67 was 32% (range 22-56). Thirteen patients (68%) completed all four 177Lu-DOTATATE cycles. Best response (N = 18 evaluable) was: 5/18 (28%) partial response, 8/18 (44%) stable disease, and 5/18 (28%) disease progression. Median PFS was 13.1 months (95% CI: 8.7-20.9). Most common treatment-related toxicities were thrombocytopenia (9 patients, 47%; G3/4, 1 patient, 5%), anemia (7 patients, 37%; G3/4, 2 patients, 11%), leukopenia (6 patients, 32%; G3/4, 0 patients), and liver function test elevation (4 patients, 21%; G3/4, 0 patients). NGS results were available from 13/19 tumors (68%). The most observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations identified., Conclusion: We observed a meaningful disease control rate of 72% during treatment of WD HG NETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of patients received all four treatment cycles with toxicities largely bone marrow-related. As would be expected in WD NETs, the vast majority had alterations in chromatin remodeling genes and no RB1 alterations., (© 2022 S. Karger AG, Basel.)

Aim: To determine whether functional impairments and autonomic symptoms are correlated in young people with developmental and epileptic encephalopathies (DEEs)., Method: Cross-sectional, online surveys (2018-2020) of parents recruited from family groups obtained information on several aspects of children's conditions including functional abilities (mobility, hand use, eating, and communication), 18 autonomic symptoms in six groups (cardiac, respiratory, sweating, temperature, gastrointestinal, and other), and parental stress. Bivariate and multivariable logistic regression analyses examined associations of dysautonomias with functional impairment, adjusted for type of DEE and age., Results: Of 313 participants with full information on function and dysautonomias, 156 (50%) were females. The median age was 8 years (interquartile range 4-12y); 255 (81%) participants had symptoms in at least one autonomic symptom group; 283 (90%) had impairment in at least one functional domain. The number of functional impairment domains and of autonomic symptom groups varied significantly across DEE groups (both p<0.001). The number of functional impairment domains and of autonomic symptom groups were correlated (Spearman's r=0.35, p<0.001) on bivariate and multivariable analysis adjusted for DEE group and age. Parental stress was also independently correlated with dysautonomias (p<0.001)., Interpretation: Parent-reported dysautonomias are common in children with DEEs. They correlate with extent of functional impairment and may contribute to caregiver stress. What this paper adds Dysautonomic symptoms are common in young people with developmental and epileptic encephalopathies (DEEs). Burden of dysautonomias is strongly correlated with burden of functional impairments. Aspects of dysautonomic function may provide biomarkers of DEE disease severity., (© 2021 Mac Keith Press.)

Background: This is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre-recorded music offered by medical staff., Objectives: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction., Selection Criteria: We included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes., Data Collection and Analysis: Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta-analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL) . We used GRADE to assess the certainty of the evidence., Main Results: We identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care. Psychological outcomes The results suggest that music interventions may have a large anxiety-reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) -10.02 to -5.44; very low-certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): -0.41, 95% CI -0.67 to -0.15; very low-certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI -0.02 to 0.97; 5 studies, 236 participants; very low-certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low-certainty evidence). Physical outcomes We found a moderate pain-reducing effect of music interventions (SMD -0.67, 95% CI -1.07 to -0.26; 12 studies, 632 adult participants; very low-certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD -0.28, 95% CI -0.46 to -0.10; 10 studies, 498 adult participants; low-certainty evidence). The results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI -0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I 2 = 56%). A small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD -0.94, 95% CI -1.9 to 0.03; very low-certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer. The majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes., Authors' Conclusions: This systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Treatment manuals play an essential role in clinical trials that aim to determine the efficacy of an intervention. Yet, the idea of needing to adhere to a treatment manual may seem counterintuitive to many music therapy clinicians. The purpose of this article is to offer clinician, supervisor, and researcher perspectives on the process of developing and executing a manualized music therapy treatment protocol in a randomized controlled trial., Method: After describing the purpose of treatment manuals in clinical trials, we present the experience of developing a treatment manual through clinician and researcher collaborations. The concept of treatment fidelity and quality assurance monitoring within clinical trials is detailed to provide an inside look at an integral aspect of enacting treatment manuals in efficacy research. We then share reflections from a research clinician and supervisor to demonstrate the opportunities and challenges when working within the guidelines of manualized clinical practice., Results: Providing a reflective perspective on implementation of a manualized treatment protocol allows for a more thorough understanding of the clinical and research processes in the conduct of randomized controlled trials., Discussion: Collaboration of researchers, clinicians and supervisors is of critical importance for the successful implementation of treatment manuals in clinical trials., Competing Interests: Disclosure statement The authors report no conflicts of interest.

We explore the idea that judgment by representativeness reflects the workings of memory. In our model, the probability of a hypothesis conditional on data increases in the ease with which instances of that hypothesis are retrieved when cued with the data. Retrieval is driven by a measure of similarity which exhibits contextual interference: a data/cue is less likely to retrieve instances of a hypothesis that occurs frequently in other data. As a result, probability assessments are context dependent. In a new laboratory experiment, participants are shown two groups of images with different distributions of colors and other features. In line with the model's predictions, we find that (a) decreasing the frequency of a given color in one group significantly increases the recalled frequency of that color in the other group; and (b) cueing different features for the same set of images entails different probabilistic assessments, even if the features are normatively irrelevant. A calibration of the model yields a good quantitative fit with the data, highlighting the central role of contextual interference. (PsycInfo Database Record (c) 2020 APA, all rights reserved).