Prosocial motives underlie scientific censorship by scientists: A perspective and research agenda.

Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.

Impact of Biotin Supplementation on Human Chorionic Gonadotropin Immunoassays Utilizing Biotin-Streptavidin Binding Methods in Urine.

BACKGROUND: Human chorionic gonadotropin (hCG) detection is indicative of pregnancy and can be indicative of some forms of cancerous tumors. The hCG drug itself, however, is a performance enhancing substance used by male athletes to increase testosterone production. Antidoping testing for hCG is conducted in urine, often on immunoanalyzer platforms, many of which utilize biotin-streptavidin dependent immunoassays in which the presence of biotin in samples is a known confounding factor. While biotin interference in serum has been well-studied, the extent of biotin interference in urine has not. METHODS: Ten active male individuals underwent a 2-week hCG administration protocol concurrent with supplementation with biotin (20 mg/day) or placebo. Urine and serum samples were collected throughout the study and analyzed for hCG and biotin concentrations. RESULTS: Urinary biotin levels in the hCG + biotin group increased 500-fold over baseline and 29-fold over corresponding serum biotin levels after biotin supplementation. When using a biotin-dependent immunoassay, the hCG + placebo group produced hCG-positive results (hCG ≥ 5 mIU/mL) in 71% of urine samples, while the hCG + biotin group produced positive results in only 19% of samples. Both groups had elevated hCG values in serum measurements by a biotin-dependent immunoassay and in urine when using a biotin-independent immunoassay. Urinary hCG measurements and biotin levels from the hCG + biotin group showed a negative correlation (Spearman r = -0.46, P < 0.0001) when measured using a biotin-dependent immunoassay. CONCLUSIONS: Biotin supplementation can severely suppress urinary hCG values in assays utilizing biotin-streptavidin binding methods and therefore these types of assays are not recommended for use in urine samples containing high levels of biotin. Clinicaltrials.gov Registration Number: NCT05450900.

Identification and synthesis of (Z)-3'-hydroxy clomiphene as a new potential doping-relevant metabolite of clomiphene.

A recent study addressed the possibility of unintentional ingestion of clomiphene through residues in chicken eggs. The method developed here helped distinguish between microdose intake of (E/Z)-clomiphene citrate and consumption of clomiphene-containing eggs by the urinary pattern of four mono-hydroxylated clomiphene metabolites. However, reanalyses of doping-control samples, which showed an adverse analytical finding for clomiphene, revealed a hydroxy clomiphene (HC) isomer that was not found after microdose intake or after consumption of clomiphene-containing eggs and could not be assigned to any of the available reference compounds. The aim of the present follow-up study was to identify this HC isomer and to characterize this metabolite with respect to its potential properties as long-term metabolite in doping controls. METHODS: (E/Z)-3'-HC and (E/Z)-4'-HC were synthesized involving the McMurry reaction. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and optimized after a derivatization step with dansyl chloride to separate eight HC isomers. Using this method, urine samples from a controlled clomiphene administration study were analyzed, in which male study participants received therapeutic doses of clomiphene for 30 days and collected urine samples for up to 8 months. Thus, isomer-specific HC elimination profiles could be monitored. RESULTS: The metabolite previously found in doping-control samples was identified as (Z)-3'-HC. The elimination profiles of the different HCs confirmed previous results, with (Z)-3-HC being the most abundant urinary hydroxy metabolite shortly after administration. A new finding was that the data suggest that (Z)-3'-HC is excreted at higher relative concentrations only several weeks after drug intake. CONCLUSION: These findings might be of particular importance in sport drug testing as they can assist in the decision-making process to distinguish between intentional doping and inadvertent exposure to clomiphene via food contamination.

Benefits of hereditarian insights for mate choice and parenting.

Madole & Harden develop some good ideas about how to understand genetic causality more clearly, but they frame the benefits of behavior genetics research at a largely collective level, focused on the pros and cons of different ways to engineer the gene pool or social behavior. This neglects the individual benefits of hereditarian insights for mate choice and parenting.

A Targeted Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification of Peptides from the Carboxyl-terminal Region of Type III Procollagen, Biomarkers of Collagen Turnover.

BACKGROUND: The development of analytical approaches to help reduce the risk of growth hormone (GH) doping is important to fair competition and the health of athletes. However, the reliable detection of GH use remains challenging. The identification of novel biomarkers of GH administration could lead to a better understanding of the physiological response to GH, more sensitive detection of the illicit use of GH in sport, and better management of patients treated for GH disorders. METHODS: We developed a targeted liquid chromatography-tandem mass spectrometry method to simultaneously quantify the carboxyl-terminal propeptide of type III procollagen (P-III-CP) and type III collagen degradation products in human serum. Following proteolysis, we instituted a simple acid precipitation step to reduce digested sample complexity before peptide immunoenrichment, which improved the recovery of one target peptide from serum. We evaluated the concentration of each biomarker at different age ranges and after GH administration in healthy participants. RESULTS: The assay was linear over an estimated concentration range of 0.3 to1.0 nM and 0.1 to 0.4 nM for each surrogate peptide of P-III-CP and collagen fragments, respectively. Intra-day and inter-day coefficients of variation were ≤15%. Biomarker concentrations appeared to vary with age and to reflect age-specific collagen turnover. Moreover, their concentrations changed after GH administration. CONCLUSIONS: Our method quantifies the proteins belonging to the family of P-III-CP and type III collagen degradation products in human serum, which could be used to detect GH administration in athletes and better understand diseases involving GH therapy or altered type III collagen turnover.

Measurement of Immature Reticulocytes in Dried Blood Spots by Mass Spectrometry.

BACKGROUND: Immature reticulocytes (IRC) are the first cells to respond to changes in erythropoiesis. For antidoping applications, measurement of IRC may improve detection of blood doping practices. Unfortunately, this small cell population has limited stability in liquid blood samples and is difficult to measure with optimal precision. We developed a method to measure 3 IRC membrane proteins in dried blood spots (DBS) to monitor changes in erythropoiesis. METHODS: DBS spots were washed with buffers to remove soluble proteins, membrane proteins remaining in the spot were digested with trypsin, and one peptide for each protein was measured by LC-MS/MS. IRC protein concentration was determined using a DBS single point calibrator. RESULTS: Intraassay precision for IRC proteins was between 5%-15%. IRC proteins were stable in DBS for 29 days at room temperature. In a longitudinal study of 25 volunteers, the mean intraindividual variation for 3 IRC proteins was 17%, 20%, and 24% from capillary blood DBS. In comparison, the mean longitudinal variation for IRC counts measured on an automated hematology analyzer was 38%. IRC protein concentration from capillary blood DBS correlated well with venous blood DBS protein concentrations. CONCLUSIONS: Measurement of IRC proteins in DBS samples provides a method to measure changes in erythropoiesis with improved analytical sensitivity, stability, and precision. When combined with the inherent advantages of capillary blood collection in the field, this method may substantially improve the detection of blood doping practices.

Tracking immature reticulocyte proteins for improved detection of recombinant human erythropoietin (rhEPO) abuse.

Athletes abuse recombinant human erythropoietin (rhEPO) and erythropoiesis stimulating agents to increase hemoglobin mass and improve performance. To evade detection, athletes have developed sophisticated blood doping regimens, which often include rhEPO micro-dosing. Detection of these methods requires biomarkers with increased sensitivity and a sample matrix that is more amenable to frequent testing in the field. We have developed a method to measure two immature reticulocyte proteins, CD71 and ferrochelatase (FECH), and one total erythrocyte protein, Band 3, in dried blood spots (DBS). This method was tested in response to rhEPO administration after low doses, 40 IU/kg, micro-doses, 900 IU, or saline injection in 20 healthy subjects. During administration of low-dose rhEPO, the mean CD71/Band 3 and FECH/Band 3 ratio increased by 412 ± 197% and 250 ± 44%, respectively. The mean response for the current biomarker, RET%, increased by 195 ± 35%. During administration of rhEPO micro-doses, CD71/Band 3 increased to 127 ± 25% on day 35 and 139 ± 36% on day 39, while no increase was observed in RET%. After rhEPO administration, during the washout phase, mean values decreased to a minimum of 64 ± 4% and 64 ± 11% for CD71/Band 3 and RET%, respectively. However, CD71/Band 3 remained below 75% of baseline for at least 4 weeks after rhEPO injection, while RET% returned to baseline levels. The results demonstrate that immature reticulocyte proteins have a larger response to rhEPO administration than the current biomarker, RET%, and can be monitored in the DBS matrix.

Advanced Digital Health Technologies for COVID-19 and Future Emergencies.

Background: Coronavirus disease 2019 (COVID-19) has led to a national health care emergency in the United States and exposed resource shortages, particularly of health care providers trained to provide critical or intensive care. This article describes how digital health technologies are being or could be used for COVID-19 mitigation. It then proposes the National Emergency Tele-Critical Care Network (NETCCN), which would combine digital health technologies to address this and future crises. Methods: Subject matter experts from the Society of Critical Care Medicine and the Telemedicine and Advanced Technology Research Center examined the peer-reviewed literature and science/technology news to see what digital health technologies have already been or could be implemented to (1) support patients while limiting COVID-19 transmission, (2) increase health care providers' capability and capacity, and (3) predict/prevent future outbreaks. Results: Major technologies identified included telemedicine and mobile care (for COVID-19 as well as routine care), tiered telementoring, telecritical care, robotics, and artificial intelligence for monitoring. Several of these could be assimilated to form an interoperable scalable NETCCN. NETCCN would assist health care providers, wherever they are located, by obtaining real-time patient and supplies data and disseminating critical care expertise. NETCCN capabilities should be maintained between disasters and regularly tested to ensure continual readiness. Conclusions: COVID-19 has demonstrated the impact of a large-scale health emergency on the existing infrastructures. Short term, an approach to meeting this challenge is to adopt existing digital health technologies. Long term, developing a NETCCN may ensure that the necessary ecosystem is available to respond to future emergencies.

Learner Improvement From a Simulation-Enhanced Ultrasonography Curriculum for First-Year Medical Students.

OBJECTIVES: We describe a simulation-enhanced ultrasonography (US) curriculum for first-year medical students as part of a comprehensive curricular integration of US skills. Our goal was to assess student knowledge and performance of US and determine their satisfaction with the integrated curriculum. METHODS: A committee of basic science, clinical, and interinstitutional faculty developed 7 educational US modules integrated into existing anatomy and physiology courses. First-year students in years 2012 through 2014 were administered a demographic survey and a knowledge-based pretest at the outset of the US program and assessed with a posttest, satisfaction survey, and their image acquisition abilities in an objective structured clinical examination with standardized patients on completion of the program. RESULTS: Data from 390 students showed a significant increase in knowledge from the pretest to the posttest [t(389) = 58.027; P < .0001]. Students with higher spatial abilities or some previous US experience performed better on the posttest. The objective structured clinical examination results showed that about 83% of the students were able to capture acceptable or marginally acceptable images. Ninety-five percent of students indicated that the US educational experience enhanced their medical education. CONCLUSIONS: Initial results show that we were able to successfully develop, implement, and evaluate performance of first-year medical students on their fundamental knowledge and performance of basic US using a model that emphasized hands-on simulation-enhanced training. Furthermore, most students found the experience to be a beneficial component of their education and indicated a desire for more US training in the medical curricula.

Clitorally Stimulated Orgasms Are Associated With Better Control of Sexual Desire, and Not Associated With Depression or Anxiety, Compared With Vaginally Stimulated Orgasms.

INTRODUCTION: Most women report that clitoral stimulation is an integral aspect of their orgasm experience. Thus, recent claims that vaginal stimulation and vaginally generated orgasms are superior to clitoral stimulation and clitorally generated orgasms pathologize most women and maintain a clitoral vs vaginal dichotomy that might not accurately reflect the complexity of women's sexual experience. AIM: To have women report on their experienced source of orgasm, including combinations of vaginal and clitoral stimulation, the solo or partnered context of the stimulation, and the intensity of the orgasms from different sources and to predict indicators of mental health and sexual health using the orgasm source. METHODS: Eighty-eight women 18 to 53 years old answered detailed questions about their usual and recent orgasm experiences, sexual history, depression, and anxiety. Then, they viewed a series of neutral and sexual films. They were instructed to increase or decrease their sexual arousal or respond "as usual" to the sexual films. They reported their sexual arousal after each film. MAIN OUTCOME MEASURES: Outcomes assessed included mental health (depression and anxiety) and sexual health (orgasm quality, ability to regulate sexual response to sex films). Reported sexual arousal was analyzed for the regulation task. RESULTS: Most women (64%) reported that clitoral and vaginal stimulation contributed to their usual method of reaching orgasm. Women who reported that clitoral stimulation was primarily responsible for their orgasm reported a higher desire to self-stimulate and demonstrated greater control over their self-reported sexual arousal. The primary stimulation site for orgasm was unrelated to measurements of depression or anxiety despite sufficient statistical power. CONCLUSION: Most women reported that clitoral and vaginal stimulation is important in orgasm. Women experience orgasms in many varied patterns, a complexity that is often ignored by current methods of assessing orgasm source. The reported source of orgasm was unrelated to orgasm intensity, overall sex-life satisfaction, sexual distress, depression, or anxiety. Women who reported primarily stimulating their clitoris to reach orgasm reported higher trait sexual drive and higher sexual arousal to visual sexual stimulation and were better able to increase their sexual arousal to visual sexual stimulation when instructed than women who reported orgasms primarily from vaginal sources.

Biracial Faces Offer Visual Cues of Successful Intergroup Contact: Genetic Admixture and Coalition Detection.

This research explores how biracial facial cues affect racial perception and social judgment. We tested a coalition-signaling hypothesis of biracial cues in two studies conducted in the United States (n = 227) and China (n = 116). From the perspective of intergroup and interpersonal relations theories in social psychology, biracial features would likely be perceived as cues of threat or resource competition. In contrast, we propose an evolutionary hypothesis that biracial facial cues reveal the ancestral history of intergroup alliances between members of two races or ethnic groups. When racial cues are mixed, we predict that biracial individuals may be viewed more positively than other-race or even own-race members who often compete for limited ingroup resources. The participants observed facial images that ranged from 100% Asian to 100% Caucasian, including morphed biracial composites of 30%, 40%, 50%, 60%, and 70% Caucasian or Asian. The participants evaluated each image regarding perceived Caucasianness (Asianness), attractiveness, trustworthiness, health, intelligence, and career prospects. The US and Chinese samples yielded a similar pattern of own-race bias in racial perception and biracial favoritism in social judgment. The social judgment ratings were not correlated with the racial perception scores and were independent of the sex of the participants or biracial images, indicating a coalitional motive, instead of a mating motive, underlying social perception of biracial individuals. Overall, the results suggest that biracial facial features signal a successful genetic admixture and coalition in parental generations and thus increase the trustworthiness and cooperative potential of a biracial person.

Is blood blood? Comparing quantitation of endogenous steroids and luteinizing hormone in concurrently collected venous serum and Tasso+ SST capillary serum samples.

The monitoring of endogenous steroids in urine has been an important component of the Athlete Biological Passport (ABP) for the last decade. Recently, the quantitation of endogenous steroids in blood has been incorporated into the ABP to increase sensitivity in circumstances where the excretion of urinary ABP biomarkers is low. Current ABP guidelines mandate the use of venous blood draws for blood steroid sample collections, however, recent efforts have focused on investigating the use of less invasive sample collection methods, such as capillary blood collected from the upper arm. The focus of this study was to compare the analytical results of venous and capillary blood collected weekly from 20 individuals, 10 males and 10 females, over six weeks. The two primary biomarkers of the blood steroid ABP module, testosterone (T) and the testosterone/androstenedione (T/A4) ratio, were compared, as well as luteinizing hormone (LH) and the T/LH ratio in male participants, two biomarkers known to be responsive to T use. All biomarkers showed excellent agreement between venous and capillary blood. Longitudinal stability between sample types within individuals was also comparable for all biomarkers. Finally, storage of simultaneously collected capillary samples at room temperature and frozen conditions was compared with evaluate the potential impact of non-cold chain shipping conditions. Most biomarkers showed excellent agreement between frozen and room temperature storage conditions. These results indicate capillary blood collections represent a promising alternative to venous blood collections for the blood steroid module of the ABP.

Assessing EPO stability in urine and comparing recombinant EPO detectability in matched urine, venous serum, and capillary serum following a controlled epoetin alfa administration.

The instability of erythropoietin receptor agonists (ERAs, i.e., EPO) in urine presents a challenge to their detectability in doping control samples; however, this issue is not often seen in blood (serum) samples. With the anti-doping field beginning to transition into alternative blood collection technologies, it is important to understand recombinant EPO (rEPO) detectability in serum samples collected from one such capillary collection device, the Tasso+ SST. Twelve individuals were administered a single, 40 IU/kg dose of rEPO (epoetin alfa, EPOGEN®). Following administration, matched urine, venous serum, and capillary serum samples were concurrently collected. Urine aliquots were subject to various storage times and temperatures mimicking shipping conditions of doping control urine samples to assess EPO stability, while other urine aliquots, venous serum, and capillary serum aliquots were frozen until analysis to understand rEPO detectability across all three matrices. EPO and rEPO instability was identified in urine collected from 8 of 12 participants, especially in aliquots stored at room temperature and 37°C. In some of these unstable samples, rEPO was still detectable, while in others, no recombinant nor endogenous EPO was detectable and would have resulted in negative sample reports. Analyzing the concurrently collected urine, venous, and capillary serum samples, rEPO detectability was identical across the three matrices. In most cases, rEPO was detectable for at least 168 h post-administration. Noting greater stability in blood compared with urine, it is recommended that anti-doping authorities utilize this novel capillary serum collection technology to improve overall ERA detectability in doping control samples.

Evaluation of Minimum Reporting Limits to Determine In-Competition Use of Stimulants.

The applicability of urinary minimum reporting limits (MRLs) to determine in-competition use of prohibited substances is an evolving topic. Most stimulants are subject to a universal MRL, despite the wide range of commercially available dosages for commonly used stimulants. Further, it is unknown whether the urinary MRL is reflective of a pharmacological dose ingested after the start of the in-competition period. To evaluate whether urinary MRLs can distinguish between in-competition and out-of-competition use, a controlled administration study was performed with three commonly used stimulants-amphetamine, methylphenidate, and modafinil at relatively low but therapeutically relevant dosages. Four to six volunteers were administered a particular drug once per day for five consecutive days. Urine, serum, dried blood spots (DBS), and oral fluid (OF) were collected during the active administration period and for 48 h after cessation of use. For all participants, urinary concentrations for all target analytes exceeded the MRL even 48 h after cessation of use. In serum and DBS, most volunteers showed detectable amounts at 48 h post use. Peak concentrations were variable between target compounds even with similar administered dosages. Further, there was a reproducible difference between serum and DBS concentrations. Interpretation of results from OF measurements was challenging due to the inability to normalize for hydration status and OF viscosity. Analyte concentrations decreased steadily over the washout period but did not correlate across matrices for all target analytes. The study reiterates the challenges associated with determining in-competition use by relying on urinary concentrations.

Taboos and Self-Censorship Among U.S. Psychology Professors.

We identify points of conflict and consensus regarding (a) controversial empirical claims and (b) normative preferences for how controversial scholarship-and scholars-should be treated. In 2021, we conducted qualitative interviews (n = 41) to generate a quantitative survey (N = 470) of U.S. psychology professors' beliefs and values. Professors strongly disagreed on the truth status of 10 candidate taboo conclusions: For each conclusion, some professors reported 100% certainty in its veracity and others 100% certainty in its falsehood. Professors more confident in the truth of the taboo conclusions reported more self-censorship, a pattern that could bias perceived scientific consensus regarding the inaccuracy of controversial conclusions. Almost all professors worried about social sanctions if they were to express their own empirical beliefs. Tenured professors reported as much self-censorship and as much fear of consequences as untenured professors, including fear of getting fired. Most professors opposed suppressing scholarship and punishing peers on the basis of moral concerns about research conclusions and reported contempt for peers who petition to retract papers on moral grounds. Younger, more left-leaning, and female faculty were generally more opposed to controversial scholarship. These results do not resolve empirical or normative disagreements among psychology professors, but they may provide an empirical context for their discussion.

Shared fate was associated with sustained cooperation during the COVID-19 pandemic.

Did the COVID-19 pandemic bring people together or push them apart? While infectious diseases tend to push people apart, crises can also bring people together through positive interdependence. We studied this question by asking an international sample (N = 1,006) about their inclinations to cooperate, perceptions of interdependence (i.e., shared fate), and perceived risk as well as local prevalence of COVID-19 infection across 14 time points from March to August, 2020. While perceived interdependence with others tended to increase during this time period, inclinations to cooperate decreased over time. At the within-person level, higher local prevalence of COVID-19 attenuated increases in perceived interdependence with others, and was associated with lower inclinations to cooperate. At the between-person level, people with high perceived interdependence with others reported more stable, or increasing, inclinations to cooperate over time than people with low perceived interdependence. Establishing a high sense of perceived interdependence with others may thus allow people to maintain cooperation during crises, even in the face of challenging circumstances such as those posed by a highly transmissible virus.

A Novel High-Throughput Immunoaffinity LC-MS/MS Assay for P-III-NP and Other Fragments of Type III Procollagen in Human Serum.

The amino-terminal propeptide of type III procollagen (P-III-NP) is used with IGF-I to detect the illicit use of growth hormone and to monitor growth hormone therapy. However, the only currently available assays for P-III-NP are immunoassays, which are not well harmonized. In addition, other fragments of type III procollagen may better evaluate collagen turnover. We aimed to develop a high-throughput assay using immunoaffinity enrichment coupled to ultra-high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify peptides belonging to three different regions of type III procollagen in human serum simultaneously. To facilitate higher throughput, we transferred the assay from microcentrifuge tubes to a 96-well plate format with partially automated pipetting. The method was linear (Pearson's R ≥ 0.994) over an estimated concentration range of 1.35-13.3 nM, 0.04-2.28 nM, and 0.26-5.1 nM for each surrogate peptide of P-III-NP, collagen degradation products, and the carboxyl-terminal propeptide, respectively. Intra-day and inter-day imprecision were both < 13.6%, and the results of robustness testing were also encouraging. The method was successfully applied to capillary blood samples obtained using Tasso+ microsampling devices. Modest correlation of P-III-NP concentration was observed between our new method and a WADA-approved immunoassay (N = 40, Pearson's R = 0.789) with a significant bias of -87.8%. Our method simultaneously quantifies four peptides belonging to three regions of type III procollagen in human serum. High bias between assays highlights the need for common higher-order calibrators or reference materials to help improve the comparability of results across laboratories.

Multidomain targeting of Bcr-Abl by disruption of oligomerization and tyrosine kinase inhibition: toward eradication of CML.

The oncoprotein Bcr-Abl, the causative agent of chronic myeloid leukemia (CML), requires homo-oligomerization via a coiled-coil domain to function [Bartram, C. R.; et al. Nature 1983, 306 (5940), 277-280; and Zhao, X.; et al. Nat. Struct. Biol. 2002, 9(2), 117-120]. While tyrosine kinase inhibitors (TKIs) have shown great efficacy as treatment options for CML, their use may cause an acquisition of mutations in the tyrosine kinase domain, which prevent TKI binding and lead to a loss in activity [Woessner, D. W.; et al. Cancer J. 2011, 17(6), 477-486]. Previously, we have shown that a rationally modified coiled-coil domain (CC(mut3)) can disrupt this oligomerization, inhibit proliferation, and induce apoptosis in CML cells [Dixon, A. S.; et al. Mol. Pharmaceutics 2012, 9(1), 187-195]. Here, we show that using the most recently approved TKI, ponatinib (Iclusig), in combination with CC(mut3) allows a dose reduction of ponatinib and increased therapeutic efficacy in vitro measured by reduction in kinase activity, induction of apoptosis via caspase-3/7 and 7-AAD/Annexin V assays, and reduced transformative ability measured by a colony forming assay. The combination was effective not only in cells containing wild-type Bcr-Abl (K562, Ba/F3-p210) but also cells with Bcr-Abl containing the T315I mutation (Ba/F3-p210-T315I). In addition, we report for the first time the ability of CC(mut3) alone to inhibit the T315I mutant form of Bcr-Abl. This novel combination may prove to be more potent than single agent therapies and should be further explored for clinical use.