What's in a Badge? A Computational Reproducibility Investigation of the Open Data Badge Policy in One Issue of Psychological Science.

In April 2019, Psychological Science published its first issue in which all Research Articles received the Open Data badge. We used that issue to investigate the effectiveness of this badge, focusing on the adherence to its aim at Psychological Science: sharing both data and code to ensure reproducibility of results. Twelve researchers of varying experience levels attempted to reproduce the results of the empirical articles in the target issue (at least three researchers per article). We found that all 14 articles provided at least some data and six provided analysis code, but only one article was rated to be exactly reproducible, and three were rated as essentially reproducible with minor deviations. We suggest that researchers should be encouraged to adhere to the higher standard in force at Psychological Science. Moreover, a check of reproducibility during peer review may be preferable to the disclosure method of awarding badges.

A reassessment of the Resistance to Framing scale.

Risky-choice and attribute framing effects are well-known cognitive biases, where choices are influenced by the way information is presented. To assess susceptibility to these framing types, the Resistance to Framing scale is often used, although its performance has rarely been extensively tested. In an online survey among university students from Bulgaria (N = 245) and North America (N = 261), we planned to examine the scale's psychometric properties, structural validity, and measurement invariance. However, some of these examinations were not possible because the scale displayed low and mostly non-significant inter-item correlations as well as low item-total correlations. Followingly, exploratory item response theory analyses indicated that the scale's reliability was low, especially for high levels of resistance to framing. This suggests problems with the scale at a basic level of conceptualization, namely that the items may not represent the same content domain. Overall, the scale in its current version is of limited use, at least in university student samples, due to the identified problems. We discuss potential remedies to these problems, as well as provide open code and data ( https://osf.io/j5n6f ) which facilitates testing the scale in other samples (e.g., general population, different languages and countries) to obtain a comprehensive picture of its performance.

A therian mammal with sprawling kinematics? Gait and 3D forelimb X-ray motion analysis in tamanduas.

Therian mammals are known to move their forelimbs in a parasagittal plane, retracting the mobilised scapula during stance phase. Non-cursorial therian mammals often abduct the elbow out of the shoulder-hip parasagittal plane. This is especially prominent in Tamandua (Xenarthra), which suggests they employ aspects of sprawling (e.g. lizard-like) locomotion. Here, we tested whether tamanduas use sprawling forelimb kinematics, i.e. a largely immobile scapula with pronounced lateral spine bending and long-axis rotation of the humerus. We analysed high-speed videos and used X-ray motion analysis of tamanduas walking and balancing on branches of varying inclinations and provide a quantitative characterization of gaits and forelimb kinematics. Tamanduas displayed lateral sequence/lateral couplets on flat ground and horizontal branches, but increased diagonality on steeper inclines and declines, resulting in lateral sequence/diagonal couplets gaits. This result provides further evidence for high diagonality in arboreal species, probably maximising stability in arboreal environments. Further, the results reveal a mosaic of sprawling and parasagittal kinematic characteristics. The abducted elbow results from a constantly internally rotated scapula about its long axis and a retracted humerus. Scapula retraction contributes considerably to stride length. However, lateral rotation in the pectoral region of the spine (range: 21 deg) is higher than reported for other therian mammals. Instead, it is similar to that of skinks and alligators, indicating an aspect generally associated with sprawling locomotion is characteristic for forelimb kinematics of tamanduas. Our study contributes to a growing body of evidence of highly variable non-cursorial therian mammal locomotor kinematics.

Readmissions of patients with diabetes mellitus and foot ulcers after infra-popliteal bypass surgery - attacking the problem by an integrated case management model.

BACKGROUND: Patients with neuroischemic diabetic foot syndrome (DFS) may need arterial revascularization, minor amputations, débridements as well as meticulous wound care. Unfortunately, postoperative outpatient care is frequently inadequate. This is especially true for Germany, where the in- and outpatient sectors are funded and managed separately, with poor communication between the two. Thus, many patients may be readmitted to the hospital following successful treatment and discharge. In an attempt to overcome these problems, we looked at whether an integrated case management (CM) system for outpatient care according to in-hospital standards might improve patients care and avoid readmissions. In addition we analyzed the length of hospital stay (LOS) as well as hospital costs. PATIENTS AND METHODS: In this retrospective cohort study patients with DFS, bypass surgery and foot surgery after implementation of the CM (study group; n = 376) were compared with a matched historic control group (HCG; n = 190) including the flat rate revenues (G-DRG K01B). Following a standardized assessment, integrated trans-sectoral CM care was offered to 116 patients (CMP). RESULTS: The proportion of patients who were readmitted to hospital was reduced in CMP compared to HCG (8.8 vs. 16.4 %; p < 0.01), with consequent reduction of case consolidations (9.7 % versus 17.8 %, p < 0.001). Although initially, the mean LOS was higher in the CMP patients, the reduction in readmissions meant that this integrated CM program improved the hospital's economic situation. CONCLUSIONS: A hospital-based integrated CM system significantly reduces the hospital readmissions in patients with neuroischemic DFS following bypass surgery, with lower hospital costs.

Anthracycline-induced cardiotoxicity: cardiac monitoring by continuous wave-Doppler ultrasound cardiac output monitoring and correlation to echocardiography.

BACKGROUND: Anthracyclines are agents with a wellknown cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using realtime continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. METHODS: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). RESULTS: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (▵T0-T4, T0 71 ± 7.8%, T4 69.5 ± 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (▵T0-T4, T0 54 ± 19.2 ml, T4 50.5 ± 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. CONCLUSIONS: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography.

Mortality of patients with hematological malignancy after admission to the intensive care unit.

BACKGROUND: The admission of patients with malignancies to an intensive care unit (ICU) still remains a matter of substantial controversy. The identification of factors that potentially influence the patient outcome can help ICU professionals make appropriate decisions. PATIENTS AND METHODS: 90 adult patients with hematological malignancy (leukemia 47.8%, high-grade lymphoma 50%) admitted to the ICU were analyzed retrospectively in this single-center study considering numerous variables with regard to their influence on ICU and day-100 mortality. RESULTS: The median simplified acute physiology score (SAPS) II at ICU admission was 55 (ICU survivors 47 vs. 60.5 for non-survivors). The overall ICU mortality rate was 45.6%. With multivariate regression analysis, patients admitted with sepsis and acute respiratory failure had a significantly increased ICU mortality (sepsis odds ratio (OR) 9.12, 95% confidence interval (CI) 1.1- 99.7, p = 0.04; respiratory failure OR 13.72, 95% CI 1.39-136.15, p = 0.025). Additional factors associated with an increased mortality were: high doses of catecholamines (ICU: OR 7.37, p = 0.005; day 100: hazard ratio (HR) 2.96, p < 0.0001), renal replacement therapy (day 100: HR 1.93, p = 0.026), and high SAPS II (ICU: HR 1.05, p = 0.038; day 100: HR 1.2, p = 0.027). CONCLUSION: The decision for or against ICU admission of patients with hematological diseases should become increasingly independent of the underlying malignant disease.

Mechanical ventilation with positive end-expiratory pressure in critically ill patients: comparison of CW-Doppler ultrasound cardiac output monitoring (USCOM) and thermodilution (PiCCO).

BACKGROUND: Aggressive mechanical ventilation can markedly and unpredictably affect cardiac function. The fall in cardiac output (CO) is due to a reduction in left ventricular stroke volume (SV). The aim of the present pilot study was to assess the effects of different positive end-expiratory pressure (PEEP) levels on circulatory function and to compare them with continuous wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and a thermodilution-based haemodynamic monitoring system (PiCCO). METHODS: Twenty mechanically ventilated (PEEP < or = 10 mbar) adult patients (female n = 6, male n = 14, mean age 62 years, mean SAPS II-score 48.5), the majority with pneumonia and septic shock) were followed with USCOM and PiCCO at stepwise increased PEEP-levels from 0-10 mbar (1 mbar steps). The changes in CO/SV were recorded. RESULTS: With both methods, an increase of PEEP resulted in a decrease of SV and CO. Although the absolute decrease was consistently higher by USCOM, the changes of the parameters were qualitatively comparable. CO fell from 8.83 L/min (+/- 2.39) by 0.4 L/min to 8.49 L/min (+/- 2.48) with PiCCO and from 9.3 L/min (+/- 3.43) by 1.0 L/min to 8.3 L/min (+/- 3.2) with USCOM. The median CO/SV fell by 4.5%/5.2% with PiCCO and 10.8%/9% with USCOM, respectively. Correlation of CO values with the two methods by Bland-Altman yielded comparable results (mean percentage error at PEEP 0 mbar 13%, PEEP 10 mbar 18%). An adequate flow signal with USCOM was achieved in all patients. CONCLUSIONS: A significant influence of mechanical ventilation with PEEP on haemodynamic parameters was evident both with USCOM and PiCCO. While thermodilution methods like PiCCO are well established but time-consuming and invasive, CW-Doppler based USCOM constitutes an important tool for easy, rapid and reliable diagnosis and haemodynamic monitoring of critically ill patients.

Long-term follow-up of patients with metastatic breast cancer: results of a retrospective, single-center analysis from 2000 to 2005.

Recent epidemiological studies suggest that chemotherapy for metastatic breast cancer (MBC) has not contributed to a marked improvement in the patient outcome during the last decades. Randomized trials that investigated the efficacy of a first-line schedule for MBC, observed a median survival of 18-24 months. This study aimed to analyze patients with MBC who have been treated in a single university outpatient clinic for survival. Patients with MBC who had received their complete anticancer treatment in our outpatient clinic between 2000 and 2005 were analyzed for treatment schedules and survival. A total of 232 patients [median age, 53 years; range, 27-87 years; estrogen receptor and/or progesterone-positive hormone receptor, n=174 (75%); human epidermal growth factor receptor 2 overexpression (human epidermal growth factor receptor 2 positive), n=79 (34%)] were included in this analysis, of which 43.7% of hormone receptor-positive patients received 1-2, 28.3% received 3-4, and 1.7% received more than four hormonal regimens. In addition, 53.4% of all patients received up to three chemotherapeutic agents in palliative intent, whereas four to six regimens were applied in 22.1, and 12.9% received more than six subsequent regimens. An increased number of regimens were associated with an improvement in survival. The median overall survival was 44 months (95% confidence interval: 39-49). HR positivity, bone only, or single-site metastases were associated with an improved survival. An improved survival was also shown in patients who underwent locoregional procedures for oligometastatic disease (n=31; median overall survival >50 months), whereas triple-negative breast cancer was related to worse outcome (16 months; 95% confidence interval: 7-25). These data collected from a selective patient population of a single center support the hypothesis that the sequential use of all treatment modalities for MBC to its full potential may result in an increased survival. Whether innovative medicine, a step-by-step escalation of all treatment modalities according to standard guidelines and individualized clinical requirements, and a multidisciplinary treatment approach contribute to these good outcomes is debatable.

Biplanar High-Speed Fluoroscopy of Pony Superficial Digital Flexor Tendon (SDFT)-An In Vivo Pilot Study.

The superficial digital flexor tendon (SDFT) is the most frequently injured structure of the musculoskeletal system in sport horses and a common cause for early retirement. This project's aim was to visualize and measure the strain of the sound, injured, and healing SDFTs in a pony during walk and trot. For this purpose, biplanar high-speed fluoroscopic kinematography (FluoKin), as a high precision X-ray movement analysis tool, was used for the first time in vivo with equine tendons. The strain in the metacarpal region of the sound SDFT was 2.86% during walk and 6.78% during trot. When injured, the strain increased to 3.38% during walk and decreased to 5.96% during trot. The baseline strain in the mid-metacarpal region was 3.13% during walk and 6.06% during trot and, when injured, decreased to 2.98% and increased to 7.61%, respectively. Following tendon injury, the mid-metacarpal region contributed less to the overall strain during walk but showed increased contribution during trot. Using this marker-based FluoKin technique, direct, high-precision, and long-term strain measurements in the same individual are possible. We conclude that FluoKin is a powerful tool for gaining deeper insight into equine tendon biomechanics.

Smart Distance Lab's art fair, experimental data on social distancing during the COVID-19 pandemic.

In the absence of a vaccine, social distancing behaviour is pivotal to mitigate COVID-19 virus spread. In this large-scale behavioural experiment, we gathered data during Smart Distance Lab: The Art Fair (n = 839) between August 28 and 30, 2020 in Amsterdam, the Netherlands. We varied walking directions (bidirectional, unidirectional, and no directions) and supplementary interventions (face mask and buzzer to alert visitors of 1.5 metres distance). We captured visitors' movements using cameras, registered their contacts (defined as within 1.5 metres) using wearable sensors, and assessed their attitudes toward COVID-19 as well as their experience during the event using questionnaires. We also registered environmental measures (e.g., humidity). In this paper, we describe this unprecedented, multi-modal experimental data set on social distancing, including psychological, behavioural, and environmental measures. The data set is available on figshare and in a MySQL database. It can be used to gain insight into (attitudes toward) behavioural interventions promoting social distancing, to calibrate pedestrian models, and to inform new studies on behavioural interventions.

The general fault in our fault lines.

Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.

Adjuvant cisplatin-based chemotherapy for resected NSCLC: one size fits all?

The standard of care for resected stage II - IIIA non-small-cell lung cancer includes adjuvant chemotherapy based on the results of randomized trials using cisplatin regimens. A recent meta-analysis (Lung Adjuvant Cisplatin Evaluation) showed no survival benefit for this modality in stage IB disease. Therefore, the role for stage IB disease remains controversial. The Lung Adjuvant Cisplatin Evaluation meta-analysis, which is based on pooled data of five randomized trials, has shown a 5.3% absolute survival benefit at 5 years. However, long-term results of the International Adjuvant Lung Cancer Trial evaluating adjuvant cisplatin-based chemotherapy in resected non-small-cell lung cancer indicated a possible late adjuvant chemotherapy-related over-mortality. Tumor stage currently is the benchmark standard use for identifying patients who would benefit from adjuvant treatment. In the knowledge of late adjuvant chemotherapy-related over-mortality it is therefore critical to identify subsets of patients who would or would never benefit from adjuvant cisplatin. This review will discuss the extent to which individualized adjuvant treatment can be provided.

Anticancer therapy induced cardiotoxicity: review of the literature.

Innovative anticancer strategies have contributed to an improved survival of patients suffering from malignancies, and in some cases, have turned cancer into a chronic disease. Therefore, the early and particularly late onsets of adverse cardiovascular effects of systemic anticancer treatments are of increasing interest. Among a rapidly increasing variety of anticancer drugs, the anthracyclines and the monoclonal antibody, trastuzumab, are the agents with a well-known cardiotoxicity. The diagnostic work-up, the cardiotoxic risk of anthracyclines and trastuzumab, and additionally, cardiotoxicity as a risk factor of a multimodal therapeutic approach in breast cancer patients is discussed in this study.

Nucleosomes as a new prognostic marker in early cerebral stroke.

BACKGROUND: The prognostic relevance of blood markers in cerebral stroke is still a matter of controversial debate. PATIENTS AND METHODS: In sera of 63 patients, nucleosomes, neuronspecific enolase (NSE), S100 protein, and C-reactive protein (CRP) were determined daily during the first week after cerebral stroke. Infarction volume was quantified by CT or MRI and the clinical status by Barthel Index (BI) at admission, discharge, and after 12 months (prognosis). All markers were evaluated by univariate and multivariate analysis on their prognostic relevance. RESULTS: During observation time (12 months), three patients died and 33 reached complete recovery. Infarction volume, nucleosomes, NSE, S100, and CRP correlated significantly with clinical status at admission. The same markers except CRP and initial BI correlated with recovery after 12 months. Almost all patients with initial BI double dagger 50 reached complete recovery. In patients with initially severe defects (BI < 50), nucleosomes and S100, both at day 3, were found to be prognostically relevant. At 100%-specificity for non-recovery, only nucleosomes maintained their prognostic power (sensitivity 52.6%; p = 0.014), whereas S100 did not (sensitivity 16.7%; p = 0.25). In multivariate analysis, nucleosomes and BI at admission showed independent prognostic relevance (p = 0.039). CONCLUSION: Circulating nucleosomes and clinical scores provide independent prognostic information concerning the later outcome in patients with initially severe defects after stroke.

Does brain specific 24S-hydroxycholesterol in plasma indicate the disruption of the blood-brain barrier in patients with ischemic stroke?

Determination of plasma 24S-hydroxycholesterol, which is produced almost exclusively in the brain and is released only in small amounts into circulation under physiological conditions, might be a marker to monitor non-invasively the time course and the extent of the disintegration of the blood-brain barrier after cerebral ischemia. We investigated the plasma concentrations for 4 to 10 days of 24S-hydroxycholesterol, and compared the concentration with the liver-specific oxysterol 7alpha-hydroxycholesterol, the ubiquitously produced 27-hydroxycholesterol, and cholesterol itself in six patients who were admitted to the hospital within 24 h after symptoms of stroke. Quantification of oxysterols was performed by isotope dilution mass spectrometry and cholesterol by gas-liquid chromatography. Initial concentrations of cholesterol, 24S-, 7alpha-, and 27-hydroxycholesterol in stroke patients were not different from data of healthy controls given in the literature. During the following days, no changes could be observed in the concentrations of cholesterol nor in the other oxysterols. Particularly the brain specific 24S-hydroxycholesterol was very constant and showed only minimal changes. Furthermore, comparison of patients with extended or small lesions did not reveal any differences in the concentrations of oxysterols. Therefore, circulating levels of 24S-hydroxycholesterol are supposed to be only of limited value for monitoring the brain-blood barrier function in patients with acute ischemic stroke.

Cardiotoxicity After Anthracycline Treatment in Survivors of Adult Cancers: Monitoring by USCOM, Echocardiography and Serum Biomarkers.

BACKGROUND: Anthracyclines are agents with a well known documented anti-tumoral activity. Cardiac side effects are the principal toxicity. Here we evaluate and monitor the onset of late anthracycline-induced cardiotoxicity with real-time CW-Doppler ultrasound cardiac output monitoring (USCOM®) and echocardiography in combination with serum biomarkers. METHODS: Fifty-two patients without cardiac disease who had received an anthracycline-based regimen for various cancer types were included in this study. Patients' hemodynamic parameters as stroke volume (SV USCOM (mL)) and ejection fraction (EF ECHOCARDIOGRAPHY (%)) were measured with USCOM and echocardiography and correlated to serum biomarkers (NT-pro-BNP and cTnT). RESULTS: Eighteen patients (34.6%) developed cardiac disease (NYHA I-III). An increasing cumulative anthracycline dose was associated with a decrease of the EF determined by echocardiography as well the SV by USCOM and with a higher NYHA class. Those patients who experienced cardiac disease showed a reduction of the EF and SV and increased serum biomarkers. CONCLUSIONS: Real-time CW-Doppler USCOM, is a fast and reliable method to monitor late hemodynamic changes as a symptom of anthracycline-induced cardiotoxicity comparable to the findings by echocardiography and serum biomarkers.

Cardiac Output Measurements in Septic Patients: Comparing the Accuracy of USCOM to PiCCO.

USCOM is an ultrasound-based method which has been accepted for noninvasive hemodynamic monitoring in various clinical conditions (USCOM, Ultrasonic cardiac output monitoring). The present study aimed at comparing the accuracy of the USCOM device with that of the thermodilution technique in patients with septicemia. We conducted a prospective observational study in a medical but noncardiological ICU of a university hospital. Septic adult patients (median age 55 years, median SAPS-II-Score 43 points) on mechanical ventilation and catecholamine support were monitored with USCOM and PiCCO (n = 70). Seventy paired left-sided CO measurements (transaortic access = CO(US-A)) were obtained. The mean CO(US-A) were 6.55 l/min (±2.19) versus CO(PiCCO) 6.5 l/min (±2.18). The correlation coefficient was r = 0.89. Comparison by Bland-Altman analysis revealed a bias of -0.36 l/min (±0.99 l/min) leading to a mean percentage error of 29%. USCOM is a feasible and rapid method to evaluate CO in septic patients. USCOM does reliably represent CO values as compared to the reference technique based on thermodilution (PiCCO). It seems to be appropriate in situations where CO measurements are most pertinent to patient management.

Bone loss after allogeneic haematopoietic stem cell transplantation: a pilot study on the use of zoledronic Acid.

Purpose. Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT). The study aimed on tolerance and efficacy of zoledronic acid (ZA) in patients after allo-HSCT. Methods. 40 patients' with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs). BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip). Patients were evaluated for deoxypyridinoline (Dpd) and calcium excretion by longitudinal measurements. Results. 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group). Among these patients, BMD increased from 0.97 ± 0.15 to 1.10 ± 0.18 g/cm² (LS baseline-2 yrs, Δ+11.6 ± 6.0%, P < 0.001) and from 0.82 ± 0.10 to 0.91 ± 0.10 g/cm(²) (FH baseline-2 yrs, Δ+7.5 ± 7.0%, P < 0.001). Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion. ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT.

Clinical relevance of circulating nucleosomes in cancer.

Nucleosomes, complexes of DNA and histone proteins, are released during cell death into the blood circulation. Elevated serum and plasma levels have been found in various forms of cancer, but also in autoimmune diseases and acute situations such as stroke, trauma, and during sepsis. Here, the clinical relevance of circulating nucleosomes for diagnosis, staging, prognosis, and therapeutic monitoring of cancer is reviewed. Several studies have shown that levels of nucleosomes are significantly higher in serum and plasma of cancer patients in comparison to healthy controls. However, because of elevations of nucleosome levels in patients with benign diseases relevant for differential diagnosis, they are not suitable for cancer diagnosis. Concerning tumor staging, nucleosome levels correlate with tumor stage and presence of metastases in gastrointestinal cancer, but not in other tumor types. Prognostic value of circulating nucleosomes is found in lung cancer in univariate analyses, but not in multivariate analyses. Circulating nucleosomes are most informative for the monitoring of cytotoxic therapy. Strongly decreasing levels are mainly found in patients with remission of disease, whereas constantly high or increasing values are associated with progressive disease during chemo- and radiotherapy. In addition, therapy outcome is already indicated by the nucleosomal course during the first week of chemo- and radiotherapy in patients with lung, pancreatic, and colorectal cancer as well as in hematologic malignancies. Despite their non-tumor-specificity, kinetics of nucleosomes are valuable markers for the early estimation of therapeutic efficacy and may be helpful to adapting early cancer therapy in the future.