Swimming behaviour of Atlantic salmon kelts migrating past a hydropower plant dam: Effects of hydraulics and dam operations.

Hydropower plants commonly impede the downstream migration of Atlantic salmon (Salmo salar) kelts. Thus, understanding the effects of hydraulic conditions on kelt behaviour and passage performance at dams is crucial for developing effective mitigation measures. In this study, we investigated the influence of hydraulic conditions on kelt passage performance and swimming behaviour at a Norwegian hydropower plant. We combined biological data from 48 kelts collected via acoustic telemetry with hydraulic data modelled using computational fluid dynamics. We assessed kelt passage performance using metrics such as time-to-pass, total number of detections, and total number of detections per day. Additionally, we analysed swimming depths and speeds in relation to the hydraulic conditions created by different dam operating conditions. We found that the dam operation schedule impacted the kelts' ability to find a route past the dam. Though kelts could have passed the dam throughout the study period via a submerged pipe at the dam (which had seemingly sufficient discharge for the kelts to find), 98 % of the kelts instead waited for a spill gate to open partway through the study period. The swimming depth analysis indicated diel variation, with kelts swimming nearer to the water surface during the night. We found that swimming speed increased with increasing kelt body length, particularly under high turbulence kinetic energy and during the day. Furthermore, kelts swam faster as water velocity increased, but slowed down again as turbulence intensity increased. Our findings reveal the effects of hydraulic conditions and dam operations on the migration behaviour of Atlantic salmon kelts. This provides valuable insights for developing strategies to optimise dam operations and improve fish passage performance, including the need to spill enough water to increase passage success and will contribute to sustainable management of Atlantic salmon populations in regulated rivers.

Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation.

Neuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as genetic covariates, biomarkers, vascular risk factors, neuropsychological tests etc.) might provide useful predictions of clinical outcomes during the progression towards Alzheimer's disease (AD). The use of multiple features in predictive frameworks for clinical outcomes has become increasingly prevalent in AD research. However, many studies do not focus on systematically and accurately evaluating combinations of multiple input features. Hence, the aim of the present work is to explore and assess optimal combinations of various features for MR-based prediction of (1) cognitive status and (2) biomarker positivity with a multi-kernel learning Gaussian process framework. The explored features and parameters included (A) combinations of brain tissues, modulation, smoothing, and image resolution; (B) incorporating demographics & clinical covariates; (C) the impact of the size of the training data set; (D) the influence of dimensionality reduction and the choice of kernel types. The approach was tested in a large German cohort including 959 subjects from the multicentric longitudinal study of cognitive impairment and dementia (DELCODE). Our evaluation suggests the best prediction of memory performance was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF biomarkers explaining 57% of outcome variance in out-of-sample predictions. The highest performance for Aß42/40 status classification was achieved for a combination of demographics, ApoE4, and a memory score while usage of structural MRI further improved the classification of individual patient's pTau status.

Examining outpatients' hand hygiene behaviour and its relation to COVID-19 infection prevention measures.

BACKGROUND: The increasing demand for outpatient care is associated with a higher risk of infection transmission in these settings. However, there is limited research on infection prevention and control practices in ambulatory clinics, and none focuses on patients. AIM: To examine outpatients' hand hygiene behaviours, their determinants, and their associations with other infection prevention measures during the COVID-19 pandemic. METHODS: We observed the hand hygiene behaviour of one cohort of patients in one outpatient clinic and surveyed a separate sample in five clinics about their hand hygiene practice in outpatient facilities. A questionnaire based on the Theoretical Domains Framework (TDF) was used to examine predictors of the behaviour. Moreover, patients indicated their compliance with COVID-19 infection prevention measures, vaccination status, disease risk perception, and vaccine hesitancy. FINDINGS: Observed hand hygiene rates among 618 patients were low (12.8%), while 67.3% of the 300 surveyed patients indicated sanitizing their hands upon entering the clinic. The TDF domains 'memory, attention, and decision processes' and 'emotions' significantly predicted both current (today's) and general hand hygiene behaviour in outpatient clinics. Hand hygiene behaviour and compliance with COVID-19 infection prevention showed a positive association; however, no significant connection was found with patients' vaccination status, suggesting different behavioural motivators. CONCLUSION: Hand hygiene among outpatients should be improved through interventions focusing on helping patients remember to clean their hands. More research on infection prevention in outpatient facilities is needed to ensure patient safety.

Effect of environmental and spatial factors on the phylogenetic and functional diversity of the Mediterranean tree communities of Europe.

The tree flora of the Mediterranean Basin contains an outstanding taxonomic richness and a high proportion of endemic taxa. Contrary to other regions of the Mediterranean biome, a comprehensive phylogenetic analysis of the relationship between phylogenetic diversity, trait diversity and environmental factors in a spatial ecological context is lacking. We inferred the first calibrated phylogeny of 203 native tree species occurring in the European Mediterranean Basin based on 12 DNA regions. Using a set of four functional traits, we computed phylogenetic diversity for all 10,042 grid cells of 10 × 10 km spatial resolution to completely cover Mediterranean Europe. Then, we tested the spatial influence of environmental factors on tree diversity. Our results suggest that the nature of the relationship between traits and phylogeny varies among the different studied traits and according to the evolutionary distance considered. Phylogenetic diversity and functional diversity of European Mediterranean trees correlated strongly with species richness. High values of these diversity indices were located in the north of the study area, at high altitude, and minimum temperature of the coldest month. In contrast, the two phylogenetic indices that were not correlated with species richness (Mean Phylogenetic Distance, Phylogenetic Species Variability) were located in the south of the study area and were positively correlated with high altitude, soil organic carbon stock and sand soil texture. Our study provides support for the use of phylogenies in conservation biology to assess ecosystem functioning, and provides insights for the implementation of sustainable forest ecosystem management.

Sex and country differences in gout: cross-country comparison between Sweden and the UK.

OBJECTIVE: Compare characteristics, sex differences, and management of gout in Sweden and the UK. METHOD: The results from two separate primary care gout surveys from Sweden and the UK were compared. Participants aged ≥18 years with gout were sent a questionnaire asking about lifestyle, gout characteristics, uratelowering therapy (ULT), comorbidities, disability, and disease impact. For sex comparison, participants were pooled across countries. RESULTS: In total, 784 (80% male) participants from Sweden and 500 (87% male) from the UK were included. Swedish patients were significantly older at gout onset, mean (SD) age 72 (12) versus 63 (13) years, (p<0.0001), with more comorbidities, and more frequent use of ULT (48% vs 35%, p=0.0005, age-adjusted). Use of alcohol and diuretics was significantly more common among UK patients, who also reported a higher number of gout flares, mean (SD) 2.2 (1.7) versus 1.6 (3.6), (p=0.003) age-adjusted. Females with gout were older at gout onset, mean (SD) age 67 (13) versus 56 (15), (p<0.0001), more often obese, and reported higher use of diuretics. Furthermore, females reported greater impact of gout, more pain and physical limitations, whereas no sex differences were seen in ULT or flares. CONCLUSIONS: In the UK, gout was more frequently associated with modifiable risk factors. People with gout in Sweden were more commonly taking ULT and had lower frequency of gout flares and impact of gout. Females with gout more commonly took diuretics, had higher body mass index, and reported greater physical disability, which should be considered when managing gout in women.

Palliative care outpatients in a German comprehensive cancer center-identifying indicators for early and late referral.

PURPOSE: Despite that early integration of palliative care is recommended in advanced cancer patients, referrals to outpatient specialised palliative care (SPC) frequently occur late. Well-defined referral criteria are still missing. We analysed indicators associated with early (ER) and late referral (LR) to SPC of an high volume outpatient unit of a comprehensive cancer center. METHODS: Characteristics, laboratory parameters and symptom burden of 281 patients at first SPC referral were analysed. Timing of referral was categorized as early, intermediate and late (> 12, 3-12 and < 3 months before death). Ordinal logistic regression analysis was used to identify factors related to referral timing. Kruskal-Wallis test was used to determine symptom severity and laboratory parameter in each referral category. RESULTS: LRs (50.7%) had worse scores of weakness, loss of appetite, drowsiness, assistance of daily living (all p < 0.001) and organisation of care (p < 0.01) in contrast to ERs. The mean symptom sum score was significantly higher in LRs than ERs (13.03 vs. 16.08; p < 0.01). Parameters indicative of poor prognosis, such as elevated LDH, CRP and neutrophil-to-lymphocyte ratio (NLR) (p < 0.01) as well as the presence of ascites (p < 0.05), were significantly higher (all p < 0.001) in LRs. In univariable analyses, psychological distress (p < 0.05) and female gender (p < 0.05) were independently associated with an ER. CONCLUSION: A symptom sum score and parameters of poor prognosis like NLR or LDH might be useful to integrate into palliative care screening tools.

Prevalence of anxiety and depression in people with different types of cancer or haematologic malignancies: a cross-sectional study.

AIMS: Cancer patients often present with psychological symptoms that affect their quality of life, physical health outcomes and survival. Two of the most frequent psychiatric comorbidities are anxiety and depression. However, the prevalence of these disorders among cancer patients remains unclear, as studies frequently report varying rates. In the present study, we aimed to provide robust point estimates for the prevalence of anxiety and depression for both a mixed cancer sample and for 13 cancer types separately, considering confounding variables. METHODS: In a sample of 7509 cancer outpatients (51.4% female), we used the Hospital Anxiety and Depression Scale to assess rates of anxiety and depression. Applying ordinal logistic regression models, we compared the prevalence of anxiety and depression between different cancer types, controlling for age and gender. RESULTS: About one third of our sample showed symptoms of anxiety (35.2%) or depression (27.9%), and every sixth patient had a very likely psychiatric condition, with women being more frequently affected. Elderly patients more often showed signs of depression. The prevalence of anxiety and depression was significantly higher in lung and brain cancer patients, than in other cancer patients. Lowest depression rates were found in breast cancer patients. CONCLUSIONS: The prevalence of anxiety and depression is high in cancer patients. Type of cancer is an important predictor for anxiety and depressive symptoms, with lung and brain cancer patients being highly burdened. Considering a personalised medicine approach, physicians should take into account the high prevalence of psychiatric comorbidities and include psychiatric consultations in the treatment plan.

Estudio retrospectivo en pacientes con Cáncer de Colon etapa III. ¿El tratamiento adyuvante es iniciado de forma oportuna?

Introducción: En Chile, el Cáncer colorrectal (CC) abarca el 11,5% de todas las neoplasias malignas. La cirugía es la piedra angular del tratamiento del cáncer de colon, y en pacientes en etapa III, la quimioterapia adyuvante forma parte del tratamiento estándar. Materiales y Métodos: Estudio descriptivo retrospectivo transversal, de centro único, de pacientes con cáncer de colon en estadio III patológico. Objetivo principal de este estudio es conocer si, en pacientes con cáncer de colon etapa III, la quimioterapia adyuvante se entrega de manera oportuna. Resultados: En el período comprendido entre abril de 2016 y abril de 2021 se operaron 35 pacientes con cáncer de colon en estadio III patológico. Se realizó quimioterapia adyuvante en un 80%, y en siete pacientes durante las primeras ocho semanas poscirugía. La dehiscencia de anastomosis ocurrió en un 11,4%, aumentando la mediana de hospitalización en 2,2 veces. Discusión: En nuestro estudio, la adyuvancia en cáncer de colon etapa III se administró a un alto porcentaje de los pacientes (80%), pero observamos un retraso importante, ya que sólo en un 25% se inició el tratamiento durante las primeras 8 semanas poscirugía, lo cual puede ser explicado por múltiples factores, siendo la dehiscencia de anastomosis un punto importante a considerar. Conclusión: En estadio III de CC la adyuvancia puede verse retrasada por múltiples factores, lo que puede repercutir en la sobrevida de los pacientes, por lo tanto, conocer las causas de este retraso podría ayudar a instaurar nuevas estrategias, como la neoadyuvancia, para mejorar los resultados oncológicos.

Introduction: In Chile, colorectal cancer covers 11.5% of all malignant neoplasms. Surgery is the cor- nerstone of colon cancer treatment and in stage III patients adjuvant chemotherapy is part of standard treatment. Materials and Methods: A descriptive, retrospective, cross-sectional study, single center, of patients with pathological stage III colon cancer. Main objective of this study is to know if in patients with stage III colon cancer adjuvant chemotherapy is delivered in a timely manner. Results: Between April 2016 and April 2021, 35 patients with pathological stage III colon cancer were operated on. Adjuvant chemotherapy was performed in 80%, and in seven patient during the first eight weeks after surgery. Anastomotic dehiscence occurred in 11.4%, the median hospitalization increased by 2.2 times. Discussion: In this study, adjuvant stage III colon cancer was administered to a high percentage of patients (80%), but we observed a significant delay, since only 25% began treatment during the first 8 weeks post-surgery, which can be explained by multiple factors, with anastomotic dehiscence being an important point to consider. Conclusion: In stage III CC, adjuvant treatment can be delayed by multiple factors, which may affect patient survival; therefore, knowing the causes of this delay could help to establish new strategies, such as neoadjuvant therapy, to improve oncological results.

Characteristics and outcomes of COVID-19 in heart transplantation recipients in the Netherlands.

BACKGROUND: Immunocompromised patients are at high risk of complicated severe acute respiratory coronavirus 2 infection. The aim of this retrospective study was to describe the characteristics and outcomes of heart transplantation (HTx) recipients with coronavirus disease 2019 (COVID-19) in the Netherlands. METHODS: HTx patients from one of the three HTx centres in the Netherlands with COVID-19 (proven by positive reverse-transcription polymerase chain reaction or serology test result) between February 2020 and June 2021 were included. The primary endpoint was all-cause mortality and the secondary endpoint was disease severity. RESULTS: COVID-19 was diagnosed in 54/665 HTx patients (8%), with a mean (±â€¯standard deviation (SD)) time after HTx of 11 ± 8 years. Mean (±â€¯SD) age was 53 ± 14 years and 39% were female. Immunosuppressive therapy dosage was reduced in 37% patients (20/54). Hospitalisation was required in 39% patients (21/54), and 13% patients (7/54) had severe COVID-19 (leading to intensive care unit (ICU) admission or death). In-hospital mortality was 14% (3/21), and all-cause mortality was 6%. Compared with patients with moderate COVID-19 (hospitalised without ICU indication), severe COVID-19 patients tended to be transplanted earlier and had a significantly higher mean (±â€¯SD) body mass index (26 ± 3 vs 30 ± 3 kg/m2, p = 0.01). Myocardial infarction, cellular rejection and pulmonary embolism were observed once in three different HTx patients. CONCLUSION: HTx patients were at increased risk of complicated COVID-19 with frequent hospitalisation, but the all-cause mortality was substantially lower than previously described (7-33%).

Enthesis: not the same in each localisation - a molecular, histological and biomechanical study.

The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location. The present study aimed to characterise three of the most relevant sites of enthesis injury in a rat model: the patellar tendon, the Achilles tendon and the supraspinatus enthesis, in terms of biomechanics, histology and genetic expression. The patellar enthesis presented the highest ultimate load and lowest stiffness of the three, while the supraspinatus was the weakest and stiffest. The histological characterisation revealed key differences at the insertion site for each enthesis. The patellar enthesis showed a large cartilaginous area at the tendon-to-bone interphase whilst this interphase was smaller in the supraspinatus entheses samples. Furthermore, the Achilles tendon enthesis displayed a more abrupt transition from tendon to bone. Additionally, each enthesis exhibited a particular and distinct pattern of expression of tenogenic, chondrogenic and osteogenic markers. This study provided valuable insights for a better understanding of the three entheses at relevant anatomical sites. Moreover, the larger cross-sectional area of the patellar enthesis, the strong mechanical properties and the easier surgical access to this location led to the conclusion that the patellar tendon enthesis site could be most suitable for the development of a preclinical model for general enthesis regeneration studies in rats.

F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial.

AIM: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. METHODS: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3-14 days before (pre-ICIT) and 21-28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). RESULTS: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. CONCLUSION: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03426657.

Mechanical and strain behaviour of human Achilles tendon during in vitro testing to failure.

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.

A neuronal mechanism for motivational control of behavior.

Acting to achieve goals depends on the ability to motivate specific behaviors based on their predicted consequences given an individual's internal state. However, the underlying neuronal mechanisms that encode and maintain such specific motivational control of behavior are poorly understood. Here, we used Ca2+ imaging and optogenetic manipulations in the basolateral amygdala of freely moving mice performing noncued, self-paced instrumental goal-directed actions to receive and consume rewards. We found that distinct neuronal activity patterns sequentially represent the entire action-consumption behavioral sequence. Whereas action-associated patterns integrated the identity, value, and expectancy of pursued goals, consumption-associated patterns reflected the identity and value of experienced outcomes. Thus, the interplay between these patterns allows the maintenance of specific motivational states necessary to adaptively direct behavior toward prospective rewards.

Talbot-Lau x-ray deflectometer: Refraction-based HEDP imaging diagnostic.

Talbot-Lau x-ray interferometry has been implemented to map electron density gradients in High Energy Density Physics (HEDP) experiments. X-ray backlighter targets have been evaluated for Talbot-Lau X-ray Deflectometry (TXD). Cu foils, wires, and sphere targets have been irradiated by 10-150 J, 8-30 ps laser pulses, while two pulsed-power generators (∼350 kA, 350 ns and ∼200 kA, 150 ns) have driven Cu wire, hybrid, and laser-cut x-pinches. A plasma ablation front generated by the Omega EP laser was imaged for the first time through TXD for densities >1023 cm-3. Backlighter optimization in combination with x-ray CCD, image plates, and x-ray film has been assessed in terms of spatial resolution and interferometer contrast for accurate plasma characterization through TXD in pulsed-power and high-intensity laser environments. The results obtained thus far demonstrate the potential of TXD as a powerful diagnostic for HEDP.

Pump-depletion dynamics and saturation of stimulated Brillouin scattering in shock ignition relevant experiments.

As an alternative inertial confinement fusion scheme, shock ignition requires a strong converging shock driven by a high-intensity laser pulse to ignite a precompressed fusion capsule. Understanding nonlinear laser-plasma instabilities is crucial to assess and improve the laser-shock energy coupling. Recent experiments conducted on the OMEGA EP laser facility have demonstrated that such instabilities can ∼100% deplete the first 0.5 ns of the high-intensity laser. Analyses of the observed laser-generated blast wave suggest that this pump-depletion starts at ∼0.02 critical density and progresses to 0.1-0.2 critical density, which is also confirmed by the time-resolved stimulated Raman backscattering spectra. The pump-depletion dynamics can be explained by the breaking of ion-acoustic waves in stimulated Brillouin scattering. Such pump depletion would inhibit the collisional laser energy absorption but may benefit the generation of hot electrons with moderate temperatures for electron shock ignition [Phys. Rev. Lett. 119, 195001 (2017)PRLTAO0031-900710.1103/PhysRevLett.119.195001].

Is extracapsular dissection for pleomorphic adenoma rather a euphemism for enucleation that jeopardises the intactness of the capsule?

The aim of this study was to compare several surgical modalities with respect to the incidence of positive margins and focal capsular exposure of pleomorphic adenoma of the parotid gland. The clinical records and histopathological findings of all patients who underwent parotidectomy for pleomorphic adenoma between 2006 and 2020 were retrospectively evaluated (n = 845). The lesion was removed by extracapsular dissection in 577 cases (68%) and facial nerve dissection in 268 (32%). Our analysis did not reveal a statistically significant difference between the examined modalities regarding positive margins (p=0.648) or capsular exposure (p=0.112). Recurrences were detected in 7/845 cases (0.82%) with a mean (range) follow-up time of 82.3 (6-183) months. The choice of surgical method does not seem to have a significant effect on the incidence of positive margins, or on the capsular exposure of a pleomorphic adenoma.

Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients.

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.