Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Frontal fibrosing alopecia: survey of severity assessment methods in routine clinical practice and validation of the International Frontal Fibrosing Alopecia Cooperative Group measurement guidance.

BACKGROUND: The lack of validated and responsive outcome measures in the management of frontal fibrosing alopecia (FFA) significantly limits assessment of disease progression and treatment response over time. AIM: To understand how FFA extent and progression is currently assessed in UK specialist centres, to validate components of the International FFA Cooperative Group (IFFACG) statement on FFA assessment, and to identify pragmatic advice to improve FFA management in clinic. METHODS: Consultant dermatologists with a specialist interest in hair loss (n = 17) were invited to take part. Preferred FFA assessment methods were explored using questionnaires and clinical scenarios. Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images (Questionnaire 1), with assessment repeated 3 months later to assess intraindividual variability (Questionnaire 2) and 12 months later to test whether interindividual accuracy could be improved with simple instruction (Questionnaire 3). RESULTS: All 17 clinicians (100%) completed the questionnaire at each time interval. We identified a wide variation in assessment techniques used by our experts. Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession. Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement [intraclass coefficient (ICC) = 0.61; 95% CI 0.40-0.85], yet intrarater reliability was found to be poor with wide limits of agreement (-8.71 mm to 9.92 mm) on follow-up. Importantly, when clear guidance was provided on how the hairline should be identified (Questionnaire 3), inter-rater reliability improved significantly, with ICC = 0.70, suggesting moderate agreement (95% CI 0.51-0.89; P < 0.001). A similar pattern was seen with temporal hairline measurements, which again improved in accuracy with instruction. CONCLUSION: We found that accuracy of measurements in FFA can be improved with simple instruction and we have validated components of the IFFACG measurement recommendations.

Influence of season, age, sex, and time of day on the endocrine profile of the common bottlenose dolphin (Tursiops truncatus).

Understanding baseline hormone levels, the magnitude of intra-individual variability, and their variation as a function of life history is difficult in toothed whales (e.g. dolphins and porpoises) because of the effects of capture stress. To determine the endocrine profile of the common bottlenose dolphin (Tursiops truncatus) as a function of season, time of day (TOD), age, sex, and reproductive status, blood corticosteroids, thyroid hormones, and catecholamines were repeatedly measured in a managed-care population exposed to ambient light and water temperatures of San Diego Bay. Additionally, fecal hormone metabolites were assessed for cortisol, aldosterone, and triiodothyronine. Samples were collected at two to four-week intervals over a period of two years, and multiple times within a day at monthly intervals over a year. Samples were collected through the voluntary participation of the dolphins in the blood draws and fecal collections in order to avoid the effects of handling stress. All serum hormones except aldosterone significantly varied with season and all serum hormones except total thyroxine significantly varied as a function of TOD. Fecal glucocorticoid metabolites significantly correlated with circulating cortisol levels, and there was a significant seasonal effect on triiodothyronine fecal metabolites. Strong seasonal effects demonstrated complex interactions with age and sex suggesting that contextual information is critical to interpreting differences in endocrine profiles. Strong circadian patterns further suggest that sampling design is important to the interpretation of blood or fecal collections, particularly since diurnal changes in some serum hormone levels are similar to the magnitude of seasonal differences. Despite potential impacts of feeding schedules on diurnal patterns, managed care populations can provide important insights into seasonal and age-related endocrine changes in toothed whales.

Measuring food intake with digital photography.

The digital photography of foods method accurately estimates the food intake of adults and children in cafeterias. When using this method, images of food selection and leftovers are quickly captured in the cafeteria. These images are later compared with images of 'standard' portions of food using computer software. The amount of food selected and discarded is estimated based upon this comparison, and the application automatically calculates energy and nutrient intake. In the present review, we describe this method, as well as a related method called the Remote Food Photography Method (RFPM), which relies on smartphones to estimate food intake in near real-time in free-living conditions. When using the RFPM, participants capture images of food selection and leftovers using a smartphone and these images are wirelessly transmitted in near real-time to a server for analysis. Because data are transferred and analysed in near real-time, the RFPM provides a platform for participants to quickly receive feedback about their food intake behaviour and to receive dietary recommendations for achieving weight loss and health promotion goals. The reliability and validity of measuring food intake with the RFPM in adults and children is also reviewed. In sum, the body of research reviewed demonstrates that digital imaging accurately estimates food intake in many environments and it has many advantages over other methods, including reduced participant burden, elimination of the need for participants to estimate portion size, and the incorporation of computer automation to improve the accuracy, efficiency and cost-effectiveness of the method.

Quantifying the impact of interventions against Plasmodium vivax: A model for country-specific use.

In order to evaluate the impact of various intervention strategies on Plasmodium vivax dynamics in low endemicity settings without significant seasonal pattern, we introduce a simple mathematical model that can be easily adapted to reported case numbers similar to that collected by surveillance systems in various countries. The model includes case management, vector control, mass drug administration and reactive case detection interventions and is implemented in both deterministic and stochastic frameworks. It is available as an R package to enable users to calibrate and simulate it with their own data. Although we only illustrate its use on fictitious data, by simulating and comparing the impact of various intervention combinations on malaria risk and burden, this model could be a useful tool for strategic planning, implementation and resource mobilization.

Behavioral mediators of treatment effects in the weight loss maintenance trial.

BACKGROUND: The Weight Loss Maintenance Trial tested strategies for maintenance of weight loss. Personal contact was superior to interactive technology and self-directed conditions. PURPOSE: We aimed to identify behavioral mediators of the superior effect of personal contact vs. interactive technology and of personal contact vs. self-directed arms. METHODS: Overweight/obese adults at risk for cardiovascular disease (n = 1,032) who lost at least 4 kg were randomized to personal contact, interactive technology, or self-directed. After 30 months, 880 participants had data on weight and behavioral strategies. RESULTS: Reported increase of intake of fruits and vegetables and physical activity and more frequent self-weighing met criteria as mediators of the better outcome of personal contact vs. interactive technology. Increased intake of fruits and vegetables, more frequent self-weighing, and decreased dessert consumption were mediators of the difference between personal contact vs. self-directed. CONCLUSION: Inducing changes in the identified behaviors might yield better outcomes in future weight loss maintenance trials.

Improved sub-milimeter range-verification method for proton therapy using a composite hadron tumour marker (HTM).

Objective.The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented.Approach.The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring theγ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery.Main results.Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure theγ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate theγ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm.Significance.Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.

Effect of diet composition on energy expenditure during weight loss: the POUNDS LOST Study.

BACKGROUND: Weight loss reduces energy expenditure, but the contribution of different macronutrients to this change is unclear. HYPOTHESIS: We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss. DESIGN: A substudy of 99 participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial had total energy expenditure (TEE) measured by doubly labeled water, and resting energy expenditure (REE) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants. Participants were randomly assigned to one of four diets with either 15 or 25% protein and 20 or 40% fat. RESULTS: TEE and REE were positively correlated with each other and with fat-free mass and body fat, at baseline and 6 months. The average weight loss of 8.1 ± 0.65 kg (least-square mean ± s.e.) reduced TEE by 120 ± 56 kcal per day and REE by 136 ± 18 kcal per day. A greater weight loss at 6 months was associated with a greater decrease in TEE and REE. Participants eating the high-fat diet (HF) lost significantly more fat-free mass (1.52 ± 0.55 kg) than the low-fat (LF) diet group (P<0.05). Participants eating the LF diet had significantly higher measures of physical activity than the HF group. CONCLUSION: A greater weight loss was associated with a larger decrease in both TEE and REE. The LF diet was associated with significant changes in fat-free body mass and energy expenditure from physical activity compared with the HF diet.

First direct mass measurement of the two-neutron halo nucleus 6He and improved mass for the four-neutron halo 8He.

The first direct mass measurement of {6}He has been performed with the TITAN Penning trap mass spectrometer at the ISAC facility. In addition, the mass of {8}He was determined with improved precision over our previous measurement. The obtained masses are m({6}He)=6.018 885 883(57) u and m({8}He)=8.033 934 44(11) u. The {6}He value shows a deviation from the literature of 4σ. With these new mass values and the previously measured atomic isotope shifts we obtain charge radii of 2.060(8) and 1.959(16) fm for {6}He and {8}He, respectively. We present a detailed comparison to nuclear theory for {6}He, including new hyperspherical harmonics results. A correlation plot of the point-proton radius with the two-neutron separation energy demonstrates clearly the importance of three-nucleon forces.

Measurement of the W boson mass with the D0 detector.

We present a measurement of the W boson mass using data corresponding to 4.3 fb(-1) of integrated luminosity collected with the D0 detector during Run II at the Fermilab Tevatron pp collider. With a sample of 1,677,394 W → eν candidate events, we measure M(W) = 80.367 ± 0.026 GeV. This result is combined with an earlier D0 result determined using an independent Run II data sample, corresponding to 1 fb(-1) of integrated luminosity, to yield M(W) = 80.375 ± 0.023 GeV.

Search for charged massive long-lived particles.

We report on a search for charged massive long-lived particles (CMLLPs), based on 5.2 fb(-1) of integrated luminosity collected with the D0 detector at the Fermilab Tevatron pp collider. We search for events in which one or more particles are reconstructed as muons but have speed and ionization energy loss (dE/dx) inconsistent with muons produced in beam collisions. CMLLPs are predicted in several theories of physics beyond the standard model. We exclude pair-produced long-lived gauginolike charginos below 267 GeV and Higgsino-like charginos below 217 GeV at 95% C.L., as well as long-lived scalar top quarks with mass below 285 GeV.

Search for universal extra dimensions in pp collisions.

We present a search for Kaluza-Klein (KK) particles predicted by models with universal extra dimensions (UED) using a data set corresponding to an integrated luminosity of 7.3 fb(-1), collected by the D0 detector at a pp center-of-mass energy of 1.96 TeV. The decay chain of KK particles can lead to a final state with two muons of the same charge. This signature is used to set a lower limit on the compactification scale of R(-1)>260 GeV in a minimal UED model.

Measurements of WW and WZ production in W + jets final states in pp collisions.

We study WW and WZ production with ℓνqq (ℓ=e,µ) final states using data collected by the D0 detector at the Fermilab Tevatron Collider corresponding to 4.3 fb(-1) of integrated luminosity from pp collisions at sqrt[s]=1.96 TeV. Assuming the ratio between the production cross sections σ(WW) and σ(WZ) as predicted by the standard model, we measure the total WV (V=W,Z) cross section to be σ(WV)=19.6(-3.0)(+3.2) pb and reject the background-only hypothesis at a level of 7.9 standard deviations. We also use b-jet discrimination to separate the WZ component from the dominant WW component. Simultaneously fitting WW and WZ contributions, we measure σ(WW)=15.9(-3.2)(+3.7) pb and σ(WZ)=3.3(-3.3)(+4.1) pb, which is consistent with the standard model predictions.

Evidence for spin correlation in t Ì t production.

We present a measurement of the ratio of events with correlated t and t ̅t spins to the total number of t ̅t events. This ratio f is evaluated using a matrix-element-based approach in 729 t ̅t candidate events with a single lepton ℓ (electron or muon) and at least four jets. The analyzed p ̅p collisions data correspond to an integrated luminosity of 5.3 fb(-1) and were collected with the D0 detector at the Fermilab Tevatron collider operating at a center-of-mass energy √s=1.96 TeV. Combining this result with a recent measurement of f in dileptonic final states, we find f in agreement with the standard model. In addition, the combination provides evidence for the presence of spin correlation in t ̅t events with a significance of more than 3 standard deviations.

Search for doubly charged Higgs boson pair production in pp¯ collisions at √s=1.96 TeV.

We present a search for pair production of doubly charged Higgs bosons in the processes qq¯â†’H(++)H(--) decaying through H(±±)→τ(±)τ(±),µ(±)τ(±),µ(±)µ(±). The search is performed in pp¯ collisions at a center-of-mass energy of √s = 1.96 TeV using an integrated luminosity of up to 7.0 fb(-1) collected by the D0 experiment at the Fermilab Tevatron Collider. The results are used to set 95% C.L. limits on the pair production cross section of doubly charged Higgs bosons and on their mass for different H(±±) branching fractions. Models predicting different H(±±) decays are investigated. Assuming B(H(±±)→τ(±)τ(±))=1 yields an observed (expected) lower limit on the mass of a left-handed H(L)(±±) boson of 128 (116) GeV and assuming B(H(±±)→µ(±)τ(±))=1 the corresponding limits are 144 (149) GeV. In a model with B(H(±±)→τ(±)τ(±))=B(H(±±)→µ(±)τ(±))=B(H(±±)→µ(±)µ(±))=1/3, we obtain M(H(L)(±±))>130 (138) GeV.

Diet type and changes in food cravings following weight loss: findings from the POUNDS LOST Trial.

Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment. The present study, which was part of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults. A sample of 811 adults were recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: 1) low fat (20% of energy), average protein (15% of energy); 2) moderate fat (40%), average protein (15%); 3) low fat (20%), high protein (25%); 4) moderate fat (40%), high protein (25%). With few exceptions, the type of diet that participants were assigned did not differentially affect changes in specific food cravings. Participants assigned to the high-fat diets, however, had reduced cravings for carbohydrates at month 12 (p<0.05) and fruits and vegetables at month 24. Also, participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 (ps<0.05). Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods (i.e., high fat foods, fast food fats, sweets, and carbohydrates/starches; all ps<0.05). Cravings for fruits and vegetables, however, were increased at month 24 (p<0.05). Calorically restricted diets (regardless of their macronutrient composition) yielded significant reductions in cravings for fats, sweets, and starches whereas cravings for fruits and vegetables were increased.

Wγ production and limits on anomalous WWγ couplings in pp collisions at sqrt[s] = 1.96 TeV.

We measure the cross section and the difference in rapidities between photons and charged leptons for inclusive W(→lν) + γ production in eγ and µÎ³ final states. Using data corresponding to an integrated luminosity of 4.2 fb(-1) collected with the D0 detector at the Fermilab Tevatron Collider, the measured cross section times branching fraction for the process pp → Wγ + X → lνγ + X and the distribution of the charge-signed photon-lepton rapidity difference are found to be in agreement with the standard model. These results provide the most stringent limits on anomalous WWγ couplings for data from hadron colliders: -0.4<Δκ(γ)<0.4 and -0.08<λ(γ)<0.07 at the 95% C.L.

Precision measurement of the ratio B(t→Wb)/B(t→Wq) and extraction of V(tb).

We present a measurement of the ratio of top quark branching fractions R=B(t→Wb)/B(t→Wq), where q can be a d, s, or b quark, in the lepton+jets and dilepton tt final states. The measurement uses data from 5.4 fb(-1) of pp collisions collected with the D0 detector at the Fermilab Tevatron Collider. We measure R=0.90±0.04, and we extract the Cabibbo-Kobayashi-Maskawa (CKM) matrix element |V(tb)| as |V(tb)|=0.95±0.02, assuming unitarity of the 3×3 CKM matrix.