Adaptive two-stage inverse sampling design to estimate density, abundance, and occupancy of rare and clustered populations

Sampling rare and clustered populations is challenging because of the effort required to find rare units. Heuristically, a practitioner would prefer to discontinue sampling in areas where rare units of interest are apparently extremely sparse or absent. We take advantage of the characteristics of inverse sampling to adaptively inform practitioners when it is efficient to move on to sample new areas. We introduce Adaptive Two-stage Inverse Sampling (ATIS), which is designed to leave a selected area after observation of an a priori number of only non-rare units and to continue sampling in the area when rare units are observed. ATIS is efficient in many cases and yields more rare units than conventional sampling for a rare and clustered population. We derive unbiased estimators of population total and variance. We also introduce an easy-to-compute estimator, which is nearly as efficient as the unbiased estimator. A simulation study on a rare plant population of buttercups (Ranunculus) shows that ATIS even with the easy-to-compute estimator is more efficient than its conventional sampling counterparts and is more efficient than Two-stage Adaptive Cluster Sampling (TACS) for small and moderate final sample sizes. Additional simulations reveal that ATIS is efficient for binary data (e.g., presence or absence) whereas TACS is inefficient for binary data. The overall results indicate that ATIS is consistently efficient compared to conventional sampling and to adaptive cluster sampling in some important cases.

Characterization of oligometastatic disease in a real-world nationwide cohort of 3,447 patients with de novo metastatic breast cancer

Background Observational studies in metastatic breast cancer (MBC) show that long-term overall survival (OS) is associated with limited tumor burden, or oligo-MBC (OMBC). However, a uniform definition of OMBC is lacking. In this real-world nationwide cohort, we aimed to define the optimal OMBC threshold and factors associated with survival in patients with OMBC. Methods 3,535 patients <80 years at diagnosis of de novo MBC in the Netherlands between January 2000 and December 2007 were included. Detailed clinical, therapy, and outcome data were collected from medical records of a sample of the patients. Using inverse-sampling-probability weighting (IPW) the analysis cohort (n = 3,447) was constructed. We assessed OS according to number of metastases at diagnosis to determine the optimal OMBC threshold. Next, we applied Cox-regression models with IPW to study associations with OS and progression-free survival (PFS) in OMBC. All statistical tests were two-sided. Results Compared with >5 distant metastases, adjusted hazard ratios for OS (with 95% CI based on robust standard errors) for 1, 2–3, and 4–5 metastases were: 0.70 (0.52–0.96), 0.63 (0.45–0.89) and 0.91 (0.61–1.37), respectively. Ten-year OS-estimates for patients with ≤3 versus >3 metastases were 14.9% and 3.4% (P < .001). In multivariable analyses, pre-/perimenopausal status, absence of lung metastases and local therapy of metastases (surgery/radiotherapy) added to systemic therapy were statistically significantly associated with better OS and PFS in OMBC, independent of local therapy of the primary tumor. Conclusion OMBC defined as MBC limited to 1–3 metastases was associated with favorable OS. In OMBC local therapy of metastases was associated with better OS, particularly if patients were pre-/perimenopausal without lung metastases.

Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study

Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin collected before ART treatment and mortality among individuals with advanced HIV. Methods: We conducted a pilot case-cohort study among HIV infected adults and adolescents over 13 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin collected at baseline (before ART) and after 4 weeks of treatment was measured in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived (non-cases). Association with mortality was assessed using Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4+ count (0-24, 25-49, and 50-99 cells/mm3). Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions. Conclusions: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted.

Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study

Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin at initiation of ART and mortality among individuals with advanced HIV. Methods: We conducted a pilot case-cohort study among HIV infected adults and children over 5 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin was measured by ELISA in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived for 48 weeks (non-cases) for whom samples were available. Factors associated with baseline plasma calprotectin were investigated using linear regression. To test association with mortality, Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4 count were fitted. Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions. Conclusion: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted.

Monte Carlo simulation of coherently scattered photons based on the inverse-sampling technique

The acceptance–rejection technique has been widely used in several Monte Carlo simulation packages for Rayleigh scattering of photons. However, the models implemented in these packages might fail to reproduce the corresponding experimental and theoretical results. The discrepancy is attributed to the fact that all current simulations implement an elastic scattering model for the angular distribution of photons without considering anomalous scattering effects. In this study, a novel Rayleigh scattering model using anomalous scattering factors based on the inverse-sampling technique is presented. Its performance was evaluated against other simulation algorithms in terms of simulation accuracy and computational efficiency. The computational efficiency was tested with a general-purpose Monte Carlo package named Particle Transport in Media (PTM). The evaluation showed that a Monte Carlo model using both atomic form factors and anomalous scattering factors for the angular distribution of photons (instead of the atomic form factors alone) produced Rayleigh scattering results in closer agreement with experimental data. The comparison and evaluation confirmed that the inverse-sampling technique using atomic form factors and anomalous scattering factors exhibited improved computational efficiency and performed the best in reproducing experimental measurements and related scattering matrix calculations. Furthermore, using this model to sample coherent scattering can provide scientific insight for complex systems.