Statistical Communication Theory

Contains reports on eleven research projects.National Institutes of Health (Grant MH-04737-03)National Science Foundation (Grant G-16526)National Aeronautics and Space Administration (Grant NsG-496

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.<p></p> Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.<p></p> Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.<p></p> Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Harm reduction behaviors are associated with carrying naloxone among patients on methadone treatment

Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The “Cascade of Care” (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors. Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors. Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02–8.52), college education (aOR = 8.11, 95% CI 1.76–37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00–2.11). We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.https://doi.org/10.1186/s12954-023-00745-

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

TGF-β1 Induces an Age-Dependent Inflammation of Nerve Ganglia and Fibroplasia in the Prostate Gland Stroma of a Novel Transgenic Mouse

TGF-β1 is overexpressed in wound repair and in most proliferative disorders including benign prostatic hyperplasia and prostate cancer. The stromal microenvironment at these sites is reactive and typified by altered phenotype, matrix deposition, inflammatory responses, and alterations in nerve density and biology. TGF-β1 is known to modulate several stromal responses; however there are few transgenic models to study its integrated biology. To address the actions of TGF-β1 in prostate disorders, we targeted expression of an epitope tagged and constitutively active TGF-β1 via the enhanced probasin promoter to the murine prostate gland epithelium. Transgenic mice developed age-dependent lesions leading to severe, yet focal attenuation of epithelium, and a discontinuous basal lamina. These changes were associated with elevated fibroplasia and frequency of collagenous micronodules in collapsed acini, along with an induced inflammation in nerve ganglia and small vessels. Elevated recruitment of CD115+ myeloid cells but not mature macrophages was observed in nerve ganglia, also in an age-dependent manner. Similar phenotypic changes were observed using a human prostate epithelium tissue recombination xenograft model, where epithelial cells engineered to overexpress TGF-β1 induced fibrosis and altered matrix deposition concurrent with inflammation in the stromal compartment. Together, these data suggest that elevated TGF-β1 expression induces a fibroplasia stromal response associated with breach of epithelial wall structure and inflammatory involvement of nerve ganglia and vessels. The novel findings of ganglia and vessel inflammation associated with formation of collagenous micronodules in collapsed acini is important as each of these are observed in human prostate carcinoma and may play a role in disease progression

The positive impact of red palm oil in school meals on vitamin A status: study in Burkina Faso

BACKGROUND: Vitamin A (VA) deficiency is widespread in sub-Saharan Africa and school-age children are a vulnerable group. In Burkina Faso, the production and consumption of red palm oil (RPO) is being promoted as a food supplement for VA. The objective of the study was to assess the impact on serum retinol of adding RPO to school lunch in two test zones of Burkina Faso. METHODS: Over one school year, 15 ml RPO was added to individual meals 3 times a week in selected primary schools in two sites. Serum retinol was measured with HPLC at baseline and exactly 12 months later to take account of seasonality. A simple pre-post test design was used in the Kaya area (north-central Burkina), where 239 pupils from 15 intervention schools were randomly selected for the evaluation. In Bogandé (eastern Burkina), 24 schools were randomised for the controlled intervention trial: 8 negative controls (G1) with only the regular school lunch; 8 positive controls (G2) where the pupils received a single VA capsule (60 mg) at the end of the school year; and 8 schools with RPO through the school year (G3). A random sample of 128 pupils in each school group took part in the evaluation. RESULTS: In Kaya, serum retinol went from 0.77 ± 0.37 μmol/L at baseline to 1.07 ± 0.40 μmol/L one year later (p < 0.001). The rate of low serum retinol (<0.7 μmol/L) declined from 47.2% to 13.1%. In Bogandé, serum retinol increased significantly (p < 0.001) only in the capsule and RPO groups, going from 0.77 ± 0.28 to 0.98 ± 0.33 μmol/L in the former, and from 0.82 ± 0.3 to 0.98 ± 0.33 μmol/L in the latter. The rate of low serum retinol went from 46.1 to 17.1% in the VA capsule group and from 40.4% to 14.9% in the RPO group. VA-deficient children benefited the most from the capsule or RPO. Female sex, age and height-for-age were positively associated with the response to VA capsules or RPO. CONCLUSION: RPO given regularly in small amounts appears highly effective in the reduction of VA deficiency. RPO deserves more attention as a food supplement for VA and as a potential source of rural income in Sahelian countries

Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden

We investigated effects of occupational physical activity on relative risk for prostate cancer. From Swedish nationwide censuses in 1960 and 1970, we defined two cohorts of men whose occupational titles allowed classification of physical activity levels at work in 1960 (n=1 348 971) and in 1970 (n=1 377 629). A third cohort included only men whose jobs required a similar level of physical activity in both 1960 and 1970 (n=673 443). The incidence of prostate cancer between 1971 and 1989 was ascertained through record linkage to the Swedish Cancer Register. A total of 43 836, 28 702, and 19 670 prostate cancers, respectively, occurred in the three cohorts. In all three cohorts, the relative risk for prostate cancer increased with decreasing level of occupational physical activity (P<0.001), using Poisson regression. Among men with the same physical activity levels in 1960 and 1970, the rate ratio was 1.11 for men with sedentary jobs as compared with those whose jobs had very high/high activity levels after adjustment for age at follow-up, calendar year of follow-up and place of residence (95% CI 1.05–1.17; P for trend <0.001). There was no association between occupational activity and prostate cancer mortality. Since we had no data on other potential risk factors the observed associations for both incidence and mortality might have been confounded. Further studies are needed to better understand the potential role of physical activity for prostate cancer

Measurement of neutron production in atmospheric neutrino interactions at the Sudbury Neutrino Observatory

Neutron production in GeV-scale neutrino interactions is a poorly studied process. We have measured the neutron multiplicities in atmospheric neutrino interactions in the Sudbury Neutrino Observatory experiment and compared them to the prediction of a Monte Carlo simulation using GENIE and a minimally modified version of GEANT4. We analyzed 837 days of exposure corresponding to Phase I, using pure heavy water, and Phase II, using a mixture of Cl in heavy water. Neutrons produced in atmospheric neutrino interactions were identified with an efficiency of $15.3\%$ and $44.3\%$, for Phase I and II respectively. The neutron production is measured as a function of the visible energy of the neutrino interaction and, for charged current quasi-elastic interaction candidates, also as a function of the neutrino energy. This study is also performed classifying the complete sample into two pairs of event categories: charged current quasi-elastic and non charged current quasi-elastic, and $\nu_{\mu}$ and $\nu_e$. Results show good overall agreement between data and Monte Carlo for both phases, with some small tension with a statistical significance below $2\sigma$ for some intermediate energies

Search for invisible modes of nucleon decay in water with the SNO+ detector

This paper reports results from a search for nucleon decay through invisible modes, where no visible energy is directly deposited during the decay itself, during the initial water phase of SNO+. However, such decays within the oxygen nucleus would produce an excited daughter that would subsequently deexcite, often emitting detectable gamma rays. A search for such gamma rays yields limits of 2.5×1029  y at 90% Bayesian credibility level (with a prior uniform in rate) for the partial lifetime of the neutron, and 3.6×1029  y for the partial lifetime of the proton, the latter a 70% improvement on the previous limit from SNO. We also present partial lifetime limits for invisible dinucleon modes of 1.3×1028  y for nn, 2.6×1028  y for pn and 4.7×1028  y for pp, an improvement over existing limits by close to 3 orders of magnitude for the latter two