Radiological characterization of the tailings of an abandoned copper mine using a neural network and geostatistical analysis through the Co-Kriging method.

The radiological characterization of soil contaminated with natural radionuclides enables the classification of the area under investigation, the optimization of laboratory measurements, and informed decision-making on potential site remediation. Neural networks (NN) are emerging as a new candidate for performing these tasks as an alternative to conventional geostatistical tools such as Co-Kriging. This study demonstrates the implementation of a NN for estimating radiological values such as ambient dose equivalent (H*(10)), surface activity and activity concentrations of natural radionuclides present in a waste dump of a Cu mine with a high level of natural radionuclides. The results obtained using a NN were compared with those estimated by Co-Kriging. Both models reproduced field measurements equivalently as a function of spatial coordinates. Similarly, the deviations from the reference concentration values obtained in the output layer of the NN were smaller than the deviations obtained from the multiple regression analysis (MRA), as indicated by the results of the root mean square error. Finally, the method validation showed that the estimation of radiological parameters based on their spatial coordinates faithfully reproduced the affected area. The estimation of the activity concentrations was less accurate for both the NN and MRA; however, both methods gave statistically comparable results for activity concentrations obtained by gamma spectrometry (Student's t-test and Fisher's F-test).

Randomized, Open-Label Phase 3 Study Evaluating Immunogenicity, Safety, and Reactogenicity of RSVPreF3 OA Coadministered with FLU-QIV-HD in Adults Aged ≥ 65.

INTRODUCTION: Respiratory syncytial virus (RSV) and influenza pose major disease burdens in older adults due to an aging immune system and comorbidities; seasonal overlap exists between these infections. In 2023, the RSV prefusion protein F3 older adult (RSVPreF3 OA) vaccine was first approved in the USA as a single dose for prevention of lower respiratory tract disease due to RSV in adults aged ≥ 60 years. The vaccine has since been approved in the European Union and elsewhere. RSVPreF3 OA and FLU-QIV-HD could be coadministered if immunogenicity, safety, and reactogenicity are not affected. METHODS: This open-label, randomized (1:1), controlled, phase 3 study in 1029 adults aged ≥ 65 years in the USA evaluated the immunogenicity (up to 1 month after last vaccine dose) and safety (up to 6 months after last vaccine dose) of RSVPreF3 OA coadministered with FLU-QIV-HD (co-ad group) versus FLU-QIV-HD alone followed by RSVPreF3 OA at a separate visit 1 month later (control group). Non-inferiority criterion was defined as an upper limit of the two-sided 95% confidence interval of the geometric mean titer (GMT) group ratio (control/co-ad) ≤ 1.5. Secondary endpoints included safety and reactogenicity. RESULTS: Proportions of participants across age categories between groups and proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Group GMT ratios for RSV-A neutralizing titers, hemagglutination inhibition titers for four influenza vaccine strains, and RSV-B neutralizing titers were non-inferior in the co-ad group versus the control group. No clinically meaningful differences in local or systemic solicited and unsolicited adverse events (AEs), serious AEs, and potential immune-mediated diseases were identified. The most common solicited AEs in both groups were injection-site pain and myalgia. CONCLUSION: In adults aged ≥ 65 years, coadministration of RSVPreF3 OA and FLU-QIV-HD was immunogenically non-inferior to the sequential administration of both vaccines 1 month apart, and had clinically acceptable safety and reactogenicity profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05559476.

Adults aged 65 years or older are vulnerable to infections caused by influenza and respiratory syncytial viruses, due to an aging immune system and other underlying conditions. Infections with both viruses increase during autumn and winter seasons in temperate climates. In 2023, a vaccine against respiratory syncytial virus, called RSVPreF3 OA, was first approved for use in adults aged 60 years or older in the USA; the vaccine has since also been approved in the European Union and elsewhere. Giving RSVPreF3 OA in the same vaccination visit (coadministration) with a high-dose influenza vaccine, called FLU-QIV-HD, which is given to adults aged 65 years or older, could help protect against both respiratory syncytial virus and influenza. This article reports the results of a phase 3 trial comparing coadministration of the RSVPreF3 OA and FLU-QIV-HD vaccines with sequential administration (FLU-QIV-HD followed by RSVPreF3 OA 1 month later) in 1029 adults aged 65 years or older in the USA. Proportions of participants across age categories between groups, and the proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Immune response to both the vaccines among participants in the coadministration arm was non-inferior to that in the sequential arm. Coadministration was well tolerated, with no meaningful differences in adverse reactions to the vaccines compared with sequential administration. The most common adverse reactions were pain at the injection site and muscle aches. This study supports the coadministration of RSVPreF3 OA and FLU-QIV-HD in adults aged 65 years or older.

Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.

Proton spot dose estimation based on positron activity distributions with neural network.

BACKGROUND: Positron emission tomography (PET) has been investigated for its ability to reconstruct proton-induced positron activity distributions in proton therapy. This technique holds potential for range verification in clinical practice. Recently, deep learning-based dose estimation from positron activity distributions shows promise for in vivo proton dose monitoring and guided proton therapy. PURPOSE: This study evaluates the effectiveness of three classical neural network models, recurrent neural network (RNN), U-Net, and Transformer, for proton dose estimating. It also investigates the characteristics of these models, providing valuable insights for selecting the appropriate model in clinical practice. METHODS: Proton dose calculations for spot beams were simulated using Geant4. Computed tomography (CT) images from four head cases were utilized, with three for training neural networks and the remaining one for testing. The neural networks were trained with one-dimensional (1D) positron activity distributions as inputs and generated 1D dose distributions as outputs. The impact of the number of training samples on the networks was examined, and their dose prediction performance in both homogeneous brain and heterogeneous nasopharynx sites was evaluated. Additionally, the effect of positron activity distribution uncertainty on dose prediction performance was investigated. To quantitatively evaluate the models, mean relative error (MRE) and absolute range error (ARE) were used as evaluation metrics. RESULTS: The U-Net exhibited a notable advantage in range verification with a smaller number of training samples, achieving approximately 75% of AREs below 0.5 mm using only 500 training samples. The networks performed better in the homogeneous brain site compared to the heterogeneous nasopharyngeal site. In the homogeneous brain site, all networks exhibited small AREs, with approximately 90% of the AREs below 0.5 mm. The Transformer exhibited the best overall dose distribution prediction, with approximately 92% of MREs below 3%. In the heterogeneous nasopharyngeal site, all networks demonstrated acceptable AREs, with approximately 88% of AREs below 3 mm. The Transformer maintained the best overall dose distribution prediction, with approximately 85% of MREs below 5%. The performance of all three networks in dose prediction declined as the uncertainty of positron activity distribution increased, and the Transformer consistently outperformed the other networks in all cases. CONCLUSIONS: Both the U-Net and the Transformer have certain advantages in the proton dose estimation task. The U-Net proves well suited for range verification with a small training sample size, while the Transformer outperforms others at dose-guided proton therapy.

Analysis of dose distribution around a computed tomography scanner in terms of exposure to scattered ionizing radiation of caregivers of pediatric patients.

OBJECTIVES: During computed tomography (CT), a large amount of ionizing radiation is emitted to ensure high quality of the obtained radiological image. This study measured the dose distribution around the CT scanner and the exposure of people staying near the CT scanner during the examination. MATERIAL AND METHODS: The measurements used an anthropomorphic phantom to assess human exposure to ionizing radiation. The probability of inducing leukemia and other cancers as a result of absorbing doses recorded around the CT device was also calculated. RESULTS: The highest exposure to scattered radiation in the proximity of the CT scanner is recorded at the gantry of the tomograph, i.e., 55.7 µGy, and the lowest, below lower detection limit of 6 µGy at the end of the diagnostic table. The whole-body detector placed on the anthropomorphic phantom located at the diagnostic table right next to the CT gantry recorded 59.5 µSv and at the end of the table 1.5 µSv. The average doses to the lenses in these locations were: 32.1 µSv and 2.9 µSv, respectively. CONCLUSIONS: The probability of induction of leukemia or other types of cancer is low, but the need for people to stay in the examination room during a CT examination should be limited to the necessary minimum. Int J Occup Med Environ Health. 2024;37(3).

Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023.

Forty-eight (48) drug products (DPs) containing amorphous solid dispersions (ASDs) have been approved by the U.S. Food and Drug Administration in the 12-year period between 2012 and 2023. These DPs comprise 36 unique amorphous drugs. Ten (10) therapeutic categories are represented, with most DPs containing antiviral and antineoplastic agents. The most common ASD polymers are copovidone (49%) and hypromellose acetate succinate (30%), while spray drying (54%) and hot melt extrusion (35%) are the most utilized manufacturing processes to prepare the ASD drug product intermediate (DPI). Tablet dosage forms are the most common, with several capsule products available. Line extensions of several DPs based on flexible oral solids and powders for oral suspension have been approved which provide patient-centric dosing to pediatric and other patient populations. The trends in the use of common excipients and film coating types are discussed. Eighteen (18) DPs are fixed-dose combinations, and some contain a mixture of amorphous and crystalline drugs. The DPs have dose/unit of amorphous drug ranging from <5 mg up to 300 mg, with the majority being ≤100 mg/unit. This review details several aspects of DPI and DP formulation and manufacturing of ASDs, as well as trends related to therapeutic category, dose, and patient-centricity.

Pharmacokinetic Interactions Between the Fixed-Dose Combination of Ezetimibe/Rosuvastatin 10/20 Mg and the Fixed-Dose Combination of Telmisartan/Amlodipine 80/5 Mg in Healthy Subjects.

Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA). Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study. Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects. Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.

Performance of calcium quantifications on low-dose photon-counting detector CT with high-pitch: A phantom study.

Purpose: To evaluate the performance of calcium quantification on photon-counting detector CT (PCD-CT) with high-pitch at low radiation doses compared to third-generation dual-source energy-integrating detector CT (EID-CT). Materials and methods: The phantom with three calcium inserts (50, 100, and 300 mg of calcium per milliliter), with and without the elliptical outer layer, was evaluated using high-pitch (3.2) and standard pitch (0.8) on PCD-CT, and standard pitch on EID-CT. Scans were performed with different tube voltages (PCD-CT: 120 and 140 kilo-voltage peak [kVp]; EID-CT: 70/Sn150 and 100/Sn150 kVp) and four radiation doses (1, 3, 5, and, 10 milli-Gray [mGy]). Utilizing the true calcium concentrations (CCtrue) of the phantom as the gold standard references, regression equations for each kVp setting were formulated to convert CT attenuations (CaCT) into measured calcium concentrations (CCm). The correlation analysis between CaCT and CCtrue was performed. The percentage absolute bias (PAB) was calculated from the differences between CCm and CCtrue and used to analyze the effects of scanning parameters on calcium quantification accuracy. Results: A strong correlation was found between CaCT and CCtrue on PCD-CT (r > 0.99) and EID-CT (r > 0.98). For high- and standard-pitch scans on PCD-CT, the accuracy of calcium quantification is comparable (p = 0.615): the median (interquartile range [IQR]) of PAB was 5.59% (2.79%-8.31%) and 4.87 % (2.62%-8.01%), respectively. The PAB median (IQR) was 7.43% (3.77%-11.75%) for EID-CT. The calcium quantification accuracy of PCD-CT is superior to EID-CT at the large phantom (5.46% [2.68%-9.55%] versus 9.01% [6.22%-12.74%]), and at the radiation dose of 1 mGy (4.43% [2.08%-8.59%] versus 13.89% [8.93%-23.09%]) and 3 mGy (4.61% [2.75%-6.51%] versus 9.97% [5.17%-14.41%]), all p < 0.001. Conclusions: Calcium quantification using low-dose PCD-CT with high-pitch scanning is feasible and accurate, and superior to EID-CT.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

Characteristics of radioactive aerosols during the pre-decommission phase of the experimental shielding reactor.

The decommissioning of nuclear reactors is a global concern, in part because of the generation of radioactive aerosols that can lead to internal radiation exposure. At present, radioactive aerosols generated during nuclear decommissioning have not been actively studied, and data collected from the actual decommissioning are limited. This paper presents a study of radioactive aerosols generated during the pre-decommission phase of an experimental shielding reactor. Among all the on-site operations, cutting resulted in the highest levels of radioactivity. Plasma arc cutting, in particular, had a maximum gross α and ß radioactivity over 0.10 and 0.14 Bq/m3, respectively. Assumed AMAD (activity median aerodynamic diameter) values are employed to assess the impact of particle size on the internal exposure dose resulting from the inhalation of 137Cs aerosols based on the Human Respiratory Tract Model of International Commission on Radiological Protection. When cutting stainless steel by plasma arc, the internal exposure dose caused by 137Cs aerosols with an AMAD of 0.1 µm is estimated to be nearly four times as that of aerosols with an AMAD of 10 µm. Results show that the internal exposure dose is highly dependent on the AMAD, implying the importance of measuring size-related parameters of radioactive aerosols in the future nuclear decommissioning. This study has revealed some characteristics of radioactive aerosols released in decommissioning operations, which can serve as a valuable reference for controlling and removing aerosols during the decommissioning of nuclear facilities.

Association of dietary glycemic index and glycemic load with the risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis.

OBJECTIVE: To comprehensively assess the dose-response association between dietary glycemic index (GI) and glycemic load (GL) and gestational diabetes mellitus (GDM) risk. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched up to May 29, 2024. Studies with at least three exposure categories were included. Dose-response analysis was also performed when covariates were adjusted in the included studies. RESULTS: Thirteen studies involving 39,720 pregnant women were included. A linear relationship was found between GI and the risk of GDM (χ2 = 4.77, Pnon-linearity = .0923). However, association was not significant (χ2 = 0.06, p = .8000). For every unit increase in GI (range 0-30), GDM risk increased by 0.29%. After adjusting for covariates, the linear relationship persisted (χ2 = 4.95, Pnon-linearity = .084) with no significant association (χ2 = 0.08, p = .7775). For GL, a linear relationship was also found (χ2 = 4.17, Pnon-linearity =.1245), but GL was not significantly associated with GDM risk (χ2 = 2.63, p = .1049). The risk of GDM increased by 0.63% per unit increase in GL. After covariate adjustment, a significant association was observed (χ2 = 6.28, p = .0122). CONCLUSION: No significant association between GI and GDM risk was found. After adjusting for covariates, GL shows a significant association with GDM risk. Our findings emphasize the importance of considering dietary GL in managing the risk of GDM. Future research should continue to explore these relationships with standardized diagnostic criteria and robust adjustment for potential confounders.

Addressing bottlenecks in Lassa fever treatment: overcoming the ribavirin parenteral formulation challenge.

Ribavirin ampoule formulation remains a major challenge in managing Lassa fever disease. Lassa fever is an endemic viral hemorrhagic fever in the West Africa subregion, which has high-dose ribavirin as the standard of care. The high-dose therapy required makes the 200 mg/ml ampoule dosing of ribavirin a daunting task to administer, especially during disease outbreaks. This commentary highlights the challenges and makes a passionate call for vial dosage adjustment to fit the high-dose requirement of Lassa fever disease.

Subclinical dose irradiation triggers human breast cancer migration via mitochondrial reactive oxygen species.

BACKGROUND: Despite technological advances in radiotherapy, cancer cells at the tumor margin and in diffusive infiltrates can receive subcytotoxic doses of photons. Even if only a minority of cancer cells are concerned, phenotypic consequences could be important considering that mitochondrial DNA (mtDNA) is a primary target of radiation and that damage to mtDNA can persist. In turn, mitochondrial dysfunction associated with enhanced mitochondrial ROS (mtROS) production could promote cancer cell migration out of the irradiation field in a natural attempt to escape therapy. In this study, using MCF7 and MDA-MB-231 human breast cancer cells as models, we aimed to elucidate the molecular mechanisms supporting a mitochondrial contribution to cancer cell migration induced by subclinical doses of irradiation (< 2 Gy). METHODS: Mitochondrial dysfunction was tested using mtDNA multiplex PCR, oximetry, and ROS-sensitive fluorescent reporters. Migration was tested in transwells 48 h after irradiation in the presence or absence of inhibitors targeting specific ROS or downstream effectors. Among tested inhibitors, we designed a mitochondria-targeted version of human catalase (mtCAT) to selectively inactivate mitochondrial H2O2. RESULTS: Photon irradiation at subclinical doses (0.5 Gy for MCF7 and 0.125 Gy for MDA-MB-231 cells) sequentially affected mtDNA levels and/or integrity, increased mtROS production, increased MAP2K1/MEK1 gene expression, activated ROS-sensitive transcription factors NF-κB and AP1 and stimulated breast cancer cell migration. Targeting mtROS pharmacologically by MitoQ or genetically by mtCAT expression mitigated migration induced by a subclinical dose of irradiation. CONCLUSION: Subclinical doses of photon irradiation promote human breast cancer migration, which can be countered by selectively targeting mtROS.

Dose and Time Effects of Renin-Angiotensin Inhibitors on Patients With Advanced Stages 4 to 5 of Diabetic Kidney Disease.

Context: Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). Objective: To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Methods: Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. Results: RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. Conclusion: This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.

The immunologic outcomes and adverse events of COVID-19 vaccine booster dose in immunosuppressed people: A systematic review.

Introduction: This study examines the efficacy and safety of three COVID-19 booster vaccines including mRNA-based vaccines (BNT162b2 (BioNTech/Pfizer) and/or mRNA-1273 (Moderna)), Non-Replicating Viral-Vector vaccines (ChAdOx1 nCoV-19 vaccine (AstraZeneca) and/or Ad26. COV2.S (Johnson & Johnson)), and Protein Subunit vaccine (SpikoGen) in immunosuppressed patients. Methods: Relevant articles were systematically searched using medical subject heading (MeSH) and keywords "COVID-19" and "booster dose" or "booster vaccine" or ''fourth dose" in the online databases of PubMed, Embase, Scopus, and Web of Science. To identify eligible studies, a two-phase screening process was implemented. Initially, three researchers evaluated the studies based on the relevancy of the title and abstract. Results: A total of 58 studies met the inclusion criteria and were included in this review. The findings suggest that booster doses offer greater protection against the disease than the primary dose. The study also compared various vaccine types, revealing that viral vector and nucleic acid vaccines outperformed inactivated vaccines. Results indicated that individuals receiving booster doses experienced superior outcomes compared to those without boosters. Vaccination against COVID-19 emerged as the most effective preventive measure against infection and symptom severity. Elevated antibody levels post-booster dose vaccination in the population signaled robust immune responses, underscoring the benefits of supplementary vaccine doses. Conclusion: This systematic review highlights preliminary evidence supporting the immunologic outcomes and safety of COVID-19 vaccine boosters in enhancing immune responses against SARS-CoV-2. However, further research is needed to determine optimal timing intervals between primary vaccination series and boosters while considering global equity issues and variant-specific considerations.

A marginal structural model for normal tissue complication probability.

The goal of radiation therapy for cancer is to deliver prescribed radiation dose to the tumor while minimizing dose to the surrounding healthy tissues. To evaluate treatment plans, the dose distribution to healthy organs is commonly summarized as dose-volume histograms (DVHs). Normal tissue complication probability (NTCP) modeling has centered around making patient-level risk predictions with features extracted from the DVHs, but few have considered adapting a causal framework to evaluate the safety of alternative treatment plans. We propose causal estimands for NTCP based on deterministic and stochastic interventions, as well as propose estimators based on marginal structural models that impose bivariable monotonicity between dose, volume, and toxicity risk. The properties of these estimators are studied through simulations, and their use is illustrated in the context of radiotherapy treatment of anal canal cancer patients.

Automating population dose survey processing-An Australian feasibility study.

BACKGROUND: A comprehensive collection of data on doses in adult computed tomography procedures in Australia has not been undertaken for some time. This is largely due to the effort involved in collecting the data required for calculating the population dose. This data collection effort can be greatly reduced, and the coverage increased, if the process can be automated without major changes to the workflow of the imaging facilities providing the data. Success would provide a tool to determine a truly national assessment of the dose incurred through diagnostic imaging in Australia. PURPOSE: The aims of this study were to develop an automated tool to categorize electronic records of imaging procedures into a standardized set of broad procedure types, to validate the tool by applying it to data collected from nine facilities, and to assess the feasibility of applying the automated tool to compute population dose and determine the data manipulations required. METHODS: A rule-based classifier was implemented capitalizing on semantic and clinical rules. The keyword list was initially built from 609 unique study descriptions. It was then refined using an additional 414 unique study descriptions. The classifier was then tested on an additional 1198 unique study descriptions. Input from a radiologist provided the ground truth for the refinement of the classifier. RESULTS: From a sample of 238 139 studies containing 2794 unique study descriptions, the classifier correctly classified 2789 study types with only five misclassifications, demonstrating the feasibility of automating the process and the need for data pre-processing. Dose statistics for 21 categories were compiled using the 238 139 studies. CONCLUSION: The classifier achieved excellent classification results using the testing data supplied by the facilities. However, since all data supplied were from public facilities, the performance of the classifier may be biased. The performance of the classifier is yet to be tested on a more representative mix of private and public facilities.

Statistical Assessment of the Effectiveness of Multiple COVID-19 Vaccinations on Daily Confirmed Cases in Seoul City.

This study investigates the effectiveness of multiple COVID-19 vaccinations on daily confirmed cases in Seoul City. Utilizing comprehensive data on vaccinated individuals and confirmed cases sourced from the official website of the Korean Ministry of the Interior and Safety, we conducted detailed statistical analyses to assess the impact of each vaccination dose. The study covers data from April 21, 2021, to September 29, 2022. Statistical multiple linear regression was employed to analyze the relationship between daily confirmed cases (positive outcomes from PCR tests) and multiple vaccine doses, using p-values as the criteria for determining the effectiveness of each dose. The analysis included data from four vaccination doses. The analysis reveals that the first, second, and third doses of the COVID-19 vaccines have a statistically significant positive effect associated with the daily confirmed cases. However, the study finds that the fourth dose does not show a statistically significant impact on the reduction of daily confirmed cases. This suggests that while the initial three doses are crucial for establishing and maintaining high levels of immunity, the incremental benefit of subsequent doses may diminish.

Effects of early institutionalization involving psychosocial deprivation on cognitive functioning 60 years later: Findings of the LifeStories project.

BACKGROUND: Institutionalization involving psychosocial deprivation affects child development negatively. However, there are few longitudinal studies, and no prospective study has yet examined the consequences of institutionalization in late adulthood. OBJECTIVE: Investigating effects of psychosocial deprivation on cognitive functioning 60 years later. PARTICIPANTS AND SETTING: A population-based survey of institutionalized infants and toddlers was conducted in Switzerland from 1958 to 1961 (n = 387; Mage = 0.93 years, SD = 0.53, 48 % female, 48 % Swiss nationality). In parallel, a comparison group of 399 family-raised children were assessed (Mage = 0.85 years, SD = 0.50, 46 % female, 100 % Swiss nationality). Six decades later, data on cognitive functioning were collected for 88 of the institutionalized group (Mage = 62.63 years, SD = 1.32), and 148 of the comparison group (Mage = 65.06, SD = 1.32). METHODS: Standardized tests were used: the Brunet-Lézine Developmental Test in early childhood and a short form of the Wechsler Adult Intelligence Scale in late adulthood. RESULTS: Formerly institutionalized individuals scored lower on cognitive functioning (d = - 0.67, p < .001), with the greatest difference in working memory (d = -0.78, p < .001). Longer duration of institutionalization increased the risk of lower cognitive functioning, indicating a dose-response effect. Institutionalization's impact on adult cognitive functioning was mediated by early childhood developmental status but not by later educational attainment. CONCLUSIONS: This study confirms the early experience hypothesis, indicating that early life conditions have lasting effects on human development, even into late adulthood.