School holidays and respiratory syncytial virus transmission in Sweden: An interrupted time series analysis.

AIM: Respiratory syncytial virus (RSV) represents a significant cause of morbidity for children worldwide, especially for newborns. As RSV vaccines are not routinely used for children yet, non-pharmaceutical interventions (NPIs) represent the main strategy for prevention. The objective of this study was to investigate the correlation between school holidays and RSV transmission. METHODS: Data were collected from the weekly reports on RSV incidence for the 2021/2022 and 2022/2023 seasons in Sweden. The 7-day cumulative incidence of RSV was compared before and after the designated school holidays (Fall, Christmas, and Winter holidays). RESULTS: Our findings reveal an immediate (-1.7%, p < 0.001, 95% CI [-3.1%, -0.4%]) and gradual (-1.4%/week, p < 0.001, 95%CI [-1.8, -1.0]) reduction in RSV incidence following the Fall holiday in 2021, especially among children under 1 year of age, both immediately (-107.6%, p < 0.05, 95% CI [-203.7, -11.5]) and gradually afterwards (-58.5%/week, p < 0.001, 95% CI [-72.7, -44.3]). Mixed results were obtained for the Fall in 2022/2023 and for the Winter and holidays in both the studied years. CONCLUSIONS: While the Fall holiday in 2021/2022 was associated with a decrease in RSV incidence in Sweden, our results do not support a universal effect of school holidays on reducing RSV transmission.

Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study.

BACKGROUND: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. METHODS: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. RESULTS: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. CONCLUSIONS: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

Association of time spent on social media with youth cigarette smoking and e-cigarette use in the UK: a national longitudinal study.

BACKGROUND: Social media may influence children and young people's health behaviour, including cigarette and e-cigarette use. METHODS: We analysed data from participants aged 10-25 years in the UK Household Longitudinal Study 2015-2021. The amount of social media use reported on a normal weekday was related to current cigarette smoking and e-cigarette use. Generalised estimating equation (GEE) logistic regression models investigated associations of social media use with cigarette smoking and e-cigarette use. Models controlled for possible confounders including age, sex, country of UK, ethnicity, household income and use of cigarette/e-cigarettes by others within the home. RESULTS: Among 10 808 participants with 27 962 observations, current cigarette smoking was reported by 8.6% of participants for at least one time point, and current e-cigarette use by 2.5% of participants. In adjusted GEE models, more frequent use of social media was associated with greater odds of current cigarette smoking. This was particularly apparent at higher levels of use (eg, adjusted odds ratio (AOR) 3.60, 95% CI 2.61 to 4.96 for ≥7 hours/day vs none). Associations were similar for e-cigarettes (AOR 2.73, 95% CI 1.40 to 5.29 for ≥7 hours/day social media use vs none). There was evidence of dose-response in associations between time spent on social media and both cigarette and e-cigarette use (both p<0.001). Analyses stratified by sex and household income found similar associations for cigarettes; however, for e-cigarettes associations were concentrated among males and those from higher household income groups. CONCLUSIONS: Social media use is associated with increased risk of cigarette smoking and e-cigarette use. There is a need for greater research on this issue as well as potential policy responses.

Reproductive system, temperature, and genetic background effects in experimentally evolving populations of Caenorhabditis elegans.

Experimental evolution (EE) is a powerful research framework for gaining insights into many biological questions, including the evolution of reproductive systems. We designed a long-term and highly replicated EE project using the nematode C. elegans, with the main aim of investigating the impact of reproductive system on adaptation and diversification under environmental challenge. From the laboratory-adapted strain N2, we derived isogenic lines and introgressed the fog-2(q71) mutation, which changes the reproductive system from nearly exclusive selfing to obligatory outcrossing, independently into 3 of them. This way, we obtained 3 pairs of isogenic ancestral populations differing in reproductive system; from these, we derived replicate EE populations and let them evolve in either novel (increased temperature) or control conditions for over 100 generations. Subsequently, fitness of both EE and ancestral populations was assayed under the increased temperature conditions. Importantly, each population was assayed in 2-4 independent blocks, allowing us to gain insight into the reproducibility of fitness scores. We expected to find upward fitness divergence, compared to ancestors, in populations which had evolved in this treatment, particularly in the outcrossing ones due to the benefits of genetic shuffling. However, our data did not support these predictions. The first major finding was very strong effect of replicate block on populations' fitness scores. This indicates that despite standardization procedures, some important environmental effects were varying among blocks, and possibly compounded by epigenetic inheritance. Our second key finding was that patterns of EE populations' divergence from ancestors differed among the ancestral isolines, suggesting that research conclusions derived for any particular genetic background should never be generalized without sampling a wider set of backgrounds. Overall, our results support the calls to pay more attention to biological variability when designing studies and interpreting their results, and to avoid over-generalizations of outcomes obtained for specific genetic and/or environmental conditions.

Understanding the social-emotional components of our "number sense": insights from a novel non-symbolic numerical comparison task.

Introduction: A large body of work has identified a core sense of number supported by the Approximate Number System (ANS) that is present in infancy and across species. Although it is commonly assumed that the ANS directly processes perceptual input and is relatively independent from affective factors, some evidence points at a correlation between ANS performance and math anxiety. However, the evidence is mixed. We tested whether giving participants active control in completing a numerical task would change the relationship between math anxiety on performance. Methods: Adult participants (N = 103) completed a novel four-alternative-forced-choice non-symbolic numerical comparison task. In a repeated-measures design, participants either passively viewed different dot arrays or actively chose to view each array (i.e., active information-seeking) before deciding on the largest quantity. Participants also provided confidence judgments during the passive version of the task. Results: We replicated the ratio-dependent signature in participants' accuracy in both the passive and active versions of the task using this novel paradigm, as well as in trial-level confidence judgments and information-seeking behavior. Participants' self-reported math anxiety significantly correlated with their accuracy on the passive version of the task. Critically, the correlation disappeared in the active version of the task. Gender also emerged as a predictor of confidence judgments and a moderator of the effect of task on overall accuracy and the effect of active information seeking on accuracy in the active version of the task. Exploratory analysis of estimated Weber Fraction suggests that these results may be driven by auxiliary factors instead of changes in ANS acuity. Conclusion: These findings have implications for understanding the relationship between math anxiety and performance on numerical tasks.

A miniaturized culture platform for control of the metabolic environment.

The heart is a metabolic "omnivore" and adjusts its energy source depending on the circulating metabolites. Human cardiac organoids, a three-dimensional in vitro model of the heart wall, are a useful tool to study cardiac physiology and pathology. However, cardiac tissue naturally experiences shear stress and nutrient fluctuations via blood flow in vivo, whilst in vitro models are conventionally cultivated in a static medium. This necessitates the regular refreshing of culture media, which creates acute cellular disturbances and large metabolic fluxes. To culture human cardiac organoids in a more physiological manner, we have developed a perfused bioreactor for cultures in a 96-well plate format. The designed bioreactor is easy to fabricate using a common culture plate and a 3D printer. Its open system allows for the use of traditional molecular biology techniques, prevents flow blockage issues, and provides easy access for sampling and cell assays. We hypothesized that a perfused culture would create more stable environment improving cardiac function and maturation. We found that lactate is rapidly produced by human cardiac organoids, resulting in large fluctuations in this metabolite under static culture. Despite this, neither medium perfusion in bioreactor culture nor lactate supplementation improved cardiac function or maturation. In fact, RNA sequencing revealed little change across the transcriptome. This demonstrates that cardiac organoids are robust in response to fluctuating environmental conditions under normal physiological conditions. Together, we provide a framework for establishing an easily accessible perfusion system that can be adapted to a range of miniaturized cell culture systems.

Tumor tracking with non-linear internal/external correlation models in the presence of respiratory motion baseline drifts and phase shifts.

PURPOSE: In CyberKnife® respiratory tracking, tumor positions are predicted from external marker positions using correlation models. With available models, prediction accuracy may deteriorate when respiratory motion baseline drifts occur. Previous investigations have demonstrated that for linear models this can be mitigated by adding a time-dependent term. In this study, we have focused on added value of time-dependent terms for the available non-linear correlation models, and on phase shifts between internal and external motion tracks. METHODS: Treatment simulations for tracking with and without time-dependent terms were performed using computer generated respiratory motion tracks for 60.000 patients with variable baseline drifts and phase shifts. The protocol for acquisition of X-ray images was always the same. Tumor position prediction accuracies in simulated treatments were largely based on cumulative error-time histograms and quantified with R95: in 95% of time the prediction error is < R95 mm. RESULTS: For all available correlation models, prediction accuracy improved by adding a time-dependent term in case of occurring baseline drifts, with and without phase shifts present. For the most accurate model and 150 s between model updates, adding time dependency reduced R95 from 3.9 to 3.1 mm and from 5.4 to 3.3 mm for 0.25 and 0.50 mm/min drift, respectively. Tumor position prediction accuracy improvements with time-dependent models were obtained without increases in X-ray imaging. CONCLUSIONS: Using available correlation models with an added time-dependent term could largely mitigate negative impact of respiratory motion baseline drifts on tumor position prediction accuracy, also in case of large phase shifts.

Socio-economic inequalities in smoking and drinking in adolescence: Assessment of social network dynamics.

AIMS: We investigated whether (1) adolescents selected friends with a similar socio-economic status (SES), (2) smoking and alcohol consumption spread in networks and (3) the exclusion of non-smokers or non-drinkers differed between SES groups. DESIGN: This was a longitudinal study using stochastic actor-oriented models to analyze complete social network data over three waves. SETTING: Eight Hungarian secondary schools with socio-economically diverse classes took part. PARTICIPANTS: This study comprised 232 adolescents aged between 14 and 15 years in the first wave. MEASUREMENTS: Self-reported smoking behavior, alcohol consumption behavior and friendship ties were measured. SES was measured based upon entitlement to an income-tested regular child protection benefit. FINDINGS: Non-low-SES adolescents were most likely to form friendships with peers from their own SES group [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.02-1.11]. Adolescents adjusted their smoking behavior (OR = 24.05, 95% CI = 1.27-454.86) but not their alcohol consumption (OR = 1.65, 95% CI = 0.62-4.39) to follow the behavior of their friends. Smokers did not differ from non-smokers in the likelihood of receiving a friendship nomination (OR = 0.98, 95% CI = 0.87-1.10), regardless of their SES. Alcohol consumers received significantly more friendship nominations than non-consumers (OR = 1.16, 95% CI = 1.01-1.33), but this association was not significantly different according to SES. CONCLUSIONS: Hungarian adolescents appear to prefer friendships within their own socio-economic status group, and smoking and alcohol consumption spread within those friendship networks. Socio-economic groups do not differ in the extent to which they encourage smoking or alcohol consumption.

A New Look at the Mechanism of Cocrystal Formation and Coformers Exchange in Processes Forced by Mechanical and/or Thermal Stimuli - ex situ and in†situ Studies of Low-Melting Eutectic Mixtures.

Three different devices: ball mill, hot stage melting, and magic angle spinning (MAS) NMR rotor were used for the preparation of ethenzamide (ET) cocrystals with glutaric acid (GLU), ethylmalonic acid (EMA) and maleic acid (MAL) as coformers. In each case, well-defined binary systems (ET:EMA, ET:GLU, ET:MAL) were obtained. The common features of the two solvent free methods of cocrystal formation (grinding, melting) are presented on the basis of arguments obtained by solid state NMR spectroscopy. Thermal analysis (Differential Scanning Calorimetry) proved that the eutectic phase arises over a wide range of molar ratios of components for each of the binary systems. NMR techniques, supported by theoretical calculations, allowed to provide details about the pathway of the reaction mechanism with atomic accuracy. It was found that the formation of ET cocrystals is a complex process that requires five steps. Each step has been recognized and described. Variable temperature 1D and 2D MAS NMR experiments allowed to track physicochemical processes taking place in a molten state. Moreover, it was found that in a multicomponent mixture consisting of all four components, ET, EMA, GLU, and MAL, ET in the molten phase behaves as a specific selector choosing only one partner to form binary cocrystals according to energy preferences. The process of exchange of coformers in binary systems during grinding, melting, and NMR measurements is described. The stabilization energies (Estab ) and molecular electrostatic potential (MEP) maps computed for the cocrystals under discussion and their individual components rationalize the selection rules and explain the relationships between individual species.

Genetic Interactions in Various Environmental Conditions in Caenorhabditis elegans.

Although it is well known that epistasis plays an important role in many evolutionary processes (e.g., speciation, evolution of sex), our knowledge on the frequency and prevalent sign of epistatic interactions is mainly limited to unicellular organisms or cell cultures of multicellular organisms. This is even more pronounced in regard to how the environment can influence genetic interactions. To broaden our knowledge in that respect we studied gene-gene interactions in a whole multicellular organism, Caenorhabditis elegans. We screened over one thousand gene interactions, each one in standard laboratory conditions, and under three different stressors: heat shock, oxidative stress, and genotoxic stress. Depending on the condition, between 7% and 22% of gene pairs showed significant genetic interactions and an overall sign of epistasis changed depending on the condition. Sign epistasis was quite common, but reciprocal sign epistasis was extremally rare. One interaction was common to all conditions, whereas 78% of interactions were specific to only one environment. Although epistatic interactions are quite common, their impact on evolutionary processes will strongly depend on environmental factors.

Associations of social media use with smoking and e-cigarettes: a national longitudinal study.

BACKGROUND: Social media use is high among children and young people and might influence health behaviours. We examined social media use and use of tobacco and e-cigarettes in the UK. METHODS: We used data from participants aged 10-25 years from the UK Household Longitudinal Study (January 2015-January 2022). Participants were asked: "On a normal weekday, that is Monday to Friday, how many hours do you spend chatting or interacting with friends through a social website or app like that?". Specific social media platforms were not specified. Responses were none, less than 1 h, 1-3 h, 4-6 h, 7 h or more. Outcomes were current tobacco smoking and e-cigarette use. Generalised Estimating Equation (GEE) logistic regression models investigated associations of social media use with tobacco and e-cigarette use, and fixed effects analyses investigated changes in social media use with uptake of both products. Models included possible confounders such as age, sex, household income, ethnicity (White vs non-White) and use of tobacco or e-cigarettes by others within the home. All participants gave written informed consent. FINDINGS: The analytic sample included 10 808 participants with 27 962 observations (mean age 15·7 years [SD 3·8], 5080 [47%] male, 5728 [53%] female, and 7868 [73%] White). Current tobacco smoking was reported at one or more timepoints by 929 (8·6%) participants, and current e-cigarette use by 270 (2·5%) participants. In adjusted GEE models, all levels of social media use were associated with greater odds of current smoking than no use. This association was particularly apparent at higher levels of use adjusted odds ratio [aOR] 3·11, 95% CI 2·41-4·03 for ≥7 h use vs no use), with similar associations for e-cigarettes (aOR 3·04, 2·11-4·40 for ≥7 h use vs no use). Fixed effects analyses also found increased use of social media to be associated with increased uptake of both products (eg, changing to using social media for ≥7 h/day was associated with >2 times the odds of taking up tobacco smoking [aOR 2·33, 1·28-4·24]). INTERPRETATION: These analyses suggest an association between social media use and e-cigarette and tobacco use. Potential pathways include promotion of these products on social media. Further research with details on specific platforms would be useful as well as with longer follow-up time. FUNDING: Cancer Research UK.

Bacteriophage steering of Burkholderia cenocepacia toward reduced virulence and increased antibiotic sensitivity.

Antibiotic resistance in bacteria is a growing global concern and has spurred increasing efforts to find alternative therapeutics, such as the use of bacterial viruses, or bacteriophages. One promising approach is to use phages that not only kill pathogenic bacteria but also select phage-resistant survivors that are newly sensitized to traditional antibiotics, in a process called "phage steering." Members of the bacterial genus Burkholderia, which includes various human pathogens, are highly resistant to most antimicrobial agents, including serum immune components, antimicrobial peptides, and polymixin-class antibiotics. However, the application of phages in combination with certain antibiotics can produce synergistic effects that more effectively kill pathogenic bacteria. Herein, we demonstrate that Burkholderia cenocepacia serum resistance is due to intact lipopolysaccharide (LPS) and membranes, and phage-induced resistance altering LPS structure can enhance bacterial sensitivity not only to immune components in serum but also to membrane-associated antibiotics such as colistin. IMPORTANCE Bacteria frequently encounter selection pressure from both antibiotics and lytic phages, but little is known about the interactions between antibiotics and phages. This study provides new insights into the evolutionary trade-offs between phage resistance and antibiotic sensitivity. The creation of phage resistance through changes in membrane structure or lipopolysaccharide composition can simultaneously be a major cause of antibiotic sensitivity. Our results provide evidence of synergistic therapeutic efficacy in phage-antibiotic interactions and have implications for the future clinical use of phage steering in phage therapy applications.

Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1.

Glutaric acidemia type 1 (GA1) is a neurotoxic metabolic disorder due to glutaryl-CoA dehydrogenase (GCDH) deficiency. The high number of missense variants associated with the disease and their impact on GCDH activity suggest that disturbed protein conformation can affect the biochemical phenotype. We aimed to elucidate the molecular basis of protein loss of function in GA1 by performing a parallel analysis in a large panel of GCDH missense variants using different biochemical and biophysical methodologies. Thirteen GCDH variants were investigated in regard to protein stability, hydrophobicity, oligomerization, aggregation, and activity. An altered oligomerization, loss of protein stability and solubility, as well as an augmented susceptibility to aggregation were observed. GA1 variants led to a loss of enzymatic activity, particularly when present at the N-terminal domain. The reduced cellular activity was associated with loss of tetramerization. Our results also suggest a correlation between variant sequence location and cellular protein stability (p < 0.05), with a more pronounced loss of protein observed with variant proximity to the N-terminus. The broad panel of variant-mediated conformational changes of the GCDH protein supports the classification of GA1 as a protein-misfolding disorder. This work supports research toward new therapeutic strategies that target this molecular disease phenotype.

Increasing the transparency of systematic reviews: presenting a generalized registration form.

This paper presents a generalized registration form for systematic reviews that can be used when currently available forms are not adequate. The form is designed to be applicable across disciplines (i.e., psychology, economics, law, physics, or any other field) and across review types (i.e., scoping review, review of qualitative studies, meta-analysis, or any other type of review). That means that the reviewed records may include research reports as well as archive documents, case law, books, poems, etc. Items were selected and formulated to optimize broad applicability instead of specificity, forgoing some benefits afforded by a tighter focus. This PRISMA 2020 compliant form is a fallback for more specialized forms and can be used if no specialized form or registration platform is available. When accessing this form on the Open Science Framework website, users will therefore first be guided to specialized forms when they exist. In addition to this use case, the form can also serve as a starting point for creating registration forms that cater to specific fields or review types.

Patterns of cigarette and e-cigarette use among UK adolescents: a latent class analysis of the Millennium Cohort Study.

BACKGROUND: Patterning of cigarette and e-cigarette use among young people remains poorly characterized. We aimed to describe these patterns in the UK Millennium Cohort Study at age 14 and 17 years. METHODS: Data on cigarette and e-cigarette use come from 9731 adolescents. Latent class analysis assigned participants to membership of classes of product use and multinomial logistic regression analyses assessed differences in the likelihood of belonging to classes by sociodemographic (age, gender, ethnicity, household income, maternal education and country of residence) and smoking-related social factors (caregiver tobacco use, caregiver e-cigarette use and peer smoking). RESULTS: We identified four classes of use: 45.8% of adolescents 'continued to abstain' from cigarettes or e-cigarettes; 21.3% 'experimented' (used once or in the past but not currently) with cigarettes and/or e-cigarettes by age 17 but were not current users; 19.0% were 'late adopters', characterized by low levels of use at age 14 but high levels of experimentation and current use at age 17; and 13.9% were 'early adopters', characterized by high levels of experimentation and current use at ages 14 and 17. At age 17, 70.4% of 'early adopters' smoked cigarettes regularly plus an additional 27.3% experimented with cigarettes. Corresponding percentages for e-cigarettes were 37.9% and 58.9%. Tobacco and e-cigarette use by caregivers, and cigarette use by peers, were associated with being both 'late adopters' and 'early adopters'. CONCLUSIONS: Approximately one in seven adolescents in the UK are 'early adopters' of nicotine products. This highlights the need to develop and implement effective policies to prevent nicotine use uptake.

Task features change the relation between math anxiety and number line estimation performance with rational numbers: Two large-scale online studies.

Math performance is negatively related to math anxiety (MA), though MA may impact certain math skills more than others. We investigated whether the relation between MA and math performance is affected by task features, such as number type (e.g., fractions, whole numbers, percentages), number format (symbolic vs. nonsymbolic), and ratio component size (small vs. large). Across two large-scale studies (combined n = 3,822), the MA-performance relation was strongest for large whole numbers and fractions, and stronger for symbolic than nonsymbolic fractions. The MA-performance relation was also stronger for smaller relative to larger components, and MA relating to specific number types may be a better predictor of performance than general MA for certain tasks. The relation between MA and estimation performance changes depending on task features, which suggests that MA may relate to certain math skills more than others, which may have implications for how people reason with numerical information and may inform future interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Multistate transition modelling of e-cigarette use and cigarette smoking among youth in the UK.

INTRODUCTION: E-cigarette use remains a controversial topic, with questions over how people transition between e-cigarette use and cigarette smoking. This paper examined transitions into and out of nicotine product use in a representative sample of UK youth. METHODS: We used Markov multistate transition probability models on data from 10 229 participants (10-25 years old) in the UK Household Longitudinal Study (2015-2021). We used four product use states ('never', 'non-current use', 'e-cigarette only' and 'smoking and dual use') and estimated likelihood of transitions according to sociodemographic characteristics. RESULTS: Among participants who had never used nicotine products, most were still non-users a year later (92.9% probability; 95% CI 92.6%, 93.2%); a small proportion transitioned to using e-cigarettes only (4.0%; 95% CI 3.7%, 4.2%) and cigarettes (2.2%; 95% CI 2.0%, 2.4%). Those aged 14-17 years were the most likely to start using a nicotine product. E-cigarette use was less persistent overtime than cigarette smoking, with a 59.1% probability (95% CI 56.9%, 61.0%) of e-cigarette users still using after 1 year compared with 73.8% (95% CI 72.1%, 75.4%) for cigarette smoking. However, there was a 14% probability (95% CI 12.8%, 16.2%) that e-cigarette users went onto smoke cigarettes after 1 year, rising to 25% (95% CI 23%, 27%) after 3 years. CONCLUSION: This study found that although overall nicotine product use was relatively rare, participants were more likely to experiment with e-cigarette use than cigarette smoking. This was mostly not persistent over time; however, approximately one in seven transitioned to cigarette smoking. Regulators should aim to deter all nicotine product use among children.

A novel external/internal tumor tracking approach to compensate for respiratory motion baseline drifts.

Objective.Real-time respiratory tumor tracking as implemented in a robotic treatment unit is based on continuous optical measurement of the position of external markers and a correlation model between them and internal target positions, which are established with X-ray imaging of the tumor, or fiducials placed in or around the tumor. Correlation models are created with fifteen simultaneously measured external/internal marker position pairs divided over the respiratory cycle. Every 45-150 s, the correlation model is updated by replacing the three first acquired data pairs with three new pairs. Tracking simulations for >120.000 computer-generated respiratory tracks demonstrated that this tracking approach resulted in relevant inaccuracies in internal target position predictions, especially in case of presence of respiratory motion baseline drifts.Approach.To better cope with drifts, we introduced a novel correlation model with an explicit time dependence, and we proposed to replace the currently applied linear-motion tracking (LMT) by mixed-model tracking (MMT). In MMT, the linear correlation model is extended with an explicit time dependence in case of a detected baseline drift. MMT prediction accuracies were then established for the same >120.000 computer-generated patients as used for LMT.Main results.For 150 s update intervals, MMT outperformed LMT in internal target position prediction accuracy for 93.7 ∣ 97.2% of patients with 0.25 ∣ 0.5 mm min-1linear respiratory motion baseline drifts with similar numbers of X-ray images and similar treatment times. For the upper 25% of patients, mean 3D internal target position prediction errors reduced by 0.7 ∣ 1.8 mm, while near maximum reductions (upper 10% of patients) were 0.9 ∣ 2.0 mm.Significance.For equal numbers of acquired X-ray images, MMT greatly improved tracking accuracy compared to LMT, especially in the presence of baseline drifts. Even with almost 50% less acquired X-ray images, MMT still outperformed LMT in internal target position prediction accuracy.

Unexpected Factors Affecting the Kinetics of Guest Molecule Release from Investigation of Binary Chemical Systems Trapped in a Single Void of Mesoporous Silica Particles.

In this work, we present results for loading of well-defined binary systems (cocrystal, solid solution) and untreated materials (physical mixtures) into the voids of MCM-41 mesoporous silica particles employing three different filling methods. The applied techniques belong to the group of "wet methods" (diffusion supported loading - DiSupLo) and "solvent-free methods" (mechanical ball-mill loading - MeLo, thermal solvent free - TSF). As probes for testing the guest1-guest2 interactions inside the MCM-41 pores we employed the benzoic acid (BA), perfluorobenzoic acid (PFBA), and 4-fluorobenzoic acid (4-FBA). The guests intermolecular contacts and phase changes were monitored employing magic angle spinning (MAS) NMR Spectroscopy techniques and powder X-ray diffraction (PXRD). Since mesoporous silica materials are commonly used in drug delivery system research, special attention has been paid to factors affecting guest release kinetics. It has been proven that not only the content and composition of binary systems, but also the loading technique have a strong impact on the rate of guests release. Innovative methods of visualizing differences in release kinetics are presented.