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PloS One 2024To improve the accuracy of modal analysis for a four-stage centrifugal-pump rotor system with a balancing disc based on the concentrated-mass analytical method, a...
To improve the accuracy of modal analysis for a four-stage centrifugal-pump rotor system with a balancing disc based on the concentrated-mass analytical method, a simplified concentrated mass mathematical model and an ANSYS simulation model are established. The results from these two models are compared to determine factors that cause significant differences in the mode shapes. Subsequently, an optimized mathematical model based on the corrected mass moment of an inertia matrix and stiffness correction coefficients is proposed, and the effectiveness of this optimized mathematical model is validated using a four-stage centrifugal pump with back blades. The results show that the natural frequencies obtained from the ANSYS simulations are consistently higher than those obtained using the analytical method. The simplification of the moment of inertia at the impeller and balancing disc contributes primarily to the calculated errors. The optimized mathematical model reduces the errors in the natural frequencies from 12.96%, 12.13%, 9.96%, 5.85%, and 8.74% to 2.45%, 1.56%, 0.65%, 5.34%, and 2.28%, respectively. The optimization of natural frequencies offers better performance at lower-order modes, whereas its effects on higher-order modes are less significant. The optimization method is applicable to centrifugal pumps with back blades and reduces the error in theoretical calculations, based on reductions in the concentrated mass from 13.11%, 12.85%, 9.91%, and 7.2% to 3.7%, 3.86%, 0.57%, and 2.87%, respectively, thus further confirming the feasibility of the optimized model design.
Topics: Centrifugation; Models, Theoretical; Computer Simulation; Equipment Design
PubMed: 38941321
DOI: 10.1371/journal.pone.0306061 -
PLOS Global Public Health 2024Nested serosurveys within routine service delivery platforms such as planned supplemental immunization activities (SIAs) provide an opportunity to collect information...
Feasibility and acceptability of collecting dried blood spots (DBS) from children after vaccination during supplementary immunization activities to estimate measles and rubella seroprevalence.
Nested serosurveys within routine service delivery platforms such as planned supplemental immunization activities (SIAs) provide an opportunity to collect information that can be used to answer valuable questions on the effectiveness and efficiency of the delivery model to inform future activities. However, integrating research data collection in SIAs is rarely done due to concerns it will negatively impact the program. We conducted a serosurvey nested within the November 2020 measles-rubella SIA integrated with the Child Health Week activities in Zambia to evaluate this approach. In-depth interviews with the study teams and vaccination campaign staff at the vaccination sites were conducted. Recorded interviews were transcribed, transcripts were coded and then grouped into themes based on a process evaluation framework. A multi-methods analytical approach was used to assess the feasibility and acceptability of collecting dried blood spots from children during the SIA. This included a quantitative assessment of participant enrollment. The serosurvey successfully enrolled 90% of children from Child Health Week due to close coordination and teamwork between the vaccination teams and serosurvey team, in addition to substantial social mobilization efforts. Continually adjusting the sampling interval that was used to select eligible children allowed us to enroll throughout the SIA and capture a representative sample of children in attendance although it was challenging for the staff involved. As vaccination programs aim to tailor their approaches to reach the hardest-to-reach children, embedding research questions in SIAs will allow evaluation of the successes and challenges and compare alternative approaches. Lessons learned from this experience collecting data during an SIA can be applicable to future research activities embedded in SIAs or other delivery platforms.
PubMed: 38941295
DOI: 10.1371/journal.pgph.0002985 -
JAMA Network Open Jun 2024Understanding the cost of drug development can help inform the development of policies to reduce costs, encourage innovation, and improve patient access to drugs.
IMPORTANCE
Understanding the cost of drug development can help inform the development of policies to reduce costs, encourage innovation, and improve patient access to drugs.
OBJECTIVE
To estimate the cost of drug development by therapeutic class and trends in pharmaceutical research and development (R&D) intensity over time.
DESIGN, SETTING, AND PARTICIPANTS
In this economic evaluation study, an analytical model of drug development constructed using public and proprietary sources that collectively cover data from 2000 to 2018 was used to estimate the cost of bringing a drug to market, overall and for specific therapeutic classes. The analysis for the study was completed in October 2020.
MAIN OUTCOMES AND MEASURES
Three measures of development cost from nonclinical through postmarketing stages were estimated: mean out-of-pocket cost or cash outlay, mean expected cost, and mean expected capitalized cost. Pharmaceutical R&D intensity, defined as the ratio of R&D spending to total sales, from 2008 to 2019, based on the time frame for available data, was also analyzed.
RESULTS
The estimated mean cost of developing a new drug was approximately $172.7 million (2018 dollars) (range, $72.5 million for genitourinary to $297.2 million for pain and anesthesia), inclusive of postmarketing studies. The cost increased to $515.8 million when cost of failures was included. When the costs of failures and capital were included, the mean expected capitalized cost of drug development increased to $879.3 million (range, $378.7 million for anti-infectives to $1756.2 million for pain and anesthesia); results varied widely by therapeutic class. The pharmaceutical industry as a whole experienced a decline of 15.6% in sales but increased R&D intensity from 11.9% to 17.7% from 2008 to 2019. By contrast, R&D intensity of large pharmaceutical companies increased from 16.6% to 19.3%, whereas sales increased by 10.0% (from $380.0 to $418.0 billion) over the same 2008 to 2019 period, even though the cost of drug development remained relatively stable or may have even decreased.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of new drug development costs, even though the cost of drug development appears to have remained stable, R&D intensity of large pharmaceutical companies remained relatively unchanged, despite substantial growth in revenues during this period. These findings can inform the design of drug-related policies and their potential impacts on innovation and competition.
Topics: Drug Development; United States; Humans; Drug Costs; Drug Industry; Pharmaceutical Research
PubMed: 38941099
DOI: 10.1001/jamanetworkopen.2024.15445 -
JAMA Health Forum Jun 2024Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of...
IMPORTANCE
Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of psychedelics, approximately one-twentieth to one-fifth of a full dose, over prolonged periods). Analyzing Google search queries can provide insights into public interest and help address this gap.
OBJECTIVE
To analyze trends in public interest in microdosing in the US through Google search queries and assess their association with cannabis and psychedelic legislative reforms.
DESIGN, SETTING, AND PARTICIPANTS
In this cross-sectional study, a dynamic event-time difference-in-difference time series analysis was used to assess the impact of cannabis and psychedelic legislation on microdosing search rates from January 1, 2010, to December 31, 2023. Google search rates mentioning "microdosing," "micro dosing," "microdose," or "micro dose" within the US and across US states were measured in aggregate.
EXPOSURE
Enactment of (1) local psychedelic decriminalization laws; (2) legalization of psychedelic-assisted therapy and statewide psychedelic decriminalization; (3) statewide medical cannabis use laws; (4) statewide recreational cannabis use laws; and (5) all cannabis and psychedelic use restricted.
MAIN OUTCOME AND MEASURES
Microdosing searches per 10 million Google queries were measured, examining annual and monthly changes in search rates across the US, including frequency and nature of related searches.
RESULTS
Searches for microdosing in the US remained stable until 2014, then increased annually thereafter, with a cumulative increase by a factor of 13.4 from 2015 to 2023 (7.9 per 10 million to 105.6 per 10 million searches, respectively). In 2023, there were 3.0 million microdosing searches in the US. Analysis at the state level revealed that local psychedelic decriminalization laws were associated with an increase in search rates by 22.4 per 10 million (95% CI, 7.5-37.2), statewide psychedelic therapeutic legalization and decriminalization were associated with an increase in search rates by 28.9 per 10 million (95% CI, 16.5-41.2), statewide recreational cannabis laws were associated with an increase in search rates by 40.9 per 10 million (95% CI, 28.6-53.3), and statewide medical cannabis laws were associated with an increase in search rates by 11.5 per 10 million (95% CI, 6.0-16.9). From August through December 2023, 27.0% of the variation in monthly microdosing search rates between states was explained by differences in cannabis and psychedelics legal status.
CONCLUSION AND RELEVANCE
This cross-sectional study found that state-led legislative reforms on cannabis and psychedelics were associated with increased public interest in microdosing psychedelics.
Topics: Hallucinogens; Humans; United States; Cross-Sectional Studies; Cannabis; Legislation, Drug
PubMed: 38941086
DOI: 10.1001/jamahealthforum.2024.1653 -
Cell Biology and Toxicology Jun 2024Structural cardiotoxicity (SCT) presents a high-impact risk that is poorly tolerated in drug discovery unless significant benefit is anticipated. Therefore, we aimed to...
Structural cardiotoxicity (SCT) presents a high-impact risk that is poorly tolerated in drug discovery unless significant benefit is anticipated. Therefore, we aimed to improve the mechanistic understanding of SCT. First, we combined machine learning methods with a modified calcium transient assay in human-induced pluripotent stem cell-derived cardiomyocytes to identify nine parameters that could predict SCT. Next, we applied transcriptomic profiling to human cardiac microtissues exposed to structural and non-structural cardiotoxins. Fifty-two genes expressed across the three main cell types in the heart (cardiomyocytes, endothelial cells, and fibroblasts) were prioritised in differential expression and network clustering analyses and could be linked to known mechanisms of SCT. This transcriptomic fingerprint may prove useful for generating strategies to mitigate SCT risk in early drug discovery.
Topics: Humans; Cardiotoxicity; Transcriptome; Myocytes, Cardiac; Induced Pluripotent Stem Cells; Gene Expression Profiling; Computational Biology; Machine Learning; Cardiotoxins; Fibroblasts; Endothelial Cells
PubMed: 38940987
DOI: 10.1007/s10565-024-09880-7 -
Journal of Radiation Research Jun 2024The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and...
The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations.
PubMed: 38940734
DOI: 10.1093/jrr/rrae050 -
Cancer Medicine Jul 2024To evaluate the impact of training quitline staff in lung cancer screening (LCS) on knowledge and attitudes towards connecting quitline callers to LCS educational...
OBJECTIVE
To evaluate the impact of training quitline staff in lung cancer screening (LCS) on knowledge and attitudes towards connecting quitline callers to LCS educational materials.
METHODS
We conducted a pre-post evaluation within a larger implementation project in the U.S. to support LCS among quitline callers. From July 2020 to June 2021, staff from four quitline service providers completed surveys before and after training on LCS knowledge. After training, staff completed the acceptability of intervention measure, intervention appropriateness measure, and feasibility of the intervention measure.
RESULTS
A total of 245 staff completed the initial demographic survey (analytic sample), 130 completed the pre-training survey, and 225 completed the post-training survey. Staff were on average 47.4 years old and 76.7% were female. LCS knowledge improved after the training (n = 120, mean difference = +26.5%, 95% CI 21.6, 31.4, p < 0.001). Overall, staff felt that connecting quitline callers to LCS education materials was acceptable (M = 4.0, SD = 0.8), appropriate (M = 4.1, SD = 0.7), and feasible (M = 4.0, SD = 0.7).
CONCLUSIONS
Receiving training about LCS eligibility and the benefits and harms of screening improved LCS knowledge among quitline staff. Quitline staff found that connecting callers with LCS educational materials is acceptable, appropriate, and feasible, and aligned with their primary mission.
Topics: Humans; Female; Male; Lung Neoplasms; Middle Aged; Early Detection of Cancer; Health Knowledge, Attitudes, Practice; Smoking Cessation; Adult; Hotlines; Surveys and Questionnaires; Attitude of Health Personnel
PubMed: 38940442
DOI: 10.1002/cam4.7443 -
Bioinformatics (Oxford, England) Jun 2024Quantitative dynamical models facilitate the understanding of biological processes and the prediction of their dynamics. The parameters of these models are commonly...
MOTIVATION
Quantitative dynamical models facilitate the understanding of biological processes and the prediction of their dynamics. The parameters of these models are commonly estimated from experimental data. Yet, experimental data generated from different techniques do not provide direct information about the state of the system but a nonlinear (monotonic) transformation of it. For such semi-quantitative data, when this transformation is unknown, it is not apparent how the model simulations and the experimental data can be compared.
RESULTS
We propose a versatile spline-based approach for the integration of a broad spectrum of semi-quantitative data into parameter estimation. We derive analytical formulas for the gradients of the hierarchical objective function and show that this substantially increases the estimation efficiency. Subsequently, we demonstrate that the method allows for the reliable discovery of unknown measurement transformations. Furthermore, we show that this approach can significantly improve the parameter inference based on semi-quantitative data in comparison to available methods.
AVAILABILITY AND IMPLEMENTATION
Modelers can easily apply our method by using our implementation in the open-source Python Parameter EStimation TOolbox (pyPESTO) available at https://github.com/ICB-DCM/pyPESTO.
Topics: Models, Biological; Software; Algorithms; Computer Simulation; Computational Biology
PubMed: 38940161
DOI: 10.1093/bioinformatics/btae210 -
Chemical & Biomedical Imaging Jun 2024There is significant and increasing interest in using the photothermal effect to record infrared (IR) absorption spectra localized to volumes that are considerably...
There is significant and increasing interest in using the photothermal effect to record infrared (IR) absorption spectra localized to volumes that are considerably smaller than the wavelength of excitation, i.e., subdiffraction imaging. As opposed to conventional IR microscopy, in which absorption and scattering of the illuminating light is measured, subdiffraction imaging can be achieved through detection of the sample's thermal response to IR absorption-induced heating. While this relationship has been examined by a variety of coarse-grained models, a generalized analysis of the dependence of temperature and surface deformation arising from an absorber below the surface has not been reported. Here, we present an analytical model to understand a sample's thermoelastic response in photothermal measurements. The model shows important dependence of the ability to record subdiffraction data on modulation frequency of exciting light, limitations imposed by optical sensing, and the potential to discern location of objects ultimately limited by noise and sharpness of the detecting mechanism. This foundational analysis should allow for better modeling, understanding, and harnessing of the relationship between absorption and sample response that underlies IR photothermal measurements.
PubMed: 38939874
DOI: 10.1021/cbmi.4c00018 -
Acta Medica Philippina 2024To determine the effect of the impacted position of the maxillary canine on the root resorption of the adjacent incisor using Cone-beam Computed Tomography (CBCT)...
OBJECTIVE
To determine the effect of the impacted position of the maxillary canine on the root resorption of the adjacent incisor using Cone-beam Computed Tomography (CBCT) imaging.
METHODS
This was an analytic quantitative study. The research sample determined CBCT images of treatment patients at the Orthodontic Specialist Policlinic in Dental Hospital of Airlangga University over a three-year period and secondary data taken from Pramita Laboratory. CBCT photos that met the inclusion criteria, including mesially impacted canine or close to central or lateral incisors with completely formed anatomy were then analyzed. Multiple linear regression was used to determine x-axis, y-axis, z-axis position of the impacted canine on the severity of root resorption of the adjacent incisor, and the effect of impacted canines on all axes simultaneously on the severity of root resorption of the adjacent incisors.
RESULTS
The position of the impacted canine in the x-axis and z-axis planes had a significant influence on the root resorption of the adjacent incisor. Meanwhile, impacted canine from the y-axis plane showed non-significant influence on the root resorption.
CONCLUSION
The position of the impacted canine when viewed in all planes of the tooth axis has a significant effect on the severity of root resorption of the adjacent incisor.
PubMed: 38939849
DOI: 10.47895/amp.vi0.4321