Relative Effectiveness Research Articles

Primary study of the relative and compound biological effectiveness model for boron neutron capture therapy based on nanodosimetry.

The current radiobiological model employed for boron neutron capture therapy (BNCT) treatment planning, which relies on microdosimetry, fails to provide an accurate representation the biological effects of BNCT. The precision in calculating the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) plays a pivotal role in determining the therapeutic efficacy of BNCT. Therefore, this study focuses on how to improve the accuracy of the biological effects of BNCT. The purpose of this study is to propose new radiation biology models based on nanodosimetry to accurately assess RBE and CBE for BNCT. Nanodosimetry, rooted in ionization cluster size distributions (ICSD), introduces a novel approach to characterize radiation quality by effectively delineating RBE through the ion track structure at the nanoscale. In the context of prior research, this study presents a computational model for the nanoscale assessment of RBE and CBE. We establish a simplified model of DNA chromatin fiber using the Monte Carlo code TOPAS-nBio to evaluate the applicability of ICSD to BNCT and compute nanodosimetric parameters. Our investigation reveals that both homogeneous and heterogeneous nanodosimetric parameters, as well as the corresponding biological model coefficients α and β, along with RBE values, exhibit variations in response to varying intracellular 10B concentrations. Notably, the nanodosimetric parameter effectively captures the fluctuations in model coefficients α and RBE. Our model facilitates a nanoscale analysis of BNCT, enabling predictions of nanodosimetric quantities for secondary ions as well as RBE, CBE, and other essential biological metrics related to the distribution of boron. This contribution significantly enhances the precision of RBE calculations and holds substantial promise for future applications in treatment planning.

Induction of Chromosomal Aberrations after Exposure to the Auger Electron Emitter Iodine-125, the β--emitter Tritium and Cesium-137 γ rays.

High-LET-type cell survival curves have been observed in cells that were allowed to incorporate 125I-UdR into their DNA. Incorporation of tritiated thymidine into the DNA of cells has also been shown to result in an increase in relative biological effectiveness in cell survival experiments, but the increase is smaller than observed after incorporation of 125I-UdR. These findings are explained in the literature by the overall complexity of the induced DNA damage resulting from energies of the ejected electron(s) during the decay of 3H and 125I. Chromosomal aberrations (CA) are defined as morphological or structural changes of one or more chromosomes, and can be induced by ionizing radiation. Whether the number of CA is associated with the linear energy transfer (LET) of the radiation and/or the actual complexity of the induced DNA double-strand breaks (DSB) remains elusive. In this study, we investigated whether DNA lesions induced at different cell cycle stages and by different radiation types [Auger-electrons (125I), β- particles (3H), or γ radiation (137Cs)] have an impact on the number of CA induced after induction of the same number of DSB as determined by the γ-H2AX foci assay. Cells were synchronized and pulse-labeled in S phase with low activities of 125I-UdR or tritiated thymidine. For decay accumulation, cells were cryopreserved either after pulse-labeling in S phase or after progression to G2/M or G1 phase. Experiments with γ irradiation (137Cs) were performed with synchronized and cryopreserved cells in S, G2/M or G1 phase. After thawing, a CA assay was performed. All experiments were performed after a similar number of DSB were induced. CA induction after 125I-UdR was incorporated was 2.9-fold and 1.7-fold greater compared to exposure to γ radiation and radiation from incorporated tritiated thymidine, respectively, when measured in G2/M cells. In addition, measurement of CA in G2/M cells after incorporation of 125I-UdR was 2.5-fold greater when compared to cells in G1 phase. In contrast, no differences were observed between the three radiation qualities with respect to exposure after cryopreservation in S or G1 phase. The data indicate that the 3D organization of replicated DNA in G2/M cells seems to be more sensitive to induction of more complex DNA lesions compared to the DNA architecture in S or G1 cells. Whether this is due to the DNA organization itself or differences in DNA repair capability remains unclear.

Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

Temperature and hospital admissions in the Eastern Mediterranean: a case study in Cyprus

Exposure to extreme temperatures can trigger a cascade of adverse cardiovascular and respiratory events. However, in Cyprus, a hotspot of climate change in the Eastern Mediterranean region, little is known about the temperature-related cardiorespiratory morbidity risks. We analyzed daily counts of hospital admissions for cardiovascular and respiratory diseases from four general hospitals in three districts in Cyprus from 2000 through 2019. For each district, we fitted time-series quasi-Poisson regression with distributed lag non-linear models to analyze the associations between daily mean temperature (lag 0–21 d) and hospital admissions for cardiorespiratory, cardiovascular, and respiratory diseases. A random-effects meta-analytical model was then applied to pool the district-specific estimates and obtain the national average associations. We analyzed 20 years of cause-specific hospitalization data with a total of 179 988 cardiovascular and respiratory events. The relationships between cardiorespiratory morbidity and temperature were overall U-shaped. During extreme temperature days, 15.85% (95% empirical CI [eCI]: 8.24, 22.40%) excess cardiovascular hospitalizations and 9.59% (95% eCI: −0.66, 18.69%) excess respiratory hospitalizations were attributable to extreme cold days (below the 2.5th percentile). Extreme hot days (above the 97.5th percentile) accounted for 0.17% (95% eCI: 0.03, 0.29%) excess cardiovascular hospitalizations and 0.23% (95% eCI: 0.07, 0.35%) excess respiratory hospitalizations. We found evidence of increased cardiovascular morbidity risk associated with extreme temperatures in Cyprus. Our study highlights the necessity to implement public health interventions and adaptive measures to mitigate the related temperature effects in an understudied region.

Salvage skull base surgery after proton beam therapy for recurrent sinonasal malignancies: A retrospective study.

This study aimed to examine treatment outcomes and postoperative complications associated with salvage skull base surgery following radical proton beam therapy (PBT). Nine patients who underwent salvage skull base surgery following curative PBT as the initial treatment at our institution between September 2002 and May 2023 were retrospectively reviewed. The cohort comprised four males and five females with a mean age of 48.1 years. The average proton dose administered during initial therapy was 68.5 Gy (relative biological effectiveness). Among the salvage surgeries, eight were anterior skull base surgeries, and one was an anterior middle skull base surgery. No local recurrences or perioperative deaths were observed. Postoperative complications occurred in three patients (33.3%), all experiencing surgical site infections, with one also having cerebrospinal fluid leakage. The study demonstrates that salvage skull base surgery after PBT effectively achieves local control and safety in patients with recurrent sinonasal malignancies.

The threaten of typhoons to the health of residents in inland areas: a study on the vulnerability of residents to death risk during typhoon “Lekima”

BackgroundStudies had suggested increased risk of death of residents was associated with typhoons, particularly coastal regions. However, these findings ignored the impact of inland typhoons on the health of residents, especially the indirect death risk caused by typhoons. This study aimed to investigate the acute death risk of residents during inland typhoon Lekima in Jinan, further identify vulnerable populations and areas.MethodsWe selected the daily death from 11 to 27th August 2019 in Jinan as case period, and conducted a time-stratified case-crossover design to match the contemporaneous data from 2016 to 2018 as control period. We used the generalized linear Poisson models to estimate the related effects of death risk during typhoon Lekima and lag days.ResultsDuring the Lekima typhoon month, there were 3,366 deaths occurred in Jinan. Compared to unexposed periods, the acute death risk of non-accidental diseases (especially circulatory diseases), female and the older adults increased significantly in the second week after the typhoon. The maximum significant effect of circulatory disease deaths, female and older adult deaths were appeared on lag9, lag9, and lag13 respectively. And the typhoon-associated RR were 1.19 (95%CI:1.05,1.34), 1.28 (95%CI:1.08,1.52), and 1.22 (95%CI:1.06,1.42) respectively. The acute death risk of residents living in TQ and CQ increased significantly on Lag2 and Lag6 after the typhoon, respectively, while those living in LX, LC, HY, JY, and SH occurred from Lag 8 to Lag 13 after the typhoon. LC lasted the longest days.ConclusionsTyphoons would increase the vulnerability of residents living in Jinan which mainly occurred from the seventh day after the typhoon. Residents suffering from non-accidental diseases (circulatory diseases), female and the older adults were more vulnerable. The vulnerability of TQ and CQ occurred on Lag2 and Lag6 after typhoon Lekima, respectively, and the other areas except ZQ and PY occurred from Lag 8 to Lag 13. LC lasted the longest duration. Our findings emphasized the importance of the emergency response, which would help policymakers to identify vulnerable regions and populations accurately during typhoons and formulate the emergency response plan.

Influence of Relative Age on Physical Condition and Academic Performance in Adolescents.

Annual age grouping is a common organizational strategy in academics and sports. This strategy could promote the relative effects of age, which refers to the (dis)advantages that subjects who were born in the first or last months of the year may suffer. The consequences could be minimized, resulting in better physical and/or academic results. The objective of the study was to evaluate the influence of the quarter of birth and examine the correlation between physical condition variables and academic performance. The sample included 79 students (51.90% females) 13.46 ± 0.21 years old in the second year of Obligatory Secondary Education. The physical variables of this study were explosive power, cardiorespiratory capacity, speed, flexibility, and muscle strength. They were evaluated using the horizontal jump tests, Cooper test, 50 m sprint, sit-and-reach test, and medicine ball exercises, respectively. The academic variables were obtained from the average academic grade, grouped by key competencies. An Analysis of Covariance (ANCOVA), controlling for gender, body mass, and height, revealed significant differences between male students born in the first quarter compared to those born in subsequent quarters in all physical condition variables (except for cardiorespiratory capacity). For female students, significant differences were observed only in the explosive power variable. No statistically significant intra-sex differences were evident in academic performance at any time of measurement. Additionally, moderate to large correlations were found in the physical condition and academic variables. It is concluded in relation to the need to implement diverse strategies regarding the process of developing physical conditions in adolescence that satisfy the growth needs of students based on age and sex.

Comparative Efficacy of Talquetamab vs. Current Treatments in the LocoMMotion and MoMMent Studies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma.

Talquetamab, a bispecific antibody targeting GPRC5D × CD3, is approved for the treatment of patients with triple-class -exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phaseI/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. real-world physician's choice of therapy (RWPC) was assessed using adjusted comparisons. An external control arm for MonumenTAL-1 (subcutaneously administered talquetamab 0.4mg/kg weekly [QW] and 0.8mg/kg every other week [Q2W]) was created from two observational real-world studies: LocoMMotion and MoMMent. Imbalances in baseline covariates were adjusted using inverse probability weighting. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), ≥ very good partial response (VGPR), and ≥ complete response (CR); odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional hazards model. After reweighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, patients treated with talquetamab QW (n = 143) had significantly improved outcomes vs. RWPC; RRs were ORR 2.67, p < 0.0001; ≥ VGPR 4.70, p < 0.0001; ≥ CR 78.05, p = 0.0002; and HRs were PFS 0.52, p < 0.0001; TTNT 0.48, p < 0.0001; OS 0.36, p < 0.0001. Patients treated with talquetamab Q2W (n = 145) also had significantly improved outcomes vs. RWPC; RRs were ORR 2.62, p < 0.0001; ≥ VGPR 5.04, p < 0.0001; ≥ CR 101.14, p = 0.0002; and HRs were PFS 0.40, p < 0.0001; TTNT 0.39, p < 0.0001; OS 0.37, p < 0.0001. Effectiveness of talquetamab for both schedules was significantly better than RWPC for ORR, ≥ VGPR, ≥ CR, PFS, OS, and TTNT, highlighting its clinical benefit for patients with TCE RRMM. MonumenTAL-1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584.

Performance Shortfall, Executive Social Relations and the Choice Between Shared and Full Control for New Overseas Entries

ABSTRACT Integrating the behavioral theory of the firm and social capital theory, this study examines how performance shortfalls and executive social relations jointly affect firms’ trade-offs between the shared-control entry mode and full-control entry mode. This study argues that, for new overseas entries, performance shortfalls cause firms to prefer the shared-control entry mode. This is attributed to the fact that performance shortfalls increase firms’ resource constraints and reduce their information search scope. This, in turn, leads decision-makers to prefer the shared-control entry mode, because that mode requires fewer resources, less information collection, and lower processing capabilities. In addition, guided by social capital theory, this study also finds that the positive effect of performance shortfalls on the shared-control entry mode is weakened when executives have social relations, either overseas or in banks. Further analysis shows that, compared with less-developed economies, firms facing a performance shortfall are more inclined to adopt the shared-control mode to enter developed economies. By clarifying the joint effect of performance shortfalls and executive social relations on firms’ overseas equity entry modes, this study deepens the understanding of firms’ choices of overseas equity entry modes.

ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity.

In this study, we investigated the roles of ROCK1 in regulating structural and functional features of caveolae located at the cell membrane of cardiomyocytes, adipocytes, and mouse embryonic fibroblasts (MEFs) as well as related physiopathological effects. Caveolae are small bulb-shaped cell membrane invaginations, and their roles have been associated with disease conditions. One of the unique features of caveolae is that they are physically linked to the actin cytoskeleton that is well known to be regulated by RhoA/ROCKs pathway. In cardiomyocytes, we observed that ROCK1 deficiency is coincident with an increased caveolar density, clusters, and caveolar proteins including caveolin-1 and -3. In the mouse cardiomyopathy model with transgenic overexpressing Gαq in myocardium, we demonstrated the reduced caveolar density at cell membrane and reduced caveolar protein contents. Interestingly, coexisting ROCK1 deficiency in cardiomyocytes can rescue these defects and preserve caveolar compartmentalization of β-adrenergic signaling molecules including β1-adrenergic receptor and type V/VI adenylyl cyclase. In cardiomyocytes and adipocytes, we detected that ROCK1 deficiency increased insulin signaling with increased insulin receptor activation in caveolae. In MEFs, we identified that ROCK1 deficiency increased caveolar and total levels of caveolin-1 and cell membrane repair ability after mechanical or chemical disruptions. Together, these results demonstrate that ROCK1 can regulate caveolae plasticity and multiple functions including compartmentalization of signaling molecules and cell membrane repair following membrane disruption by mechanical force and oxidative damage. These findings provide possible molecular insights into the beneficial effects of ROCK1 deletion/inhibition in cardiomyocytes, adipocytes, and MEFs under certain diseased conditions.

Side Effects of Sulfur‐Based Geoengineering Due To Absorptivity of Sulfate Aerosols

AbstractSulfur‐based stratospheric aerosol intervention (SAI) can cool the climate, but also heats the tropical lower stratosphere if done with injections at low latitudes. We explore the role of this heating in the climate response to SAI, by using mechanistic experiments that remove the effects of longwave absorption of sulfate aerosols above the tropopause. If longwave absorption by stratospheric aerosols is disabled, the heating of the tropical tropopause and most of the related side effects are strongly alleviated and the cooling per Tg‐S injected is 40% bigger. Such side‐effects include the poleward expansion of eddy‐driven jets, acceleration of the stratospheric residual circulation, and delay of Antarctic ozone recovery. Our results add to other recent findings on SAI side effects and demonstrate that SAI scenarios with low‐latitude injections of absorptive materials may result in atmospheric effects and regional climate changes that are comparable to those produced by the CO2 warming signal.

Allyl isothiocyanate, a TRPA1 agonist, protects against olanzapine-induced hypothalamic and hepatic metabolic aberrations in female mice

Olanzapine, a widely prescribed atypical antipsychotic, poses a great risk to the patient’s health by fabricating a plethora of severe metabolic and cardiovascular adverse effects eventually reducing life expectancy and patient compliance. Its heterogenous receptor binding profile has made it difficult to point out a specific cause or treatment for the related side effects. Growing body of evidence suggest that transient receptor potential (TRP) channel subfamily Ankyrin 1 (TRPA1) has pivotal role in pathogenesis of type 2 diabetes and obesity. With this background, we aimed to investigate the role of pharmacological manipulations of TRPA1 channels in antipsychotic (olanzapine)-induced metabolic alterations in female mice using allyl isothiocyanate (AITC) and HC-030031 (TRPA1 agonist and antagonist, respectively). It was found that after 6 weeks of treatment, AITC prevented olanzapine-induced alterations in body weight and adiposity; serum, and liver inflammatory markers; glucose and lipid metabolism; and hypothalamic appetite regulation, nutrient sensing, inflammatory and TRPA1 channel signaling regulating genes. Furthermore, several of these effects were absent in the presence of HC-030031 (TRPA1 antagonist) indicating protective role of TRPA1 agonism in attenuating olanzapine-induced metabolic alterations. Supplementary in-depth studies are required to study TRPA1 channel effect on other aspects of olanzapine-induced metabolic alterations.

The relative effectiveness of conditioning one or two attributes to a brand.

Attribute conditioning refers to the phenomenon that target stimuli acquire specific attributes by pairing them with stimuli possessing these attributes. We apply attribute conditioning to a marketing context where brands are often displayed with stimuli possessing semantic attributes to establish brand-attribute associations. In particular, we examine whether it is more effective from a brand image perspective to associate a brand with only one attribute, two related attributes, or two unrelated attributes. Across four experimental studies, we find that pairing a single attribute (e.g., athletic) with a brand is most effective for building brand-attribute associations and that pairing multiple, related attributes (athletic and healthy) is more effective than pairing multiple, unrelated attributes (athletic and smart). Supplementing this finding, an analysis of observational data from real brands suggests that attributing two orthogonal attributes to a brand is associated with negative effects on marketing-relevant outcomes. Our findings extend previous research on multiattribute conditioning and highlight the importance of the number and relationship between attributes for building effective brand associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparison of Clinical Decision Support Tools to Improve Pediatric Lipid Screening

ObjectiveTo test whether different clinical decision support tools increase clinician orders and patient completions relative to standard practice and each other. Study designA pragmatic, patient-randomized clinical trial in the electronic health record was conducted between October 2019 and April 2020 at Geisinger Health System in Pennsylvania, with four arms: care gap—a passive listing recommending screening; alert—a panel promoting and enabling lipid screen orders; both; and a standard practice—no guideline-based notification—control arm. Data were analyzed for 13,346 9 to 11 year-old patients seen within Geisinger primary care, cardiology, urgent care, or nutrition clinics, or who had an endocrinology visit. Principal outcomes were lipid screening orders by clinicians and completions by patients within one week of orders. ResultsActive (care gap and/or alert) versus control arm patients were significantly more likely (p<.05) to have lipid screening tests ordered and completed, with odds ratios ranging from 1.67 (95% CI: 1.28–2.19) to 5.73 (4.46–7.36) for orders and 1.54 (1.04–2.27) to 2.90 (95% CI: 2.02–4.15) for completions. Alerts, with or without care gaps listed, outperformed care gaps alone on orders, with odds ratios ranging from 2.92 (95% CI: 2.32–3.66) to 3.43 (2.73–4.29). ConclusionsElectronic alerts can increase lipid screening orders and completions, suggesting clinical decision support can improve guideline-concordant screening. The study also highlights electronic record-based patient randomization as a way to determine relative effectiveness of support tools.

The Needle Shield Size and Applied Force of Subcutaneous Autoinjectors Significantly Influence the Injection Depth.

This study examines how shield-triggered autoinjectors (AIs), for subcutaneous drug delivery, affect injection depth. It focuses on shield size and applied force, parameters that could potentially lead to inadvertent intramuscular (IM) injections due to tissue compression. A blinded ex-vivo study was performed to assess the impact of shield size and applied force on injection depth. Shields of 15, 20, and 30 mm diameters and forces from 2 to 10 N were investigated. The study involved 55 injections in three Landrace, Yorkshire, and Duroc (LYD) pigs, with injection depths measured with computed tomography (CT). An in-vivo study, involving 20 injections in three LYD pigs, controlled the findings, using fluoroscopy (FS) videos for depth measurement. The CT study revealed that smaller shield sizes significantly increased injection depth. With a 15 mm diameter shield, 10 N applied force, and 5 mm needle protrusion, the injection depth exceeded the needle length by over 3 mm. Injection depth increased with higher applied forces until a plateau was reached around 8 N. Both applied force and size were significant factors for injection depth (analysis of variance [ANOVA], P < .05) in the CT study. The FS study confirmed the ex-vivo findings in an in-vivo setting. The study demonstrates that shield size has a greater impact on injection depth than the applied force. While conducted in porcine tissue, the study provides useful insights into the relative effects of shield size and applied force. Further investigations in humans are needed to confirm the predicted injection depths for AIs.

Month of Birth and Cognitive Effort: A Laboratory Study of the Relative Age Effect among Fifth Graders

Abstract All around the world, school-entry cohorts are organized on an annual calendar so that the age of students in the same cohort differs by up to one year. It is a well-established finding that this age gap entails a consequential (dis)advantage for academic performance referred to as the relative age effect (RAE). This study contributes to a recent strand of research that has turned to investigate the RAE on non-academic outcomes such as personality traits. An experimental setup is used to estimate the causal effect of monthly age on cognitive effort in a sample of 798 fifth-grade students enrolled in the Spanish educational system, characterized by strict enrolment rules. Participants performed three different real-effort tasks under three different incentive conditions: no rewards; material rewards; and material and status rewards. We observe that older students outwork their youngest peers by two-fifths of a standard deviation, but only when material rewards for performance are in place. Despite the previously reported higher taste for competition among the older students within a school-entry cohort, we do not find that the RAE on cognitive effort increases after inducing competition for peer recognition. Finally, the study also provides suggestive evidence of a larger RAE among boys and students from lower social strata. Implications for sociological research on educational inequality are discussed. To conclude, we outline policy recommendations such as implementing evaluation tools that nudge teachers toward being mindful of relative age differences.

Revisiting the complex time-varying effect of non-pharmaceutical interventions on COVID-19 transmission in the United States.

Although the global COVID-19 emergency ended, the real-world effects of multiple non-pharmaceutical interventions (NPIs) and the relative contribution of individual NPIs over time were poorly understood, limiting the mitigation of future potential epidemics. Based on four large-scale datasets including epidemic parameters, virus variants, vaccines, and meteorological factors across 51 states in the United States from August 2020 to July 2022, we established a Bayesian hierarchical model with a spike-and-slab prior to assessing the time-varying effect of NPIs and vaccination on mitigating COVID-19 transmission and identifying important NPIs in the context of different variants pandemic. We found that (i) the empirical reduction in reproduction number attributable to integrated NPIs was 52.0% (95%CI: 44.4, 58.5%) by August and September 2020, whereas the reduction continuously decreased due to the relaxation of NPIs in following months; (ii) international travel restrictions, stay-at-home requirements, and restrictions on gathering size were important NPIs with the relative contribution higher than 12.5%; (iii) vaccination alone could not mitigate transmission when the fully vaccination coverage was less than 60%, but it could effectively synergize with NPIs; (iv) even with fully vaccination coverage >60%, combined use of NPIs and vaccination failed to reduce the reproduction number below 1 in many states by February 2022 because of elimination of above NPIs, following with a resurgence of COVID-19 after March 2022. Our results suggest that NPIs and vaccination had a high synergy effect and eliminating NPIs should consider their relative effectiveness, vaccination coverage, and emerging variants.

Development of an Untargeted LC-MS Metabolomics Method with Postcolumn Infusion for Matrix Effect Monitoring in Plasma and Feces.

Untargeted metabolomics based on reverse phase LC-MS (RPLC-MS) plays a crucial role in biomarker discovery across physiological and disease states. Standardizing the development process of untargeted methods requires paying attention to critical factors that are under discussed or easily overlooked, such as injection parameters, performance assessment, and matrix effect evaluation. In this study, we developed an untargeted metabolomics method for plasma and fecal samples with the optimization and evaluation of these factors. Our results showed that optimizing the reconstitution solvent and sample injection amount was critical for achieving the balance between metabolites coverage and signal linearity. Method validation with representative stable isotopically labeled standards (SILs) provided insights into the analytical performance evaluation of our method. To tackle the issue of the matrix effect, we implemented a postcolumn infusion (PCI) approach to monitor the overall absolute matrix effect (AME) and relative matrix effect (RME). The monitoring revealed distinct AME and RME profiles in plasma and feces. Comparing RME data obtained for SILs through postextraction spiking with those monitored using PCI compounds demonstrated the comparability of these two methods for RME assessment. Therefore, we applied the PCI approach to predict the RME of 305 target compounds covered in our in-house library and found that targets detected in the negative polarity were more vulnerable to the RME, regardless of the sample matrix. Given the value of this PCI approach in identifying the strengths and weaknesses of our method in terms of the matrix effect, we recommend implementing a PCI approach during method development and applying it routinely in untargeted metabolomics.

Effect of inclusion of zinc-glycine chelate and zinc sulphate on live performance, immunity and lipid peroxidation in broilers

ABSTRACT Zinc (Zn) is a biologically significant trace mineral, serving as a cofactor in various metabolic functions. This study aimed to assess the relative effectiveness of organic and inorganic Zn on the growth performance, lipid peroxidation and humoral immune response in broiler chickens (Ross 308). A total of 450 d-old broilers were divided into five groups: the control group, a group receiving a basal diet with 50 mg/kg organic Zn (T1), another with 60 mg/kg organic Zn (T2), and two groups with basal diets supplemented with inorganic Zn at rates of 50 and 60 mg/kg zinc sulfate for the fourth (T3) and fifth (T4) groups, respectively. The experiment spanned 35 days. Results indicated that zootechnical characteristics such as weekly weight gain, feed intake, feed conversion ratio and dressing percentage were significantly higher (P < 0.05) in T1 compared to both the control and the inorganic Zn supplementation groups. Additionally, the antibody titre against Newcastle disease was significantly (P < 0.05) elevated, while malondialdehyde (MDA) levels were significantly (P < 0.05) lower in T1 and T2 compared to the control and the inorganic Zn supplementation groups. In conclusion, broilers supplemented with 50 mg/kg organic Zn exhibited significantly improved growth performance, reduced MDA levels, and enhanced humoral immune response.

Does crouch alter the effects of neuromuscular impairments on gait? A simulation study

Cerebral palsy (CP) is a neurologic injury that impacts control of movement. Individuals with CP also often develop secondary impairments like weakness and contracture. Both altered motor control and secondary impairments influence how an individual walks after neurologic injury. However, understanding the complex interactions between and relative effects of these impairments makes analyzing and improving walking capacity in CP challenging. We used a sagittal-plane musculoskeletal model and neuromuscular control framework to simulate crouch and nondisabled gait. We perturbed each simulation by varying the number of synergies controlling each leg (altered control), and imposed weakness and contracture. A Bayesian Additive Regression Trees (BART) model was also used to parse the relative effects of each impairment on the muscle activations required for each gait pattern. By using these simulations to evaluate gait-pattern specific effects of neuromuscular impairments, we identified some advantages of crouch gait. For example, crouch tolerated 13 % and 22 % more plantarflexor weakness than nondisabled gait without and with altered control, respectively. Furthermore, BART demonstrated that plantarflexor weakness had twice the effect on total muscle activity required during nondisabled gait than crouch gait. However, crouch gait was also disadvantageous in the presence of vasti weakness: crouch gait increased the effects of vasti weakness on gait without and with altered control. These simulations highlight gait-pattern specific effects and interactions between neuromuscular impairments. Utilizing computational techniques to understand these effects can elicit advantages of gait deviations, providing insight into why individuals may select their gait pattern and possible interventions to improve energetics.