Use of Hybrid Stage I to Stratify Between Single Ventricle Palliation and Biventricular Repair.

Background: Hybrid stage I palliation (HS1P) has been utilized for patients with single ventricle (SV) congenital heart disease (CHD). To date, reports on the use of HS1P for other indications including biventricular (BiV) CHD have been limited. Methods: We performed a single-center retrospective cohort study of patients who underwent HS1P with an anticipated physiologic outcome of BiV repair, or with an undetermined SV versus BiV outcome. Patient characteristics and outcomes from birth through definitive repair or palliation were collected and reported with descriptive statistics. Results: Nineteen patients underwent HS1P with anticipated BiV repair. Extracardiac and intracardiac risk factors (ICRF) were common. Ultimately, 13 (68%) patients underwent BiV repair, 1 (5%) underwent SV palliation, and 5 (26%) died prior to further palliation or repair. Resolution of ICRF tracked with BiV outcome (6/6, 100%), persistence of ICRF tracked with SV outcome or death (3/3, 100%). Twenty patients underwent HS1P with an undetermined outcome. Ultimately, 13 (65%) underwent BiV repair, 6 (30%) underwent SV palliation, and 1 (5%) underwent transplant. There were no deaths. Intracardiac risk factors were present in 15 of 20 patients (75%); BiV repair only occurred when all ICRF resolved (67%). Post-HS1P complications and reinterventions occurred frequently in both groups, through all phases of care. Conclusions: Hybrid stage 1 palliation can be used to defer BiV repair and to delay decision between SV palliation and BiV repair. Resolution of ICRF was associated with ultimate outcome. In this high-risk group, complications are common, and mortality especially in the marginal BiV patient is high.

Accounting for regression to the mean under the bivariate t-distribution.

Regression to the mean occurs when an unusual observation is followed by a more typical outcome closer to the population mean. In pre- and post-intervention studies, treatment is administered to subjects with initial measurements located in the tail of a distribution, and a paired sample t-test can be utilized to assess the effectiveness of the intervention. The observed change in the pre-post means is the sum of regression to the mean and treatment effects, and ignoring regression to the mean could lead to erroneous conclusions about the effectiveness of the treatment effect. In this study, formulae for regression to the mean are derived, and maximum likelihood estimation is employed to numerically estimate the regression to the mean effect when the test statistic follows the bivariate t-distribution based on a baseline criterion or a cut-off point. The pre-post degrees of freedom could be equal but also unequal such as when there is missing data. Additionally, we illustrate how regression to the mean is influenced by cut-off points, mixing angles which are related to correlation, and degrees of freedom. A simulation study is conducted to assess the statistical properties of unbiasedness, consistency, and asymptotic normality of the regression to the mean estimator. Moreover, the proposed methods are compared with an existing one assuming bivariate normality. The p-values are compared when regression to the mean is either ignored or accounted for to gauge the statistical significance of the paired t-test. The proposed method is applied to real data concerning schizophrenia patients, and the observed conditional mean difference called the total effect is decomposed into the regression to the mean and treatment effects.

Current trends and obstacles in off-the-job nursing ethics training in Japanese hospitals: a cross-sectional study.

Objectives: This study aims to fill the existing gap by examining the current status of off-the-job nursing ethics training in large hospitals in Japan and its integration with on-the-job training to provide targeted insights for enhancing future ethics training. Method: A cross-sectional study was conducted among the nursing education staff of large Japanese hospitals [N=309] by self-administered questionnaire. The questionnaire was the following main points 1) current trends in nursing ethics training 2) planners' concerns, and 3) the link between training and clinical practice. Descriptive statistics were used, closed-ended questions were analyzed through simple tabulations while open-ended questions underwent textual analysis. Results: The hospitals of 76.6% (309) conducted off-the-job nursing ethics training. Their training consists of a combination of lectures and exercises. The focus was to raise nurses' awareness of ethical problems or improve their analytical ability. The objectives were to be able to participate in discussions from an ethical perspective. The main problems were the lack of connection with on-the-job, and a shortage of training personnel. Conclusions: The key to providing off-the-job and on-the-job is to create a mechanism for circulation. The implications of the results are the necessity of constructing ethics education in medicine to develop medical professionals who can discuss and act from ethical perspectives. Future research is expected to include the creation of a multidisciplinary ethics training program for the hospital.

Leachate reduction and pollution control strategies for landfills in hilly areas based on site condition analysis and numerical simulation.

Landfill is an important means of municipal solid waste treatment. Previous studies have shown that the combination of "cut-off wall and pumping well" technology is an effective measure to deal with the leachate emission reduction and pollution control of landfill, and has been widely used in plain areas. However, for landfills in hilly areas with complex terrain and geological conditions, there is still a lack of clear and referable ideas and operational strategies for leachate emission reduction and pollution control. In this study, we proposed strategies for determining the position and depth of cut-off walls and pumping wells and reasonable combinations of the cut-off wall depth and pumping quantity for leachate reduction and pollution prevention of landfills in hilly areas. The determination of leachate reduction and pollution control strategy need to be achieved in two stages, qualitative and quantitative: (1) In the qualitative stage, the natural conditions (Weathering degree, groundwater flow characteristics, topography condition, hydrometeor condition, and aquifer thickness) and engineering conditions (Operation status, landfill location, and excavation status) of the study area are analysed in detail, and then the depth range and location of the cut-off wall and pumping well are determined. (2) In the quantitative stage, we need to quantify the combination of the cut-off wall depth and pumping quantity by using profile particle tracing and pollutant transport modelling. A reasonable cut-off wall depth needs to control the leakage of pollutants inside the wall, and a reasonable pumping quantity needs to ensure that the depth of the pollutant distribution is equivalent to the depth of the separation line, which separates the water flow towards the pumping well and the water flow downstream. (3) The effectiveness of the leachate reduction and prevention strategies proposed in this study was verified through an example of a landfill in Northeast China. This study provides a reference and operation method for leachate emission reduction and pollution control of landfills in hilly areas.

Efficacy and safety evaluation of cross-reactive Fibroblast activation protein scFv-based CAR-T cells.

Introduction: Fibroblast activation protein (FAP) overexpression on cancer-associated fibroblasts (CAFs) is associated with poor prognosis and worse clinical outcomes. Selective ablation of pro-tumorgenic FAP+ stromal cells with CAR-T cells may be a new therapeutic strategy. However, the clinical use of FAP-CAR T cells is suggested to proceed with caution for occasional poor efficacy and induction of on-target off-tumor toxicity (OTOT), including lethal osteotoxicity and cachexia. Hence, more investigations and preclinical trials are required to optimize the FAP-CAR T cells and to approve their safety and efficacy. Methods: In this study, we designed second-generation CAR T cells targeting FAP with 4-1BB as a co-stimulatory molecule, and tested their cytotoxicity against FAP-positive cells (hFAP-HT1080 cells and a variety of primary CAFs) in vitro and in Cell line-derived xenograft (CDX) and a patient-derived xenograft (PDX) model. Results: Results showed that our FAP-CAR T cells were powerfully potent in killing human and murine FAP-positive tumor cells and CAFs in multiple types of tumors in BALB/c and C57BL/6 mice and in patient-derived xenografts (PDX) model. And they were proved to be biologically safe and exhibit low-level OTOT. Discussion: Taken together, the human/murine cross-reactive FAP-CAR T cells were powerfully potent in killing human and murine FAP positive tumor cells and CAFs. They were biologically safe and exhibit low-level OTOT, warranting further clinical investigation into our FAP-CAR T cells.

[Current state and future prospects of off-the-shelf allogeneic CAR NK therapy].

Chimeric antigen receptor-transduced autologous T (CAR-T) cell therapy targeting CD19 has revolutionized the treatment of CD19-positive hematological tumors, including acute lymphoblastic leukemia and large B-cell lymphoma. However, despite the high response rate, many problems such as exceedingly high cost, complex logistics, insufficient speed, and manufacturing failures have become apparent. One solution for these problems is to use an allogeneic cell as an effector cell for genetic modification with CAR. Allogeneic, or "off-the-shelf", CAR-expressing immune-effector cells include 1) genome-edited, T-cell receptor (TCR) gene-deleted CAR-T cells generated using healthy adult donor T cells, 2) induced pluripotent stem cell-derived CAR-T cells, and 3) CAR NK cells. NK cells are notorious for their poor ex-vivo expansion and low susceptibility to genetic modification. In this article, I will review the current state and future prospects of allogeneic CAR cell therapies, with special reference to CAR NK cells.

Cut-off value of glycated hemoglobin A1c for detecting diabetic retinopathy in the Chinese population.

BACKGROUND: Glycated hemoglobin A1c (HbA1c) is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and convenience. However, the effect of HbA1c on diabetic retinopathy (DR) in the Han and Korean populations in Jilin, China, remains inconclusive. AIM: To determine the best cut-off of HbA1c for diagnosing DR among the Chinese. METHODS: This cross-sectional study included 1933 participants from the Yanbian area of Jilin Province, China. Trained investigators employed a questionnaire-based survey, physical examination, laboratory tests, and fundus photography for the investigation. The best cut-off value for HbA1c was established via the receiver operating characteristic curve. The factors associated with HbA1c-associated risk factors were determined via linear regression. RESULTS: The analysis included 887 eligible Chinese Han and Korean participants, 591 of whom were assigned randomly to the training set and 296 to the validation set. The prevalence of DR was 3.27% in the total population. HbA1c of 6.2% was the best cut-off value in the training set, while it was 5.9% in the validation set. In both Chinese Han and Korean populations, an HbA1c level of 6.2% was the best cut-off value. The optimal cut-off values of fasting blood glucose (FBG) ≥ 7 mmol/L and < 7 mmol/L were 8.1% and 6.2% respectively in Han populations, while those in Korean populations were 6.9% and 5.3%, respectively. Age, body mass index, and FBG were determined as the risk factors impacting HbA1c levels. CONCLUSION: HbA1c may serve as a useful diagnostic indicator for DR. An HbA1c level of 6.2% may be an appropriate cut-off value for DR detection in the Chinese population.

Electron transport through two interacting channels in Azurin-based solid-state junctions.

The fundamental question of "what is the transport path of electrons through proteins?" initially introduced while studying long-range electron transfer between localized redox centers in proteins in vivo is also highly relevant to the transport properties of solid-state, dry metal-protein-metal junctions. Here, we report conductance measurements of such junctions, Au-(Azurin monolayer ensemble)-Bismuth (Bi) ones, with well-defined nanopore geometry and ~103 proteins/pore. Our results can be understood as follows. (1) Transport is via two interacting conducting channels, characterized by different spatial and time scales. The slow and spatially localized channel is associated with the Cu center of Azurin and the fast delocalized one with the protein's polypeptide matrix. Transport via the slow channel is by a sequential (noncoherent) process and in the second one by direct, off-resonant tunneling. (2) The two channels are capacitively coupled. Thus, with a change in charge occupation of the weakly coupled (metal center) channel, the broad energy level manifold, responsible for off-resonance tunneling, shifts, relative to the electrodes' Fermi levels. In this process, the off-resonance (fast) channel dominates transport, and the slow (redox) channel, while contributing only negligibly directly, significantly affects transport by intramolecular gating.

Effect of yeast (Saccharomyces cerevisiae) fermentation on conformational changes in pig liver proteins and their ability to bind to characteristic aldehydes.

This study aimed to explore the potential of a fermentation technology to reduce off-flavour perception and its underlying mechanisms. Results revealed that yeast fermentation (YF) significantly ameliorated the off-flavour of pig liver (p < 0.05). Specifically, YF pre-treatment decreased the relative abundance of α-helix and fluorescence intensity while increasing the surface hydrophobicity and SS level and loosening the microstructure of myofibrillar proteins (MPs) in pig liver. Additionally, the appropriate fermentation treatments enhanced the MP-aldehyde binding capacity by 0.25-1.30 times, demonstrating that YF-induced conformational modifications in pig liver proteins made them more prone to interacting with characteristic aldehydes. Moreover, molecular docking results confirmed that hydrophobic interactions are the primary drivers of MP-aldehyde binding. These findings suggest that YF technology holds immense promise for modulating off-flavour perception in liver products by altering protein conformation.

The peptide-based bispecific CAR T cells target EGFR and tumor stroma for effective cancer therapy.

BACKGROUND AND PURPOSE: The efficacy of chimeric antigen receptor (CAR)-T cell for solid tumors is limited partially because of the lack of tumor-specific antigens and off-target effects. Low molecular weight peptides allowed CAR T cell to display several antigen receptors to reduce off-target effects. Here, we develop a peptide-based bispecific CAR for EGFR and tumor stroma, which are expressed in a variety of tumor types. EXPERIMENTAL APPROACH AND KEY RESULTS: The peptide-based CAR T cells show excellent proliferation, cytotoxicity activity and are only activated by tumor cells overexpressing EGFR instead of normal cells with low EGFR expressing. In mouse xenograft models, the peptide bispecific CAR T cells can be delivered into the inner of tumor masses and thus are effective in inhibiting tumor growth. Meanwhile, they show strong expansion capacity and the property of maintaining long-term function in vivo. During treatment, no off-tumor toxicity is observed on healthy organs expressing lower levels of EGFR. CONCLUSIONS & IMPLICATIONS: Our findings demonstrate that peptide-based bispecific CAR T holds great potential in solid tumor therapy due to an excellent targeting ability towards tumors and tumor microenvironment.

Electron Delocalization Disentangles Activity-Selectivity Trade-Off of Transition Metal Phosphide Catalysts in Oxidative Desulfurization.

Breaking the activity-selectivity trade-off has been a long-standing challenge in catalysis. Here, we proposed a nanoheterostructure engineering strategy to overcome the trade-off in metal phosphide catalysts for the oxidative desulfurization (ODS) of fuels. Experimental and theoretical results demonstrated that electron delocalization was the key driver to simultaneously achieve high activity and high selectivity for the molybdenum phosphide (MoP)/tungsten phosphide (WP) nanoheterostructure catalyst. The electron delocalization not only promoted the catalytic pathway transition from predominant radicals to singlet oxygens in H2O2 activation but also simultaneously optimized the adsorption of reactants and intermediates on Mo and W sites. The presence of such dual-enhanced active sites ideally compensated for the loss of activity due to the nonradical catalytic pathway, consequently disentangling the activity-selectivity trade-off. The resulting catalyst (MoWP2/C) unprecedentedly achieved 100% removal of thiophenic compounds from real diesel at an initial concentration of 2676 ppm of sulfur with a high turnover frequency (TOF) of 105.4 h-1 and a minimal O/S ratio of 4. This work provides fundamental insight into the structure-activity-selectivity relationships of heterogeneous catalysts and may inspire the development of high-performance catalysts for ODS and other catalytic fields.

Discovery of novel disease-causing mutation in SSBP1 and its correction using adenine base editor to improve mitochondrial function.

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.Arg91Gln) in single-stranded DNA-binding protein 1 (SSBP1), a crucial protein involved in mtDNA replisome. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy. This mutation impeded multimer formation and DNA-binding affinity, leading to reduced efficiency of mtDNA replication, altered mitochondria dynamics, and compromised mitochondrial function. To correct this mutation, we tested two adenine base editor (ABE) variants on patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), showed higher editing efficacy (≤30%) and enhanced mitochondrial replication and function, despite off-target editing frequencies; however, risks from bystander editing were limited due to silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (≤10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. Taken together, base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated with SSBP1 mutations.

Machine Learning Prediction of On/Off Target-driven Clinical Adverse Events.

OBJECTIVE: Currently, 90% of clinical drug development fails, where 30% of these failures are due to clinical toxicity. The current extensive animal toxicity studies are not predictive of clinical adverse events (AEs) at clinical doses, while current computation models only consider very few factors with limited success in clinical toxicity prediction. We aimed to address these issues by developing a machine learning (ML) model to directly predict clinical AEs. METHODS: Using a dataset with 759 FDA-approved drugs with known AEs, we first adapted the ConPLex ML model to predict IC 50 values of these FDA-approved drugs against their on-target and off-target binding among 477 protein targets. Subsequently, we constructed a new ML model to predict clinical AEs using IC 50 values of 759 drugs' primary on-target and off-target effects along with tissue-specific protein expression profiles. RESULTS: The adapted ConPLex model predicted drug-target interactions for both on- and off-target effects, as shown by co-localization of the 6 small molecule kinase inhibitors with their respective kinases. The coupled ML models demonstrated good predictive capability of clinical AEs, with accuracy over 75%. CONCLUSIONS: Our approach provides a new insight into the mechanistic understanding of in vivo drug toxicity in relationship with drug on-/off-target interactions. The coupled ML models, once validated with larger datasets, may offer advantages to directly predict clinical AEs using in vitro/ex vivo and preclinical data, which will help to reduce drug development failure due to clinical toxicity.

Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A2 and mitochondrial respiration.

Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1) which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid ß-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize etomoxir to etomoxir-carnitine (ETO-carnitine) prior to nearly complete etomoxir-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine structure. On the basis of these data, ETO-carnitine was successfully differentiated from isobaric structures (e.g., 3-hydroxy-C18:0 carnitine and 3-hydroxy-C18:1 carnitine). Mechanistically, generation of ETO-carnitine from mitochondria required exogenous Mg2+, ATP or ADP, CoASH, and L-carnitine indicating that thioesterification by long-chain acyl-CoA synthetase to form ETO-CoA precedes its conversion to ETO-carnitine by CPT1. CPT1-dependent generation of ETO-carnitine was substantiated by an orthogonal approach using ST1326 (a CPT1 inhibitor) which effectively inhibits mitochondrial ETO-carnitine production. Surprisingly, purified ETO-carnitine potently inhibited calcium-independent PLA2γ and PLA2ß as well as mitochondrial respiration independent of CPT1. Robust production and release of ETO-carnitine from HepG2 cells incubated in the presence of ETO was also demonstrated. Collectively, this study identifies the chemical mechanism for the biosynthesis of a novel pharmaco-metabolite of etomoxir, ETO-carnitine, that is generated by CPT1 in mitochondria and likely impacts multiple downstream (non-CPT1 related) enzymes and processes in multiple subcellular compartments.

Modelling take-off moment arms in an ornithocheiraean pterosaur.

Take-off is a vital part of powered flight which likely constrains the size of birds, yet extinct pterosaurs are known to have reached far larger sizes. Three different hypothesised take-off motions (bipedal burst launching, bipedal countermotion launching, and quadrupedal launching) have been proposed as explanations for how pterosaurs became airborne and circumvented this proposed morphological limit. We have constructed a computational musculoskeletal model of a 5 m wingspan ornithocheiraean pterosaur, reconstructing thirty-four key muscles to estimate the muscle moment arms throughout the three hypothesised take-off motions. Range of motion constrained hypothetical kinematic sequences for bipedal and quadrupedal take-off motions were modelled after extant flying vertebrates. Across our simulations we did not find higher hindlimb moment arms for bipedal take-off motions or noticeably higher forelimb moment arms in the forelimb for quadrupedal take-off motions. Despite this, in all our models we found the muscles utilised in the quadrupedal take-off have the largest total launch applicable moment arms throughout the entire take-off sequences and for the take-off pose. This indicates the potential availability of higher leverage for a quadrupedal take-off than hypothesised bipedal motions in pterosaurs pending further examination of muscle forces.

Comparative mitogenomics of marine angelfishes (F: Pomacanthidae).

The targeted capture of ultraconserved elements (UCEs) has substantially increased the amount of genetic data available for phylogenomic reconstructions. These capture datasets frequently contain mitochondrial DNA as a by-product, often in the form of complete mitogenomes. These can be efficiently harvested to expand existing datasets without additional costs. Here, we present new mitochondrial genomes for six marine angelfish species (F: Pomacanthidae), assembled and annotated from off-target UCE reads. We provide the first comparative analysis of all mitochondrial genomes available for the Pomacanthidae. Results showed that the average length of pomacanthid mitogenomes is 16.8 kbp. Total GC and AT content varied between 44.5% and 46.3%, and 53.7% and 55.5%, respectively. The architecture of angelfish mitogenomes was comparable to that seen in other fish species with 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes and the control region. All 13 PCGs evolved under purifying selection, highlighting a high level of selection pressure and gene expression to preserve genetic integrity. The ND6 and ATP8 genes had the highest ratio of non-synonymous (dN) to synonymous (dS) substitutions, indicating a relaxation of purifying selection constraints. Finally, these newly assembled mitogenomes will allow further investigations of the population genetics, systematics and evolutionary biology of one of the most prominent reef fish family in the aquarium trade.

Setting epidemiological cut-off values relevant to MIC and disc diffusion data for Aeromonas salmonicida generated by a standard method.

The Clinical and Laboratory Standards Institute has published epidemiological cut-off values for susceptibility data generated at 22°°C and read after 44-48 h for florfenicol, oxolinic acid and oxytetracycline against Aeromonas salmonicida. The cut-off values for the minimum inhibitory concentration (MIC) and disc diffusion were derived from data obtained by 1 laboratory and 2 laboratories respectively. The present work reports the generation of susceptibility data from additional laboratories and the calculation of provisional cut-off values from aggregations of these data with previously published data. With respect to MIC data, the provisional cut-off values, derived from aggregations of the data from 4 laboratories, were ≤4 µg ml-1 for florfenicol, ≤0.0625 µg ml-1 for oxolinic acid and ≤1 µg ml-1 for oxytetracycline. For disc diffusion data, the provisional cut-off values derived from aggregations of the data from 5 laboratories were ≥30 mm for florfenicol, ≥32 mm for oxolinic acid and ≥25 mm for oxytetracycline. In addition, a cut-off value of ≥29 mm for ampicillin was derived from the aggregation of data from 4 laboratories.

Peptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity.

Although CRISPR-Cas9 gene therapies have proven to be a powerful tool across many applications, improvements are necessary to increase the specificity of this technology. Cas9 cutting in off-target sites remains an issue that limits CRISPR's application in human-based therapies. Treatment of autosomal dominant diseases also remains a challenge when mutant alleles differ from the wild-type sequence by only one base pair. Here, we utilize synthetic peptide nucleic acids (PNAs) that bind selected spacer sequences in the guide RNA (gRNA) to increase Cas9 specificity up to 10-fold. We interrogate variations in PNA length, binding position, and degree of homology with the gRNA. Our findings reveal that PNAs bound in the region distal to the protospacer adjacent motif (PAM) site effectively enhance specificity in both on-target/off-target and allele-specific scenarios. In addition, we demonstrate that introducing deliberate mismatches between PNAs bound in the PAM-proximal region of the gRNA can modulate Cas9 activity in an allele-specific manner. These advancements hold promise for addressing current limitations and expanding the therapeutic potential of CRISPR technology.

Improving the estimation of countermovement jump height from force plate recordings by considering the interaction between multiple procedural steps: An optimisation approach.

Force plates are used as standalone measurement systems in research and practice to evaluate metrics such as jump height. Calculating jump height involves multiple procedural steps, but previous investigations aiming to improve calculation procedures have only considered the influence of a single procedural step in isolation. The purpose of this study was to investigate if considering the interacting influence of multiple procedural steps in conjunction would impact the accuracy of jump height calculated from force plate recordings. An optimisation procedure was used to determine the combination of filter type, filter order, filter cut-off, integration start point and instant of take-off, that would minimize the root mean squared difference between force plate calculated jump height and a kinematic criterion. The best filter approach was a fifth order Butterworth filter with a 6 Hz cut-off frequency or a third order Chebyshev filter with a 5 Hz cut-off frequency. The best starting point for integration was approximately 0.25 s prior to the onset of the jump and the instant of take-off was best identified by finding the first instant that the force-time signal decreased by the magnitude of system weight. The presented optimisation technique provides an improved quantitative approach to develop standard procedures.