Investigation of Head Kinematics and Brain Strain Response During Soccer Heading Using a Custom-Fit Instrumented Mouthguard.

Association football, also known as soccer in some regions, is unique in encouraging its participants to intentionally use their head to gain a competitive advantage, including scoring a goal. Repetitive head impacts are now being increasingly linked to an inflated risk of developing long-term neurodegenerative disease. This study investigated the effect of heading passes from different distances, using head acceleration data and finite element modelling to estimate brain injury risk. Seven university-level participants wore a custom-fitted instrumented mouthguard to capture linear and angular acceleration-time data. They performed 10 headers within a laboratory environment, from a combination of short, medium, and long passes. Kinematic data was then used to calculate peak linear acceleration, peak angular velocity, and peak angular acceleration as well as two brain injury metrics: head injury criterion and rotational injury criterion. Six degrees of freedom acceleration-time data were also inputted into a widely accepted finite element brain model to estimate strain-response using mean peak strain and cumulative strain damage measure values. Five headers were considered to have a 25% concussion risk. Mean peak linear acceleration equalled 26 ± 7.9 g, mean peak angular velocity 7.20 ± 2.18 rad/s, mean peak angular acceleration 1730 ± 611 rad/s2, and 95th percentile mean peak strain 0.0962 ± 0.252. Some of these data were similar to brain injury metrics reported from American football, which supports the need for further investigation into soccer heading.

Fluorescent azobenzene-confined coiled-coil mesofibers.

Fluorescent protein biomaterials have important applications such as bioimaging in pharmacological studies. Self-assembly of proteins, especially into fibrils, is known to produce fluorescence in the blue band. Capable of self-assembly into nanofibers, we have shown we can modulate its aggregation into mesofibers by encapsulation of a small hydrophobic molecule. Conversely, azobenzenes are hydrophobic small molecules that are virtually non-fluorescent in solution due to their highly efficient photoisomerization. However, they demonstrate fluorogenic properties upon confinement in nanoscale assemblies by reducing the non-radiative photoisomerization. Here, we report the fluorescence of a hybrid protein-small molecule system in which azobenzene is confined in our protein assembly leading to fiber thickening and increased fluorescence. We show our engineered protein Q encapsulates AzoCholine, bearing a photoswitchable azobenzene moiety, in the hydrophobic pore to produce fluorescent mesofibers. This study further investigates the photocontrol of protein conformation as well as fluorescence of an azobenze-containing biomaterial.

Brain trauma exposure for American tackle football players 5 to 9 and 9 to 14 years of age.

American football helmets used by youth players are currently designed and tested to the same standards as professionals. The National Operating Committee on Standard and Safety requested research aiming at understanding the differences in brain trauma in youth American football for players aged five to nine and nine to fourteen years old to inform a youth specific American football standard. Video analysis and laboratory reconstructions of head impacts were undertaken to measure differences in head impact frequency, event types, and magnitudes of maximum principal strain (MPS) for the two age groups. Overall frequencies and frequencies for five categories of MPS representing different magnitudes of risk were tabulated. The MPS categories were very low (<0.08), low (0.08-0.169), medium (0.17-0.259), high (0.26-0.349) and very high (>0.35). Both cohorts experienced a majority of head impacts (>56%) at very low magnitude of MPS. Youth American football players aged 9-14 yrs. sustained a greater frequency of head impacts at MPS between 0.08 and 0.169 % associated with changes in brain structure and function. There were no differences in overall frequency, or in frequency of head impacts in other categories of MPS. The proportion of impacts considered injurious (MPS > 0.08) was greater in the 5-9 group (44%), than the 9-14 group (39%), and impacts above 0.35 % were only reported for the younger age group. The larger helmet-to-shoulder ratio in the younger age groups may have contributed to this finding suggesting that youth American football players under the age of nine would benefit from a child-specific football helmet.

Education: A compassionate use of cefiderocol to treat osteomyelitis caused by an XDR Pseudomonas aeruginosa.

We report a 59-year-old male with left leg osteomyelitis caused by an XDR Pseudomonas aeruginosa strain following a road traffic accident. Limited treatment options and adverse antimicrobial reaction led to consideration of cefiderocol together with appropriate surgical intervention. Improved bony remodelling over the tibia and fibula was observed with good bony alignment and no adverse features. Physiotherapy support was continued for 4 months following treatment, which resulted in good functional mobility, improved proprioception and full ability to bear weight. This case also adds to multiple reports that describe safe and successful use of cefiderocol to treat MDR, aerobic Gram-negative infections.

Prediction of improved therapeutics for fabry disease patients generated by mutagenesis of the α-galactosidase A active site, dimer interface, and glycosylation region.

Fabry disease is an X-linked lysosomal storage disorder caused by the deficiency of the enzyme, α-galactosidase A that induces the accumulation of the substrate globotriaosylceramide. Currently approved enzyme replacement therapy using recombinant human α-galactosidase A improves patient symptoms but a majority of patients experience adverse events due to the multiple infusions required for full therapeutic efficacy. Our approach is to use medicinal chemistry and phylogenic comparisons to introduce mutations into the human enzyme to increase catalytic activity and/or stability to generate an improved therapeutic enzyme that may require fewer infusions. We designed mutations at three regions of the human α-galactosidase A: the active site, the dimer interface, and a site for glycosylation. The M208E mutation, adjacent to the Y207 active site residue, increased enzyme activity 3.01-fold. This mutation introduced a charged Glu residue that is adjacent to the Y207 active site residue and close to a site of N-glycosylation. The W277C mutation, designed to promote dimer stability, introduced a strong thiol-aromatic interaction (Cys-Phe) at the dimer interface and increased activity 2.31-fold. The W277C and M208E mutations modify the structure of the enzyme into forms with enhanced thermal stability 3.7- and 3.9-fold, respectively and positive cooperativity resulting in increased Hill coefficient from 1.0 to 4.60 and 3.47, respectively. Enhanced thermal stability and positive cooperativity predict improved in vivo activity and superior therapeutic properties. Our results demonstrate the value of in vitro mutagenesis for α-galactosidase A and support future perspectives to validate these results in Fabry disease patients.

γ-Secretase Partitioning into Lipid Bilayers Remodels Membrane Microdomains after Direct Insertion.

γ-Secretase is a multisubunit complex that catalyzes intramembranous cleavage of transmembrane proteins. The lipid environment forms membrane microdomains that serve as spatio-temporal platforms for proteins to function properly. Despite substantial advances in the regulation of γ-secretase, the effect of the local membrane lipid microenvironment on the regulation of γ-secretase is poorly understood. Here, we characterized and quantified the partitioning of γ-secretase and its substrates, the amyloid precursor protein (APP) and Notch, into lipid bilayers using solid-supported model membranes. Notch substrate is preferentially localized in the liquid-disordered (Ld) lipid domains, whereas APP and γ-secretase partition as single or higher complex in both phases but highly favor the ordered phase, especially after recruiting lipids from the ordered phase, indicating that the activity and specificity of γ-secretase against these two substrates are modulated by membrane lateral organization. Moreover, time-elapse measurements reveal that γ-secretase can recruit specific membrane components from the cholesterol-rich Lo phase and thus creates a favorable lipid environment for substrate recognition and therefore activity. This work offers insight into how γ-secretase and lipid modulate each other and control its activity and specificity.

Renal nitrate clearance in chronic kidney disease.

BACKGROUND: Nitric oxide (NO) is rapidly oxidised in humans to nitrite and nitrate, with nitrate being present in much greater abundance. These oxidation products can be recycled back into nitric oxide via a complex entero-salivary pathway, thus preserving NO activity. Approximately 65% of circulating nitrate is excreted in the urine in 48 h, with the excretory pathway of the remainder unknown. The effect of declining renal function on nitrate clearance is unknown METHODS: Forty five subjects, 21 M, 24F, median age 69 (range 27-75 years) with renal function assessed by CKD-EPI eGFR between 9 and 89 ml/min/1.73 m2 completed the study. Following a 24 h low nitrate diet a microplate spectrophotometric method was employed to measure plasma nitrate concentration and 24 h urinary nitrate excretion were measured to determine renal nitrate clearance. RESULTS: There was a strong positive correlation between urinary nitrate clearance and eGFR, (Spearman R = 0.7665, p < 0.0001) with a moderate negative correlation between plasma nitrate concentration and CKD-EPI eGFR, (Spearman's R = -0.37, p = 0.012). There was a trend between fractional excretion of nitrate and CKD-EPI eGFR (ml/min/1.73 m2) Spearman's R 0.27, p = 0.07 though this did not reach statistical significance. Plasma nitrate concentration and serum creatinine concentration were positively correlated, Spearman's R = 0.39, p = 0.008. CONCLUSIONS: We have observed a strong positive association between renal nitrate clearance and renal function such that plasma nitrate rises as renal function falls. Fractional excretion of nitrate appears to decline as renal function falls. As such, urinary nitrate excretion is unlikely to be a reliable marker of endogenous NO synthesis in settings where renal function is altered.

Apoptosis detection via automated algorithms to analyze biomarker translocation in reporter cells.

Rapid, efficient, and robust quantitative analyses of dynamic apoptotic events are essential in a high-throughput screening workflow. Currently used methods have several bottlenecks, specifically, limitations in available fluorophores for downstream assays and misinterpretation of statistical image data analysis. In this study, we developed cytochrome-C (Cyt-C) and caspase-3/-8 reporter cell lines using lung (PC9) and breast (T47D) cancer cells, and characterized them from the response to apoptotic stimuli. In these two reporter cell lines, the spatial fluorescent signal translocation patterns served as reporters of activations of apoptotic events, such as Cyt-C release and caspase-3/-8 activation. We also developed a vision-based, tunable, automated algorithm in MATLAB to implement the robust and accurate analysis of signal translocation in single or multiple cells. Construction of the reporter cell lines allows live monitoring of apoptotic events without the need for any other dyes or fixatives. Our algorithmic implementation forgoes the use of simple image statistics for more robust analytics. Our optimized algorithm can achieve a precision greater than 90% and a sensitivity higher than 85%. Combining our automated algorithm with reporter cells bearing a single-color dye/fluorophore, we expect our approach to become an integral component in the high-throughput drug screening workflow.

Antibiotic prescribing in general medical and surgical specialties: a prospective cohort study.

Background: Qualitative work has described the differences in prescribing practice across medical and surgical specialties. This study aimed to understand if specialty impacts quantitative measures of prescribing practice. Methods: We prospectively analysed the antibiotic prescribing across general medical and surgical teams for acutely admitted patients. Over a 12-month period (June 2016 - May 2017) 659 patients (362 medical, 297 surgical) were followed for the duration of their hospital stay. Antibiotic prescribing across these cohorts was assessed using Chi-squared or Wilcoxon rank-sum, depending on normality of data. The t-test was used to compare age and length of stay. A logistic regression model was used to predict escalation of antibiotic therapy. Results: Surgical patients were younger (p < 0.001) with lower Charlson Comorbidity Index scores (p < 0.001). Antibiotics were prescribed for 45% (162/362) medical and 55% (164/297) surgical patients. Microbiological results were available for 26% (42/164) medical and 29% (48/162) surgical patients, of which 55% (23/42) and 48% (23/48) were positive respectively. There was no difference in the spectrum of antibiotics prescribed between surgery and medicine (p = 0.507). In surgery antibiotics were 1) prescribed more frequently (p = 0.001); 2) for longer (p = 0.016); 3) more likely to be escalated (p = 0.004); 4) less likely to be compliant with local policy (p < 0.001) than medicine. Conclusions: Across both specialties, microbiology investigation results are not adequately used to diagnose infections and optimise their management. There is significant variation in antibiotic decision-making (including escalation patterns) between general surgical and medical teams. Antibiotic stewardship interventions targeting surgical specialties need to go beyond surgical prophylaxis. It is critical to focus on of review the patients initiated on therapeutic antibiotics in surgical specialties to ensure that escalation and continuation of therapy is justified.

Planning to halve Gram-negative bloodstream infection: getting to grips with healthcare-associated Escherichia coli bloodstream infection sources.

BACKGROUND: A thorough understanding of the local sources, risks, and antibiotic resistance for Escherichia coli bloodstream infection (BSI) is required to focus prevention initiatives and therapy. AIM: To review the sources and antibiotic resistance of healthcare-associated E. coli BSI. METHODS: Sources and antibiotic resistance profiles of all 250 healthcare-associated (post 48 h) E. coli BSIs that occurred within our secondary and tertiary care hospital group from April 2014 to March 2017 were reviewed. Epidemiological associations with urinary source, gastrointestinal source, and febrile neutropenia-related BSIs were analysed using univariable and multivariable binary logistic regression models. FINDINGS: E. coli BSIs increased 9% from 4.0 to 4.4 per 10,000 admissions comparing the 2014/15 and 2016/17 financial years. Eighty-nine cases (36%) had a urinary source; 30 (34%) of these were classified as urinary catheter-associated urinary tract infections (UTIs). Forty-five (18%) were related to febrile neutropenia, and 38 (15%) had a gastrointestinal source. Cases were rarely associated with surgical procedures (11, 4%) or indwelling vascular devices (seven, 3%). Female gender (odds ratio: 2.3; 95% confidence interval: 1.2-4.6) and older age (1.02; 1.00-1.05) were significantly associated with a urinary source. No significant associations were identified for gastrointestinal source or febrile neutropenia-related BSIs. Forty-seven percent of the isolates were resistant to ciprofloxacin, 37% to third-generation cephalosporins, and 22% to gentamicin. CONCLUSION: The gastrointestinal tract and febrile neutropenia together accounted for one-third of E. coli BSI locally but were rare associations nationally. These sources need to be targeted locally to reduce an increasing trend of E. coli BSIs.

Supervised machine learning for the prediction of infection on admission to hospital: a prospective observational cohort study.

BACKGROUND: Infection diagnosis can be challenging, relying on clinical judgement and non-specific markers of infection. We evaluated a supervised machine learning (SML) algorithm for diagnosing bacterial infection using routinely available blood parameters on presentation to hospital. METHODS: An SML algorithm was developed to classify cases into infection versus no infection using microbiology records and six available blood parameters (C-reactive protein, white cell count, bilirubin, creatinine, ALT and alkaline phosphatase) from 160203 individuals. A cohort of patients admitted to hospital over a 6 month period had their admission blood parameters prospectively inputted into the SML algorithm. They were prospectively followed up from admission to classify those who fulfilled clinical case criteria for a community-acquired bacterial infection within 72 h of admission using a pre-determined definition. Predictive ability was assessed using receiver operating characteristics (ROC) with cut-off values for optimal sensitivity and specificity explored. RESULTS: One hundred and four individuals were included prospectively. The median (range) cohort age was 65 (21-98) years. The majority were female (56/104; 54%). Thirty-six (35%) were diagnosed with infection in the first 72 h of admission. Overall, 44/104 (42%) individuals had microbiological investigations performed. Treatment was prescribed for 33/36 (92%) of infected individuals and 4/68 (6%) of those with no identifiable bacterial infection. Mean (SD) likelihood estimates for those with and without infection were significantly different. The infection group had a likelihood of 0.80 (0.09) and the non-infection group 0.50 (0.29) (P < 0.01; 95% CI: 0.20-0.40). ROC AUC was 0.84 (95% CI: 0.76-0.91). CONCLUSIONS: An SML algorithm was able to diagnose infection in individuals presenting to hospital using routinely available blood parameters.

Correction to 'An empirical measure of nonlinear strain for soft tissue indentation'.

[This corrects the article DOI: 10.1098/rsos.170894.].

Indentation of heterogeneous soft tissue: Local constitutive parameter mapping using an inverse method and an automated rig.

In the domain of soft tissue biomechanics, the development of numerical simulations has raised the experimental challenge of identifying local internal mechanical constitutive data of heterogeneous organs (e.g. brain tissue). In this context, this paper presents an ex-vivo alternative characterization method to full-field imaging techniques. It is based on automated, multiple indentations of an organ section using a custom-built rig, effectively allowing to map the viscoelastic and hyperelastic constitutive parameters of the tissue at the millimetre scale, under dynamic conditions. In this paper, this technique is described and used to map the constitutive data of three sections from porcine liver, kidney and brain tissues. The results of this mapping present strong evidence of correlation between the organ constituents (e.g. white/grey matter distribution) and the identified constitutive parameters. It was also found that brain and kidney tissues are highly heterogeneous in terms of identified properties, suggesting that such a technique is essential for fully characterizing their mechanical behaviour. This method opens the way to 3D mapping of constitutive parameters to feed finite element models of the organs with region-specific properties.

The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control.

BACKGROUND: Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS: 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS: People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (ß) -0.096, p = <0.008 and -0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (ß -0.099; p = 0.006 and -0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (ß -0.043; p = 0.3), but not between HbA1c and SNP (ß -0.105; p = 0.02). CONCLUSIONS: In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for "advanced disease" than concomitant CVD, although this requires prospective validation.

Effect of adding a mobile health intervention to a multimodal antimicrobial stewardship programme across three teaching hospitals: an interrupted time series study.

Objectives: To evaluate the impact of adding a mobile health (mHealth) decision support system for antibiotic prescribing to an established antimicrobial stewardship programme (ASP). Methods: In August 2011, the antimicrobial prescribing policy was converted into a mobile application (app). A segmented regression analysis of interrupted time series was used to assess the impact of the app on prescribing indicators, using data (2008-14) from a biannual point prevalence survey of medical and surgical wards. There were six data points pre-implementation and six data points post-implementation. Results: There was an increase in compliance with policy (e.g. compliance with empirical therapy or expert advice) in the two specialties of medicine (6.48%, 95% CI = -1.25 to 14.20) and surgery (6.63%, 95% CI = 0.15-13.10) in the implementation period, with a significant sudden change in level in surgery ( P < 0.05). There was an increase, though not significant, in medicine (15.20%, 95% CI = -17.81 to 48.22) and surgery (35.97%, 95% CI = -3.72 to 75.66) in the percentage of prescriptions that had a stop/review date documented. The documentation of indication decreased in both medicine (-16.25%, 95% CI = -42.52 to 10.01) and surgery (-14.62%, 95% CI = -42.88 to 13.63). Conclusions: Introducing the app into an existing ASP had a significant impact on the compliance with policy in surgery, and a positive, but not significant, effect on documentation of stop/review date in both specialties. The negative effect on the third indicator may reflect a high level of compliance pre-intervention, due to existing ASP efforts. The broader value of providing an antimicrobial policy on a digital platform, e.g. the reach and access to the policy, should be measured using indicators more sensitive to mHealth interventions.

Phase Composition Control in Microsphere-Supported Biomembrane Systems.

The popularization of studies in membrane protein lipid phase coexistence has prompted the development of new techniques to construct and study biomimetic systems with cholesterol-rich lipid microdomains. Here, microsphere-supported biomembranes with integrated α-helical peptides, referred to as proteolipobeads (PLBs), were used to model peptide/protein partitioning within DOPC/DPPC/cholesterol phase-separated membranes. Due to the appearance of compositional heterogeneity and impurities in the formation of model PLB assemblies, fluorescence-activated cell sorting (FACS) was used to characterize and sort PLB populations on the basis of disordered phase (Ld) content. In addition, spectral imaging was used to assess the partitioning of FITC-labeled α-helical peptide between fluorescently labeled Ld phase and unlabeled ordered phase (Lo) phase lipid microdomains. The apparent peptide partition coefficient, Kp,app, was measured to be 0.89 ± 0.06, indicating a slight preference of the peptide for the Lo phase. A biomimetic motif of the Lo phase concentration enhancement of the biotinyl-peptide ligand display in proteolipobeads was also observed. Finally, peptide mobility was measured by FRAP separately in each lipid phase, yielding diffusivities of 0.036 ± 0.005 and 0.014 ± 0.003 µm2/s in the Ld and Lo phases, respectively.

Monodisperse polystyrene foams via polymerization of foamed emulsions: structure and mechanical properties.

Foamed styrene-in-water emulsions can serve as templates for solid polystyrene foams as the pore size dpore in the solid polystyrene foam matches the bubble size dbubble of the liquid foam template. By producing monodisperse foamed emulsions with a microfluidic device it is possible to adjust the pore size, the connectivity of the pores, as well as the density of the solid polystyrene foams. The pore size can be tuned either by varying the gas pressure used to form the emulsion or by varying the chip dimension. Using three different chip dimensions we are able to produce monodisperse polystyrene foams with pore sizes ranging from 115 µm up to 588 µm. The relative density can be varied easily in a range from 0.10 to 0.30. Increasing the liquid fraction leads initially to smaller interconnections and ultimately to a mainly closed cell foam. It is practically impossible to produce a fully closed cell foam since, even at high liquid fractions, two adjacent bubbles eventually touch and form a film that will rupture during polymerization. By closely investigating the structure of the polystyrene foams we noticed an additional porosity in the pore walls which matches the water content of the styrene-in-water emulsion. During polymerization, the styrene droplets in the aqueous matrix fuse and build up a continuous but porous structure which makes up the pore walls of the macropores. This additionally porosity also leads to lower Young's and shear moduli than expected, as predicted by Gibson and Ashby's model. The relationship between relative density and moduli is in good agreement with the model.

Behaviour change interventions to influence antimicrobial prescribing: a cross-sectional analysis of reports from UK state-of-the-art scientific conferences.

BACKGROUND: To improve the quality of antimicrobial stewardship (AMS) interventions the application of behavioural sciences supported by multidisciplinary collaboration has been recommended. We analysed major UK scientific research conferences to investigate AMS behaviour change intervention reporting. METHODS: Leading UK 2015 scientific conference abstracts for 30 clinical specialties were identified and interrogated. All AMS and/or antimicrobial resistance(AMR) abstracts were identified using validated search criteria. Abstracts were independently reviewed by four researchers with reported behavioural interventions classified using a behaviour change taxonomy. RESULTS: Conferences ran for 110 days with >57,000 delegates. 311/12,313(2.5%) AMS-AMR abstracts (oral and poster) were identified. 118/311(40%) were presented at the UK's infectious diseases/microbiology conference. 56/311(18%) AMS-AMR abstracts described behaviour change interventions. These were identified across 12/30(40%) conferences. The commonest abstract reporting behaviour change interventions were quality improvement projects [44/56 (79%)]. In total 71 unique behaviour change functions were identified. Policy categories; "guidelines" (16/71) and "service provision" (11/71) were the most frequently reported. Intervention functions; "education" (6/71), "persuasion" (7/71), and "enablement" (9/71) were also common. Only infection and primary care conferences reported studies that contained multiple behaviour change interventions. The remaining 10 specialties tended to report a narrow range of interventions focusing on "guidelines" and "enablement". CONCLUSION: Despite the benefits of behaviour change interventions on antimicrobial prescribing, very few AMS-AMR studies reported implementing them in 2015. AMS interventions must focus on promoting behaviour change towards antimicrobial prescribing. Greater focus must be placed on non-infection specialties to engage with the issue of behaviour change towards antimicrobial use.

A new formulation of slight compressibility for arterial tissue and its Finite Element implementation.

In order to avoid the numerical difficulties in locally enforcing the incompressibility constraint using the displacement formulation of the Finite Element Method, slight compressibility is typically assumed when simulating the mechanical response of arterial tissue. The current standard method of accounting for slight compressibility of hyperelastic soft tissue assumes an additive decomposition of the strain-energy function into a volumetric and a deviatoric part. This has been shown, however, to be inconsistent with the linear theory and results in cubes retaining their cuboid shape under hydrostatic tension and compression, which seems at variance with the reinforcement of arterial tissue with two families of collagen fibres. A remedy for these defects is proposed here, a solution which generalises the current standard model of slight compressibility to include two additional terms, one of which is quadratic in the [Formula: see text] invariants and the other quadratic in [Formula: see text]. Experimental data are used to motivate typical values for the associated material constants of these additional terms. Some simulations are performed to allow contrasts and comparisons to be made between the current standard model of slight compressibility and its generalisation proposed here.