Associative white matter tracts selectively predict sensorimotor learning.

Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing microstructure of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in learning a sensorimotor task, and further, if the mapping between tract microstructure and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then practiced drawing a set of 40 unfamiliar symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and measured visual recognition learning for the symbols using an old/new 2-AFC task. Results demonstrated that tract microstructure selectively predicted learning outcomes, with left hemisphere pArc and SLF3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated using repeat, held-out data and supported with complementary analyses. Results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes.

Associative white matter tracts selectively predict sensorimotor learning.

Human learning is a complex phenomenon that varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing myelination of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in the potential for learning a sensorimotor task, and further, if the mapping between the microstructure of major white matter tracts and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then underwent training and subsequent testing to evaluate learning. During training, participants practiced drawing a set of 40 novel symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and visual recognition learning as the performance accuracy in an old/new 2-AFC recognition task. Results demonstrated that the microstructure of major white matter tracts selectively predicted learning outcomes, with left hemisphere pArc and SLF 3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated in a repeat, held-out data set and supported with complementary analyses. Overall, results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes and open avenues of inquiry concerning the impact of existing tract myelination in the potential for learning. Significance statement: A selective mapping between tract microstructure and future learning has been demonstrated in the murine model and, to our knowledge, has not yet been demonstrated in humans. We employed a data-driven approach that identified only two tracts, the two most posterior segments of the arcuate fasciculus in the left hemisphere, to predict learning a sensorimotor task (drawing symbols) and this prediction model did not transfer to other learning outcomes (visual symbol recognition). Results suggest that individual differences in learning may be selectively related to the tissue properties of major white matter tracts in the human brain.

Oral immune dysfunction is associated with the expansion of FOXP3+PD-1+Amphiregulin+ T cells during HIV infection.

Residual systemic inflammation and mucosal immune dysfunction persist in people living with HIV, despite treatment with combined anti-retroviral therapy, but the underlying immune mechanisms are poorly understood. Here we report that the altered immune landscape of the oral mucosa of HIV-positive patients on therapy involves increased TLR and inflammasome signaling, localized CD4+ T cell hyperactivation, and, counterintuitively, enrichment of FOXP3+ T cells. HIV infection of oral tonsil cultures in vitro causes an increase in FOXP3+ T cells expressing PD-1, IFN-γ, Amphiregulin and IL-10. These cells persist even in the presence of anti-retroviral drugs, and further expand when stimulated by TLR2 ligands and IL-1ß. Mechanistically, IL-1ß upregulates PD-1 expression via AKT signaling, and PD-1 stabilizes FOXP3 and Amphiregulin through a mechanism involving asparaginyl endopeptidase, resulting in FOXP3+ cells that are incapable of suppressing CD4+ T cells in vitro. The FOXP3+ T cells that are abundant in HIV-positive patients are phenotypically similar to the in vitro cultured, HIV-responsive FOXP3+ T cells, and their presence strongly correlates with CD4+ T cell hyper-activation. This suggests that FOXP3+ T cell dysregulation might play a role in the mucosal immune dysfunction of HIV patients on therapy.

Infrared spectroscopy and anharmonic theory of H3 +Ar2,3 complexes: The role of symmetry in solvation.

The vibrational spectra of H3 +Ar2,3 and D3 +Ar2,3 are investigated in the 2000 cm-1 to 4500 cm-1 region through a combination of mass-selected infrared laser photodissociation spectroscopy and computational work including the effects of anharmonicity. In the reduced symmetry of the di-argon complex, vibrational activity is detected in the regions of both the symmetric and antisymmetric hydrogen stretching modes of H3 +. The tri-argon complex restores the D3h symmetry of the H3 + ion, with a concomitant reduction in the vibrational activity that is limited to the region of the antisymmetric stretch. Throughout these spectra, additional bands are detected beyond those predicted with harmonic vibrational theory. Anharmonic theory is able to reproduce some of the additional bands, with varying degrees of success.

Evaluating anti-tumor activity of palbociclib plus radiation in anaplastic and radiation-induced meningiomas: pre-clinical investigations.

PURPOSE: Meningiomas are common brain tumors, the majority of which are considered benign. Despite surgery and/or radiation therapy, recurrence rates are approximately 8-10%. One likely cause is the dysregulation of cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, which controls the cell cycle restriction point. This pathway is commonly dysregulated in anaplastic meningioma cell lines (AM) and radiation-induced meningioma cells (RIM), making it a rational target for anti-meningioma therapy. In this study, we investigate the effect of a CDK4/6 inhibitor, palbociclib, with radiation in relevant pre-clinical models. METHODS: In vitro cell culture, ex vivo slice culture and in vivo cell line-derived orthotopic xenograft animal models of AM/RIM were utilized to assess treatment efficacy with palbociclib plus radiation. Treatment effects were examined by immunoblot, cell viability, apoptosis, and cell cycle progression. RESULTS: The in vitro and ex vivo studies demonstrate that palbociclib plus radiation treatment reduced proliferation and has additional effects on cell cycling, including induction of an RB-associated G (1) arrest in Rb+ AM and RIM cells, but not in Rb- cells. Our results also demonstrated reduced CDK4 and CDK6 expression as well as reduced E2F target gene expression (CCNA2 and CCNE2) with the combination therapy. MRI results in vivo demonstrated reduced tumor size at 5 weeks when treated with 14 days palbociclib (10 mg/kg) plus 6 Gy radiation compared to saline-treated tumors. Finally, no hepatic toxicity was found after treatments. CONCLUSION: A pre-clinical murine model provides preclinical evidence for use of palbociclib plus radiation as a therapeutic agent for Rb+ meningiomas.

National survey of occupational advice for lower limb arthroplasty patients.

BACKGROUND: Little is known what advice or support patients are given about return to work (RTW) after hip or knee replacement surgery. AIMS: This study aims to understand the delivery, timing and content of 'RTW' advice currently delivered by surgical teams offering hip and knee replacements across the UK. METHODS: National online survey exploring five specific areas relating to 'RTW' advice: (i) timings of interactions between hospital orthopaedic teams and patients prior to surgery, (ii) routine delivery of 'RTW' advice, (iii) methods used to deliver 'RTW' advice, (iv) confidence delivering advice and (v) need for an occupational 'RTW' advice intervention. RESULTS: A total of 152 participants including surgeons, physiotherapists, occupational therapists and nurses from 59 different public and private health providers responded. Only 20% (n = 30) of respondents reported that working patients were identified as a specific subgroup in need of additional support. Overall, 62% (n = 92) stated that they did not routinely offer 'RTW' advice. When given, 'RTW' advice was almost always verbal, generic advice using blanket timescales and based on the respondent's anecdotal experience rather than the patients individualized needs. Overall, 116 (78%) felt an occupational advice intervention was needed. CONCLUSIONS: This national survey demonstrated wide variation in the timing, content and delivery of information and advice for patients in work and intending to RTW after hip and knee replacement surgery. Current RTW advice provided to hip and knee replacement patients is inadequate.

Level of adherence to prescribed exercise in spondyloarthritis and factors affecting this adherence: a systematic review.

Adherence is a primary determinant of the effectiveness of any intervention. Exercise is considered essential in the management of spondyloarthritis (SpA); however, the overall adherence to exercise programmes and factors affecting adherence are unknown. The aim of this systematic review was to examine measures of, and factors influencing adherence to, prescribed exercise programmes in people with SpA. A search was performed in August 2018 using five data bases; the Cochrane library, CINAHL, EMBASE, MEDLINE, and Web of Science Collections. Inclusion criteria were: studies with adults (> 18 years) with SpA, with a prescribed exercise intervention or educational programme with the aim of increasing exercise participation. Article quality was independently assessed by two assessors. Extracted descriptive data included: populations, interventions, measures of adherence and factors affecting adherence. Percentage adherence rates to prescribed exercises were calculated if not reported. Nine studies were included with a total of 658 participants, 95% of participants had a diagnosis of ankylosing spondylitis. Interventions and measurement of adherence varied, making comparisons difficult. Rates of adherence ranged from 51.4 to 95%. Single studies identified; adherence improved following educational programmes, and higher disease severity and longer diagnostic delays were associated with higher adherence. Conflicting evidence was found as to whether supervision of exercise improved adherence. Three consecutive studies demonstrated adherence reduced over time. Adherence to prescribed exercise in SpA was poorly reported and predominately for people with AS. The levels of adherence and factors affecting prescribed exercise in SpA remain unclear. Future research should measure adherence across a longer time period and investigate possible factors which may influence adherence.

Near-Infrared Spectroscopy and Anharmonic Theory of Protonated Water Clusters: Higher Elevations in the Hydrogen Bonding Landscape.

Near-infrared spectroscopy measurements are presented for protonated water clusters, H+(H2O) n, in the size range of n = 1-8. Clusters are produced in a pulsed-discharge supersonic expansion, mass selected, and studied with infrared laser photodissociation spectroscopy in the regions of 3600-4550 and 4850-7350 cm-1. Although there is some variation with cluster size, the main features of these spectra are a broad absorption near 5300 cm-1, a sharp doublet near 7200 cm-1, as well as a structured absorption near 4100 cm-1 for n ≥ 2. The vibrational patterns measured for the hydronium, Zundel, and Eigen ions are compared to those predicted by different forms of anharmonic theory. Second-order vibrational perturbation theory (VPT2) and a local mode treatment of the OH stretches both capture key aspects of the spectra but suffer understandable deficiencies in the quantitative description of band positions and intensities.

Trauma to the Superior Mesenteric Artery and Superior Mesenteric Vein: A Narrative Review of Rare but Lethal Injuries.

Mesenteric vessels, including the superior mesenteric artery (SMA) and vein (SMV), provide and drain the rich blood supply of the midgut and hindgut. SMA and SMV injuries are rare and often lethal. Clinical management of these injuries is not well established, but treatment options include operative, non-operative, and endovascular strategies. A narrative review of the literature was conducted using MEDLINE Complete-EBSCO. Relevant studies, specifically those focusing on diagnosis and management of SMA and SMV injuries, were selected. Only original reports and collected series were selected to prevent duplication of cases. A search of the literature for mesenteric arterial injuries yielded 87 studies. Vessel-specific breakdown of the studies yielded 40 with SMA injuries and 41 with SMV injuries. These searches were winnowed to 26 individual studies, which were included in this collective review. Limitations of this study are similar to all narrative literature reviews: the dependence on previously published research and availability of references as outlined in our methodology. Although historically rare, mesenteric vessel injuries are seen with increasing incidence and continue to present a challenge to trauma surgeons due to their daunting mortality rates. Currently, universal treatment guidelines do not exist, but the various options for their management have been extensively reviewed in the literature.

Comparing the Mechanical Response of Di-, Tri-, and Tetra-functional Resin Epoxies with Reactive Molecular Dynamics.

The influence of monomer functionality on the mechanical properties of epoxies is studied using Molecular Dynamics (MD) with the Reax Force Field (ReaxFF). From deformation simulations, the Young's modulus, yield point, and Poisson's ratio are calculated and analyzed. The results demonstrate an increase in stiffness and yield strength with increasing resin functionality. Comparison between the network structures of distinct epoxies is further advanced by the Monomeric Degree Index (MDI). Experimental validation demonstrates the MD results correctly predict the relationship in Young's moduli. Therefore, ReaxFF is confirmed to be a useful tool for studying the mechanical behavior of epoxies.

Traumatic pulmonary pseudocyst: An underreported entity.

BACKGROUND: Traumatic pulmonary pseudocysts (TPP) are underreported cavitary lesions of the pulmonary parenchyma that can develop following blunt chest trauma. Although the occurrence of traumatic pulmonary pseudocyst is rare, this condition should be considered in the differential diagnosis of any cavitary lesion. Awareness of this injury and its clinical significance is important for successful management in order to avoid medical errors in the course of treatment. METHODS: A literature search was conducted through Medline using the key phrases "traumatic pulmonary pseudocyst" and "traumatic pneumatocele." Relevant articles, especially those with focus on diagnosis and management of traumatic pneumatocele in adults, were selected. Due to the scarcity of literature and lack of Level I evidence on this subject, studies published in any year were considered. RESULTS: A search of "traumatic pulmonary pseudocyst" and "traumatic pneumatocele" yielded 114 studies. Most of these were excluded based on inclusion and exclusion criteria. Thirty-five articles were reviewed. The majority of these were individual case studies; only eight articles were considered large case studies (greater than eight patients). CONCLUSION: Traumatic pulmonary pseudocysts are lesions that occur secondary to blunt chest trauma. Diagnosis is based on a history of trauma and appearance of a cystic lesion on CT. Accurate diagnosis of traumatic pulmonary pseudocyst is imperative to achieve successful outcomes. Failure to do so may lead to unnecessary procedures and complications.

Communication: Trapping a proton in argon: Spectroscopy and theory of the proton-bound argon dimer and its solvation.

Ion-molecule complexes of the form H+Arn are produced in pulsed-discharge supersonic expansions containing hydrogen and argon. These ions are analyzed and mass-selected in a reflectron spectrometer and studied with infrared laser photodissociation spectroscopy. Infrared spectra for the n = 3-7 complexes are characterized by a series of strong bands in the 900-2200 cm-1 region. Computational studies at the MP2/aug-cc-pVTZ level examine the structures, binding energies, and infrared spectra for these systems. The core ion responsible for the infrared bands is the proton-bound argon dimer, Ar-H+-Ar, which is progressively solvated by the excess argon. Anharmonic vibrational theory is able to reproduce the vibrational structure, identifying it as arising from the asymmetric proton stretch in combination with multiple quanta of the symmetric argon stretch. Successive addition of argon shifts the proton vibration to lower frequencies, as the charge is delocalized over more ligands. The Ar-H+-Ar core ion has a first solvation sphere of five argons.

Avoiding Pandemic Fears in the Subway and Conquering the Platypus.

Metagenomics is increasingly used not just to show patterns of microbial diversity but also as a culture-independent method to detect individual organisms of intense clinical, epidemiological, conservation, forensic, or regulatory interest. A widely reported metagenomic study of the New York subway suggested that the pathogens Yersinia pestis and Bacillus anthracis were part of the "normal subway microbiome." In their article in mSystems, Hsu and collaborators (mSystems 1(3):e00018-16, 2016, http://dx.doi.org/10.1128/mSystems.00018-16) showed that microbial communities on transit surfaces in the Boston subway system are maintained from a metapopulation of human skin commensals and environmental generalists and that reanalysis of the New York subway data with appropriate methods did not detect the pathogens. We note that commonly used software pipelines can produce results that lack prima facie validity (e.g., reporting widespread distribution of notorious endemic species such as the platypus or the presence of pathogens) but that appropriate use of inclusion and exclusion sets can avoid this issue.

The technique of delivery of peri-operative analgesia does not affect the rehabilitation or outcomes following total knee arthroplasty.

AIMS: This non-blinded randomised controlled trial compared the effect of patient-controlled epidural analgesia (PCEA) versus local infiltration analgesia (LIA) within an established enhanced recovery programme on the attainment of discharge criteria and recovery one year after total knee arthroplasty (TKA). The hypothesis was that LIA would increase the proportion of patients discharged from rehabilitation by the fourth post-operative day but would not affect outcomes at one year. PATIENTS AND METHODS: A total of 242 patients were randomised; 20 were excluded due to failure of spinal anaesthesia leaving 109 patients in the PCEA group and 113 in the LIA group. Patients were reviewed at six weeks and one year post-operatively. RESULTS: There was no difference in the proportion of patients discharged from rehabilitation by the fourth post-operative day, (77% in the PCEA group, 82% in the LIA group, p = 0.33), mean length of stay (four days in each group, p = 0.540), day of first mobilisation (p = 0.013) or pain (p = 0.278). There was no difference in mean Oxford Knee Scores (41 points in each group, p = 0.915) or the rate of complications in the two groups. CONCLUSION: Both techniques provided adequate pain relief, enabled early mobilisation and accelerated rehabilitation and good patient-reported outcomes up to one year post-operatively. PCEA and LIA are associated with similar clinical outcomes following TKA. Cite this article: Bone Joint J 2016;98-B1189-96.

Osteopathology in the Equine Distal Phalanx Associated With the Development and Progression of Laminitis.

Although the equine distal phalanx and hoof lamellae are biomechanically and physiologically integrated, bony changes in the distal phalanx are poorly described in laminitis. The aims of this study were (1) to establish a laminitis grading scheme that can be applied to the wide spectrum of lesions seen in naturally occurring cases and (2) to measure and describe changes in the distal phalanx associated with laminitis using micro-computed tomography (micro-CT) and histology. Thirty-six laminitic and normal feet from 15 performance and nonperformance horses were evaluated. A laminitis grading scheme based on radiographic, gross, histopathologic, and temporal parameters was developed. Laminitis severity grades generated by this scheme correlated well with clinical severity and coincided with decreased distal phalanx bone volume and density as measured by micro-CT. Laminitic hoof wall changes included progressive ventral rotation and distal displacement of the distal phalanx with increased thickness of the stratum internum-corium tissues with lamellar wedge formation. Histologically, there was epidermal lamellar necrosis with basement membrane separation and dysplastic regeneration, including acanthosis and hyperkeratosis, corresponding to the lamellar wedge. The changes detected by micro-CT corresponded to microscopic findings in the bone, including osteoclastic osteolysis of trabecular and osteonal bone with medullary inflammation and fibrosis. Bone changes were identified in horses with mild/early stages of laminitis as well as severe/chronic stages. The authors conclude that distal phalangeal pathology is a quantifiable and significant component of laminitis pathology and may have important implications for early detection or therapeutic intervention of equine laminitis.

Ropivacaine plasma levels following high-dose local infiltration analgesia for total knee arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 28 patients aged 65 years or over undergoing unilateral total knee arthroplasty. Patients received infiltration of ropivacaine 400 mg followed by infusion at 20 mg.h(-1) through an intra-articular catheter. Total and free plasma levels of ropivacaine were measured at specified time intervals during a 24-h period after tourniquet release. Patients were monitored for symptoms and signs of local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.147 to 3.093 µg.ml(-1) (mean (SD) 1.105 (0.518) µg.ml(-1) ). Free levels of plasma ropivaca-ine varied from 0.001 to 0.104 µg.ml(-1) (mean (SD) 0.037 (0.020) µg.ml(-1) ). Six samples had total plasma ropivacaine levels greater the toxic threshold of 2.2 µg.ml(-1) . No samples reached the toxic threshold for free venous ropivacaine concentration. We conclude that the use of high-dose ropivacaine infiltration and catheter infusion for total knee arthroplasty in an elderly population does not result in free plasma ropivacaine levels previously associated with toxicity but that raised total plasma levels may be observed.

Ropivacaine plasma levels following local infiltration analgesia for primary total hip arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri-capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 µg.ml(-1) (mean (SD) 0.953 (0.323) µg.ml(-1) ). Free levels of plasma ropivacaine varied from 0.000 to 0.053 µg.ml(-1) (mean (SD) 0.024 (0.011) µg.ml(-1) ). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 µg.ml(-1) , free 0.15 µg.ml(-1) ) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients.

Effects on tumor development and metastatic dissemination by the NKG2D lymphocyte receptor expressed on cancer cells.

The stimulatory NKG2D lymphocyte receptor together with its tumor-associated ligands enable the immune system to recognize and destroy cancer cells. However, with dynamic changes unfolding, cancers exploit NKG2D and its ligands for immune evasion and suppression. Recent findings have added yet another functional dimension, wherein cancer cells themselves co-opt NKG2D for their own benefit to complement the presence of its ligands for self-stimulation of parameters of tumorigenesis. Those findings are here extended to in vivo tumorigenicity testing by employing orthotopic xenotransplant breast cancer models in mice. Using human cancer lines with ectopic NKG2D expression and RNA interference (RNAi)-mediated protein depletion among other controls, we show that NKG2D self-stimulation has tumor-promoting capacity. NKG2D signals had no notable effects on cancer cell proliferation and survival but acted at the level of angiogenesis, thus promoting tumor growth, tumor cell intravasation and dissemination. NKG2D-mediated effects on tumor initiation may represent another factor in the observed overall enhancement of tumor development. Altogether, these results may have an impact on immunotherapy approaches, which currently do not account for such NKG2D effects in cancer patients and thus could be misdirected as underlying assumptions are incomplete.

Effectiveness comparison of multiple sticky-trap configurations for sampling Pseudacteon spp. phorid flies (Diptera: Phoridae).

A variety of traps have been developed for monitoring introduced populations of Pseudacteon spp. phorid flies (Diptera: Phoridae) across their established range in the United States. Such traps typically exploit common aspects of phorid fly biology and behavior, such as their attraction to live or dead red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae), as well as the perching behavior of these parasitoids. However, populations of multiple species of phorid flies have been established in the United States to serve as biological control agents against S. invicta, and it is unclear if all trap designs are equally effective in sampling this variety of phorid species. This study investigated the effectiveness of six trap designs simultaneously during three sampling events in south-central Texas. Interactions between two species of phorid flies (Pseudacteon tricuspis Borgmeier and P. curvatus B.) and their hosts have been intensively studied at this location for over eight years. When analyzed independently, there were no significant differences in the mean number of P. curvatus or P. tricuspis phorids collected by any of the trap designs during any of the sampling events. However, when the total number of phorids collected were combined, significant trap performance differentials were observed during the October 2010 sampling event. Furthermore, there were significant differences among male flies during the September 2012 observation. Additionally, a trap component cost comparison is provided. The consistent and relatively equivalent performance of the phorid traps investigated in these trials suggests that all are appropriate for phorid surveillance, and cost and ease-of-use considerations may be the most important criteria when selecting a trap design.

An anatomic study of local infiltration analgesia in total knee arthroplasty.

BACKGROUND: Local infiltration analgesia (LIA) is a relatively novel technique developed for effective pain control following total knee arthroplasty (TKA), reducing requirements for epidural or parenteral postoperative analgesia. This study investigated the anatomical spread of an LIA used in TKA to identify the nerve structures reached by the injected fluid. METHODS: Six fresh-frozen cadaveric lower limbs were injected according to a standardised LIA technique with a solution of latex and India ink to enable visualisation. Wounds were closed and limbs placed flat in a freezer at -20°C for two weeks. Limbs were then either sliced or dissected to identify solution locations. RESULTS: Solution was found from the proximal thigh to the middle of the lower leg. The main areas of concentration were the popliteal fossa, the anterior aspect of the femur and the subcutaneous tissue of the anterior aspect of the knee. There was less solution in the lower popliteal fossa. The solution was found to reach the majority of nerves, with good infiltration of nerves supplying the knee. CONCLUSIONS: These results support the positive clinical outcomes with this LIA technique. However, the lack of infiltration into the lower popliteal fossa suggests more fluid or a different injection point could be used. The solution reaching the extensor muscles of the lower leg is likely to have no beneficial analgesic effect for a TKA patient. The LIA technique is already used in clinical practice following total knee arthroplasty. Results from this study show there may be scope to optimise the injection sites in LIA technique.