Non-invasive assessment of lower limb alignment is accurate for pre-operative planning and post-operative follow up

Knee alignment is a fundamental measurement in the assessment, monitoring and surgical management of patients with OA. In spite of extensive research into the consequences of malalignment, there is a lack of data regarding the potential variation between supine and standing (functional) conditions. The purpose of this study was to explore this relationship in asymptomatic, osteoarthritic and prosthetic knees. Our hypothesis was that the change in alignment of these three groups would be different. Infrared position capture was used to assess knee alignment for 30 asymptomatic controls and 31 patients with OA, before and after TKA. Coronal and sagittal mechanical femorotibial (MFT) angles in extension (negative values varus/hyperextension) were measured supine and in bi-pedal stance and changes analysed using a paired t-test. To quantify this change in 3D, vector plots of ankle centre displacement relative to the knee centre were produced. Alignment in both planes changed significantly from supine to standing for all three groups, most frequently towards relative varus and extension. In the coronal plane, the mean±SD(°) of the supine/standing MFT angles was 0.1±2.5/−1.1±3.7 for asymptomatic (p=0.001), −2.5±5.7/−3.6±6.0 for osteoarthritic (p=0.009) and −0.7±1.4/ −2.5±2.0 for prosthetic knees (p<0.001). In the sagittal plane, the mean±SD(°) of the supine/standing MFT angles was −1.7±3.3/−5.5±4.9 for asymptomatic (p<0.001), 7.7±7.1/1.8±7.7 for osteoarthritic (p<0.001) and 6.8±5.1/1.4±7.6 for prosthetic knees (p<0.001). The vector plots showed that the trend of relative varus and extension in stance was similar in overall magnitude and direction between the groups. The similarities between each group did not support our hypothesis. The consistent kinematic pattern for different knee types suggests that soft tissue restraints rather than underlying joint deformity may be more influential in dynamic control of alignment from lying to standing. This potential change should be considered when positioning TKA components on supine limbs as post-operative functional alignment may be different

Encountering authority and avoiding trouble: Young migrant men’s narratives of negotiation in Europe

Drawing on data from seven European countries (Czech Republic, Finland, France, Germany, Ireland, Italy and the United Kingdom), this article seeks to identify how young migrant men engage with authority and avoid conflict against a backdrop of increasing hostility towards migrants in many European countries. As this article contends, even those with permanent residency status in the host country often find themselves having to justify their legitimacy to carry out daily tasks, resulting in many young male migrants living with feelings of perpetual insecurity. As such, a number of coping strategies are employed by young migrant men in order to assuage such feelings and mitigate potential risks. Focusing on the lived experiences of this group, as described in narrative interviews, our study found that many young migrant men are required to enter into negotiations with authority figures, where there is a considerable power differential. Acting as risk assessors, they find themselves forced to navigate complex and challenging social relations and support networks. We show how self-limiting behaviour intended to avoid or control interactions with authority and the negotiations conducted to minimize the risk of ‘trouble’ by young migrant men not only are problematic in the context of day-to-day activities but can very often have a detrimental impact on their lives

Non-invasive computer-assisted measurement of knee alignment

The quantification of knee alignment is a routine part of orthopaedic practice and is important for monitoring disease progression, planning interventional strategies, and follow-up of patients. Currently available technologies such as radiographic measurements have a number of drawbacks. The aim of this study was to validate a potentially improved technique for measuring knee alignment under different conditions. An image-free navigation system was adapted for non-invasive use through the development of external infrared tracker mountings. Stability was assessed by comparing the variance (F-test) of repeated mechanical femoro-tibial (MFT) angle measurements for a volunteer and a leg model. MFT angles were then measured supine, standing and with varus-valgus stress in asymptomatic volunteers who each underwent two separate registrations and repeated measurements for each condition. The mean difference and 95% limits of agreement were used to assess intra-registration and inter-registration repeatability. For multiple registrations the range of measurements for the external mountings was 1° larger than for the rigid model with statistically similar variance (p=0.34). Thirty volunteers were assessed (19 males, 11 females) with a mean age of 41 years (range: 20-65) and a mean BMI of 26 (range: 19-34). For intra-registration repeatability, consecutive coronal alignment readings agreed to almost ±1°, with up to ±0.5° loss of repeatability for coronal alignment measured before and after stress maneuvers, and a ±0.2° loss following stance trials. Sagittal alignment measurements were less repeatable overall by an approximate factor of two. Inter-registration agreement limits for coronal and sagittal supine MFT angles were ±1.6° and ±2.3°, respectively. Varus and valgus stress measurements agreed to within ±1.3° and ±1.1°, respectively. Agreement limits for standing MFT angles were ±2.9° (coronal) and ±5.0° (sagittal), which may have reflected a variation in stance between measurements. The system provided repeatable, real-time measurements of coronal and sagittal knee alignment under a number of dynamic, real-time conditions, offering a potential alternative to radiographs

Lower limb alignment and laxity measures before, during and after total knee arthroplasty : a prospective cohort study

Background. This study compared knee alignment and laxity in patients before, during and after total knee arthroplasty, using methodologically similar procedures, with an aim to help inform pre-operative planning.Methods. Eighteen male and 13 female patients were recruited, mean age 66 years (51-82) and mean body mass index of 33 (23-43). All were assessed pre- and postoperatively using a non-invasive infrared position capture system and all underwent total knee arthroplasty using a navigation system. Knee kinematic data were collected and comparisons made between preoperative clinical and intraoperative measurements for osteoarthritic knees, and between postoperative clinical and intraoperative measurements for prosthetic knees. Findings. There was no difference in unstressed coronal mechanical femoral-tibial angles for either osteoarthritic or prosthetic knees. However, for sagittal alignment the knees were in greater extension intraoperatively (osteoarthritic 5.2° p<0.001, prosthetic 7.2° p<0.001). For osteoarthritic knees, both varus and valgus stress manoeuvres had greater angular displacements intraoperatively by a mean value of 1.5° for varus (p=0.002) and 1.6° for valgus (p<0.001). For prosthetic knees, only valgus angular displacement was greater intraoperatively (0.9°, p=0.002)

Lower limb alignment becomes more varus and hyperextended from supine to bipedal stance in asymptomatic, osteoarthritic and prosthetic neutral or varus knees

Introduction: Knee alignment is a fundamental measurement in the assessment, monitoring and surgical management of patients with osteoarthritis. There is a lack of data regarding how static tibiofemoral alignment varies between supine and standing conditions. This study aimed to quantify the relationship between supine and standing lower limb alignment in asymptomatic, osteoarthritic (OA) and prosthetic (TKA) knees. Methods: A non-invasive position capture system was used to assess knee alignment for 30 asymptomatic controls and 31 patients with OA both before and after TKA. Coronal and sagittal mechanical femorotibial angles were measured supine with the lower limb in extension and in bi-pedal stance. Changes between conditions were analysed using paired t-tests. Vector plots of ankle centre displacement relative to the knee centre from supine to standing were produced to allow three-dimensional visualisation. Results: All groups showed a trend towards varus and extension when going from supine to standing. Mean change for asymptomatic knees was 1.2° more varus (p=0.001) and 3.8° more extended (p<0.001). For OA knees this was 1.1° more varus (varus (p=0.009) and 5.9° more extended (p<0.001) and TKA knees 1.9° more varus (p<0.001) and 5.6° more extended (p<0.001). Conclusion: The observed consistent changes in lower limb alignment between supine and standing positions across knee types suggests the soft tissue envelope restraining the knee may have a greater influence on dynamic alignment changes than the underlying bony deformity. This highlights the importance of quantifying soft tissue behaviour when planning, performing and evaluating alignment dependent surgical interventions of the knee. When routinely assessing any type of knee, clinicians should be aware that subtle consistent alignment changes occur under weightbearing conditions and tailor their treatments accordingly

Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia.

All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins

Why Are Regulations Changed? A Parcel Analysis of Upzoning in Los Angeles

Planners, officials, and neighborhood groups often debate zoning changes, yet there is little empirical evidence explaining why zoning and other land use regulations are changed. I use logistic regression models to examine density-enabling rezoning (“upzoning”) in Los Angeles. I find that upzoning occurs where there are development opportunities combined with limited political resistance. Upzoning is most likely on well-located parcels zoned for low-intensity, nonresidential uses. Meanwhile, homeowners—and particularly homeowners with access to valuable amenities—are associated with regulatory stasis. I conclude by recommending strategies for addressing homeowners’ concerns about higher density housing

Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26±32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product

Oral abstracts 1: SpondyloarthropathiesO1. Detecting axial spondyloarthritis amongst primary care back pain referrals

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interes