A preliminary modelling investigation into the safe correction zone for high tibial osteotomy

Purpose: High tibial osteotomy (HTO) re-aligns the weight-bearing axis (WBA) of the lower limb. The surgery reduces medial load (reducing pain and slowing progression of cartilage damage) while avoiding overloading the lateral compartment. The optimal correction has not been established. This study investigated how different WBA re-alignments affected load distribu- tion in the knee, to consider the optimal post-surgery re-alignment. Methods: We collected motion analysis and 7T MRI data from 3 healthy sub- jects, and combined this data to create sets of subject-specific finite element models (total=45 models). Each set of models simulated a range of potential post-HTO knee re-alignments. We shifted the WBA from its native align- ment to between 40% and 80% medial-lateral tibial width (corresponding to 2.8◦-3.1◦ varus and 8.5◦-9.3◦ valgus), in 3% increments. We then compared stress/pressure distributions in the models. Results/Discussion: Correcting the WBA to 50% tibial width (0◦ varus- valgus) approximately halved medial compartment stresses, with minimal changes to lateral stress levels, but provided little margin for error in under- correction. Correcting the WBA to a more commonly-used 62%-65% tibial width (3.4◦-4.6◦ valgus) further reduced medial stresses but introduced the danger of damaging lateral compartment tissues. To balance optimal loading environment with that of the historical risk of under-correction, we propose a new target: WBA correction to 55% tibial width (1.7◦-1.9◦ valgus), which anatomically represented the apex of the lateral tibial spine. Conclusions: Finite element models can successfully simulate a variety of HTO re-alignments. Correcting the WBA to 55% tibial width (1.7◦-1.9◦ valgus) optimally distributes medial and lateral stresses/pressures

Arthroscopic hip surgery compared with physiotherapy and activity modification for the treatment of symptomatic femoroacetabular impingement: multicentre randomised controlled trial.

OBJECTIVE: To compare arthroscopic hip surgery with physiotherapy and activity modification for improving patient reported outcome measures in patients with symptomatic femoroacetabular impingement (FAI). DESIGN: Two group parallel, assessor blinded, pragmatic randomised controlled trial. SETTING: Secondary and tertiary care centres across seven NHS England sites. PARTICIPANTS: 222 participants aged 18 to 60 years with symptomatic FAI confirmed clinically and with imaging (radiography or magnetic resonance imaging) were randomised (1:1) to receive arthroscopic hip surgery (n=112) or a programme of physiotherapy and activity modification (n=110). Exclusion criteria included previous surgery, completion of a physiotherapy programme targeting FAI within the preceding 12 months, established osteoarthritis (Kellgren-Lawrence grade ≥2), and hip dysplasia (centre-edge angle <20 degrees). INTERVENTIONS: Participants in the physiotherapy group received a goal based programme tailored to individual patient needs, with emphasis on improving core stability and movement control. A maximum of eight physiotherapy sessions were delivered over five months. Participants in the arthroscopic surgery group received surgery to excise the bone that impinged during hip movements, followed by routine postoperative care. MAIN OUTCOME MEASURES: The primary outcome measure was the hip outcome score activities of daily living subscale (HOS ADL) at eight months post-randomisation, with a minimum clinically important difference between groups of 9 points. Secondary outcome measures included additional patient reported outcome measures and clinical assessment. RESULTS: At eight months post-randomisation, data were available for 100 patients in the arthroscopic hip surgery group (89%) and 88 patients in the physiotherapy programme group (80%). Mean HOS ADL was 78.4 (95% confidence interval 74.4 to 82.3) for patients randomised to arthroscopic hip surgery and 69.2 (65.2 to 73.3) for patients randomised to the physiotherapy programme. After adjusting for baseline HOS ADL, age, sex, and study site, the mean HOS ADL was 10.0 points higher (6.4 to 13.6) in the arthroscopic hip surgery group compared with the physiotherapy programme group (P<0.001)). No serious adverse events were reported in either group. CONCLUSIONS: Patients with symptomatic FAI referred to secondary or tertiary care achieve superior outcomes with arthroscopic hip surgery than with physiotherapy and activity modification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01893034.NIHR BRC oxfor

Reclamation of reactive metal oxides from complex minerals using alkali roasting and leaching- an improved approach to process engineering

In nature, the commonly occurring reactive metal oxides of titanium, chromium, aluminium, and vanadium often chemically combine with the transition metal oxides such as iron oxides and form complex minerals. Physico-chemical separation of transition metal oxides from the remaining reactive metal oxides is therefore an important step in the purification of reactive oxide constituents. Each purification step has quite a high energy requirement at present. Current practice in industry yields sulphate and neutralized chloride waste from titanium dioxide enrichment, red mud from bauxite refining, slag and leach residues from vanadium extraction and chromite ore process residue (COPR) from chromate processes. In this review article, a novel alkali-based oxidative roasting and aqueous leaching for the extraction of mineral oxides is explained in the context of the original work of Le Chatelier in 1850, which was unsuccessful in the industrialization of bauxite processing for alumina extraction. However, much later in the 19th century the alkali-based oxidative mineral roasting was successfully developed for industrial scale manufacturing of chromate chemicals, which yields COPR. The crystal chemistry of mineral oxides, namely alumina, titanium dioxide, and chromium oxide in naturally occurring minerals is briefly reviewed in the context of chemical extraction, which is then developed as a model for developing thermodynamic chemical equilibrium principles for analyzing the physical separation and enrichment of such reactive metal oxides by forming water-soluble and water-insoluble alkali complexes. The involvement of the alkali roasting chemistry of non-magnetic titaniferous mineral waste is also reported in the initial separation of rare-earth oxide mixtures for subsequent separation of individual oxides. The paper concludes with a generic approach to process chemistry which minimizes waste generation and therefore helps in reducing the overall process and energy costs. Examples of recovering alkali from high pH solution using carbon dioxide are also demonstrated

Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanoma

In vitro differentiated CD8+ T cells have been the primary focus of immunotherapy of cancer with little focus on CD4+ T cells. Immunotherapy involving in vitro differentiated T cells given after lymphodepleting regimens significantly augments antitumor immunity in animals and human patients with cancer. However, the mechanisms by which lymphopenia augments adoptive cell therapy and the means of properly differentiating T cells in vitro are still emerging. We demonstrate that naive tumor/self-specific CD4+ T cells naturally differentiated into T helper type 1 cytotoxic T cells in vivo and caused the regression of established tumors and depigmentation in lymphopenic hosts. Therapy was independent of vaccination, exogenous cytokine support, CD8+, B, natural killer (NK), and NKT cells. Proper activation of CD4+ T cells in vivo was important for tumor clearance, as naive tumor-specific CD4+ T cells could not completely treat tumor in lymphopenic common gamma chain (γc)–deficient hosts. γc signaling in the tumor-bearing host was important for survival and proper differentiation of adoptively transferred tumor-specific CD4+ T cells. Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4+ T cells

Cross-Sectional Study of Sleep Quantity and Quality and Amnestic and Non-Amnestic Cognitive Function in an Ageing Population: The English Longitudinal Study of Ageing (ELSA)

Background The aim was to investigate the association between sleep disturbances and cognitive function in younger and older individuals from an ageing population. Methods 3,968 male and 4,821 female white participants, aged 50 years and over, from the English Longitudinal Study of Ageing (ELSA) were studied. Information on sleep quality and quantity as well as both amnestic (memory, ACF) and non-amnestic (non-memory, nACF) function was available at Wave 4 (2008). Analysis of covariance was used to evaluate the relationship between sleep and cognitive function. Results After adjustment for multiple confounders in the younger group (50–64 years) duration of sleep explained 15.2% of the variance in ACF (p = 0.003) and 20.6% of nACF (p = 0.010). In the older group (65+ years) the estimates were 21.3% (p<0.001) and 25.6% (p<0.001), respectively. For sleep quality, there was a statistically significant association between sleep quality and both ACF (p<0.001) and nACF (p<0.001) in the older age group, but not in the younger age group (p = 0.586 and p = 0.373, respectively; interaction between age and sleep quality in the study sample including both age groups: p<0.001 for ACF and p = 0.018 for nACF). Sleep quality explained between 15.1% and 25.5% of the variance in cognition. The interaction with age was independent of duration of sleep. At any level of sleep duration there was a steeper association between sleep quality and ACF in the older than the younger group. Conclusions The associations between sleep disturbances and cognitive function vary between younger and older adults. Prospective studies will determine the temporal relationships between sleep disturbances and changes in cognition in different age groups

Arthroscopic hip surgery compared with physiotherapy and activity modification for the treatment of symptomatic femoroacetabular impingement: multicentre randomised controlled trial

Objective To compare arthroscopic hip surgery with physiotherapy and activity modification for improving patient reported outcome measures in patients with symptomatic femoroacetabular impingement (FAI). Design Two group parallel, assessor blinded, pragmatic randomised controlled trial. Setting Secondary and tertiary care centres across seven NHS England sites. Participants 222 participants aged 18 to 60 years with symptomatic FAI confirmed clinically and with imaging (radiography or magnetic resonance imaging) were randomised (1:1) to receive arthroscopic hip surgery (n=112) or a programme of physiotherapy and activity modification (n=110). Exclusion criteria included previous surgery, completion of a physiotherapy programme targeting FAI within the preceding 12 months, established osteoarthritis (Kellgren-Lawrence grade ≥2), and hip dysplasia (centre-edge angle <20 degrees). Interventions Participants in the physiotherapy group received a goal based programme tailored to individual patient needs, with emphasis on improving core stability and movement control. A maximum of eight physiotherapy sessions were delivered over five months. Participants in the arthroscopic surgery group received surgery to excise the bone that impinged during hip movements, followed by routine postoperative care. Main outcome measures The primary outcome measure was the hip outcome score activities of daily living subscale (HOS ADL) at eight months post-randomisation, with a minimum clinically important difference between groups of 9 points. Secondary outcome measures included additional patient reported outcome measures and clinical assessment. Results At eight months post-randomisation, data were available for 100 patients in the arthroscopic hip surgery group (89%) and 88 patients in the physiotherapy programme group (80%). Mean HOS ADL was 78.4 (95% confidence interval 74.4 to 82.3) for patients randomised to arthroscopic hip surgery and 69.2 (65.2 to 73.3) for patients randomised to the physiotherapy programme. After adjusting for baseline HOS ADL, age, sex, and study site, the mean HOS ADL was 10.0 points higher (6.4 to 13.6) in the arthroscopic hip surgery group compared with the physiotherapy programme group (P<0.001)). No serious adverse events were reported in either group. Conclusions Patients with symptomatic FAI referred to secondary or tertiary care achieve superior outcomes with arthroscopic hip surgery than with physiotherapy and activity modification. Trial registration ClinicalTrials.gov NCT01893034

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Rethinking naive realism

Perceptions are externally-directed - they present us with a mind-independent reality, and thus contribute to our abilities to think about this reality, and to know what is objectively the case. But perceptions are also internally-dependent - their phenomenal characters depend on the neuro-computational properties of the subject. A good theory of perception must account for both these facts. But Naive realism has been criticized for failing to accommodate the latter one. This paper evaluates and responds to this criticism. It first argues that a certain version of naive realism, often called “selectionism”, does indeed struggle with the internal-dependence of perceptions. It then develops an alternate version of naive realism which does not. This alternate version, inspired by an idea of Martin's, accommodates the internal-dependence of perceptions by recognizing the role that the subject's neuro-computational properties play in shaping perceptual phenomenology. At the same time, it retains the distinctive naive realist account of the external-directedness of perceptions