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Purpose The aim of this study was to identify the minimal clinically important difference (MCID) in the Oxford knee score (OKS) and Short Form (SF-) 12 score after total knee arthroplasty (TKA). Methods Prospective pre-operative and 1 year post-operative OKS and SF-12 scores for 505 patients undergoing a primary TKA for osteoarthritis were collected during a one-year period. Patient satisfaction with their (1) patient relief and (2) functional outcome was used as the anchor questions. Their response to each question was recorded using a 5-point Likert scale: excellent, very well, well, fair, and poor. Simple linear regression was used to calculate the MCID for improvement in the OKS and physical component of the SF-12 score according to the level of patient satisfaction with their pain relief and function. Results The OKS improved by 15.5 (95 % CI 14.7–16.4) points and the SF-12 physical component score improved by 10.1 (95 % CI 9.1–11.2) points for the study cohort. The level of patient satisfaction with their pain relief and function correlated with the improvement in the OKS ( r  = 0.56; p  < 0.001, and r  = 0.56; p  < 0.001) and the physical component of the SF-12 score ( r  = 0.51; p  < 0.001, and r  = 0.60; p  < 0.001), respectively. The MCID for the OKS was 5.0 (95 % CI 4.4–5.5) and 4.3 (95 % CI 3.8–4.8) points and for the physical component of the SF-12, it was 4.5 (95 % CI 3.9–5.2) and 4.8 (95 % CI 4.2–5.4) points for pain relief and function, respectively. Conclusion The MCID identified for the OKS and SF-12 physical component score after TKA is the best available estimate and can be used to power studies and ensure that a statistical difference is also recognised by a patient. Level of evidence Retrospective diagnostic study, Level III.

Many of the sitters in this collection were John Singer Sargent's close friends. They are posed informally, sometimes in the act of painting or singing, and it is evident from the bold way they confront us that they are personalities of a creative stamp. Notable as these pictures are as works of art and studies of character, they are also records of relationships, allegiances, influences, and aspirations. This volume aims to explore these friendships in depth and draw out their significance in the story of Sargent's life and the development of his art.

Obsessive-compulsive disorder (OCD) is characterized by distressing thoughts and repetitive behaviors that are interfering, time-consuming, and difficult to control. Although OCD was once thought to be untreatable, the last few decades have seen great success in reducing symptoms with exposure and response prevention (ERP), which is now considered to be the first-line psychotherapy for the disorder. Despite these significant therapeutic advances, there remain a number of challenges in treating OCD. In this review, we will describe the theoretical underpinnings and elements of ERP, examine the evidence for its effectiveness, and discuss new directions for enhancing it as a therapy for OCD.

Understanding how activity patterns in specific neural circuits coordinate an animal’s behavior remains a key area of neuroscience research. Genetic tools and a brain of tractable complexity make Drosophila a premier model organism for these studies. Here, we review the wealth of reagents available to map and manipulate neuronal activity with light.

A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction and attention deficit hyperactivity disorder. As disruption of D2R signaling in the ventral striatum—including the nucleus accumbens (NAc)—impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that postsynaptic D2R overexpression in the NAc specifically increases an animal’s willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc.

Approximately 2%–3% of the population suffers from obsessive–compulsive disorder (OCD). Several brain regions have been implicated in the pathophysiology of OCD, but their various contributions remain unclear. We examined changes in structural and functional neuroimaging before and after a variety of therapeutic interventions as an index into identifying the underlying networks involved. We identified 64 studies from 1990 to 2020 comparing pretreatment and post-treatment imaging of patients with OCD, including metabolic and perfusion, neurochemical, structural, functional and connectivity-based modalities. Treatment class included pharmacotherapy, cognitive–behavioural therapy/exposure and response prevention, stereotactic lesions, deep brain stimulation and transcranial magnetic stimulation. Changes in several brain regions are consistent and correspond with treatment response despite the heterogeneity in treatments and neuroimaging modalities. Most notable are decreases in metabolism and perfusion of the caudate, anterior cingulate cortex, thalamus and regions of prefrontal cortex (PFC) including the orbitofrontal cortex (OFC), dorsolateral PFC (DLPFC), ventromedial PFC (VMPFC) and ventrolateral PFC (VLPFC). Modulating activity within regions of the cortico-striato-thalamo-cortical system may be a common therapeutic mechanism across treatments. We identify future needs and current knowledge gaps that can be mitigated by implementing integrative methods. Future studies should incorporate a systematic, analytical approach to testing objective correlates of treatment response to better understand neurophysiological mechanisms of dysfunction.

Throughout the Ebola virus disease (EVD) epidemic in West Africa, field laboratory testing for EVD has relied on complex, multi-step real-time reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR test would reduce time to results and potentially increase access to testing. We evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR (\"Trombley assay\"). This study was conducted in the Public Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens (n = 218) were collected from suspected or confirmed EVD patients between April 1 and July 20, 2015. BS specimens (n = 71) were collected as part of a national postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were reported as \"invalid\" or \"error\" and were excluded, leaving 211 WB and 64 BS samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%-100%), and 181/189 Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence interval (CI) 91.8%-98.2%). Seven of the eight Trombley-negative, Xpert-positive (Xpert cycle threshold [Ct] range 37.7-43.4) WB samples were confirmed to be follow-up submissions from previously Trombley-positive EVD patients, suggesting a revised Xpert specificity of 99.5% (95% CI 97.0%-100%). For Xpert-positive WB samples (n = 22), Xpert NP Ct values were consistently lower than GP Ct values (mean difference -4.06, 95% limits of agreement -6.09, -2.03); Trombley (NP) Ct values closely matched Xpert NP Ct values (mean difference -0.04, 95% limits of agreement -2.93, 2.84). Xpert results (positive/negative) for WB sampled by pipette versus swab were concordant for 78/79 (98.7%) WB samples, with comparable Ct values for positive results. For BS specimens, 20/20 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 83.2%-100%), and 44/44 Trombley-negative samples were Xpert-negative (specificity 100%, 95% CI 92.0%-100%). This study was limited to testing residual diagnostic samples, some of which had been frozen before use; it was not possible to test the performance of the Xpert Ebola assay at point of care. The Xpert Ebola assay had excellent performance compared to an established RT-PCR benchmark on WB and BS samples in a field laboratory setting. Future studies should evaluate feasibility and performance outside of a biocontainment laboratory setting to facilitate expanded access to testing.

Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.

Personal weather stations (PWS) can provide useful data on urban climates by densifying the number of weather measurements across major cities. They do so at a lower cost than official weather stations by national meteorological services. Despite the increasing use of PWS data, little attention has yet been paid to the underlying socio-economic and environmental inequalities in PWS coverage. Using social deprivation, demographic, and environmental indicators in England and Wales, we characterize existing inequalities in the current coverage of PWS. We find that there are fewer PWS in more deprived areas which also observe higher proportions of ethnic minorities, lower vegetation coverage, higher building height and building surface fraction, and lower proportions of inhabitants under 65 years old. This implies that data on urban climate may be less reliable or more uncertain in particular areas, which may limit the potential for climate adaptation and empowerment in those communities. Crowdsourced personal weather data are sought to cope with weather data scarcity. But, in England and Wales, more deprived areas are less covered. This limits the potential for climate adaptation of communities living in these environments.