A systematic review of patient reported outcome measures in patients with anti-neutrophil cytoplasmic antibody associated vasculitis.

OBJECTIVES: ANCA associated vasculitis (AAV) is associated with significant morbidity, fatigue, pain and poor health-related quality of life (HRQoL). This review aims to assess the comprehensiveness of existing patient reported outcome measures (PROMs) used in AAV and identify associations with poorer HRQoL outcomes. METHODS: A literature review of studies using PROMs, including those labelled HRQoL in people with AAV as a primary or secondary study outcome were screened and reviewed up to July 2023. Quality was assessed using the Critical Appraisal Skills Programme. RESULTS: A total of 30 articles were included which utilised 22 different PROM tools. 76.7% (n = 23) used the SF-36 or a variation as a generic measure of health status and or HRQoL. Two studies developed a disease specific PROM. The AAV-PRO showed good psychometric properties but potential limitations in capturing all relevant aspects of the disease experience for AAV patients. Factors associated with poorer HRQoL included: neurological and sinonasal involvement, women and younger patients. 86.6% of studies showed no meaningful relationships between the SF-36 and BVAS, VDI or disease duration. Depression and anxiety were common and socioeconomic factors such as unemployment were significantly associated with poorer mental health outcomes. Glucocorticoids were found to be independently associated with worse SF-36 scores. CONCLUSION: Generic PROMs are useful in measuring significant changes but lack sensitivity to specific symptoms and unique AAV-related issues, while existing disease specific PROMs have limitations and may not fully capture AAV patient's perspective on disease and treatment burden.

Robust Coding of Eye Position in Posterior Parietal Cortex despite Context-Dependent Tuning.

Neurons in posterior parietal cortex (PPC) encode many aspects of the sensory world (e.g., scene structure), the posture of the body, and plans for action. For a downstream computation, however, only some of these dimensions are relevant; the rest are "nuisance variables" because their influence on neural activity changes with sensory and behavioral context, potentially corrupting the read-out of relevant information. Here we show that a key postural variable for vision (eye position) is represented robustly in male macaque PPC across a range of contexts, although the tuning of single neurons depended strongly on context. Contexts were defined by different stages of a visually guided reaching task, including (1) a visually sparse epoch, (2) a visually rich epoch, (3) a "go" epoch in which the reach was cued, and (4) during the reach itself. Eye position was constant within trials but varied across trials in a 3 × 3 grid spanning 24° × 24°. Using demixed principal component analysis of neural spike-counts, we found that the subspace of the population response encoding eye position is orthogonal to that encoding task context. Accordingly, a context-naive (fixed-parameter) decoder was nevertheless able to estimate eye position reliably across contexts. Errors were small given the sample size (∼1.78°) and would likely be even smaller with larger populations. Moreover, they were comparable to that of decoders that were optimized for each context. Our results suggest that population codes in PPC shield encoded signals from crosstalk to support robust sensorimotor transformations across contexts.SIGNIFICANCE STATEMENT Neurons in posterior parietal cortex (PPC) which are sensitive to gaze direction are thought to play a key role in spatial perception and behavior (e.g., reaching, navigation), and provide a potential substrate for brain-controlled prosthetics. Many, however, change their tuning under different sensory and behavioral contexts, raising the prospect that they provide unreliable representations of egocentric space. Here, we analyze the structure of encoding dimensions for gaze direction and context in PPC during different stages of a visually guided reaching task. We use demixed dimensionality reduction and decoding techniques to show that the coding of gaze direction in PPC is mostly invariant to context. This suggests that PPC can provide reliable spatial information across sensory and behavioral contexts.

Temporal change and the influence of climate and weather factors on mercury concentrations in Hudson Bay polar bears, caribou, and seabird eggs.

Temporal trends of mercury in Arctic wildlife are inconsistent within and between species and are often insignificant, which limits data interpretation. Recent multivariate analyses have shown that weather and climate factors (e.g. temperatures, sea ice conditions) are related to total Hg (THg) concentrations in wildlife tissues, though relatively few studies have explored these relationships. The present study compared time series of THg concentrations in liver of polar bear (Ursus maritimus, 2007/08-2015/16), eggs of thick-billed murres (Uria lomvia, 1993-2015) and kidney of caribou (Rangifer tarandus groenlandicus, 2006-2015) from the Hudson Bay region of Canada and statistically modelled THg over time with available climate and weather data. Significant temporal trends of THg concentrations were not detected in any species. However, in multivariate models that included time-lagged sea ice freeze up dates, THg concentrations increased 4.4% yr-1 in Qamanirjuaq caribou. Sea ice conditions were also related to THg levels in polar bear liver but not those in eggs of murres, though year was not a signifcant factor. Greater precipitation levels one to two years prior to sampling were associated with greater THg concentrations in polar bears and caribou, likely due to greater deposition, flooding and discharge from nearby wetlands and rivers. Time-lagged Arctic and/or North Atlantic Oscillation (AO/NAO) indices also generated significant, inverse models for all three species, agreeing with relationships in other time series of similar length. The magnitude and direction of many relationships were affected by season, duration of time-lags, and the length of the time series. Our findings support recent observations suggesting that temporal studies monitoring Hg in Arctic wildlife should consider including key climatic or weather factors to help identify consistent variables of influence and to improve temporal analyses of THg time series.

Automated Computational Detection of Disease Activity in ANCA-Associated Glomerulonephritis Using Raman Spectroscopy: A Pilot Study.

Biospectroscopy offers the ability to simultaneously identify key biochemical changes in tissue associated with a given pathological state to facilitate biomarker extraction and automated detection of key lesions. Herein, we evaluated the application of machine learning in conjunction with Raman spectroscopy as an innovative low-cost technique for the automated computational detection of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Consecutive patients with active AAGN and those in disease remission were recruited from a single UK centre. In those with active disease, renal biopsy samples were collected together with a paired urine sample. Urine samples were collected immediately prior to biopsy. Amongst those in remission at the time of recruitment, archived renal tissue samples representative of biopsies taken during an active disease period were obtained. In total, twenty-eight tissue samples were included in the analysis. Following supervised classification according to recorded histological data, spectral data from unstained tissue samples were able to discriminate disease activity with a high degree of accuracy on blind predictive modelling: F-score 95% for >25% interstitial fibrosis and tubular atrophy (sensitivity 100%, specificity 90%, area under ROC 0.98), 100% for necrotising glomerular lesions (sensitivity 100%, specificity 100%, area under ROC 1) and 100% for interstitial infiltrate (sensitivity 100%, specificity 100%, area under ROC 0.97). Corresponding spectrochemical changes in paired urine samples were limited. Future larger study is required, inclusive of assigned variables according to novel non-invasive biomarkers as well as the application of forward feature extraction algorithms to predict clinical outcomes based on spectral features.

Visual perturbation of balance suggests impaired motor control but intact visuomotor processing in Parkinson's disease.

Postural instability marks one of the most disabling features of Parkinson's disease (PD), but it only reveals itself after affected brain areas have already been significantly damaged. Thus there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their center of pressure and their full-body motion, from which we also extracted the center of mass. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants' bodies. Patients exhibited significantly higher sway amplitudes as compared with the control subjects. However, their sway was phase locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by phase locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase locking (PL) across the body revealed a shift of the highest PL values from the upper body toward the hip region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired motor control, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.NEW & NOTEWORTHY A better understanding of visuomotor control in Parkinson's disease (PD) potentially serves as a tool for earlier diagnosis, which is crucial for improving patient's quality of life. In our study, we assess body sway responses to visual perturbations of the balance control system in patients with early-to-mid stage PD, using motion tracking along with recently established phase-locking techniques. Our findings suggest patients at this stage have an impaired muscular stability but intact visuomotor control.

Generating Options and Choosing Between Them Depend on Distinct Forms of Value Representation.

Humans have a remarkable capacity for flexible decision-making, deliberating among actions by modeling their likely outcomes. This capacity allows us to adapt to the specific features of diverse circumstances. In real-world decision-making, however, people face an important challenge: There are often an enormous number of possibilities to choose among, far too many for exhaustive consideration. There is a crucial, understudied prechoice step in which, among myriad possibilities, a few good candidates come quickly to mind. How do people accomplish this? We show across nine experiments (N = 3,972 U.S. residents) that people use computationally frugal cached value estimates to propose a few candidate actions on the basis of their success in past contexts (even when irrelevant for the current context). Deliberative planning is then deployed just within this set, allowing people to compute more accurate values on the basis of context-specific criteria. This hybrid architecture illuminates how typically valuable thoughts come quickly to mind during decision-making.

Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis.

BACKGROUND: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. METHODS: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. RESULTS: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25-36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09-0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16-0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15-3.35]). CONCLUSION: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

Propensity score matched mortality comparisons of peritoneal and in-centre haemodialysis: systematic review and meta-analysis.

BACKGROUND: Accurate comparisons of haemodialysis (HD) and peritoneal dialysis (PD) survival based on observational studies are difficult due to substantial residual confounding that arises from imbalances between treatments. Propensity score matching (PSM) comparisons confer additional advantages over conventional methods of adjustment by further reducing selection bias between treatments. We conducted a systematic review of studies that compared mortality between in-centre HD with PD using a PSM-based approach. METHODS: A sensitive search strategy identified all citations in the PubMed, Cochrane and EMBASE databases from inception through November 2018. Pooled PD versus HD mortality hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. A subsequent meta-regression explored factors to account for between-study variation. RESULTS: The systematic review yielded 214 citations with 17 cohort studies and 113 578 PSM incident dialysis patients. Cohort periods spanned the period 1993-2014. The pooled HR for PD versus HD was 1.06 (95% CI 0.99-1.14). There was considerable variation by country, however, mortality risks for PD versus HD remained virtually unchanged when stratified by geographical region with HRs of 1.04 (95% CI 0.94-1.15), 1.14 (95% CI 0.99-1.32) and 0.98 (0.87-1.10) for European, Asian and American cohorts, respectively. Subgroup meta-analyses revealed similar risks for patients with diabetes [HR 1.09 (95% CI 0.98-1.21)] and without diabetes [HR 0.99 (95% CI 0.90-1.09)]. Heterogeneity was substantial (I2 = 87%) and was largely accounted for by differences in cohort period, study type and country of origin. Together these factors explained a substantial degree of between-studies variance (R2 = 90.6%). CONCLUSIONS: This meta-analysis suggests that PD and in-centre HD carry equivalent survival benefits. Reported differences in survival between treatments largely reflect a combination of factors that are unrelated to clinical efficacy.

Inter-trial phase coherence of visually evoked postural responses in virtual reality.

Vision plays a central role in maintaining balance. When humans perceive their body as moving, they trigger counter movements. This results in body sway, which has typically been investigated by measuring the body's center of pressure (COP). Here, we aimed to induce visually evoked postural responses (VEPR) by simulating self-motion in virtual reality (VR) using a sinusoidally oscillating "moving room" paradigm. Ten healthy subjects participated in the experiment. Stimulation consisted of a 3D-cloud of random dots, presented through a VR headset, which oscillated sinusoidally in the anterior-posterior direction at different frequencies. We used a force platform to measure subjects' COP over time and quantified the resulting trajectory by wavelet analyses including inter-trial phase coherence (ITPC). Subjects exhibited significant coupling of their COP to the respective stimulus. Even when spectral analysis of postural sway showed only small responses in the expected frequency bands (power), ITPC revealed an almost constant strength of coupling to the stimulus within but also across subjects and presented frequencies. Remarkably, ITPC even revealed a strong phase coupling to stimulation at 1.5 Hz, which exceeds the frequency range that has generally been attributed to the coupling of human postural sway to an oscillatory visual scenery. These findings suggest phase-locking to be an essential feature of visuomotor control.

Evolution of flexibility and rigidity in retaliatory punishment.

Natural selection designs some social behaviors to depend on flexible learning processes, whereas others are relatively rigid or reflexive. What determines the balance between these two approaches? We offer a detailed case study in the context of a two-player game with antisocial behavior and retaliatory punishment. We show that each player in this game-a "thief" and a "victim"-must balance two competing strategic interests. Flexibility is valuable because it allows adaptive differentiation in the face of diverse opponents. However, it is also risky because, in competitive games, it can produce systematically suboptimal behaviors. Using a combination of evolutionary analysis, reinforcement learning simulations, and behavioral experimentation, we show that the resolution to this tension-and the adaptation of social behavior in this game-hinges on the game's learning dynamics. Our findings clarify punishment's adaptive basis, offer a case study of the evolution of social preferences, and highlight an important connection between natural selection and learning in the resolution of social conflicts.

Bioaccumulation of Polybrominated Diphenyl Ethers and Alternative Halogenated Flame Retardants in a Vegetation-Caribou-Wolf Food Chain of the Canadian Arctic.

The trophodynamics of halogenated flame retardants (HFRs) including polybrominated diphenyl ethers (PBDEs) and alternative HFRs were investigated in the terrestrial, vegetation-caribou-wolf food chain in the Bathurst Region of northern Canada. The greatest concentrations in vegetation (geometric mean of lichens, moss, grasses, willow, and mushrooms) were of the order 2,4,6-tribromophenyl allyl ether (TBP-AE) (10 ng g-1 lw) > BDE47 (5.5 ng g-1 lw) > BDE99 (3.9 ng g-1 lw) > BDE100 (0.82 ng g-1 lw) > 1,2,3,4,5-pentabromobenzene (PBBz) (0.72 ng g-1 lw). Bioconcentration among types of vegetation was consistent, though it was typically greatest in rootless vegetation (lichens, moss). Biomagnification was limited in mammals; only BDE197, BDE206-208 and ∑PBDE biomagnified to caribou from vegetation [biomagnification factors (BMFs) = 2.0-5.1]. Wolves biomagnified BDE28/33, BDE153, BDE154, BDE206, BDE207, and ∑PBDE significantly from caribou (BMFs = 2.9-17) but neither mammal biomagnified any alternative HFRs. Only concentrations of BDE28/33, BDE198, nonaBDEs, and ∑PBDE increased with trophic level, though the magnitude of biomagnification was low relative to legacy, recalcitrant organochlorine contaminants [trophic magnification factors (TMFs) = 1.3-1.8]. Despite bioaccumulation in vegetation and mammals, the contaminants investigated here exhibited limited biomagnification potential and remained at low parts per billion concentrations in wolves.

Habitual control of goal selection in humans.

Humans choose actions based on both habit and planning. Habitual control is computationally frugal but adapts slowly to novel circumstances, whereas planning is computationally expensive but can adapt swiftly. Current research emphasizes the competition between habits and plans for behavioral control, yet many complex tasks instead favor their integration. We consider a hierarchical architecture that exploits the computational efficiency of habitual control to select goals while preserving the flexibility of planning to achieve those goals. We formalize this mechanism in a reinforcement learning setting, illustrate its costs and benefits, and experimentally demonstrate its spontaneous application in a sequential decision-making task.

Simultaneous mapping of transcript ends at single-nucleotide resolution and identification of widespread promoter-associated non-coding RNA governed by TATA elements.

Understanding the relationships between regulatory factor binding, chromatin structure, cis-regulatory elements and RNA-regulation mechanisms relies on accurate information about transcription start sites (TSS) and polyadenylation sites (PAS). Although several approaches have identified transcript ends in yeast, limitations of resolution and coverage have remained, and definitive identification of TSS and PAS with single-nucleotide resolution has not yet been achieved. We developed SMORE-seq (simultaneous mapping of RNA ends by sequencing) and used it to simultaneously identify the strongest TSS for 5207 (90%) genes and PAS for 5277 (91%) genes. The new transcript annotations identified by SMORE-seq showed improved distance relationships with TATA-like regulatory elements, nucleosome positions and active RNA polymerase. We found 150 genes whose TSS were downstream of the annotated start codon, and additional analysis of evolutionary conservation and ribosome footprinting suggests that these protein-coding sequences are likely to be mis-annotated. SMORE-seq detected short non-coding RNAs transcribed divergently from more than a thousand promoters in wild-type cells under normal conditions. These divergent non-coding RNAs were less evident at promoters containing canonical TATA boxes, suggesting a model where transcription initiation at promoters by RNAPII is bidirectional, with TATA elements serving to constrain the directionality of initiation.

Eye-position signals in the dorsal visual system are accurate and precise on short timescales.

Eye-position signals (EPS) are found throughout the primate visual system and are thought to provide a mechanism for representing spatial locations in a manner that is robust to changes in eye position. It remains unknown, however, whether cortical EPS (also known as "gain fields") have the necessary spatial and temporal characteristics to fulfill their purported computational roles. To quantify these EPS, we combined single-unit recordings in four dorsal visual areas of behaving rhesus macaques (lateral intraparietal area, ventral intraparietal area, middle temporal area, and the medial superior temporal area) with likelihood-based population-decoding techniques. The decoders used knowledge of spiking statistics to estimate eye position during fixation from a set of observed spike counts across neurons. Importantly, these samples were short in duration (100 ms) and from individual trials to mimic the real-time estimation problem faced by the brain. The results suggest that cortical EPS provide an accurate and precise representation of eye position, albeit with unequal signal fidelity across brain areas and a modest underestimation of eye eccentricity. The underestimation of eye eccentricity predicted a pattern of mislocalization that matches the errors made by human observers. In addition, we found that eccentric eye positions were associated with enhanced precision relative to the primary eye position. This predicts that positions in visual space should be represented more reliably during eccentric gaze than while looking straight ahead. Together, these results suggest that cortical eye-position signals provide a useable head-centered representation of visual space on timescales that are compatible with the duration of a typical ocular fixation.

The shoot regeneration capacity of excised Arabidopsis cotyledons is established during the initial hours after injury and is modulated by a complex genetic network of light signalling.

Excised plant tissues (explants) can regenerate new shoot apical meristems in vitro, but regeneration rates can be inexplicably variable. Light affects rates of shoot regeneration, but the underlying mechanisms are poorly understood. Here, excised Arabidopsis cotyledons were dark-light shifted to define the timing of explant light sensitivity. Mutants and pharmacological agents were employed to uncover underlying physiological and genetic mechanisms. Unexpectedly, explants were most light sensitive during the initial hours post-excision with respect to shoot regeneration. Only ∼100 µmol m(-2 ) s(-1) of fluorescent light was sufficient to induce reactive oxygen species (ROS) accumulation in new explants. By 48 h post-excision, induction of ROS, or quenching of ROS by xanthophylls, increased or decreased shoot regeneration, respectively. Phytochrome A-mediated signalling suppressed light inhibition of regeneration. Early exposure to blue/UV-A wavelengths inhibited regeneration, involving photoreceptor CRY1. Downstream transcription factor HY5 mediated explant photoprotection, perhaps by promoting anthocyanin accumulation, a pigment also induced by cytokinin. Surprisingly, early light inhibition of shoot regeneration was dependent on polar auxin transport. Early exposure to ethylene stimulated dark-treated explants to regenerate, but inhibited light-treated explants. We propose that variability in long-term shoot regeneration may arise within the initial hours post-excision, from inadvertent, variable exposure of explants to light, modulated by hormones.

The efficacy of initial hydrocortisone administration at preventing posttraumatic distress in adult trauma patients: a randomized trial.

UNLABELLED: OBJECTIVE/INTRODUCTION: Secondary pharmacological interventions have shown promise at reducing the development of posttraumatic stress disorder symptoms (PTSS) in preclinical studies. The present study examined the preliminary efficacy of a 10-day low-dose (20 mg bid) course of hydrocortisone at preventing PTSS in traumatic injury victims. METHODS: Sixty-four traumatic injury patients (34% female) were randomly assigned in a double-blind protocol to receive either a 10-day course of hydrocortisone or placebo initiated within 12 hours of the trauma. One-month and 3-months posttrauma participants completed an interview to assess PTSS and self-report measures of depression and health-related quality of life. RESULTS: Hydrocortisone recipients reported fewer PTSD and depression symptoms, and had greater improvements in health-related quality of life during the first 3 months posttrauma than did placebo recipients. Hydrocortisone recipients who had never received prior mental health treatment had the lowest PTSD scores. CONCLUSION: Low-dose hydrocortisone may be a promising approach to the prevention of PTSD in acutely injured trauma patients, and may be particularly efficacious in acutely injured trauma victims without a history of significant psychopathology.

Intrasaccadic suppression is dominated by reduced detector gain.

Human vision requires fast eye movements (saccades). Each saccade causes a self-induced motion signal, but we are not aware of this potentially jarring visual input. Among the theorized causes of this phenomenon is a decrease in visual sensitivity before (presaccadic suppression) and during (intrasaccadic suppression) saccades. We investigated intrasaccadic suppression using a perceptual template model (PTM) relating visual detection to different signal-processing stages. One stage changes the gain on the detector's input; another increases uncertainty about the stimulus, allowing more noise into the detector; and other stages inject noise into the detector in a stimulus-dependent or -independent manner. By quantifying intrasaccadic suppression of flashed horizontal gratings at varying external noise levels, we obtained threshold-versus-noise (TVN) data, allowing us to fit the PTM. We tested if any of the PTM parameters changed significantly between the fixation and saccade models and could therefore account for intrasaccadic suppression. We found that the dominant contribution to intrasaccadic suppression was a reduction in the gain of the visual detector. We discuss how our study differs from previous ones that have pointed to uncertainty as an underlying cause of intrasaccadic suppression and how the equivalent noise approach provides a framework for comparing the disparate neural correlates of saccadic suppression.

Awareness of implicit attitudes: Large-scale investigations of mechanism and scope.

People can predict their scores on the Implicit Association Test with remarkable accuracy, challenging the traditional notion that implicit attitudes are inaccessible to introspection and suggesting that people might be aware of these attitudes. Yet, major open questions about the mechanism and scope of these predictions remain, making their implications unclear. Notably, people may be inferring their attitudes from externally observable cues (e.g., in the simplest case, their demographic information) rather than accessing them directly. This problem is exacerbated by the fact that, in past work, predictions have been obtained only for a small set of targets, attitudes toward which are demonstrably possible to infer. Here, in an adversarial collaboration with eight preregistered studies (N = 8,011), we interrogate implicit attitude awareness using more stringent tests. We demonstrate that people can predict their implicit attitudes (a) across a broad range of targets (many of which are plausibly difficult to infer without introspection), (b) far more accurately than third-party observers can based on demographic information, and (c) with similar accuracy across two different widely used implicit measures. On the other hand, predictive accuracy (a) varied widely across individuals and attitude targets and (b) was partially explained by inference over nonintrospective cues such as demographic variables and explicit attitudes; moreover, (c) explicit attitudes explained considerably larger portions of variance in predictions than implicit attitudes did. Taken together, these findings suggest that successful predictions of one's implicit attitudes may emerge from multiple mechanisms, including inference over nonintrospective cues and genuine introspective access. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Advances in remission induction therapy for ANCA-associated vasculitis.

Since its first description 40 years ago, huge strides have been made in the management of ANCA-associated vasculitis with improved patient outcomes. The use of cyclophosphamide and/or B-cell depleting therapy alongside glucocorticoids remains the cornerstone of therapy in organ or life-threatening disease, but recent trials have re-evaluated existing treatment strategies, alongside the development of new treatment targets. This has led to refinement of the role of plasma exchange, the use of reduced dosing of oral glucocorticoids with improved patient outcomes, as well as other treatment adjuvants/options of steroid minimization including C5a receptor antagonism and IL-5 inhibition. In this review we examine developments in remission induction therapy for ANCA-associated vasculitis.

Rituximab in the treatment of primary FSGS: time for its use in routine clinical practice?

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and whilst advances have been made in the pathophysiology, diagnostics and management of other podocytopathies, primary FSGS remains the most elusive. It has been assumed for a long time that a circulatory permeability factor exists that mediates podocyte injury, and the potential for autoantibody-mediated disease therefore raises the question as to whether patients may benefit from targeted B-cell therapy with rituximab. The prospective case series of seven patients by Roccatello et al. adds to the limited but growing evidence suggesting that B-cell depletion therapy can be safe and effective in the treatment of primary FSGS. In this editorial we explore the available evidence that suggests how and in whom rituximab may play a role in the management of primary FSGS, as well as the limitations and other potential future treatments. Further research and randomized controlled trials are needed to include larger numbers of patients, feature genetic screening and incorporate data on B-cell kinetics as a potential guide for dosing and frequency of rituximab.