How instructions modify perception: An fMRI study investigating brain areas involved in attributing human agency

Behavioural studies suggest that the processing of movement stimuli is influenced by beliefs about the agency behind these actions. The current study examined how activity in social and action related brain areas differs when participants were instructed that identicalmovement stimuli were either human or computer generated.Participants viewed a series of point-light animation figures derived frommotion-capture recordings of amoving actor, while functional magnetic resonance imaging (fMRI) was used to monitor patterns of neural activity. The stimuli were scrambled to produce a range of stimulus realism categories; furthermore, before each trial participants were told that they were about to view either a recording of human movement or a computersimulated pattern of movement. Behavioural results suggested that agency instructions influenced participants' perceptions of the stimuli. The fMRI analysis indicated different functions within the paracingulate cortex: ventral paracingulate cortex was more active for human compared to computer agency instructed trials across all stimulus types, whereas dorsal paracingulate cortex was activated more highly in conflicting conditions (human instruction, lowrealismor vice versa). These findings support the hypothesis that ventral paracingulate encodes stimuli deemed to be of human origin,whereas dorsal paracingulate cortex is involvedmore in the ascertainment of human or intentional agency during the observation of ambiguous stimuli. Our results highlight the importance of prior instructions or beliefs on movement processing and the role of the paracingulate cortex in integrating prior knowledge with bottom-up stimuli

The role of discharge variability in the formation and preservation of alluvial sediment bodies

Extant, planform-based facies models for alluvial deposits are not fully fit for purpose, because they over-emphasise plan form whereas there is little in the alluvial rock record that is distinctive of any particular planform, and because the planform of individual rivers vary in both time and space. Accordingly, existing facies models have limited predictive capability. In this paper, we explore the role of inter-annual peak discharge variability as a possible control on the character of the preserved alluvial record. Data from a suite of modern rivers, for which long-term gauging records are available, and for which there are published descriptions of subsurface sedimentary architecture, are analysed. The selected rivers are categorized according to their variance in peak discharge or the coefficient of variation (CVQp = standard deviation of the annual peak flood discharge over the mean annual peak flood discharge). This parameter ranges over the rivers studied between 0.18 and 1.22, allowing classification of rivers as having very low ( 0.90) annual peak discharge variance. Deposits of rivers with very low and low peak discharge variability are dominated by cross-bedding on various scales and preserve macroform bedding structure, allowing the interpretation of bar construction processes. Rivers with moderate values preserve mostly cross-bedding, but records of macroform processes are in places muted and considerably modified by reworking. Rivers with high and very high values of annual peak discharge variability show a wide range of bedding structures commonly including critical and supercritical flow structures, abundant in situ trees and transported large, woody debris, and their deposits contain pedogenically modified mud partings and generally lack macroform structure. Such a facies assemblage is distinctively different from the conventional fluvial style recorded in published facies models but is widely developed both in modern and ancient alluvial deposits. This high-peak-variance style is also distinctive of rivers that are undergoing contraction in discharge over time because of the gradual annexation of the channel belt by the establishment of woody vegetation. We propose that discharge variability, both inter-annual peak variation and “flashiness” may be a more reliable basis for classifying the alluvial rock record than planform, and we provide some examples of three classes of alluvial sediment bodies (representing low, intermediate, and high/very high discharge variability) from the rock record that illustrate this point

Aragonite bias exhibits systematic spatial variation in the late Cretaceous Western Interior Seaway, North America

Preferential dissolution of the biogenic carbonate polymorph aragonite promotes preservational bias in shelly marine faunas. Whilst field studies have documented the impact of preferential aragonite dissolution on fossil molluscan diversity, its impact on regional and global biodiversity metrics is debated. Epicontinental seas are especially prone to conditions which both promote and inhibit preferential dissolution, which may result in spatially extensive zones with variable preservation. Here we present a multi-faceted evaluation of aragonite dissolution within the late Cretaceous Western Interior Seaway of North America. Occurrence data of molluscs from two time intervals (Cenomanian-Turonian boundary, early Campanian) are plotted on new high-resolution paleogeographies to assess aragonite preservation within the seaway. Fossil occurrences, diversity estimates and sampling probabilities for calcitic and aragonitic fauna were compared in zones defined by depth and distance from the seaway margins. Apparent range sizes, which could be influenced by differential preservation potential of aragonite between separate localities, were also compared. Our results are consistent with exacerbated aragonite dissolution within specific depth zones for both time slices, with aragonitic bivalves additionally showing a statistically significant decrease in range size compared to calcitic fauna within carbonate-dominated Cenomanian-Turonian strata. However, we are unable to conclusively show that aragonite dissolution impacted diversity estimates. Therefore, whilst aragonite dissolution is likely to have affected the preservation of fauna in specific localities, time averaging and instantaneous preservation events preserve regional biodiversity. Our results suggest that the spatial expression of taphonomic biases should be an important consideration for paleontologists working on paleobiogeographic problems

Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery

High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P < .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P < .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post–R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles

Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

Introduction: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicentre observational study evaluating bendamustine toxicity in real-world practice. Methods: Patients receiving at least one dose of bendamustine (B) +/- rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details and grade 3-5 adverse events (AEs) were analysed. Results: 323 patients were enrolled from 9 NHS hospitals. Most patients (96%) received BR and 46% R maintenance. 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%), and the relative risk highest during maintenance (54%), induction (34%) and follow-up (28%). Toxicity led to permanent treatment discontinuation in 13% of patients, and 2.8% died of bendamustine-related infections (n=5), myelodysplastic syndrome (n=3), and cardiac disease (n=1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor pre-induction PS, poor pre-maintenance PS, abnormal pre-induction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3/10 opportunistic infections occurred despite prophylaxis. Conclusion: In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to trial populations of younger, fitter patients. Poor PS, mantle cell histology and maintenance rituximab were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death warranting extended antimicrobial prophylaxis and infectious surveillance, especially in maintenance-treated patients

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

The effects of juvenile hormone on the development, behaviour and electrophysiology of Locusta migratoria

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