Gravitational collapse of a Hagedorn fluid in Vaidya geometry

The gravitational collapse of a high-density null charged matter fluid, satisfying the Hagedorn equation of state, is considered in the framework of the Vaidya geometry. The general solution of the gravitational field equations can be obtained in an exact parametric form. The conditions for the formation of a naked singularity, as a result of the collapse of the compact object, are also investigated. For an appropriate choice of the arbitrary integration functions the null radial outgoing geodesic, originating from the shell focussing central singularity, admits one or more positive roots. Hence a collapsing Hagedorn fluid could end either as a black hole, or as a naked singularity. A possible astrophysical application of the model, to describe the energy source of gamma-ray bursts, is also considered.Comment: 14 pages, 2 figures, to appear in Phys. Rev.

Domain Wall Spacetimes: Instability of Cosmological Event and Cauchy Horizons

The stability of cosmological event and Cauchy horizons of spacetimes associated with plane symmetric domain walls are studied. It is found that both horizons are not stable against perturbations of null fluids and massless scalar fields; they are turned into curvature singularities. These singularities are light-like and strong in the sense that both the tidal forces and distortions acting on test particles become unbounded when theses singularities are approached.Comment: Latex, 3 figures not included in the text but available upon reques

Acute kidney injury in patients treated with immune checkpoint inhibitors

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research

Eye movements in visual search indicate impaired saliency processing in Parkinson's disease

Previous studies have produced contradictory evidence on the nature of the visual search impairment in patients with Parkinson's disease (PD). Eye movements were measured during multi-target search in nine individuals with mild-to-moderate PD. Subjects were asked to click on a response button whenever they judged they were fixating a target for the first time. Compared to age-matched healthy volunteers, PD patients were impaired at efficient search (detecting “+”s amongst “L”s) but not inefficient search (“T”s amongst “L”s). However, these patients had normal memory for locations as indexed by their rate of re-clicking on previously inspected locations. We suggest that the pattern of gaze for efficient search may reflect impaired saliency processing in PD

Co-infection by Semliki forest virus and malarial parasite modulates viral multiplication, pathogenesis and cytokines in mice

Environmental, technological and societal factors continue to have a dramatic effect on infectious diseases worldwide and are considered to be facilitating the emergence of several infectious diseases at a time. Co-infection with different species of viral and malaria infections are currently emerging problems of dual infection in the developing as well as developed countries. Understanding of interactions between the host, malaria and virus infection is of current concern and we have initiated studies to delineate the mechanisms involved during the progression of Semliki forest virus (SFV) and Plasmodium yoelii (P. yoelii) infection in mice. Enhanced virus multiplication and up-regulation of cytokine mRNA level in P. yoelii and SFV co-infected mice were observed on day 4 post-infection compared to respective controls. Collectively, our observations indicate that malaria infection may influence virus multiplication, pathogenesis and up-regulation of cytokine mRNA during co-infection in mice

Co-infection by Semliki forest virus and malarial parasite modulates viral multiplication, pathogenesis and cytokines in mice

Environmental, technological and societal factors continue to have a dramatic effect on infectious diseases worldwide and are considered to be facilitating the emergence of several infectious diseases at a time. Co-infection with different species of viral and malaria infections are currently emerging problems of dual infection in the developing as well as developed countries. Understanding of interactions between the host, malaria and virus infection is of current concern and we have initiated studies to delineate the mechanisms involved during the progression of Semliki forest virus (SFV) and Plasmodium yoelii (P. yoelii) infection in mice. Enhanced virus multiplication and up-regulation of cytokine mRNA level in P. yoelii and SFV co-infected mice were observed on day 4 post-infection compared to respective controls. Collectively, our observations indicate that malaria infection may influence virus multiplication, pathogenesis and up-regulation of cytokine mRNA during co-infection in mice

Revisiting previously searched locations in visual neglect: role of right parietal and frontal lesions in misjudging old locations as new

Right-hemisphere patients with left neglect often demonstrate abnormal visual search, re-examining stimuli to the right while ignoring those to the left. But re-fixations alone do not reveal if patients misjudge whether they have searched a location before. Here, we not only tracked the eye movements of 16 neglect patients during search, but also asked them to click a response button only when they judged they were fixating a target for the very first time. "Re-clicking" on previously found targets would indicate that patients erroneously respond to these as new discoveries. Lesions were mapped with high-resolution MRI. Neglect patients with damage involving the right intraparietal sulcus or right inferior frontal lobe "re-clicked" on previously found targets on the right at a pathological rate, whereas those with medial occipito-temporal lesions did not. For the intraparietal sulcus patients, the probability of erroneous re-clicks on an old target increased with time since first discovering it; whereas for frontal patients it was independent of search time, suggesting different underlying mechanisms in these two types of patient. Re-click deficits correlated with degree of leftward neglect, mainly due to both being severe in intraparietal cases. These results demonstrate that misjudging previously searched locations for new ones can contribute to pathological search in neglect, with potentially different mechanisms being involved in intraparietal versus inferior frontal patients. When combined with a spatial bias to the right, such deficits might explain why many neglect patients often re-examine rightward locations, at the expense of items to their left

Involvement of prefrontal cortex in visual search

Visual search for target items embedded within a set of distracting items has consistently been shown to engage regions of occipital and parietal cortex, but the contribution of different regions of prefrontal cortex remains unclear. Here, we used fMRI to compare brain activity in 12 healthy participants performing efficient and inefficient search tasks in which target discriminability and the number of distractor items were manipulated. Matched baseline conditions were incorporated to control for visual and motor components of the tasks, allowing cortical activity associated with each type of search to be isolated. Region of interest analysis was applied to critical regions of prefrontal cortex to determine whether their involvement was common to both efficient and inefficient search, or unique to inefficient search alone. We found regions of the inferior and middle frontal cortex were only active during inefficient search, whereas an area in the superior frontal cortex (in the region of FEF) was active for both efficient and inefficient search. Thus, regions of ventral as well as dorsal prefrontal cortex are recruited during inefficient search, and we propose that this activity is related to processes that guide, control and monitor the allocation of selective attention