A computational account of transsaccadic attentional allocation based on visual gain fields.

Coordination of goal-directed behavior depends on the brain's ability to recover the locations of relevant objects in the world. In humans, the visual system encodes the spatial organization of sensory inputs, but neurons in early visual areas map objects according to their retinal positions, rather than where they are in the world. How the brain computes world-referenced spatial information across eye movements has been widely researched and debated. Here, we tested whether shifts of covert attention are sufficiently precise in space and time to track an object's real-world location across eye movements. We found that observers' attentional selectivity is remarkably precise and is barely perturbed by the execution of saccades. Inspired by recent neurophysiological discoveries, we developed an observer model that rapidly estimates the real-world locations of objects and allocates attention within this reference frame. The model recapitulates the human data and provides a parsimonious explanation for previously reported phenomena in which observers allocate attention to task-irrelevant locations across eye movements. Our findings reveal that visual attention operates in real-world coordinates, which can be computed rapidly at the earliest stages of cortical processing.

Improving the management of open tibia fractures, Malawi.

Objective: To assess the impact of an open fracture intervention bundle on clinical management and patient outcomes of adults in Malawi with open tibia fractures. Methods: We conducted a before-and-after implementation study in Malawi in 2021 and 2022 to assess the impact of an open fracture intervention bundle, including a national education course for clinical officers and management guidelines for open fractures. We recruited 287 patients with open tibia fractures. The primary outcome was a before-and-after comparison of the self-reported short musculoskeletal function assessment score, a measure of patient function. Secondary outcomes included clinical management; and clinician knowledge and implementation evaluation outcomes of 57 health-care providers attending the course. We also constructed multilevel regression models to investigate associations between clinical knowledge, patient function, and implementation evaluation before and after the intervention. Findings: The median patient function score at 1 year was 6.8 (interquartile range, IQR: 1.5 to 14.5) before intervention and 8.4 (IQR: 3.8 to 23.2) after intervention. Compared with baseline scores, we found clinicians' open fracture knowledge scores improved 1 year after the intervention was implemented (mean posterior difference: 1.6, 95% highest density interval: 0.9 to 2.4). However, we found no difference in most aspects of clinicians' open fracture management practice. Conclusion: Despite possible improvement in clinician knowledge and positive evaluation of the intervention implementation, our study showed that there was no overall improvement in clinical management, and weak evidence of worsening patient function 1 year after injury, after implementation of the open fracture intervention bundle.

Modality independent or modality specific? Common computations underlie confidence judgements in visual and auditory decisions.

The mechanisms that enable humans to evaluate their confidence across a range of different decisions remain poorly understood. To bridge this gap in understanding, we used computational modelling to investigate the processes that underlie confidence judgements for perceptual decisions and the extent to which these computations are the same in the visual and auditory modalities. Participants completed two versions of a categorisation task with visual or auditory stimuli and made confidence judgements about their category decisions. In each modality, we varied both evidence strength, (i.e., the strength of the evidence for a particular category) and sensory uncertainty (i.e., the intensity of the sensory signal). We evaluated several classes of computational models which formalise the mapping of evidence strength and sensory uncertainty to confidence in different ways: 1) unscaled evidence strength models, 2) scaled evidence strength models, and 3) Bayesian models. Our model comparison results showed that across tasks and modalities, participants take evidence strength and sensory uncertainty into account in a way that is consistent with the scaled evidence strength class. Notably, the Bayesian class provided a relatively poor account of the data across modalities, particularly in the more complex categorisation task. Our findings suggest that a common process is used for evaluating confidence in perceptual decisions across domains, but that the parameter settings governing the process are tuned differently in each modality. Overall, our results highlight the impact of sensory uncertainty on confidence and the unity of metacognitive processing across sensory modalities.

Chiral Thianthrenes.

The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in some studies of sulfoxides. The two thianthrene sulfoxides have slightly different Rf values, which allowed their separation using flash chromatography on silica. The spots run back-to-back, which posed a challenge for their separation. The pure, separated compounds in solution remain as separate, single spots on a Thin Layer Chromatography (TLC) plate.

When prion disease Isn't suspected: prion disease as the cause of terminal decline in chronic mixed dementia.

Alzheimer's Disease (AD) is the most common cause of dementia, although multiple pathologies are found in nearly half of the cases with clinically diagnosed AD. Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are rare causes of dementia and typically manifest as a rapidly progressive dementia, where symptom onset to dementia most often occurs over the course of months. In this brief report, we describe a patient's typically progressive dementia with a precipitous decline at the end of their life who, on neuropathological evaluation, was found to have multiple neurodegenerative proteinopathies as well as spongiform encephalopathy due to CJD. This case of unsuspected CJD highlights a rare, but epidemiologically important, cause of sudden decline in well-established neurodegenerative dementias.

Using a consensus meeting to enhance fracture care education in low income countries.

BACKGROUND: A key strategy to building surgical capacity in low income countries involves training care providers, particularly in the interventions highlighted by the Lancet Commission for Global Surgery, including the management of open fractures. This is a common injury, especially in areas with a high incidence of road traffic incidents. The aim of this study was to use a nominal group consensus method to design a course on open fracture management for clinical officers in Malawi. METHODS: The nominal group meeting was held over two days, including clinical officers and surgeons from Malawi and the UK with various levels of expertise in the fields of global surgery, orthopaedics and education. The group was posed with questions on course content, delivery and evaluation. Each participant was encouraged to suggest an answer and the advantages and disadvantages of each suggestion were discussed before voting through an anonymous online platform. Voting included use of a Likert scale or ranking available options. Ethical approval for this process was obtained from the College of Medicine Research and Ethics Committee Malawi and the Liverpool School of Tropical Medicine. RESULTS: All suggested course topics received an average score of greater than 8 out of 10 on a Likert scale and were included in the final programme. Videos was the highest ranking option as a method for delivering pre-course material. The highest ranking methods for each course topic included lectures, videos and practicals. When asked what practical skill should be tested at the end of the course, the highest ranking option was "initial assessment". CONCLUSION: This work outlines how a consensus meeting can be used to design an educational intervention to improve patient care and outcomes. Through combining the perspectives of both the trainer and trainee, the course aligns both agendas so that it is relevant and sustainable.

Suicide Via Multiple Shotgun Wounds: A Case Report and Review of Literature.

ABSTRACT: Suicide via multiple gunshot wounds is an uncommonly encountered phenomenon, which is important to recognize in the forensic community. Suicide by multiple shotgun wounds is a fleeting rare entity with few previously reported cases in the literature. In a review of autopsies performed at our institution during a 20-year period from 2000 to 2020, only 4 prior cases of suicide by multiple gunshot wounds were identified with no previously recorded cases of suicide by multiple shotgun wounds. Here we describe the case of a 20-year-old man with a history of depression who was discovered deceased in his secured residence with shotgun wounds of the head, neck, and chest. Because of the presence of 3 shotgun wounds, coupled with concerning initial investigative findings, an autopsy was performed. We illustrate how careful examination of the wounds and thorough investigation can allow for reconstruction of a plausible self-inflicted wound scenario.

Porous and Close Packed Supramolecular Assemblies from 2,4-Difluoronitrobenzene with Three Different Linkers and an n-Butylamine Cap.

A porous structure formed from sheets with cavities and two close packed structures were crystallised from building blocks prepared from 2,4-difluoronitrobenzene, a diamine linker and n-butylamine. The porous structure crystallised from a flexible building block prepared using 1,4-diaminobutane as linker. The close packed structures were prepared using either piperazine or 1,4-bis(aminomethyl)benzene as a linker and have less conformational freedom.

Luminance and Contrast of Images in the THINGS Database.

The THINGS database is a freely available stimulus set that has the potential to facilitate the generation of theory that bridges multiple areas within cognitive neuroscience. The database consists of 26,107 high quality digital photos that are sorted into 1,854 concepts. While a valuable resource, relatively few technical details relevant to the design of studies in cognitive neuroscience have been described. We present an analysis of two key low-level properties of THINGS images, luminance and luminance contrast. These image statistics are known to influence common physiological and neural correlates of perceptual and cognitive processes. In general, we found that the distributions of luminance and contrast are in close agreement with the statistics of natural images reported previously. However, we found that image concepts are separable in their luminance and contrast: we show that luminance and contrast alone are sufficient to classify images into their concepts with above chance accuracy. We describe how these factors may confound studies using the THINGS images, and suggest simple controls that can be implemented a priori or post-hoc. We discuss the importance of using such natural images as stimuli in psychological research.

Spatial structure, phase, and the contrast of natural images.

The sensitivity of the human visual system is thought to be shaped by environmental statistics. A major endeavor in vision science, therefore, is to uncover the image statistics that predict perceptual and cognitive function. When searching for targets in natural images, for example, it has recently been proposed that target detection is inversely related to the spatial similarity of the target to its local background. We tested this hypothesis by measuring observers' sensitivity to targets that were blended with natural image backgrounds. Targets were designed to have a spatial structure that was either similar or dissimilar to the background. Contrary to masking from similarity, we found that observers were most sensitive to targets that were most similar to their backgrounds. We hypothesized that a coincidence of phase alignment between target and background results in a local contrast signal that facilitates detection when target-background similarity is high. We confirmed this prediction in a second experiment. Indeed, we show that, by solely manipulating the phase of a target relative to its background, the target can be rendered easily visible or undetectable. Our study thus reveals that, in addition to its structural similarity, the phase of the target relative to the background must be considered when predicting detection sensitivity in natural images.

A tale of three pandemics: Shining a light on a hidden problem.

An "epidemic" is an event in which a disease, infectious or non-infectious, is actively spreading within a population and designated area. The term "pandemic" is defined as "an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people". The global response to the COVID-19 pandemic has not been seen since the outbreak of Human Immunodeficiency Virus in the early eighties. But there is another unseen pandemic running alongside the current COVID-19 pandemic, which affects a vast number of people, crossing international boundaries and occurring in every single country worldwide. The pandemic of traumatic injuries. Traumatic injuries account for 11% of the current Global Burden of Disease, resulting in nearly 5 million deaths annually and is the third-leading cause of death worldwide. For every trauma-related death, it is estimated that up to 50 people sustain permanent or temporary disabilities. Furthermore, traumatic injuries occur at disproportionately higher rates in low- and middle-income countries, with approximately 90% of injuries and more than 90% of global deaths from injury occurring these countries. Injuries are increasing worldwide, crossing international boundaries and affecting a large number of people, in the same manner Human Immunodeficiency Virus did in the 1980's and COVID-19 is today. The tremendous global effort to tackle the COVID-19 and Human Immunodeficiency Virus pandemics has occurred whilst ignoring the comparable pandemic of injury. Without change and future engagement with policy makers and international donors this disparity is likely to continue.

Sudden Unexpected Death in Epilepsy: A Report of Three Commonly Encountered Anatomic Findings in the Forensic Setting With Recommendations for Best Practices.

ABSTRACT: Sudden unexplained death in epilepsy (SUDEP) is the most common cause of death in children and young adults with epilepsy with epileptic patients harboring a 27 times increased risk of death from SUDEP. Structural brain lesions are encountered in up to 50% of autopsy cases. In this case series, we report 3 previously undiagnosed structural causes of SUDEP discovered at autopsy at our institution including schizencephaly, ganglioglioma, and focal cortical dysplasia. Our major recommendation is in cases with suspected SUDEP, formal neuropathological examination and tissue sampling should be employed to identify and characterize specific potential anatomic etiologies.

Hip fracture mortality in patients co-infected with coronavirus disease 2019: a comparison of the first two waves of the United Kingdom pandemic during the pre-vaccine era.

AIMS: In the UK, deaths associated with COVID-19 have occurred in two waves. Evidence has shown an increase in 30-day mortality for hip fracture patients co-infected with COVID-19. However, there are no studies analysing mortality trends between the first two waves of the UK pandemic. Additionally, hospital versus community acquired COVID-19 infection between the two waves has not been analysed. Furthermore, predictive factors of 30-day mortality have not been fully evaluated. METHODS: Data from two audits conducted by the CHIP collaborative group were used: a published regional audit in England of nine hospitals providing the COVID-19 negative cases and an unpublished UK national audit of 43 hospitals, which provided the COVID-19 positive cases. Data collection for the COVID-19 positive cases was from 23 March to 31 December 2020. September 1, 2020 was used to define the transition between the two waves. RESULTS: There were 517 COVID-19 positive hip fracture patients and 1445 COVID-19 negative hip fracture patients. Overall, 30-day mortality rates were 5.7% in the COVID-19 negative group and 22.4% in the COVID-19 positive patients (p < 0.001). A difference in survival function between the first and second waves was found (p = 0.038). To allow for significant demographic differences, a matched analysis of 185 patients found a 26.5% 30-day mortality in the first wave compared to 21.1% in the second wave (p = 0.222). Within the COVID-19 positive groups, the virus was hospital acquired in 66.7% of cases in the first wave and 72.8% of cases in the second wave (p = 0.130). Independent predictors of mortality were found to include COVID-19 positive status, AMTS ≤ 6, male gender and age. CONCLUSION: There was a reduction in 30-day mortality for hip fracture patients co-infected with COVID-19 between the two UK pandemic waves but this was not statistically significant. There was no reduction in hospital acquired COVID-19 infection between the two waves.

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment. METHODS: We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma, confirmed on histopathological testing, with measurable disease (contrast-enhancing tumor of ≥1 cm and ≤5.5 cm in the greatest dimension). The study evaluated seven doses, ranging between 107 and 1010 50% tissue-culture infectious doses (TCID50), first in a dose-escalation phase and then in a dose-expansion phase. RESULTS: From May 2012 through May 2017, a total of 61 patients were enrolled and received a dose of PVSRIPO. Dose level -1 (5.0×107 TCID50) was identified as the phase 2 dose. One dose-limiting toxic effect was observed; a patient in whom dose level 5 (1010 TCID50) was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed. To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use, dose level 5 was deescalated to reach the phase 2 dose. In the dose-expansion phase, 19% of the patients had a PVSRIPO-related adverse event of grade 3 or higher. Overall survival among the patients who received PVSRIPO reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months. CONCLUSIONS: Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential. The survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. (Funded by the Brain Tumor Research Charity and others; ClinicalTrials.gov number, NCT01491893 .).

Does non-visible haematuria require urgent assessment? A retrospective cohort study from a university teaching hospital.

OBJECTIVES: It is not certain from current evidence which patient groups with non-visible haematuria (NVH) require urgent investigation and which investigations are sufficient. We report referral outcomes data from Scotland to identify patient groups who will benefit from urgent assessment to rule out urological cancer (UC) and whether full set of investigations are necessary in all referred patients. MATERIALS AND METHODS: Data were collected from electronic patient records for patients referred with NVH to secondary care urology services between July 2017 and May 2020. The correlations between risk factors and final diagnosis were assessed using categorical variables in a multivariate logistic regression analysis and using chi-squared models. Statistical analysis was performed using IBM SPSS data editor version 25. RESULTS: Our study cohort comprised 525 patients (43.4% males; median age 66 years), in which UC was diagnosed in 25 patients (4.8%). Age > 60 years had sensitivity and NPV for UC of 92% and 99%, respectively. Univariate and multivariate analysis showed male sex, age ≥ 60 years and smoking were significant predictors of UC in patients with NVH (p < 0.05). There was no significant difference in UC in patients with history of LUTS, anticoagulation and previous UC. CONCLUSION: The risk of urologic cancer in NVH patients is significant and male gender, age ≥ 60 years and smoking are significant predictors of UC. Patients with risk factors of UC require complete assessment of both the upper and lower urinary tract; however, in the absence of risk factors, patients do not require urgent or complete assessment.

Understanding the remarkable difference in liquid crystal behaviour between secondary and tertiary amides: the synthesis and characterisation of new benzanilide-based liquid crystal dimers.

A number of liquid crystal dimers have been synthesised and characterised containing secondary or tertiary (N-methyl) benzanilide-based mesogenic groups. The secondary amides all form nematic phases, and we present the first example of an amide to show the twist-bend nematic (NTB) phase. Only two of the corresponding N-methylated dimers formed a nematic phase and with greatly reduced nematic-isotropic transition temperatures. Characterisation using 2D ROESY NMR experiments, DFT geometry optimisation and X-ray diffraction reveal that there is a change in the preferred conformation of the benzanilide core on methylation, from Z to E. The rotational barrier around the N-C(O) bond has been measured using variable temperature 1H NMR spectroscopy. This dramatic change in shape accounts for the remarkable difference in liquid crystalline behaviour between these secondary and tertiary amide-based materials.

Sudden Unexpected Death in a Child From Acute Myeloid Leukemia.

ABSTRACT: Acute myeloid leukemia can rarely cause sudden, unexpected death in children. Presentation may be non-specific and death may occur in children with no prior medical history. Herein we present the case of a previously healthy 2-year and 2 month-old White girl, who on autopsy, was found to have acute myeloid leukemia with KMT2A rearrangement extensively involving all major thoracic and abdominal organs. This case is presented to the forensic community to discuss the presentation and findings in sudden death caused by acute leukemia. The case highlights when acute leukemia should enter the differential as a potential cause of death, as well as potential resources available in the postmortem workup of acute leukemias.

Crystalline Forms of Trazodone Dihydrates.

In this study, treatment of anhydrous trazodone powder with ammonium carbamate in warm water crystallised two new polymorphs or dihydrates of trazodone after 5 h, whose structures were determined by X-ray single crystal diffraction. Each dihydrate contains infinite zigzag hydrogen-bonded chains of water molecules, which are stabilised by the N4 acceptor atom of the piperazine ring and the pendant carbonyl O1 atom of the triazole ring, as well as other water molecules. The strong dipole moment expected for the O1 atom makes it a good hydrogen bond acceptor for stabilising the chains of water molecules. Each molecule of trazodone has a similar conformation in both hydrates, except for the propyl chains, which adopt different conformations: anti-gauche in the ß hydrate (triazole N-C-C-C and C-C-C-piperazine N) and anti-anti in the γ hydrate. Both piperazine rings adopt chair conformations, and the exocyclic N-C bonds are in equatorial orientations. The Hirshfeld surfaces and two-dimensional fingerprint plots for the polymorphs were calculated using CrystalExplorer17, which indicated contacts significantly shorter than the sum of the van der Waals radii in the vicinity of the piperazine N4 and triazole O1 atoms corresponding to the strong hydrogen bonds accepted by these atoms.

Assessing Industrial Robot agility through international competitions.

Manufacturing and Industrial Robotics have reached a point where to be more useful to small and medium sized manufacturers, the systems must become more agile and must be able to adapt to changes in the environment. This paper describes the process for creating and the lessons learned over multiple years of the Agile Robotics for Industrial Automation Competition (ARIAC) being run by the National Institute of Standards and Technology.

Cyclophosphamide-induced cystitis results in NLRP3-mediated inflammation in the hippocampus and symptoms of depression in rats.

Recent breakthroughs demonstrate that peripheral diseases can trigger inflammation in the brain, causing psychosocial maladies, including depression. While few direct studies have been made, anecdotal reports associate urological disorders with mental dysfunction. Thus, we investigated if insults targeted at the bladder might elicit behavioral alterations. Moreover, the mechanism of neuroinflammation elicited by other peripheral diseases involves the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which is present in microglia in the brain and cleaves and activates proinflammatory cytokines such as IL-1ß. Thus, we further explored the importance of NLRP3 in behavioral and neuroinflammatory changes. Here, we used the well-studied cyclophosphamide (CP)-treated rat model. Importantly, CP and its metabolites do not cross the blood-brain barrier or trigger inflammation in the gut, so that any neuroinflammation is likely secondary to bladder injury. We found that CP triggered an increase in inflammasome activity (caspase-1 activity) in the hippocampus but not in the pons. Evans blue extravasation demonstrated breakdown of the blood-brain barrier in the hippocampal region and activated microglia were present in the fascia dentata. Both changes were dependent on NLRP3 activation and prevented with 2-mercaptoethane sulfonate sodium (Mesna), which masks the effects of the CP metabolite acrolein in the urine. Finally, CP-treated rats displayed depressive symptoms that were prevented by NLRP3 inhibition or treatment with Mesna or an antidepressant. Thus, we conclude that CP-induced cystitis causes NLRP3-dependent hippocampal inflammation leading to depression symptoms in rats. This study proposes the first-ever causative explanation of the previously anecdotal link between benign bladder disorders and mood disorders.