The creativity of cells: aneural irrational cognition.

Evidence of cognition in aneural cells is well-establish in the literature. This paper extends the exploration of the mechanisms of cognition by considering whether or not aneural cells may be capable of irrational cognition, making associations based on coincidental similarities and circumstantial factors. If aneural cells do harness such semiosic qualities, as with higher-level creativity, this might be how they are able to overcome old algorithms and invent tools for new situations. I will look at three examples of irrational learning in aneural systems in terms of semiotics: (1) generalisation in the immune system, based on viral molecular mimicry, whereby immune cells attack the self, which seems to be an overgeneralisation of an icon sign based on mere similarity, not identity, (2) the classical conditioning of pea plants to trope toward wind as a sign of light, which seems to be an association of an index sign based on mere temporal proximity, and (3) a pharmaceutical intervention to prevent pregnancy, using a conjugate to encrypt self with non-self, which seems to be an example of symbol use. We identify irrational cognition easily when it leads to 'wrong' outcomes, but, if it occurs, it may also lead to favourable outcomes and 'creative' solutions.

Systematic review of the diagnosis and management of necrotising otitis externa: Highlighting the need for high-quality research.

OBJECTIVES: To present a systematic review and critical analysis of clinical studies for necrotising otitis externa (NOE), with the aim of informing best practice for diagnosis and management. DESIGN: Medline, Embase, Cochrane Library and Web of Science were searched from database inception until 30 April 2021 for all clinical articles on NOE. The review was registered on PROSPERO (ID: CRD42020128957) and conducted in accordance with PRISMA guidelines. RESULTS: Seventy articles, including 2274 patients were included in the final synthesis. Seventy-three percent were retrospective case series; the remainder were of low methodological quality. Case definitions varied widely. Median patient age was 69.2 years; 68% were male, 84% had diabetes and 10% had no reported immunosuppressive risk factor. Otalgia was almost universal (96%), with granulation (69%) and oedema (76%) the commonest signs reported. Pseudomonas aeruginosa was isolated in 62%, but a range of bacterial and fungal pathogens were reported and 14% grew no organism. Optimal imaging modality for diagnosis or follow-up was unclear. Median antimicrobial therapy duration was 7.2 weeks, with no definitive evidence for optimal regimens. Twenty-one percent had surgery with widely variable timing, indication, or procedure. One-year disease-specific mortality was 2%; treatment failure and relapse rates were 22% and 7%, respectively. CONCLUSION: There is a lack of robust, high-quality data to support best practice for diagnosis and management for this neglected condition. A minimum set of reporting requirements is proposed for future studies. A consensus case definition is urgently needed to facilitate high-quality research.

SARS-CoV-2 vaccine breakthrough infections in Virginia, January 17, 2021 - June 30, 2021.

As COVID-19 vaccines moved from the controlled environment of clinical trials to use in real-world settings, it has been important to evaluate vaccine effectiveness. A retrospective cohort study was designed to identify cases of SARS-CoV-2 infection that occurred between January 17-June 30, 2021 in fully vaccinated Virginia residents. Of the fully vaccinated population of Virginia at the end of the study period (N = 4,271,505), 2445 (0.057 %) were reported to have experienced a vaccine breakthrough infection. Of those, 183 (7.5 %) were reported to have been hospitalized for COVID-19 and 53 (2.2 %) died from COVID-19. There were significant differences in vaccine effectiveness over time between both mRNA vaccines and the Janssen vaccine. Increasing age, pre-existing medical conditions, and male sex were associated with severe outcomes (hospitalization or death). Persons at greater risk for severe outcomes should continue to take precautions to prevent SARS-CoV-2 infection, even if fully vaccinated.

Keratoacanthoma in the External Auditory Canal.

A 63-year-old male presented with a prolonged history of bilateral ear discharge, otalgia, and hearing loss. The patient required a significant number of investigations prior to obtaining a diagnosis. Subsequent investigations identified keratoacanthoma affecting the external ear canal (EAC). There has been no case report of keratoacanthoma within the EAC till now. The only risk factor identified for the development of keratoacanthoma, in this case, was the frequent use of earbuds and subsequent long-term trauma associated with a retained bud. The histology of keratoacanthoma is difficult to differentiate from that of squamous cell carcinoma but this is essential for the ear, nose, throat (ENT) multi-disciplinary team.

High performance in risk stratification of intraductal papillary mucinous neoplasms by confocal laser endomicroscopy image analysis with convolutional neural networks (with video).

BACKGROUND AND AIMS: EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) can differentiate high-grade dysplasia/adenocarcinoma (HGD-Ca) in intraductal papillary mucinous neoplasms (IPMNs) but requires manual interpretation. We sought to derive predictive computer-aided diagnosis (CAD) and artificial intelligence (AI) algorithms to facilitate accurate diagnosis and risk stratification of IPMNs. METHODS: A post hoc analysis of a single-center prospective study evaluating EUS-nCLE (2015-2019; INDEX study) was conducted using 15,027 video frames from 35 consecutive patients with histopathologically proven IPMNs (18 with HGD-Ca). We designed 2 CAD-convolutional neural network (CNN) algorithms: (1) a guided segmentation-based model (SBM), where the CNN-AI system was trained to detect and measure papillary epithelial thickness and darkness (indicative of cellular and nuclear stratification), and (2) a reasonably agnostic holistic-based model (HBM) where the CNN-AI system automatically extracted nCLE features for risk stratification. For the detection of HGD-Ca in IPMNs, the diagnostic performance of the CNN-CAD algorithms was compared with that of the American Gastroenterological Association (AGA) and revised Fukuoka guidelines. RESULTS: Compared with the guidelines, both n-CLE-guided CNN-CAD algorithms yielded higher sensitivity (HBM, 83.3%; SBM, 83.3%; AGA, 55.6%; Fukuoka, 55.6%) and accuracy (SBM, 82.9%; HBM, 85.7%; AGA, 68.6%; Fukuoka, 74.3%) for diagnosing HGD-Ca, with comparable specificity (SBM, 82.4%; HBM, 88.2%; AGA, 82.4%; Fukuoka, 94.1%). Both CNN-CAD algorithms, the guided (SBM) and agnostic (HBM) models, were comparable in risk stratifying IPMNs. CONCLUSION: EUS-nCLE-based CNN-CAD algorithms can accurately risk stratify IPMNs. Future multicenter validation studies and AI model improvements could enhance the accuracy and fully automatize the process for real-time interpretation.

Preliminary Use of Indocyanine Green Fluorescence Angiography and Value in Predicting the Vascular Supply of Tissues Needed to Perform Cloacal, Anorectal Malformation, and Hirschsprung Reconstructions.

INTRODUCTION: Reconstructive techniques for cloaca, anorectal malformations (ARM), and Hirschsprung disease (HD) may require intestinal flaps on vascular pedicles for vaginal reconstruction and/or colonic pull-throughs. Visual assessment of tissue perfusion is typically the only modality used. We investigated the utility of intraoperative indocyanine green fluorescence angiography (ICG-FA) and hypothesized that it would be more accurate than the surgeon's eye. MATERIALS AND METHODS: Thirteen consecutive patients undergoing cloacal reconstruction (9), HD (3), and ARM repair (1) underwent ICG-FA laser SPY imaging to assess colonic, rectal, vaginal, and neovaginal tissue perfusion following intraoperative visual clinical assessment. Operative findings were correlated with healing at 6 weeks, 3 months, and 1 year postoperatively. RESULTS: ICG-FA resulted in a change in the operative plan in 4 of the 13 (31%) cases. In three cases, ICG-FA resulted in the distal bowel being transected at a level (>10 cm) higher than originally planned, and in one case the distal bowel was discarded, and the colostomy used for pull-through. CONCLUSION: ICG-FA correctly identified patients who might have developed a complication from poor tissue perfusion. Employing this technology to assess rectal or neovaginal pull-throughs in cloacal reconstructions, complex HD, and ARM cases may be a valuable technology.

Heteronomy in the arts field: state funding and British arts organizations.

For Bourdieu, the field of cultural production is comprised of an autonomous and a heteronomous sector. A heteronomous sector is one that is interpenetrated by the commercial field. I discuss an arena that, until recently, was part of the relatively autonomous sector in the field of cultural production - the supported arts sector in the United Kingdom - and argue that it became more heteronomous, due to the penetration by the state. Heteronomy due to the commercial field is present but secondary to, and driven by, the actions of the state. Political parties' attempts to diffuse and legitimate a particular economic ideology have led to state demands that arts institutions adopt neoliberal business practices in exchange for funding. Government giving to the arts, previously at arm's length, proved to be a Faustian bargain that demanded significant repayment in the form of lost autonomy. Coercive pressures from the state, enacted over time, show how the domination of one field over another can occur, even when the domination is resisted.

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis.

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy.

Head and neck teratomas in children--A series of 23 cases at Great Ormond Street Hospital.

OBJECTIVE: Head and neck teratomas are rare and malignant change is rarer still. This is a report detailing all of the teratomas treated by the ear, nose and throat or craniofacial teams over the last 28 years at our institution. Examining the common presenting and radiological features as well as our success rates compared to the current literature. METHOD: A retrospective review of all cases presenting to our institution with a head and neck teratoma were analysed. Data regarding the following characteristics were collected: antenatal history, clinical features, biological serum makers, radiological and pathological characteristics. Surgical treatment, rates of reoccurrence and the degree of post-operative follow up were also analysed. RESULTS: 23 cases in total were included: 8 cervical, 6 nasopharyngeal, 5 thyroid, 2 thymus, 2 temporal. One had malignant change. The majority of children presented at birth with respiratory distress, 5 cases were picked up antenatally and one case presented at 10 years of age. All were treated surgically; with complete excision in 20 patients. No clinical recurrence occurred but further surgery was performed for radiologically suspected residual disease in one case. DISCUSSION: This is the largest detailed case series in literature in regard to head and neck teratomas. Illustrating that this is frequently a benign disease process disease in the head and neck region and has an excellent long term prognosis following surgery. In the situation of incomplete resection careful meticulous follow up with radiological imaging and a multidisciplinary team approach is a safe and viable alternative.

Primary cervical ganglioneuroblastoma.

OBJECTIVES: Ganglioneuroblastomas represent a histological subgroup of the rare neuroblastic tumours with intermediate malignant potential arising from neural crest progenitor cells of sympathetic nerves. Diagnosis can often be difficult based on imaging alone. We describe 4 cases of children presenting with a solitary neck mass with histology ultimately revealing ganglioneuroblastoma. METHODS: A retrospective case note review was carried out of all patients with cervical ganglioneuroblastoma seen at Great Ormond Street Hospital, UK. RESULTS: Mean age at presentation was 5 years. Based on imaging, the initial diagnoses for three of the cases were: lymphatic malformation, carotid body tumour, paraganglioma, respectively, whilst the remaining case had an immediate incisional biopsy revealing the correct diagnosis. All cases were managed by surgical excision with no evidence of recurrence after a median follow up of 6 years. CONCLUSION: Otolaryngologists should be aware of ganglioneuroblastoma when establishing the differential diagnosis of a child presenting with a neck mass. Biopsy is recommended as the gold standard investigation to avoid an incorrect diagnosis.

Vulnerability in speed of visuomotor ability.

The aim of this report is to illustrate the utility of neurocognitive testing as an investigative method to establish the presence of persistent effects of concussive brain injury amongst players of a contact sport with high risk of such injury. The report reviews the outcomes of three previously published neuropsychological studies on South African Rugby Union (hereafter 'rugby') from school through to the national adult level. The diagnostic utility of differential effects per se, as well as differential practice effects on visuomotor function, as a means of distinguishing poorer neurocognitive outcome for rugby versus demographically equivalent noncontact sports players, is described. From various methodological angles, at each level of play, the reviewed studies attest to the presence of long-term vulnerability in visuomotor speed in association with participation in rugby, in turn implicating diffuse frontotemporal dysfunction due to repetitive concussive and subconcussive injury amongst rugby players. As visuomotor speed is a prime function called upon for optimal scholastic and occupational performance, the robustly demonstrated decrement is of immediate clinical importance. Of critical heuristic relevance, however, is evidence of residual brain dysfunction in association with rugby as early as school level, which may ultimately be the precursor of chronic traumatic encephalopathy.

Practice effects reveal visuomotor vulnerability in school and university rugby players.

This article reports on three pre- versus post-season prospective studies in which male university and high school contact sport players predominantly of Rugby Union (hereafter rugby) were compared with age, education, and IQ equivalent non-contact sport controls on the ImPACT (Immediate Postconcussion Assessment and Cognitive Testing) test. All analyses revealed a relative absence of practice effects on the Visual Motor Speed (VMS) composite for contact sport groups compared with controls. The VMS data for rugby players from each study were pooled and subjected to additional analysis (Rugby, n = 145; Controls, n = 106). Controls revealed significant improvement over the season (p < .001), whereas no learning effect was in evidence for rugby players whose performance remained the same (interaction effect, p = .028). It is apparent that practice effects have diagnostic potential in this context, implicating vulnerability on speeded visuomotor processing in association with participation in rugby. Pointers for further research and concussion management in the individual case are explored.

A case of effective single-session treatment for attention deficit and learning problems in a routine clinical practice: the value of a transdiagnostic approach to case formulation.

This article reports a systematic clinical case study of the psychological assessment and treatment of Daniel (9), a coloured South African boy with a diagnosis of attention deficit hyperactivity disorder (ADHD) (inattentive type). The case is of scientific interest because: (1) there was only a single treatment session, in which contingency management training was delivered to Daniel's parents and teacher; (2) there was evidence for the effectiveness of the intervention immediately and at two-year follow-up; (3) it documents the transportability to a South African context of an intervention developed by overseas research; (4) it documents the central role of case formulation in the delivery of effective psychological interventions; and (5) although Daniel met the criteria for ADHD, he also displayed symptoms of depression and social anxiety and the case supports the use of a transdiagnostic approach to case formulation. The conscientiousness with which his parents and teachers applied the programme was a major factor in the effectiveness of the intervention, and such rapid impact would not be possible where parents and teachers are unavailable or not co-operative. The publication of systematic case studies such as this one is important for the development of a local evidence-based practice in South Africa.

Computerized neuropsychological profiles of South African versus US athletes: a basis for commentary on cross-cultural norming issues in the sports concussion arena.

Computerized programs are widely used as part of the overall medical management of concussion in order to monitor recovery and facilitate safe return-to-play decisions. Typically, neurocognitive profiles of concussed athletes are compared with baseline and/or normative data in the absence of baseline scores. However, the cultural equivalence of performance on neuropsychological tests cannot be assumed and has not been sufficiently researched. The purpose of this study was to investigate the neuropsychological test profiles of the ImPACT (Immediate Postconcussion Assessment and Cognitive Testing) on age-matched South African (SA) rugby and US football players. Participants included 11 257 English-speaking, predominantly white male athletes from multiple SA and US schools and sports organizations in 3 age groups: 11 to 13 years (SA, n = 301; US, n = 775); 14 to 16 years (SA, n = 997; US, n = 4081); and 17 to 21 years (SA, n = 319; US, n = 4784). ImPACT neurocognitive composite scores (verbal and visual memory, visual motor speed, reaction time, impulse control) and the ImPACT total symptom score, derived from the initial baseline testing, were used for comparison purposes between the targeted groups. Independent t-test comparisons revealed overall equivalence between the SA and US athletes on the neurocognitive measures, but they also revealed consistently higher symptom scores for SA athletes in association with clinically relevant effect sizes. It was concluded that US neurocognitive normative data on the ImPACT test are appropriate for use on South African athletes whose first language is English, whereas culture-specific sensitivity for symptom reporting on this same population should be taken into consideration for management purposes. It is argued that neurocognitive equivalence is less likely to apply in educationally disadvantaged populations. The use of registered psychologists is deemed necessary to provide contextualized interpretations of computerized test scores, thereby protecting against misdiagnosis that may occur within the concussion management arena via actuarial approaches that fail to take sociocultural complexities into account.

Unexplained hypoglycaemia on a pump.

A 10-year-old boy on an insulin pump with frequent episodes of hypoglycaemia, admitted to administering insulin to cover sweet intake using the pump prime function, thereby bypassing the bolus history that his mother monitored. This case demonstrates children's resourcefulness and technical abilities, and the difficulties parents experience in providing appropriate support.

Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex.

Recognition memory requires judgments of the previous occurrence of stimuli made on the basis of the relative familiarity of individual objects, or by integrating information concerning objects and location, or by using recency information. The present study examined the role of the medial prefrontal cortex (mPFC) and perirhinal cortex (PRH) in these distinct recognition memory processes using a series of behavioral tests: a novel object preference task, an object-in-place task, and a temporal order memory task. Also, a disconnection procedure was used to test whether these regions form components of an integrated system for recognition memory. Male DA rats received bilateral lesions in the PRH or mPFC or unilateral lesions placed in both cortices in either the same (PRH-mPFC IPSI) or contralateral (PRH-mPFC CONTRA) hemispheres. A fifth group underwent sham surgery (SHAM). In the object-in-place and temporal order memory tasks, the PRH, mPFC, and PRH-mPFC CONTRA groups were significantly impaired. However, performance in the novel object preference task was only impaired in the PRH group. No group was impaired in the object location task. These results demonstrate that the mPFC and PRH are crucial for object-in-place associational and recency discriminations, whereas the PRH but not the mPFC is important for the discrimination of novel and familiar individual objects. Importantly, these results provide direct support for the hypothesis that to make discriminations based on associational or recency information, both cortical regions operate within an integrated neural network for recognition memory.