Two special classes of space-times admitting a non-null valence two Killing spinor

Non-conformally flat space-times admitting a non-null Killing spinor of valence two are investigated in the Geroch-Held-Penrose formalism. Contrary to popular belief these space-times are not all explicitly known. It is shown that the standard construction hinges on the tacit assumption that certain integrability conditions hold, implying two algebraic relations, KS1 and KS2, for the spin coefficients and the components of the Ricci spinor. An exhaustive list of (conformal classes of) space-times, in which either KS1 or KS2 are violated, is presented. The resulting space-times are each other's Sachs transforms, in general admit no Killing vectors and are characterized by a single arbitrary function.Comment: 12 pages; typos corrected, complex transfo added, references adde

Small cell carcinoma arising in Barrett's esophagus: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Gastrointestinal tract small cell carcinoma is an infrequent and aggressive neoplasm that represents 0.1–1% of gastrointestinal malignancies. Very few cases of small cell esophageal carcinoma arising in Barrett's esophagus have been reported in the literature. An extremely rare case of primary small cell carcinoma of the distal third of the esophagus arising from dysplastic Barrett's esophagus is herein presented.</p> <p>Case presentation</p> <p>A 62-year-old man with gastroesophageal reflux history presented with epigastric pain, epigastric fullness, dysphagia, anorexia, and weight loss. Esophagogastroscopy revealed an ulceroproliferative, intraluminar mass in the distal esophagus obstructing the esophageal lumen. Biopsy showed small cell esophageal carcinoma. Contrast-enhanced chest and abdominal computed tomography demonstrated a large tumor of the distal third of the esophagus without any lymphadenopathy or distant metastasis. Preoperative chemotherapy with cisplatine and etoposide for 3 months resulted in a significant reduction of the tumor. After en block esophagectomy with two field lymph node dissection, proximal gastrectomy, and cervical esophagogastric anastomosis, the patient was discharged on the 14^thpostoperative day. Histopathology revealed a primary small cell carcinoma of the distal third of the esophagus arising from dysplastic Barrett's esophagus. The patient received another 3 month course of postoperative chemotherapy with the same agents and remained free of disease at 12 month review.</p> <p>Conclusion</p> <p>Although small cell esophageal carcinoma is rare and its association with dysplastic Barrett's esophagus is extremely infrequent, the high carcinogenic risk of Barrett's epithelium should be kept in mind. Prognosis is quite unfavorable; a better prognosis might be possible with early diagnosis and treatment strategies incorporating chemotherapy along with oncological radical surgery and/or radiotherapy as part of a multimodality approach. Since treatment protocols are not well established due to the rarity of the neoplasm, multi-institutional studies are needed to obtain sufficiently large populations for investigation and optimization of therapy of the disease.</p

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

New methodology for optimizing transit priority at the network level

A new methodology for optimizing transit road space priority at the network level is proposed. Transit vehicles carry large numbers of passengers within congested road space efficiently. This aids justification of transit priority. Almost all studies that have investigated transit priority lanes focus at a link or an arterial road level, and no study has investigated road space allocation for priority from a network perspective. The aim of the proposed approach is to find the optimum combination of exclusive lanes in an existing operational transport network. Mode share is assumed variable, and an assignment is performed for both private and transit traffic. The problem is formulated by using bilevel programming, which minimizes the total travel time. The approach is applied to an example network and the results are discussed. The approach can identify the optimal combination of transit priority lanes and achieve the global optimum of the objective function. Areas for further development are discussed

Illness perceptions of COVID-19 in Europe: Predictors, impacts and temporal evolution

Objective: Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impacts of IP on perceived stress and preventive behaviors. Methods: This was a time-series-cross-section study of 7, 032 participants from 16 European countries using multilevel modeling from April to June 2020. IP were measured with the Brief Illness Perception Questionnaire. Temporal patterns were observed considering the date of participation and the date recoded to account the epidemiological evolution of each country. The outcomes considered were perceived stress and COVID-19 preventive behaviors. Results: There were significant trends, over time, for several IP, suggesting a small decrease in negativity in the perception of COVID-19 in the community. Age, gender, and education level related to some, but not all, IP. Considering the self-regulation model, perceptions consistently predicted general stress and were less consistently related to preventive behaviors. Country showed no effect in the predictive model, suggesting that national differences may have little relevance for IP, in this context. Conclusion: The present study provides a comprehensive picture of COVID-19 IP in Europe in an early stage of the pandemic. The results shed light on the process of IP formation with implications for health-related outcomes and their evolution. © Copyright © 2021 Dias Neto, Nunes da Silva, Roberto, Lubenko, Constantinou, Nicolaou, Lamnisos, Papacostas, Höfer, Presti, Squatrito, Vasiliou, McHugh, Monestès, Baban, Alvarez-Galvez, Paez-Blarrina, Montesinos, Valdivia-Salas, Ori, Lappalainen, Kleszcz, Gloster, Karekla and Kassianos

Patterns of psychological responses among the public during the early phase of COVID-19: A cross-regional analysis

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological flexibility, prosociality, coping and mental health, socio-demographics, lockdown-related variables and COVID-19 status were assessed. Results showed that psychological flexibility was the only significant mediator in the relationship between illness perceptions toward COVID-19 and mental health across all regions (all ps = 0.001–0.021). Seeking social support was the significant mediator across subgroups (all ps range = <0.001–0.005) except from the Hong Kong sample (p = 0.06) and the North and South American sample (p = 0.53). No mediation was found for problem-solving (except from the Northern European sample, p = 0.009). Prosociality was the significant mediator in the Hong Kong sample (p =0.016) and the Eastern European sample (p = 0.008). These findings indicate that fostering psychological flexibility may help to mitigate the adverse mental impacts of COVID-19 across regions. Roles of seeking social support, problem-solving and prosociality vary across regions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Mental Health Status of Healthcare Workers During the COVID-19 Outbreak An International Study

Background: The COVID-19 pandemic is a massive health crisis that has exerted enormous physical and psychological pressure. Mental healthcare for healthcare workers (HCWs) should receive serious consideration. This study served to determine the mental-health outcomes of 1,556 HCWs from 45 countries who participated in the COVID-19 IMPACT project, and to examine the predictors of the outcomes during the first pandemic wave. Methods: Outcomes assessed were self-reported perceived stress, depression symptom, and sleep changes. The predictors examined included sociodemographic factors and perceived social support. Results: The results demonstrated that half of the HCWs had moderate levels of perceived stress and symptoms of depression. Half of the HCWs (n = 800, 51.4%) had similar sleeping patterns since the pandemic started, and one in four slept more or slept less. HCWs reported less perceived stress and depression symptoms and higher levels of perceived social support than the general population who participated in the same project. Predictors associated with higher perceived stress and symptoms of depression among HCWs included female sex, not having children, living with parents, lower educational level, and lower social support. Discussion: The need for establishing ways to mitigate mental-health risks and adjusting psychological interventions and support for HCWs seems to be significant as the pandemic continues

Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With KCNC2 Pathogenic Variants

Background and ObjectivesKCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyze the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.MethodsIndividuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.ResultsWe identified novel KCNC2 variants in 18 patients with various forms of epilepsy, including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy, focal epilepsy, and myoclonic-atonic epilepsy. Of the 18 variants, 10 were de novo and 8 were classified as modifying variants. Eight drug-responsive patients became seizure-free using valproic acid as monotherapy or in combination, including severe DEE cases. Functional analysis of 4 variants demonstrated gain of function in 3 severely affected DEE cases and loss of function in 1 case with a milder phenotype (GGE) as the underlying pathomechanisms.DiscussionThese findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability

Mental health and adherence to covid-19 protective behaviors among cancer patients during the covid-19 pandemic: An international, multinational cross-sectional study

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective behaviors of cancer patients in comparison to non-cancer participants. Furthermore, 264 participants from 30 different countries reported being cancer patients. The median age was 51.5 years, 79.9% were female, and 28% had breast cancer. Cancer participants reported higher self-efficacy to follow recommended national guidelines regarding COVID-19 protective behaviors compared to non-cancer participants (p < 0.01). They were less stressed (p < 0.01), more psychologically flexible (p < 0.01), and had higher levels of positive affect compared to non-cancer participants. Amongst cancer participants, the majority (80.3%) reported COVID-19, not their cancer, as their priority during the first wave of the pandemic and females reported higher levels of stress compared to males. In conclusion, cancer participants appeared to have handled the unpredictable nature of the first wave of the pandemic efficiently, with a positive attitude towards an unknown and otherwise frightening situation. Larger, cancer population specific and longitudinal studies are warranted to ensure adequate medical and psychological care for cancer patients