Travelling waves for a non-monotone bistable equation with delay: existence and oscillations

We consider a bistable (0\textless{}\theta\textless{}1 being the three constant steady states) delayed reaction diffusion equation, which serves as a model in population dynamics. The problem does not admit any comparison principle. This prevents the use of classical technics and, as a consequence, it is far from obvious to understand the behaviour of a possible travelling wave in $+\infty$. Combining refined {\it a priori} estimates and a Leray Schauder topological degree argument, we construct a travelling wave connecting 0 in $-\infty$ to \lq\lq something" which is strictly above the unstable equilibrium $\theta$ in $+\infty$. Furthemore, we present situations (additional bound on the nonlinearity or small delay) where the wave converges to 1 in $+\infty$, whereas the wave is shown to oscillate around 1 in $+\infty$ when, typically, the delay is large

The FANCD2-FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2

The Fanconi Anemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2-FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here we report the first structural insight into the human FANCD2-FANCI complex by obtaining the cryo- EM structure. The complex contains an inner cavity, large enough to accommodate a double stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain is observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2-FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain

Locating the ventral intermediate thalamic nucleus for deep brain stimulation surgery: analysis of a case series comparing CT and MR targeting

\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Background: Deep brain stimulation (DBS) surgery targeting the ventral intermediate thalamic nucleus (Vim) has proven efficacy in the treatment of tremor. Aims: The primary aim is to investigate whether there is a statistically significant difference in patient outcomes when CT-guided targeting of the Vim is compared with MRI-guided targeting. Methods: This is a retrospective study concerning patients undergoing Vim-targeted DBS at the Department of Neurosurgery, Royal Victoria Infirmary in Newcastle (9th August 2012 to 4th January 2019). Fahn–Tolosa–Marin Tremor Scale (FTM TS) and EQ-5D scores were collected from patient notes. Statistical analysis was performed using IBM\uae SPSS\uae Statistics Version 24. Independent samples t-tests were used to compare means. Results: Independent samples t-test did not reveal a statistically significant difference between CT (n = 10; FTM TS mean = 65.40, SD = 11.40; EQ-5D mean = 39.50, SD = 17.87) and MR (n = 7; FTM TS mean = 60.57, SD = 7.50; EQ-5D mean = 32.14, SD = 9.94) groups in pre-surgery FTM TS (t(15) = 0.977, p = 0.344) and EQ-5D (t(15) = 0.982, p = 0.342) scores. No statistically significant difference between the CT (FTM TS mean = 24.12, SD = 20.47; EQ-5D mean = 75.56, SD = 15.63) and MR (FTM TS mean = 22.86, SD = 6.72; EQ-5D mean = 70.43, SD = 15.48) groups was revealed at 1 year assessment of FTM TS (t(14) = 0.155, p = 0.879) and EQ-5D (t(14) = 0.654, p = 0.524). The median difference between pre- and post-surgery FTM TS and EQ-5D scores in the CT group at 1 year was 43.00 and 35.00, respectively. The MR patient group median difference in pre- and post-surgery at 1 year was 35.00 and 35.00 respectively. Conclusion: No statistically significant difference between CT and MR image-guided targeting patient groups was detected

“Turning Point”: Evaluating the Impact of a Three-Month UK-Based Clinical Education Training Programme for Physicians from a Chinese Medical School

Purpose: Transnational faculty development programmes are increasingly popular in medicine, although evaluation of such activities rarely considers longer-term outcomes or the impact of language training. This study attempts to fill this gap by evaluating the lasting impacts of a three-month clinical education and English language training programme at University College London Medical School, UK, for medical educators from Ningbo University, China. Methods: In-depth, semi-structured interviews were conducted in China with 41 participants who had completed the programme between 2013 and 2018. Interview data were analysed using an inductive thematic analysis, and themes were categorised using the four primary components of the faculty development model outlined by Irby and O’Sullivan (2011) – context, facilitator, programme, and participant. Results: Contextual impacts included the importance of participants learning in the familiar environment of their own clinical discipline, the cultural enrichment gained by spending time overseas, reflecting on differences in health-care systems, and attempts to implement and disseminate learning on return to China. Facilitator-related factors included new insights into the student–educator relationship and valuing the support of programme mentors. Programme-related factors included exposure to new teaching methods and technical presentation skills, the challenges of navigating observership placements, spoken English language and pronunciation issues, and establishing a peer network of medical educators. Participant-related factors included improved confidence and self-reflection, adjusting educational approaches for different student groups, and career development in medical education. Conclusion: Participants gained teaching confidence from their engagement in the programme and many described it as a turning point in their careers as educators. Although in the period after attending, individuals changed their own practices and influenced colleagues within their organisation, often through taking on senior roles, and systematic education changes were generally not implemented. Dedicated English language classes and clinical placements were considered the most positive features of the programme

Diagnostic value of tumour markers CA-125 and CEA in the diagnostics of malignant pleural fluids

Copyright: Copyright 2016 Elsevier B.V., All rights reserved.The significance of carbohydrate (cancer) antigen 125 (Ca-125) and carcinoembryonic antigen (CEA) tumour markers levels in differential diagnostics of malignant and benign pleural effusion was studied. Within this prospective study, 121 patients with fluids of various aetiology in the pleural cavity were analysed. Malignant pleural effusion was detected in 55 patients, parapneumonic effusion in 28 patients, transudative effusion of cardiac origin in 31 patients, pancreatitis in one patient and tuberculous pleurisy in five patients. The highest accuracy in diagnosis of malignancy was observed for Ca-125 and CEA levels in the pleural fluid: 75.2% at cut-off value ≥1452 U/mL and 76.9% at cut-off value ≥6.58 ng/mL, respectively. We conclude that the level of tumour markers in pleural fluid has additional diagnostic significance in the differential diagnosis of malignant and benign pleural effusions.publishersversionPeer reviewe

Corrigendum: Evidence for the cytoplasmic localization of the L-α-Glycerophosphate oxidase in members of the "Mycoplasma mycoides cluster".

[This corrects the article DOI: 10.3389/fmicb.2019.01344.]

Influence of severe plastic deformation on the precipitation hardening of a FeSiTi steel

The combined strengthening effects of grain refinement and high precipitated volume fraction (~6at.%) on the mechanical properties of FeSiTi alloy subjected to SPD processing prior to aging treatment were investigated by atom probe tomography and scanning transmission electron microscopy. It was shown that the refinement of the microstructure affects the precipitation kinetics and the spatial distribution of the secondary hardening intermetallic phase, which was observed to nucleate heterogeneously on dislocations and sub-grain boundaries. It was revealed that alloys successively subjected to these two strengthening mechanisms exhibit a lower increase in mechanical strength than a simple estimation based on the summation of the two individual strengthening mechanisms

Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin

The cornified envelope is a layer of transglutaminase cross-linked protein that is assembled under the plasma membrane of keratinocytes in the outermost layers of the epidermis. We have determined the cDNA sequence of one of the proteins that becomes incorporated into the cornified envelope of cultured epidermal keratinocytes, a protein with an apparent molecular mass of 195 kD that is encoded by a mRNA with an estimated size of 6.3 kb. The protein is expressed in keratinizing and nonkeratinizing stratified squamous epithelia and in a number of other epithelia. Expression of the protein is upregulated during the terminal differentiation of epidermal keratinocytes in vivo and in culture. Immunogold electron microscopy was used to demonstrate an association of the 195-kD protein with the desmosomal plaque and with keratin filaments in the differentiated layers of the epidermis. Sequence analysis showed that the 195-kD protein is a member of the plakin family of proteins, to which envoplakin, desmoplakin, bullous pemphigoid antigen 1, and plectin belong. Envoplakin and the 195-kD protein coimmunoprecipitate. Analysis of their rod domain sequences suggests that the formation of both homodimers and heterodimers would be energetically favorable. Confocal immunofluorescent microscopy of cultured epidermal keratinocytes revealed that envoplakin and the 195-kD protein form a network radiating from desmosomes, and we speculate that the two proteins may provide a scaffolding onto which the cornified envelope is assembled. We propose to name the 195-kD protein periplakin

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population