Dissociation of Early And Late Face-Related Processes In Autism Spectrum Disorder And Williams Syndrome

Background: Williams syndrome (WS) and Autism Spectrum Disorders (ASD) are psychiatric conditions associated with atypical but opposite face-to-face interactions patterns: WS patients overly stare at others, ASD individuals escape eye contact. Whether these behaviors result from dissociable visual processes within the occipito-temporal pathways is unknown. Using high-density electroencephalography, multivariate signal processing algorithms and a protocol designed to identify and extract evoked activities sensitive to facial cues, we investigated how WS (N=14), ASD (N=14) and neurotypical subjects (N=14) decode the information content of a face stimulus. Results: We found two neural components in neurotypical participants, both strongest when the eye region was projected onto the subject's fovea, simulating a direct eye contact situation, and weakest over more distant regions, reaching a minimum when the focused region was outside the stimulus face. The first component peaks at 170ms, an early signal known to be implicated in low-level face features. The second is identified later, 260ms post-stimulus onset and is implicated in decoding salient face social cues.Remarkably, both components were found distinctly impaired and preserved in WS and ASD. In WS, we could weakly decode the 170ms signal based on our regressor relative to facial features, probably due to their relatively poor ability to process faces’ morphology, while the late 260ms component was highly significant. The reverse pattern was observed in ASD participants who showed neurotypical like early 170ms evoked activity but impaired late evoked 260ms signal. Conclusions: Our study reveals a dissociation between WS and ASD patients and point at different neural origins for their social impairments.

Analyticity of the Resolvent Function

Analytic dependence on a complex parameter appears at many places in the study of differential and integral equations. The display of analyticity in the solution of the Fredholm equation of the second kind is an early signal of the important role which analyticity was destined to play in spectral theory. The definition of the resolvent set is very explicit, this makes it seem plausible that the resolvent is a well behaved function. Let T be a closed linear operator in a complex Banach space X. In this paper we show that the resolvent set of T is an open subset of the complex plane and the resolvent function of T is analytic. Moreover, we show that if T is a bounded linear operator, the resolvent function of T is analytic at infinity, its value at infinity being 0 (where 0 is the bounded linear operator 0 in X). Consequently, we also show that if T is bounded in X then the spectrum of T is non-void.

Development of aquaculture water quality real-time monitoring using multi-sensory system and internet of things

Water quality is an important parameter for the health and growth of aquatic species in aquaculture farming system. The threshold values of the water main parameters should be monitored continuously. Contaminated aquaculture water will affect the health, growth and ability of animals to survive. In addition, it will also affect the harvesting yields based on the number and size of the animals. To overcome this problem, the main water parameters, namely temperature, pH, Dissolved Oxygen and Electrical Conductivity are monitored in real-time using a multi-sensory system and the internet of things. Data is acquired by a developed instrument and transmitted wirelessly via a GPRS / GSM module to a web server database. The data obtained are analyzed and monitored through the website and in real-time. Therefore, corrective action could be taken immediately for contaminated water, indicated by water parameters out of range. The system also provides an early signal to farmers based on a specific range of water quality parameters values. This will help farmers make adjustments to ensure appropriate water quality for the aquaculture system.

Investigation of MALDI-TOF Mass Spectrometry for Assessing the Molecular Diversity of Campylobacter jejuni and Comparison with MLST and cgMLST: A Luxembourg One-Health Study

There is a need for active molecular surveillance of human and veterinary Campylobacter infections. However, sequencing of all isolates is associated with high costs and a considerable workload. Thus, there is a need for a straightforward complementary tool to prioritize isolates to sequence. In this study, we proposed to investigate the ability of MALDI-TOF MS to pre-screen C. jejuni genetic diversity in comparison to MLST and cgMLST. A panel of 126 isolates, with 10 clonal complexes (CC), 21 sequence types (ST) and 42 different complex types (CT) determined by the SeqSphere+ cgMLST, were analysed by a MALDI Biotyper, resulting into one average spectra per isolate. Concordance and discriminating ability were evaluated based on protein profiles and different cut-offs. A random forest algorithm was trained to predict STs. With a 94% similarity cut-off, an AWC of 1.000, 0.933 and 0.851 was obtained for MLSTCC, MLSTST and cgMLST profile, respectively. The random forest classifier showed a sensitivity and specificity up to 97.5% to predict four different STs. Protein profiles allowed to predict C. jejuni CCs, STs and CTs at 100%, 93% and 85%, respectively. Machine learning and MALDI-TOF MS could be a fast and inexpensive complementary tool to give an early signal of recurrent C. jejuni on a routine basis.

Spread of SARS-CoV-2 Delta variant infections bearing the S:E484Q and S:T95I mutations in July and August 2021 in France

Analysing 92,598 variant screening tests performed on SARS-CoV-2 positive samples collected in France between 1 July and 31 August 2021 shows an increase of Kappa-like infections. Full genome sequencing reveals that these correspond to Delta variants bearing the S:E484Q mutation. Most of these sequences belong to a phylogenetic cluster and also bear the S:T95I mutation. Further monitoring is needed to determine if this trend is driven by undocumented superspreading events or an early signal of future viral evolutionary dynamics

Durability analysis of the highly effective BNT162b2 vaccine against COVID-19

SARS-CoV-2 breakthrough infections have been increasingly reported in fully vaccinated individuals. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2, defined as 14 days after the second dose, against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice between February 1, 2021 and August 22, 2021. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. The primary population included 652 individuals who had a positive symptomatic test after full vaccination with BNT162b2 (cases) and 5,946 individuals with at least one negative symptomatic test after full vaccination (controls). The adjusted odds of symptomatic infection were higher 120 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.21, 95% confidence interval [CI]: 1.33-7.74). Importantly, the odds of infection were still lower 150 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.3, 95% CI: 0.19-0.45), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of experiencing a non-COVID-19 hospitalization decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. Taken together, these data constitute an early signal for waning protection against symptomatic illness while also providing reassurance that BNT162b2 continues to protect against symptomatic SARS-CoV-2 infection several months after full vaccination. Continued surveillance of COVID-19 vaccine durability, particularly against severe disease, is critical to guide effective and equitable strategies to respond to the pandemic, including distribution of booster doses, development of new vaccines, and implementation of both pharmaceutical and nonpharmaceutical interventions.

Revisiting the Concept of Moderation in the Age of Populism: the akp case of Turkey

This article presents the case of Turkey within the framework of this special issue entitled “On Islamist Parties and the Inclusion-Moderation Hypothesis”. I argue that rather than a distinction between the concepts of ”tactical” and “ideological” moderation that the literature talks about, a distinction between the concepts of an “inclusionary-populist” and “moderate Islamist” party could provide a more useful insight over the role of Islamist and post-Islamist parties in democratization and de-democratization processes. Through a re-analysis of the secondary literature and a content analysis of 196 newspaper columns written by three pro-democracy intellectuals, I label the akp’s transition period from moderate-Islamism toward authoritarianism as its inclusionary populist phase. I show that in contexts marked by deep ideological divisions and unconsolidated democratic institutions, a shift in party identity from moderate-Islamism toward inclusionary populism can be taken as the early signal of an unfolding process of autocratization.

The maladaptive vascular response in COVID-19 acute respiratory distress syndrome and recovery

Vascular injury is a menacing element of acute respiratory distress syndrome (ARDS) pathogenesis. To better understand the role of vascular injury in COVID-19 ARDS, we used lung autopsy immunohistochemistry and blood proteomics from COVID-19 subjects at distinct timepoints in disease pathogenesis, including a hospitalized cohort at risk of ARDS development ("at risk", N=59), an intensive care unit cohort with ARDS ("ARDS", N=31), and a cohort recovering from ARDS ("recovery", N=12). COVID-19 ARDS lung autopsy tissue revealed an association between vascular injury and platelet-rich microthrombi. This link guided the derivation of a protein signature in the at risk cohort characterized by lower expression of vascular proteins in subjects who died, an early signal of vascular limitation termed the maladaptive vascular response. These findings were replicated in COVID-19 ARDS subjects, as well as when bacterial and influenza ARDS patients (N=29) were considered, hinting at a common final pathway of vascular injury that is more disease (ARDS) then cause (COVID-19) specific, and may be related to vascular cell death. Among recovery subjects, our vascular signature identified patients with good functional recovery one year later. This vascular injury signature could be used to identify ARDS patients most likely to benefit from vascular targeted therapies.

Dissociation of early and late face-related processes in Autism Spectrum Disorder and Williams syndrome

Williams syndrome (WS) and Autism Spectrum Disorders (ASD) are psychiatric conditions associated with atypical but opposite face-to-face interactions patterns: WS patients overly stare at others, ASD individuals escape eye contact. Whether these behaviors result from dissociable visual processes within the occipito-temporal pathways is unknown. Using high-density electroencephalography, multivariate pattern classification and group blind source separation, we searched for face-related neural signals that could best discriminate WS (N = 14), ASD (N = 14) and neurotypical populations (N = 14). We found two peaks in neurotypical participants: the first at 170ms, an early signal known to be implicated in low-level face features, the second at 260ms, a late component implicated in decoding salient face social cues. The late 260ms signal varied as a function of the distance of the eyes in the face stimulus with respect to the viewers’ fovea, meaning that it was strongest when the eyes were projected on the fovea and weakest when projected in the retinal periphery. Remarkably, both components were found distinctly impaired and preserved in WS and ASD. In WS, we could weakly decode the 170ms signal probably due to their relatively poor ability to process faces’ morphology while the late 260ms component shown to be eye sensitive was highly significant. The reverse pattern was observed in ASD participants who showed neurotypical like early 170ms evoked activity but impaired late evoked 260ms signal. Our study reveals a dissociation between WS and ASD patients and point at different neural origins for their social impairments.

A phase I/II study of hydroxychloroquine and suba-itraconazole in men with biochemical relapse of prostate cancer (HITMAN-PC): Dose escalation results.

114 Background: Preclinical data show hydroxychloroquine (HCQ) and suba-itraconazole (SI) together enhance prostate cancer cell death. The proposed mechanism is lysosome dysfunction including sequestration of cholesterol in endosomes and inhibition of gogi-lyosome trafficking. HCQ/SI could delay androgen deprivation therapy (ADT) and its associated morbidity in men with biochemical relapse of prostate cancer. In this phase I/II study, maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of HCQ/SI was investigated in such patients. Methods: Patients received escalating doses of HCQ with fixed SI 150mg BD in rolling 6 design. This will be followed by a planned phase II Simon 2-stage cohort expansion. Results: Eleven men were treated with HCQ/SI. Median age 73 (range 69-77), baseline PSA 4.4 µg/L (1.6-22.4) and doubling time 5.3 months (3.3-15.3). Two experienced dose-limiting toxicity: grade 3 diarrhoea and grade 3 alanine transferase elevation, both at HCQ 600mg BD. Most common treatment-related adverse events (AEs) were hypertension (91% all grade/18% grade 3), QTc prolongation (55%/0%), diarrhoea (36%/9%), and nausea (36%/0%). There were no grade 4 AEs or deaths. While there were no PSA responses (≥50% fall from baseline), PSA PFS by PCWG3 criteria was 5.5 months (2.0-9.0), and PSA doubling time was prolonged at 4 and 12 weeks in 82% and 45% respectively. ADT-free and metastasis-free survival are 14.3 months (95% CI 4.9-23.8) and 15.9 months (95% CI unevaluable) respectively. PK data will be presented. Conclusions: HCQ/SI demonstrated acceptable safety with MTD 600mg BD and RP2D 400mg BD. There is early signal of activity and phase II enrolment is to begin. Clinical trial information: NCT03513211.