Neural bases of reward anticipation in healthy individuals with low, mid, and high levels of schizotypy

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior

Erythroid-Specific Expression of β-globin from Sleeping Beauty-Transduced Human Hematopoietic Progenitor Cells

Gene therapy for sickle cell disease will require efficient delivery of a tightly regulated and stably expressed gene product to provide an effective therapy. In this study we utilized the non-viral Sleeping Beauty (SB) transposon system using the SB100X hyperactive transposase to transduce human cord blood CD34+ cells with DsRed and a hybrid IHK–β-globin transgene. IHK transduced cells were successfully differentiated into multiple lineages which all showed transgene integration. The mature erythroid cells had an increased β-globin to γ-globin ratio from 0.66±0.08 to 1.05±0.12 (p = 0.05), indicating expression of β-globin from the integrated SB transgene. IHK–β-globin mRNA was found in non-erythroid cell types, similar to native β-globin mRNA that was also expressed at low levels. Additional studies in the hematopoietic K562 cell line confirmed the ability of cHS4 insulator elements to protect DsRed and IHK–β-globin transgenes from silencing in long-term culture studies. Insulated transgenes had statistically significant improvement in the maintenance of long term expression, while preserving transgene regulation. These results support the use of Sleeping Beauty vectors in carrying an insulated IHK–β-globin transgene for gene therapy of sickle cell disease

Panning for gold, but finding helium: discovery of the ultra-stripped supernova SN2019wxt from gravitational-wave follow-up observations

We present the results from multi-wavelength observations of a transient discovered during the follow-up of S191213g, a gravitational wave (GW) event reported by the LIGO-Virgo Collaboration as a possible binary neutron star merger in a low latency search. This search yielded SN2019wxt, a young transient in a galaxy whose sky position (in the 80\% GW contour) and distance ($\sim$150\,Mpc) were plausibly compatible with the localisation uncertainty of the GW event. Initially, the transient's tightly constrained age, its relatively faint peak magnitude ($M_i \sim -16.7$\,mag) and the $r-$band decline rate of $\sim 1$\,mag per 5\,days appeared suggestive of a compact binary merger. However, SN2019wxt spectroscopically resembled a type Ib supernova, and analysis of the optical-near-infrared evolution rapidly led to the conclusion that while it could not be associated with S191213g, it nevertheless represented an extreme outcome of stellar evolution. By modelling the light curve, we estimated an ejecta mass of $\sim 0.1\,M_\odot$, with $^{56}$Ni comprising $\sim 20\%$ of this. We were broadly able to reproduce its spectral evolution with a composition dominated by helium and oxygen, with trace amounts of calcium. We considered various progenitors that could give rise to the observed properties of SN2019wxt, and concluded that an ultra-stripped origin in a binary system is the most likely explanation. Disentangling electromagnetic counterparts to GW events from transients such as SN2019wxt is challenging: in a bid to characterise the level of contamination, we estimated the rate of events with properties comparable to those of SN2019wxt and found that $\sim 1$ such event per week can occur within the typical GW localisation area of O4 alerts out to a luminosity distance of 500\,Mpc, beyond which it would become fainter than the typical depth of current electromagnetic follow-up campaigns.Comment: By the ENGRAVE collaboration (engrave-eso.org). 35 pages, 20 figures, final version accepted by A&

Neural bases of reward anticipation in healthy individuals with low, mid, and high levels of schizotypy

Abstract A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior

Transcollation technique in the thoracoscopic treatment of primary spontaneous pneumothorax

OBJECTIVES: The already low invasiveness of the thoracoscopic treatment of spontaneous pneumothorax may be further reduced by the transcollation® technique. Herein, we report our further experience with a new device, to coagulate blebs and bullae, compared with contrastto endostapler resection. METHODS: Data of patients with recurrent or persistent spontaneous pneumothorax, who underwent thoracoscopic treatment, were prospectively collected and reviewed. Those with blebs or bullae (Stages III and IV in accordance with Vanderschueren’s classification) were treatedwithanewdevice,basedoncouplingsalinesolutionperfusionwithradiofrequencyenergy.Thecombinationof fluidwithradiofrequencyallowsthesealing of tissue, avoiding charring or burning.Mostoperationswere performed through two1-cmincisions only. RESULTS: From 2005 to 2010, 73 patients were treated. These were 59 males (80.8%) and 14 females (19.2%), with a mean age of 27.9 years[standarddeviation(SD):11.7].Forty-threepatientsunderwentgeneral anaesthesiawithselectiveintubation,9awakeepiduralanaesthesia and 21 spontaneous breathing anaesthesia with laryngeal mask. The mean operation time was 31 min (SD: 10.2). The median postoperative drainage period and hospital stay were 2 days (range of 1–11) and 3 days (range of 2–11), respectively. Prolonged air leak occurredin 1patient (1.4%).Overamean follow-upperiod of 60 months (SD: 22.5), tworecurrences (2.7%)were reported. CONCLUSIONS: The transcollation® technique by cold coagulation of blebs and bullae seems to be effective in the treatment of primary spontaneous pneumothorax. Owing to its potential advantages, it appears to be particularly suitable to be associated with awake epidural and LMA anaesthesia

Bioreactor for blood product production

The feasibility of ex vivo blood production is limited by both biological and engineering challenges. From an engineering perspective, these challenges include the significant volumes required to generate even a single unit of a blood product, as well as the correspondingly high protein consumption required for such large volume cultures. Membrane bioreactors, such as hollow fiber bioreactors (HFBRs), enable cell densities approximately 100-fold greater than traditional culture systems and therefore may enable a significant reduction in culture working volumes. As cultured cells, and larger molecules, are retained within a fraction of the system volume, via a semipermeable membrane it may be possible to reduce protein consumption by limiting supplementation to only this fraction. Typically, HFBRs are complex perfusion systems having total volumes incompatible with bench scale screening and optimization of stem cell-based cultures. In this article we describe the use of a simplified HFBR system to assess the feasibility of this technology to produce blood products from umbilical cord blood-derived CD34+ hematopoietic stem progenitor cells (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where cells are cultured in the extracapillary space, we have cultured cells in the intracapillary space, which is likely more compatible with the large-scale production of blood cell suspension cultures. Using this platform we direct HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell density and the use of protein-free bulk medium. Our results demonstrate the potential of this system to deliver high cell densities, even in the absence of protein supplementation of the bulk medium

The novel Mechanical Ventilator Milano for the COVID-19 pandemic

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world

Toward Component-Oriented Formal Software Development: An Algebraic Approach

Component based design and development of software is one of the most challenging issues in software engineering. In this paper, we adopt a somewhat simplified view of software components and discuss how they can be conveniently modelled in a framework that provides a modular approach to formal software development by means of stepwise refinement. In particular we take into account an observational interpretation of requirements specifications and study its impact on the definition of the semantics of specifications of (parametrized) components. Our study is carried out in the context of Casl architectural specifications