Spatial organisation of the mesoscale connectome: A feature influencing synchrony and metastability of network dynamics.

Significant research has investigated synchronisation in brain networks, but the bulk of this work has explored the contribution of brain networks at the macroscale. Here we explore the effects of changing network topology on functional dynamics in spatially constrained random networks representing mesoscale neocortex. We use the Kuramoto model to simulate network dynamics and explore synchronisation and critical dynamics of the system as a function of topology in randomly generated networks with a distance-related wiring probability and no preferential attachment term. We show networks which predominantly make short-distance connections smooth out the critical coupling point and show much greater metastability, resulting in a wider range of coupling strengths demonstrating critical dynamics and metastability. We show the emergence of cluster synchronisation in these geometrically-constrained networks with functional organisation occurring along structural connections that minimise the participation coefficient of the cluster. We show that these cohorts of internally synchronised nodes also behave en masse as weakly coupled nodes and show intra-cluster desynchronisation and resynchronisation events related to inter-cluster interaction. While cluster synchronisation appears crucial to healthy brain function, it may also be pathological if it leads to unbreakable local synchronisation which may happen at extreme topologies, with implications for epilepsy research, wider brain function and other domains such as social networks.

Dithiophosphoric Acids for Polymer Functionalization.

Dithiophosphoric acids (DTPAs) are an intriguing class of compounds that are sourced from elemental sulfur and white phosphorus and are prepared from the reaction of phosphorus pentasulfide with alcohols. The electrophilic addition of DTPAs to alkenes and unsaturated olefinic substrates is a known reaction, but has not been applied to polymer synthesis and polymer functionalization. We report on the synthesis and application of DTPAs for the functionalization of challenging poly-enes, namely polyisoprene (PI) and polynorbornene (pNB) prepared by ring-opening metathesis polymerization (ROMP). The high heteroatom content within DTPA moieties impart intriguing bulk properties to poly-ene materials after direct electrophilic addition reactions to the polymer backbone introducing DTPAs as side chain groups. The resulting materials possess both enhanced optical and flame retardant properties vs the poly-ene starting materials. Finally, we demonstrate the ability to prepare crosslinked polydiene films with di-functional DTPAs, where the crosslinking density and thermomechanical properties can be directly tuned by DTPA feed ratios.

Vascular Thrombosis in Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Multicenter Study.

OBJECTIVES: Coronavirus disease 2019 has been reported to be a prothrombotic condition; however, multicenter data comparing this with other viral pneumonias in those requiring extracorporeal membrane oxygenation are lacking. We conducted a multicenter study using whole-body CT to examine the prevalence, severity, and nature of vascular complications in coronavirus disease 2019 in comparison with patients with other viral pneumonias. DESIGN: We analyzed whole-body CT scans for the presence of vascular thrombosis (defined as pulmonary artery thrombus, venous thrombus, systemic arterial thrombus, or end-organ infarct). The severity, distribution, and morphology of pulmonary artery thrombus were characterized. Competing risk cumulative incidence analysis was used to compare survival with discharge. SETTING: Three centers of the English national extracorporeal membrane oxygenation service. PATIENTS: Consecutive patients admitted with either coronavirus disease 2019 or noncoronavirus disease 2019 viral pneumonia admitted from January 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred thirty-six patients (45.2 ± 10.6 yr old, 39/146 [27%] female) requiring extracorporeal membrane oxygenation support underwent whole-body CT scans at admission. Of these, 86 had coronavirus disease 2019 pneumonia, and 50 had noncoronavirus disease 2019 viral pneumonia. Vascular thrombosis was seen more often in patients with coronavirus disease 2019 (odds ratio, 12.9 [95% CI 4.5-36.8]). In those with coronavirus disease 2019, 57 (73%) demonstrated pulmonary artery thrombus or pulmonary perfusion defects. Eighty-two percent of thrombus exhibited emboli-like morphology. The location of pulmonary artery thrombus and parenchymal perfusion defects was only concordant in 30% of cases. The risk of mortality was higher in those with coronavirus disease 2019 compared with noncoronavirus disease 2019 pneumonia (χ2 = 3.94; p = 0.047). Mortality was no different in coronavirus disease 2019 patients with or without vascular thrombosis (χ2 = 0.44; p = 0.51). CONCLUSIONS: In patients who received extracorporeal membrane oxygenation, coronavirus disease 2019 is associated with a higher prevalence of vascular thrombosis compared with noncoronavirus disease viral pneumonias. The pattern of pulmonary vascular changes suggests concurrent embolic disease and small vessel disease. Despite this, vascular thrombosis was not linked to poorer short-term prognosis in those with coronavirus disease 2019.

Impact of a Diabetes Toolkit on Weight Loss Among Veterans.

This quality improvement project aimed to answer the following clinical question: Among U.S. male veterans (N = 30) living with type 2 diabetes (T2D) receiving services from a Veterans Affairs (VA) endocrinology clinic, how does a diabetes toolkit influence knowledge and glycaemic control? All the study participants were male and from 31 to 91 years of age. A pre- and post-intervention diabetes knowledge test, body mass index (BMI), lipids, blood pressure, and lifestyle data were obtained as predictor variables. A1c levels were measured at baseline and fructosamine levels at 8-12 weeks post-intervention and converted to A1c levels. A diabetes toolkit was presented as an educational intervention to participating veterans. The pre- and post-intervention knowledge test measured an increase (p = 0.001) in diabetes knowledge. The pre- and post-intervention BMI, lipids, and blood pressure assessments measured changes in such variables associated with toolkit exposure. The regression model was marginally significant (p = 0.055) and the predictor variables explained 18.8% of variance in change of A1c. A multiple regression was conducted to determine the extent to which the following post-intervention outcome variables impacted glycemic control. Of four predictors, only one was significant: a patient's change in weight predicted (p = 0.016) a decrease in A1c.

Infrared Fingerprint Engineering: A Molecular-Design Approach to Long-Wave Infrared Transparency with Polymeric Materials.

Optical technologies in the long-wave infrared (LWIR) spectrum (7-14 µm) offer important advantages for high-resolution thermal imaging in near or complete darkness. The use of polymeric transmissive materials for IR imaging offers numerous cost and processing advantages but suffers from inferior optical properties in the LWIR spectrum. A major challenge in the design of LWIR-transparent organic materials is that nearly all organic molecules absorb in this spectral window which lies within the so-called IR-fingerprint region. We report on a new molecular-design approach to prepare high refractive index polymers with enhanced LWIR transparency. Computational methods were used to accelerate the design of novel molecules and polymers. Using this approach, we have prepared chalcogenide hybrid inorganic/organic polymers (CHIPs) with enhanced LWIR transparency and thermomechanical properties via inverse vulcanization of elemental sulfur with new organic co-monomers.

Acquisition of a Digital Intraoral Scanning Device: An Examination of Practice Volume Changes and the Economic Impact via an Interrupted Time Series Analysis.

OBJECTIVES: To evaluate the impact of digital scanning in general dental practices and orthodontic practices to determine the percentage of lift, i.e., the percent increase in gross receipts, of Invisalign® treatment starts following the introduction of an iTero® intraoral scanner. METHODS: An interrupted time series analysis was conducted on 48 months (24 pre- and 24 post-scanner introduction) of Invisalign receipt data from 1,871 general practitioner (GP) and orthodontic practices located worldwide. Analyses also explored the presence of a longer shift in the trend of monthly Invisalign receipts after scanner introduction (i.e., pre-post slope change), and projected the impact of the introduction of the scanner within a specific subset of practices (n = 319) that represented North American GPs with low initial practice volumes (i.e., 5 or fewer receipts in the 12 months prior to acquiring the scanner). RESULTS: For the entire sample, introduction of the iTero intraoral scanner at month 25 showed a significant and abrupt increase in receipts for Invisalign therapy (b = 0.49; p < 0.001). When compared to the counterfactual regression line prediction without the scanner, in month 25 Invisalign practice receipts increased from the predicted value of 2.38 to 2.88, an increase of 20.71%. When the analysis was conducted using only low-volume GP practices in North America, the introduction of the scanner at month 25 also led to a significant and abrupt increase in practice receipts (b = 0.28; p < 0.001), and this increase was still evident 24 months after scanner introduction. CONCLUSIONS: The results show that acquiring an iTero intraoral scanner as a precursor to Invisalign therapy is associated with a significant increase in Invisalign practice receipts. When projected across the first 12 months, this increase amounts to an additional 5.92 receipts for the entire sample (i.e., 1,871 GP and orthodontic practices worldwide) and an additional 3.41 receipts for the subset of 319 low-volume, North American GPs.

Ethnic differences in diabetes prevalence and ICT use.

BACKGROUND: Uptake of information and communication technology (ICT) by individuals with diabetes can assist nursing care delivery, and improve patient outcomes. However, it is unclear how such uptake relates to ethnic differences in diabetes risk. AIM: To assess the moderating effects of ICT uptake on South Asian excess diabetes prevalence over a specific elapsed timeframe, accounting for selected environmental, socio-economic, and behavioural risk factors. METHOD: Archived data from a UK Office for National Statistics household survey 2006-2011 (120 621 partly non-orthogonal participant records) were analysed using hierarchical binary logistic regression analyses. RESULTS: ICT uptake qualified ethnic differences in diabetes prevalence. Non-smoking diabetes cases living in terraced housing with a home computer were more likely to be South Asian than Caucasian. By contrast, such cases were more likely to be Caucasian if a computer was unavailable (OR: 0.61; CI: 0.43-0.86; P=0.005). Furthermore, diabetes cases from low-income, mobile-dependent homes were probably South Asian (OR: 0.05; CI: 0.00-0.50; P=0.012). CONCLUSIONS: Home computing was linked to better tobacco control among South Asians with diabetes living in terraced properties. Mobile phone dependence was pronounced in those that received income support. Implications for nursing care are considered.

Existential Issues in Psychotherapy.

Existential issues are common in patient experiences and can present as themes in any practice setting, but particularly in psychotherapy. Existential issues are any concerns that arise from distress or questions about difficult subjects, such as death, meaning, freedom, and isolation, and can be a source of psychiatric concerns or simply a modifying factor. Because of this, clinicians should be able to recognize and understand the basic tenets of addressing existential issues in psychotherapy. This article outlines the historical context and theoretical basis of existentialism. It also discusses existential issues in relation to psychotherapy and provides practical clinical tips for addressing these issues with patients, including helpful probing questions, tips for noticing existential themes, and ideas about how to address existential issues in session.

Unraveling the rheology of inverse vulcanized polymers.

Multiple relaxation times are used to capture the numerous stress relaxation modes found in bulk polymer melts. Herein, inverse vulcanization is used to synthesize high sulfur content (≥50 wt%) polymers that only need a single relaxation time to describe their stress relaxation. The S-S bonds in these organopolysulfides undergo dissociative bond exchange when exposed to elevated temperatures, making the bond exchange dominate the stress relaxation. Through the introduction of a dimeric norbornadiene crosslinker that improves thermomechanical properties, we show that it is possible for the Maxwell model of viscoelasticity to describe both dissociative covalent adaptable networks and living polymers, which is one of the few experimental realizations of a Maxwellian material. Rheological master curves utilizing time-temperature superposition were constructed using relaxation times as nonarbitrary horizontal shift factors. Despite advances in inverse vulcanization, this is the first complete characterization of the rheological properties of this class of unique polymeric material.

High-strength, healable, supramolecular polymer nanocomposites.

A supramolecular polymer blend, formed via π-π interactions between a π-electron rich pyrenyl end-capped oligomer and a chain-folding oligomer containing pairs of π-electron poor naphthalene-diimide (NDI) units, has been reinforced with cellulose nanocrystals (CNCs) to afford a healable nanocomposite material. Nanocomposites with varying weight percentage of CNCs (from 1.25 to 20.0 wt %) within the healable supramolecular polymeric matrix have been prepared via solvent casting followed by compression molding, and their mechanical properties and healing behavior have been evaluated. It is found that homogeneously dispersed films can be formed with CNCs at less than 10 wt %. Above 10 wt % CNC heterogeneous nanocomposites were obtained. All the nanocomposites formed could be rehealed upon exposure to elevated temperatures although, for the homogeneous films, it was found that the healing rate was reduced with increasing CNC content. The best combination of healing efficiency and mechanical properties was obtained with the 7.5 wt % CNC nanocomposite which exhibited a tensile modulus enhanced by as much as a factor of 20 over the matrix material alone and could be fully rehealed at 85 °C within 30 min. Thus it is demonstrated that supramolecular nanocomposites can afford greatly enhanced mechanical properties relative to the unreinforced polymer, while still allowing efficient thermal healing.

Injectable solid peptide hydrogel as a cell carrier: effects of shear flow on hydrogels and cell payload.

ß-hairpin peptide-based hydrogels are a class of injectable solid hydrogels that can deliver encapsulated cells or molecular therapies to a target site via syringe or catheter injection as a carrier material. These physical hydrogels can shear-thin and consequently flow as a low-viscosity material under a sufficient shear stress but immediately recover back into a solid upon removal of the stress, allowing them to be injected as preformed gel solids. Hydrogel behavior during flow was studied in a cylindrical capillary geometry that mimicked the actual situation of injection through a syringe needle in order to quantify effects of shear-thin injection delivery on hydrogel flow behavior and encapsulated cell payloads. It was observed that all ß-hairpin peptide hydrogels investigated displayed a promising flow profile for injectable cell delivery: a central wide plug flow region where gel material and cell payloads experienced little or no shear rate, and a narrow shear zone close to the capillary wall where gel and cells were subject to shear deformation. The width of the plug flow region was found to be weakly dependent on hydrogel rigidity and flow rate. Live-dead assays were performed on encapsulated MG63 cells 3 h after injection flow and revealed that shear-thin delivery through the capillary had little impact on cell viability and the spatial distribution of encapsulated cell payloads. These observations help us to fundamentally understand how the gels flow during injection through a thin catheter and how they immediately restore mechanically and morphologically relative to preflow, static gels.

Surface-induced phase behavior of polymer/nanoparticle blends with attractions.

In an athermal blend of nanoparticles and homopolymer near a hard wall, there is a first order phase transition in which the nanoparticles segregate to the wall and form a densely packed monolayer above a certain nanoparticle density. Previous investigations of this phase transition employed a fluids density functional theory (DFT) at constant packing fraction. Here we report further DFT calculations to probe the robustness of this phase transition. We find that the phase transition also occurs in athermal systems at constant pressure, the more natural experimental condition than constant packing fraction. Adding nanoparticle-polymer attractions increases the nanoparticle transition density, while sufficiently strong attractions suppress the first-order transition entirely. In this case the systems display a continuous transition to a bulk layered state. Adding attractions between the polymers and the wall has a similar effect of delaying and then suppressing the first-order nanoparticle segregation transition, but does not lead to any continuous phase transitions.

Unlocking wheat genetic resources for the molecular identification of previously undescribed functional alleles at the Pm3 resistance locus.

The continuous improvement of crop plants is essential for agriculture in the coming decades and relies on the use of genetic variability through breeding. However, domestication and modern breeding have reduced diversity in the crop germplasm. Global gene banks conserve diversity, but these resources remain underexplored owing to a lack of efficient strategies to isolate important alleles. Here we describe a large-scale allele-mining project at the molecular level. We first selected a set of 1,320 bread wheat landraces from a database of 16,089 accessions, using the focused identification of germplasm strategy. On the basis of a hierarchical selection procedure on this set, we then isolated 7 resistance alleles of the powdery mildew resistance gene Pm3, doubling the known functional allelic diversity at this locus. This targeted approach for molecular utilization of gene bank accessions reveals landraces as a rich resource of new functional alleles. This strategy can be implemented for other studies on the molecular diversity of agriculturally important genes, as well as for molecular breeding.

Evidence for two distinct mechanisms directing gaze in natural scenes.

Various models have been proposed to explain the interplay between bottom-up and top-down mechanisms in driving saccades rapidly to one or a few isolated targets. We investigate this relationship using eye-tracking data from subjects viewing natural scenes to test attentional allocation to high-level objects within a mathematical decision-making framework. We show the existence of two distinct types of bottom-up saliency to objects within a visual scene, which disappear within a few fixations, and modification of this saliency by top-down influences. Our analysis reveals a subpopulation of early saccades, which are capable of accurately fixating salient targets after prior fixation within the same image. These data can be described quantitatively in terms of bottom-up saliency, including an explicit face channel, weighted by top-down influences, determining the mean rate of rise of a decision-making model to a threshold that triggers a saccade. These results are compatible with a rapid subcortical pathway generating accurate saccades to salient targets after analysis by cortical mechanisms.

Continuous hemadsorption with cytokine adsorber for severe COVID-19: A case series of 15 patients.

BACKGROUND: Hyperinflammation and cytokine release has been associated with severe Covid-19. Hemadsorption cartridges may have a potential role in treatment of cytokine storm associated with the development of severe Covid-19. METHODS: We retrospectively examined the case records of patients with severe Covid-19 receiving adjunctive hemadsorption (HA) in our ICU. We analyzed inflammatory biomarkers pre- and post- HA. RESULTS: Fifteen patients received HA during the study period. All were intubated, ventilated and required renal replacement therapy. 11/15 were supported on ECMO. Mean ferritin 2652 (±3286) ng/ml, mean CRP 154 (±92) mg/ml, median D-dimer 3071 (±2689) ng/ml, mean troponin 236 (±461) ng/L. We found significant difference in pre-and post- treatment ferritin 3622 ng/ml versus 1682 ng/ml (p = 0.022), CRP 222 mg/ml versus 103 mg/ml (p = 0.008, 95% CI 22.4-126.5), lactate 2 mmol/L versus 1.3 mmol/L (p = 0.017), and procalcitonin 15.3 ng/ml versus 4.2 ng/ml (p = 0.023). No significant difference in pre- and post- treatment IL-6 14 pg/ml versus 43 pg/ml (p = 0.32), IL-10 3.4 pg/ml versus 2.6 pg/ml (p = 0.31), IL1 ß 0.37 pg/ml versus 0.77 pg/ml (p = 0.75), TNF α 12.77 pg/ml versus 12.49 pg/ml (p = 0.75), VIS 10.04 versus 6.01 (p = 0.31, 95% CI 5.98-17.16) was seen. CONCLUSIONS: The use of HA as adjunctive treatment in a critically unwell group of COVID-19 patients lead to a reduction in ferritin, CRP, procalcitonin and lactate with no significant change in other parameters. The use of HA in the treatment of severe COVID-19 requires further larger randomized studies.

A healable supramolecular polymer blend based on aromatic pi-pi stacking and hydrogen-bonding interactions.

An elastomeric, healable, supramolecular polymer blend comprising a chain-folding polyimide and a telechelic polyurethane with pyrenyl end groups is compatibilized by aromatic pi-pi stacking between the pi-electron-deficient diimide groups and the pi-electron-rich pyrenyl units. This interpolymer interaction is the key to forming a tough, healable, elastomeric material. Variable-temperature FTIR analysis of the bulk material also conclusively demonstrates the presence of hydrogen bonding, which complements the pi-pi stacking interactions. Variable-temperature SAXS analysis shows that the healable polymeric blend has a nanophase-separated morphology and that the X-ray contrast between the two types of domain increases with increasing temperature, a feature that is repeatable over several heating and cooling cycles. A fractured sample of this material reproducibly regains more than 95% of the tensile modulus, 91% of the elongation to break, and 77% of the modulus of toughness of the pristine material.

Nanoparticle agglomeration in polymer-based solar cells.

We show that the morphology of polymer-based solar cells substantially changes after annealing using small angle neutron scattering. Phenyl-C61-butyric acid methyl ester (PCBM) is found reasonably well dispersed within the poly(3-hexylthiophene) (P3HT) rich phase after initial processing (spin coating). However, the PCBM structure coarsens after annealing, clearly evidenced by the increase in scattering intensity at a small wave vector. The change in morphology at the nanoscale is related to improved device performance and the simultaneous, contradictory, increase in photoluminescence.

Expanded chain dimensions in polymer melts with nanoparticle fillers.

We apply the self-consistent polymer reference interaction site model (SC/PRISM) to liquid state calculations of the chain dimensions in polymer melts with added nanoparticle fillers. The nanoparticles are assumed to be smaller than the polymer radius of gyration and are attracted to the polymer so that they are miscible. We find that the nanoparticles perturb the chain dimensions, causing an increase in the radius of gyration with increasing nanoparticle volume fractions, assuming reasonable interaction energies between the various components. The magnitude of the expansion is in qualitative agreement with recent neutron scattering results and suggests that the SC/PRISM approach is reasonable when dealing with these apparent nonlinear phenomena present in nanocomposites in the protein limit.

Taking Optogenetics into the Human Brain: Opportunities and Challenges in Clinical Trial Design.

Optogenetics, the use of light to control the activity of suitably sensitized cells, has led to major advances in the field of basic neuroscience since it first emerged in 2005. Already, the technique has entered clinical trials for conditions such as Retinitis Pigmentosa. A major focus of interest is the use of optogenetics within the brain, where the ability to precisely control the activity of specific subsets of neurons could lead to novel treatments for a wide range of disorders from epilepsy to schizophrenia. However, since any therapy would require both the use of gene therapy techniques to introduce non-human proteins, and implantable electronic devices to provide optical stimulation, applying this technique in the brain presents a unique set of obstacles and challenges. This review looks at the reasons why researchers are exploring the use of optogenetics within the brain. It then explores the challenges facing scientists, engineers and clinicians wanting to take this technology from the lab into the first human brain, discussing different possibilities for a first-in-human clinical trial from a sponsor, patient and regulatory perspective.