Design of ternary additive for organic photovoltaics: a cautionary tale

Silicon phthalocyanines as ternary additives are a promising way to increase the performance of organic photovoltaics. The miscibility of the additive and the donor polymer plays a significant role in the enhancement of the device performance, therefore, ternary additives can be designed to better interact with the conjugated polymer. We synthesized N-9′-heptadecanyl-2,7-carbazole functionalized SiPc ((CBzPho)₂-SiPc), a ternary additive with increased miscibility in poly[N-90-heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT). The resulting additive was included into PCDTBT and [6,6]-phenyl C₇₁ butyric acid methyl ester as bulk (PC₇₁BM) heterojunction OPV devices as a ternary additive. While the (CBzPho)₂-SiPc demonstrated strong EQE >30% contribution in the range of 650–730 nm, the overall performance was reduced because (CBzPho)₂-SiPc acted as a hole trap due to its high-lying HOMO energy level. This study demonstrates the importance of the solubility, miscibility, and energy level engineering of the ternary additive when designing organic photovoltaic devices.

Silicon phthalocyanines with carbazole axial functional groups were synthesized to improve the miscibility in PCDTBT and for use as ternary additives in organic photovoltaics.     

User and Healthcare Professional Perspectives on Do-It-Yourself Artificial Pancreas Systems: A Need for Guidelines

A growing number of individuals with type 1 diabetes are choosing to use “do-it-yourself” artificial pancreas systems (DIY APS) to support their diabetes self-management. Observational and self-report data of glycemic benefits of DIY APS are promising; however, without rigorous clinical trials or regulation from governing bodies, liability and user safety continue to be central concerns for stakeholders. Despite DIY APS having been used for several years now, there are no guidelines to assist users and healthcare professionals in addressing DIY APS use in routine clinical care. This commentary reports key stakeholders’ perspectives presented at the annual Advanced Technologies and Treatments in Diabetes conference in February 2020. Important considerations to inform the development of clinical care guidelines are also presented to generate further debate.     

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s RWE Data Working Group

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.     

A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia

Cognitive decline is a common problem of aging. Whereas multiple neural and glial mechanisms may account for these declines, microglial sensitization and/or dystrophy has emerged as a leading culprit in brain aging and dysfunction. However, glial activation is consistently observed in normal brain aging as well, independent of frank neuroinflammation or functional impairment. Such variability suggests the existence of additional vulnerability factors that can impact neuronal-glial interactions and thus overall brain and cognitive health. The goal of this review is to elucidate our working hypothesis that an individual’s risk or resilience to neuroinflammatory disorders and poor cognitive aging may critically depend on their early life experience, which can change immune reactivity within the brain for the remainder of the lifespan. For instance, early-life infection in rats can profoundly disrupt memory function in young adulthood, as well as accelerate age-related cognitive decline, both of which are linked to enduring changes in glial function that occur in response to the initial infection. We discuss these findings within the context of the growing literature on the role of immune molecules and neuroimmune crosstalk in normal brain development. We highlight the intrinsic factors (e.g., chemokines, hormones) that regulate microglial development and their colonization of the embryonic and postnatal brain, and the capacity for disruption or “re-programming” of this crucial process by external events (e.g., stress, infection). An impact on glia, which in turn alters neural development, has the capacity to profoundly impact cognitive and mental health function at all stages of life.     

Microdeletions and Microduplications in Patients with Congenital Heart Disease and Multiple Congenital Anomalies

Objective. Multiple genetic syndromes are caused by recurrent chromosomal microdeletions or microduplications. The increasing use of high‐resolution microarrays in clinical analysis has allowed the identification of previously undetectable submicroscopic copy number variants (CNVs) associated with genetic disorders. We hypothesized that patients with congenital heart disease and additional dysmorphic features or other anomalies would be likely to harbor previously undetected CNVs, which might identify new disease loci or disease‐related genes for various cardiac defects. Design. Copy number analysis with single nucleotide polymorphism‐based, oligonucleotide microarrays was performed on 58 patients with congenital heart disease and other dysmorphic features and/or other anomalies. The observed CNVs were validated using independent techniques and validated CNVs were further analyzed using computational algorithms and comparison with available control CNV datasets in order to assess their pathogenic potential. Results. Potentially pathogenic CNVs were detected in twelve of 58 patients (20.7%), ranging in size from 240 Kb to 9.6 Mb. These CNVs contained between 1 and 55 genes, including NRP1, NTRK3, MESP1, ADAM19, and HAND1, all of which are known to participate in cardiac development. Conclusions. Genome‐wide analysis in patients with congenital heart disease and additional phenotypes has identified potentially pathogenic CNVs affecting genes involved in cardiac development. The identified variant loci and the genes within them warrant further evaluation in similarly syndromic and nonsyndromic cardiac cohorts.     

A surprising sweetener from enteropathogenic Escherichia coli

Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain.  N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. Hence, by blocking cell death, NleB promotes enterocyte survival and thereby prolongs EPEC attachment to the gut epithelium.     

Mothers of young children cluster into 4 groups based on psychographic food decision influencers

This study explored how mothers grouped into clusters according to multiple psychographic food decision influencers and how the clusters differed in nutrient intake and nutrient content of their household food supply. Mothers (n = 201) completed a survey assessing basic demographic characteristics, food shopping and meal preparation activities, self and spouse employment, exposure to formal food or nutrition education, education level and occupation, weight status, nutrition and food preparation knowledge and skill, family member health and nutrition status, food decision influencer constructs, and dietary intake. In addition, an in-home inventory of 100 participants' household food supplies was conducted. Four distinct clusters presented when 26 psychographic food choice influencers were evaluated. These clusters appear to be valid and robust classifications of mothers in that they discriminated well on the psychographic variables used to construct the clusters as well as numerous other variables not used in the cluster analysis. In addition, the clusters appear to transcend demographic variables that often segment audiences (eg, race, mother's age, socioeconomic status), thereby adding a new dimension to the way in which this audience can be characterized. Furthermore, psychographically defined clusters predicted dietary quality. This study demonstrates that mothers are not a homogenous group and need to have their unique characteristics taken into consideration when designing strategies to promote health. These results can help health practitioners better understand factors affecting food decisions and tailor interventions to better meet the needs of mothers.     

On the use of Orbscan II to assess the peripheral corneal thickness in humans: a comparison with ultrasound pachometry measures.

PURPOSE: To compare the measures of corneal thickness measurements obtained by an optical scanning slit method with those obtained by an ultrasound (US) pachometer, with special interest in the mid-peripheral (2.5 mm from centre) and peripheral (4.5 mm from centre) region of the cornea. METHODS: Three measures of corneal thickness were taken using Orbscan II and then by US pachometry (under topical anaesthesia with benoxinate 0.4%) on 24 adults, aged 20-58 years and with up to 8.5 D of myopia. The full Orbscan topography maps were used to extract single point data along the horizontal corneal meridian for the geometric centre, 2.5 mm from centre (nasal and temporal) and 4.5 mm (nasal and temporal) from centre. No correction factor was used for the Orbscan data. The same set of measures were made with the US pachometer. In all cases, the averages of three (centre) or six (mid-periphery and periphery) readings were taken as the measurements from each cornea. RESULTS: Orbscan readings on the right eyes averaged 0.576, 0.632 and 0.712 mm for central, mid-peripheral and peripheral sites with average values for emmetropic subjects (<1 DS, n = 12) being marginally higher than for myopic subjects (average - 4.00 DS, n = 12). For US pachometry, the average values were however 0.522, 0.554 and 0.606 mm. Similar results were obtained on left eyes. Combining data from both eyes also showed that the mean difference between Orbscan II and US measures was not constant across the cornea, being 0.055 +/- 0.014 mm at the centre, 0.080 +/- 0.019 mm at mid-peripheral locations and 0.107 +/- 0.046 mm at the peripheral sites. These differences persisted after application of the generally recommended acoustic factor (x0.92) to all of the Orbscan readings. CONCLUSIONS: A single acoustic factor correction cannot be applied to all corneal thickness measures made with an Orbscan II to equate the measures to those made with an US pachometer.