Optimization of fluorinated phenyl azides as universal photocrosslinkers for semiconducting polymers.

Fluorinated phenyl azides (FPA) enable photo-structuring of π-conjugated polymer films for electronic device applications. Despite their potential, FPAs have faced limitations regarding their crosslinking efficiency, and more importantly, their impact on critical semiconductor properties, such as charge-carrier mobility. Here, we report that azide photolysis and photocrosslinking can achieve unity quantum efficiencies for specific FPAs. This suggests preferential nitrene insertion into unactivated C‒H bonds over benzazirine and ketenimine reactions, which we attribute to rapid interconversion between the initially formed hot states. Furthermore, we establish a structure‒activity relationship for carrier mobility quenching. The binding affinity of FPA crosslinker to polymer π-stacks governs its propensity for mobility quenching in both PM6 and PBDB-T used as model conjugated polymers. This binding affinity can be suppressed by FPA ring substitution, but varies in a non-trivial way with π-stack order. Utilizing the optimal FPA, photocrosslinking enables the fabrication of morphology-stabilized, acceptor-infiltrated donor polymer networks (that is, PBDB-T: ITIC and PM6: Y6) for solar cells. Our findings demonstrate the exceptional potential of the FPA photochemistry and offer a promising approach to address the challenges of modelling realistic molecular interactions in complex polymer morphologies, moving beyond the limitations of Flory‒Huggins mean field theory.

Effects of Planarization of the Triphenylamine Unit on the Electronic and Transport Properties of Triarylamine-Fluorene Copolymers in Both Doped and Undoped Forms.

Triarylamine-alt-fluorene (TAF) copolymers are widely used for hole injection and transport in organic electronics. Despite suggestions to planarize the triphenylamine moiety, little research has been conducted. Here, we report a comprehensive investigation of the effects of planarization on the electronic and transport properties of a model TAF polymer semiconductor core. We compared the conventional twisted-propeller N-4-methoxyphenyl-N,N-diphenylamine-4',4″-diyl (TA) unit and its planarized bridged analogue (bTA) where adjacent o,o'-positions are linked by 1,1-dimethylmethylene. We studied both polyelectrolyte and non-polyelectrolyte forms of this core in both doped and undoped states. We found that planarization leads to an unprecedented trap-free transport of holes, and a pronounced enhancement of their mobility in the undoped state though less so in the doped state. Planarization also induces a slight reduction in the ionization energy of the undoped polymer, consequently lowering the work function of the doped polymer. This is accompanied by small spectral shifts: a red shift in the first absorption band of the undoped polymer and a blue shift in the first absorption band of the polaron. Furthermore, this study unveils new fundamental features of TAF polymers: (i) Doping induces the formation of three polaron bands within the subgap. (ii) Absorption of both neutral and polaron segments exhibit a linear intensity relationship with doping level. (iii) Electrical conductivity reaches a maximum at the half-doped state, varying as σ ∼ (x (1 - x))3 for 0.1 ≲ x ≲ 0.9, where x is the doping level. Finally, we demonstrate the successful integration of these self-compensated hole-doped TAF polymers as efficient hole injection layers in organic semiconductor diodes.

An Unusual Macrocyclic Hexamer of an Iso-Tellurazole N-Oxide Featuring CTe O Chalcogen Bonds is Formed by κ6 -O Complexation to Fe(II) and Ni(II).

Studies of the supramolecular chemistry of iso-tellurazole N-oxides have been confined to non-polar media until now. To overcome that limitation, an iso-tellurazole N-oxide was derivatized with a primary alcohol group; the compound is soluble in polar solvents and stable in acidic to neutral aqueous media. Nickel (II) and iron (II) form macrocyclic complexes with six molecules of that iso-tellurazole N-oxide in a hitherto not-observed macrocyclic arrangement defined by CTe⋅⋅⋅O chalcogen bonds and κ6 -O bound to the metal ion. This behaviour is in sharp contrast with the κn -Te (n=1,2,4) complexes formed by soft metal ions.

Feasibility of a Community Healthy Eating and Cooking Intervention Featuring Traditional African Caribbean Foods from Participant and Staff Perspectives.

Culturally appropriate healthy eating resources are intended to help people from different ethnic backgrounds consume diets reflecting government dietary recommendations, yet evidence on use in the target groups is lacking. This study evaluated the feasibility of a new brief culturally appropriate community intervention that aimed to introduce food-based healthy eating and recipe resources featuring African Caribbean foods, which were recently co-developed with people from these ethnic backgrounds. Working with a community organization in the UK, a single-arm study was used to collect verbal data from participants and staff on the acceptability of intervention whilst knowledge, skills and behaviours related to healthy eating were evaluated using pre-, post- and follow-up questionnaires. A total of 30 participants were recruited, and 22 completed all three questionnaires; who were mostly female aged 55 years+ (n = 17) and of African Caribbean ethnicity (45%, n = 10), with 32% (n = 7) reporting no educational attainment. At post-intervention and follow-up, most participants reported high satisfaction (n = 21, 95%) with the intervention sessions and high levels of confidence in using the resources at home within budget. The number of participants who were familiar with the healthy eating guidance featuring Caribbean foods increased from pre- (36%, n = 8) to post-intervention/follow-up (n = 22, 100%) (p < 0.05). Findings suggest the intervention is feasible in a community setting and could help increase awareness and use of culturally appropriate healthy eating guidance amongst a diverse group.

Development and validation of a quality assessment tool to assess online nutrition information.

Setting: The internet is an important source of health information but is unregulated. Little research has focused on the assessment of digital information related to nutrition. Aim: To develop and validate a novel online quality assessment tool (OQAT) for quality assessment of online nutrition information. Method: The OQAT was developed and validated in six distinct stages. After reviewing the literature, a framework and criteria were developed and formalised. Next, the quality assessment criteria were piloted on a subset of data and criteria refined. The established criteria were then validated against a previously validated assessment tool, and reliability was tested. Finally, the validated OQAT was used to assess the quality of articles from a 24-h collection period, 19 April 2021. Results: The final OQAT consisted of 10 key questions. Twenty-six news articles were assessed independently by two raters. Comparison of scores found moderate internal consistency (α = 0.382). Cohen's Kappa coefficient demonstrated high interrater agreement (k = 0.653, p < 0.001). The OQAT was tested on 291 relevant Uniform Resource Locators (URLs), which were determined to be either poor 3% (n = 9), satisfactory 49% (n = 144), or high-quality 48% (n = 139) articles. There was a statistically significant difference in OQAT scores between blogs, news articles, and press releases, χ2(2) = 23.22, p < 0.001, with a mean rank OQAT score of 138.2 for blogs, 216.6 for news articles, and 188.7 for press releases. Conclusion: This novel tool provides a reliable and objective method for assessing the quality of nutrition content online. It could potentially be used by researchers to assess the quality of online information in different settings and by organisations to inform readers of the quality of information being accessed.

Water binding and hygroscopicity in π-conjugated polyelectrolytes.

The presence of water strongly influences structure, dynamics and properties of ion-containing soft matter. Yet, the hydration of such matter is not well understood. Here, we show through a large study of monovalent π-conjugated polyelectrolytes that their reversible hydration, up to several water molecules per ion pair, occurs chiefly at the interface between the ion clusters and the hydrophobic matrix without disrupting ion packing. This establishes the appropriate model to be surface hydration, not the often-assumed internal hydration of the ion clusters. Through detailed analysis of desorption energies and O-H vibrational frequencies, together with OPLS4 and DFT calculations, we have elucidated key binding motifs of the sorbed water. Type-I water, which desorbs below 50 °C, corresponds to hydrogen-bonded water clusters constituting secondary hydration. Type-II water, which typically desorbs over 50-150 °C, corresponds to water bound to the anion under the influence of a proximal cation, or to a cation‒anion pair, at the cluster surface. This constitutes primary hydration. Type-III water, which irreversibly desorbs beyond 150 °C, corresponds to water kinetically trapped between ions. Its amount varies strongly with processing and heat treatment. As a consequence, hygroscopicity-which is the water sorption capacity per ion pair-depends not only on the ions, but also their cluster morphology.

Risk factors for hospitalisation in Welsh infants with a congenital anomaly.

OBJECTIVES: To investigate risk factor associated with hospitalisation of infants with a congenital anomaly in Wales, UK. DESIGN: A population-based cohort study. SETTING: Data from the Welsh Congenital Anomaly Register and Information Service linked to the Patient Episode Database for Wales and livebirths and deaths from the Office for National Statistics. PATIENTS: All livebirths between 1999 and 2015 with a diagnosis of a congenital anomaly, which was defined as a structural, metabolic, endocrine or genetic defect, as well as rare diseases of hereditary origin. MAIN OUTCOME MEASURES: Adjusted OR (aOR) associated with 1 or 2+ hospital admissions in infancy versus no admissions were estimated for sociodemographic, maternal and infant factors using multinomial logistic regression for the subgroups of all, isolated, multiple and cardiovascular anomalies. RESULTS: 25 523 infants affected by congenital anomalies experienced a total of 50 705 admissions in infancy. Risk factors for ≥2 admissions were younger maternal age ≤24 years (aOR: 1.17; 95% CI 1.06 to 1.30), maternal smoking (aOR: 1.20; 1.10 to 1.31), preterm birth (aOR: 2.52; 2.25 to 2.83) and moderately severe congenital heart defects (aOR: 6.25; 4.47 to 8.74). Girls had an overall decreased risk of 2+ admissions (aOR: 0.84; 0.78 to 0.91). Preterm birth was a significant risk factor for admissions in all anomaly subgroups but the effect of the other characteristics varied according to anomaly subgroup. CONCLUSIONS: Over two-thirds of infants with an anomaly are admitted to hospital during infancy. Our findings identified sociodemographic and clinical characteristics contributing to an increased risk of hospitalisation of infants with congenital anomalies.

Double-type-I charge-injection heterostructure for quantum-dot light-emitting diodes.

Enforcing balanced electron-hole injection into the emitter layer of quantum-dot light-emitting diodes (QLEDs) remains key to maximizing the quantum efficiency over a wide current density range. This was previously thought not possible for quantum dot (QD) emitters because of their very deep energy bands. Here, we show using Mesolight® blue-emitting CdZnSeS/ZnS QDs as a model that its valence levels are in fact considerably shallower than the corresponding band maximum of the bulk semiconductor, which makes the ideal double-type-I injection/confinement heterostructure accessible using a variety of polymer organic semiconductors as transport and injection layers. We demonstrate flat external quantum efficiency characteristics that indicate near perfect recombination within the QD layer over several decades of current density from the onset of device turn-on of about 10 µA cm-2, for both normal and inverted QLED architectures. We also demonstrate that these organic semiconductors do not chemically degrade the QDs, unlike the usual ZnMgO nanoparticles. However, these more efficient injection heterostructures expose a new vulnerability of the QDs to in device electrochemical degradation. The work here opens a clear path towards next-generation ultra-high-performance, all-solution-processed QLEDs.

Role of Linker Functionality in Polymers Exhibiting Main-Chain Thermally Activated Delayed Fluorescence.

Excellent performance has been reported for organic light-emitting diodes (OLEDs) based on small molecule emitters that exhibit thermally activated delayed fluorescence. However, the necessary vacuum processing makes the fabrication of large-area devices based on these emitters cumbersome and expensive. Here, the authors present high performance OLEDs, based on novel, TADF polymers that can be readily processed from a solution. These polymers are based on the acridine-benzophenone donor-acceptor motif as main-chain TADF chromophores, linked by various conjugated and non-conjugated spacer moieties. The authors' extensive spectroscopic and electronic analysis shows that in particular in case of alkyl spacers, the properties and performance of the monomeric TADF chromophores are virtually left unaffected by the polymerization. They present efficient solution-processed OLEDs based on these TADF polymers, diluted in oligostyrene as a host. The devices based on the alkyl spacer-based TADF polymers exhibit external quantum efficiencies (EQEs) ≈12%, without any outcoupling-enhancing measures. What's more, the EQE of these devices does not drop substantially upon diluting the polymer down to only ten weight percent of active material. In contrast, the EQE of devices based on the monomeric chromophore show significant losses upon dilution due to loss of charge percolation.

Detecting Cataract Using Smartphones.

OBJECTIVE: Cataract, which is the clouding of the crystalline lens, is the most prevalent eye disease accounting for 51% of all eye diseases in the U.S. Cataract is a progressive disease, and its early detection is critical for preventing blindness. In this paper, an efficient approach to identify cataract disease by adopting luminance features using a smartphone is proposed. METHODS: Initially, eye images captured by a smartphone were cropped to extract the lens, and the images were preprocessed to remove irrelevant background and noise by utilizing median filter and watershed transformation. Then, a novel luminance transformation from pixel brightness algorithm was introduced to extract lens image features. The luminance and texture features of different types of cataract disease images could be obtained accurately in this stage. Finally, by adopting support vector machines (SVM) as the classification method, cataract eyes were identified. RESULTS: From all the images that we fed into our system, our method could diagnose diseased eyes with 96.6% accuracy, 93.4% specificity, and 93.75% sensitivity. CONCLUSION: The proposed method provides an affordable, rapid, easy-to-use, and versatile method for detecting cataracts by using smartphones without the use of bulky and expensive imaging devices. This methodcan be used for bedside telemedicine applications or in remote areas that have medical shortages. Previous smartphone-based cataract detection methods include texture feature analysis with 95 % accuracy, Gray Level Co-occurrence Matrix (GLCM) method with 89% accuracy, red reflex measurement method, and RGB color feature extraction method using cascade classifier with 90% accuracy. The accuracy of cataract detection in these studies is subject to changes in smartphone models and/or environmental conditions. However, our novel luminance-based method copes with different smartphone camera sensors and chroma variations, while operating independently from sensors' color characteristics and changes in distances and camera angle. Clinical and Translational Impact-This study is an early/pre-clinical research proposing a novel luminance-based method of detecting cataract using smartphones for remote/at-home monitoring and telemedicine application.

Iso-Tellurazolium-N-Phenoxides: A Family of Te···O Chalcogen-Bonding Supramolecular Building Blocks.

Formal substitution of the oxygen atom of an iso-tellurazole N-oxide with deprotonated (ortho, meta, and para)-hydroxyphenyl groups generated molecules that readily aggregate through Te···O chalcogen bonding (ChB) interactions. The molecules undergo autoassociation in solution, as shown by variable temperature (VT) 1H NMR experiments and paralleling the behavior of iso-tellurazole N-oxides. Judicious adjustment of crystallization conditions enabled the isolation of either polymeric or macrocyclic aggregates. Among the latter, the ortho compound assembled a calixarene-like trimer, while the para isomer built a macrocyclic tetramer akin to a molecular square. The Te···O ChB distances in these structures range from 2.13 to 2.17 Å, comparable to those in the structures of iso-tellurazole N-oxides. DFT calculations estimate that the corresponding Te···O ChB energies are between -122 and -195 kJ mol-1 in model dimers and suggest that macrocyclic aggregation enhances these interactions.

Clinically Oriented Classification of Anatomic Variants of the Umbilical Fissure for Ligamentum Teres in the Human Liver.

Background In the classic descriptions of the human liver, the umbilical fissure (UF) is a long, narrow groove on the visceral surface that receives the ligamentum teres hepatis. In this study, we document the UF variations encountered in a series of cadaveric dissections. Methods We reported UF variations using the following classification: Type I refers to "normal" anatomy where there is a long, narrow groove. In type II, the UF was covered by a fibrotic band devoid of hepatic parenchyma. In type III variants, an extension of hepatic parenchyma partially covered but did not obliterate the UF. In type IV variants, the hepatic parenchyma formed a bridge over the UF, completely obliterating the groove. After institutional review board approval, we observed all consecutive cadaveric dissections over five years and recorded the characteristics and dimensions of each UF and its immediate relations. Results There were 69 cadavers, and variant UFs were present in 38 (55.1%) cadavers: type II (1.5%), type III (20.3%), and type IV (33.3%). Conclusions In this Jamaican population, only 44.9% of persons had conventional "normal" anatomy and 55.1% had UF variants. These variants are clinically significant, as they lead to misinterpretation of patient imaging and can hinder operative procedures on the liver.

Overcoming the water oxidative limit for ultra-high-workfunction hole-doped polymers.

It is widely thought that the water-oxidation reaction limits the maximum work function to about 5.25 eV for hole-doped semiconductors exposed to the ambient, constrained by the oxidation potential of air-saturated water. Here, we show that polymer organic semiconductors, when hole-doped, can show work functions up to 5.9 eV, and yet remain stable in the ambient. We further show that de-doping of the polymer is not determined by the oxidation of bulk water, as previously thought, due to its general absence, but by the counter-balancing anion and its ubiquitously hydrated complexes. The effective donor levels of these species, representing the edge of the 'chemical' density of states, can be depressed to about 6.0 eV below vacuum level. This can be achieved by raising the oxidation potential for hydronium generation, using large super-acid anions that are themselves also stable against oxidation. In this way, we demonstrate that poly(fluorene-alt-triarylamine) derivatives with tethered perfluoroalkyl-sulfonylimidosulfonyl anions can provide ambient solution-processability directly in the ultrahigh-workfunction hole-doped state to give films with good thermal stability. These results lay the path for design of soft materials for battery, bio-electronic and thermoelectric applications.

Competing Effects of Chlorination on the Strength of Te⋠⋠⋠O Chalcogen Bonds Select the Structure of Mixed Supramolecular Macrocyclic Aggregates of Iso-Tellurazole N-Oxides.

Chlorination of 3-methyl-5-phenyl-1,2-tellurazole-2-oxide yielded the λ4 Te dichloro derivative. Its crystal structure demonstrates that the heterocycle retains its ability to autoassociate by chalcogen bonding (ChB) forming macrocyclic tetramers. The corresponding Te⋅⋅⋅O ChB distances are 2.062 Å, the shortest observed to date in aggregates of this type. DFT-D3 calculations indicate that while the halogenated molecule is stronger as a ChB donor it also is a weaker ChB acceptor; the overall effect is that the ChBs in the chlorinated homotetramer are not significantly stronger. However, partial halogenation or scrambling selectively yield the 2 : 2 heterotetramer with alternating λ4 Te and λ2 Te centers, which calculations identified as the thermodynamically preferred arrangement.

Neonatal and infant mortality associated with spina bifida: A systematic review and meta-analysis.

OBJECTIVES: A systematic review was conducted in high-income country settings to analyse: (i) spina bifida neonatal and IMRs over time, and (ii) clinical and socio-demographic factors associated with mortality in the first year after birth in infants affected by spina bifida. DATA SOURCES: PubMed, Embase, Ovid, Web of Science, CINAHL, Scopus and the Cochrane Library were searched from 1st January, 1990 to 31st August, 2020 to review evidence. STUDY SELECTION: Population-based studies that provided data for spina bifida infant mortality and case fatality according to clinical and socio-demographical characteristics were included. Studies were excluded if they were conducted solely in tertiary centres. Spina bifida occulta or syndromal spina bifida were excluded where possible. DATA EXTRACTION AND SYNTHESIS: Independent reviewers extracted data and assessed their quality using MOOSE guideline. Pooled mortality estimates were calculated using random-effects (+/- fixed effects) models meta-analyses. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Meta-regression was performed to examine the impact of year of birth cohort on spina bifida infant mortality. RESULTS: Twenty studies met the full inclusion criteria with a total study population of over 30 million liveborn infants and approximately 12,000 spina bifida-affected infants. Significant declines in spina bifida associated infant and neonatal mortality rates (e.g. 4.76% decrease in IMR per 100, 000 live births per year) and case fatality (e.g. 2.70% decrease in infant case fatality per year) were consistently observed over time. Preterm birth (RR 4.45; 2.30-8.60) and low birthweight (RR 4.77; 2.67-8.55) are the strongest risk factors associated with increased spina bifida infant case fatality. SIGNIFICANCE: Significant declines in spina bifida associated infant/neonatal mortality and case fatality were consistently observed, advances in treatment and mandatory folic acid food fortification both likely play an important role. Particular attention is warranted from clinicians caring for preterm and low birthweight babies affected by spina bifida.

Improving organic photovoltaic cells by forcing electrode work function well beyond onset of Ohmic transition.

As electrode work function rises or falls sufficiently, the organic semiconductor/electrode contact reaches Fermi-level pinning, and then, few tenths of an electron-volt later, Ohmic transition. For organic solar cells, the resultant flattening of open-circuit voltage (Voc) and fill factor (FF) leads to a 'plateau' that maximizes power conversion efficiency (PCE). Here, we demonstrate this plateau in fact tilts slightly upwards. Thus, further driving of the electrode work function can continue to improve Voc and FF, albeit slowly. The first effect arises from the coercion of Fermi level up the semiconductor density-of-states in the case of 'soft' Fermi pinning, raising cell built-in potential. The second effect arises from the contact-induced enhancement of majority-carrier mobility. We exemplify these using PBDTTPD:PCBM solar cells, where PBDTTPD is a prototypal face-stacked semiconductor, and where work function of the hole collection layer is systematically 'tuned' from onset of Fermi-level pinning, through Ohmic transition, and well into the Ohmic regime.

Surface Doping of Organic Single-Crystal Semiconductors to Produce Strain-Sensitive Conductive Nanosheets.

A highly periodic electrostatic potential, even though established in van der Waals bonded organic crystals, is essential for the realization of a coherent band electron system. While impurity doping is an effective chemical operation that can precisely tune the energy of an electronic system, it always faces an unavoidable difficulty in molecular crystals because the introduction of a relatively high density of dopants inevitably destroys the highly ordered molecular framework. In striking contrast, a versatile strategy is presented to create coherent 2D electronic carriers at the surface of organic semiconductor crystals with their precise molecular structures preserved perfectly. The formation of an assembly of redox-active molecular dopants via a simple one-shot solution process on a molecularly flat crystalline surface allows efficient chemical doping and results in a relatively high carrier density of 1013 cm-2 at room temperature. Structural and magnetotransport analyses comprehensively reveal that excellent carrier transport and piezoresistive effects can be obtained that are similar to those in bulk crystals.

Paediatric Strategy Forum for medicinal product development of epigenetic modifiers for children: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The fifth multistakeholder Paediatric Strategy Forum focussed on epigenetic modifier therapies for children and adolescents with cancer. As most mutations in paediatric malignancies influence chromatin-associated proteins or transcription and paediatric cancers are driven by developmental gene expression programs, targeting epigenetic mechanisms is predicted to be a very important therapeutic approach in paediatric cancer. The Research to Accelerate Cures and Equity (RACE) for Children Act FDARA amendments to section 505B of the FD&C Act was implemented in August 2020, and as there are many epigenetic targets on the FDA Paediatric Molecular Targets List, clinical evaluation of epigenetic modifiers in paediatric cancers should be considered early in drug development. Companies are also required to submit to the EMA paediatric investigation plans aiming to ensure that the necessary data to support the authorisation of a medicine for children in EU are of high quality and ethically researched. The specific aims of the forum were i) to identify epigenetic targets or mechanisms of action associated with epigenetic modification relevant to paediatric cancers and ii) to define the landscape for paediatric drug development of epigenetic modifier therapies. DNA methyltransferase inhibitors/hypomethylating agents and histone deacetylase inhibitors were largely excluded from discussion as the aim was to discuss those targets for which therapeutic agents are currently in early paediatric and adult development. Epigenetics is an evolving field and could be highly relevant to many paediatric cancers; the biology is multifaceted and new targets are frequently emerging. Targeting epigenetic mechanisms in paediatric malignancy has in most circumstances yet to reach or extend beyond clinical proof of concept, as many targets do not yet have available investigational drugs developed. Eight classes of medicinal products were discussed and prioritised based on the existing level of science to support early evaluation in children: inhibitors of menin, DOT1L, EZH2, EED, BET, PRMT5 and LSD1 and a retinoic acid receptor alpha agonist. Menin inhibitors should be moved rapidly into paediatric development, in view of their biological rationale, strong preclinical activity and ability to fulfil an unmet clinical need. A combination approach is critical for successful utilisation of any epigenetic modifiers (e.g. EZH2 and EED) and exploration of the optimum combination(s) should be supported by preclinical research and, where possible, molecular biomarker validation in advance of clinical translation. A follow-up multistakeholder meeting focussing on BET inhibitors will be held to define how to prioritise the multiple compounds in clinical development that could be evaluated in children with cancer. As epigenetic modifiers are relatively early in development in paediatrics, there is a clear opportunity to shape the landscape of therapies targeting the epigenome in order that efficient and optimum plans for their evaluation in children and adolescents are developed in a timely manner.

Optimizing the Efficacy of Learning Objectives through Pretests.

Learning objectives (LOs) are statements that typically precede a study session and describe the knowledge students should obtain by the end of the session. Despite their widespread use, limited research has investigated the effect of LOs on learning. In three laboratory experiments, we examined the extent to which LOs improve retention of information. Participants in each experiment read five passages on a neuroscience topic and took a final test that measured how well they retained the information. Presenting LOs before each corresponding passage increased performance on the final test compared with not presenting LOs (experiment 1). Actively presenting LOs increased their pedagogical value: Performance on the final test was highest when participants answered multiple-choice pretest questions compared with when they read traditional LO statements or statements that included target facts (experiment 2). Interestingly, when feedback was provided on pretest responses, performance on the final test decreased, regardless of whether the pretest format was multiple choice or short answer (experiment 3). Together, these findings suggest that, compared with the passive presentation of LO statements, pretesting (especially without feedback) is a more active method that optimizes learning.

A Double-Blind, Phase I, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BOS161721 in Healthy Subjects.

The purpose of this study was to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of BOS161721, a humanized immunoglobulin G1 triple mutation (M252Y/S254T/T256E) monoclonal antibody that inhibits interleukin-21 (IL-21) bioactivity. This randomized, single-center, double-blind, placebo-controlled study randomized healthy volunteers 3:1 to single ascending intravenous and subcutaneous doses of BOS161721 (range 1-240 mg) or placebo. BOS161721 and placebo groups had similar rates of adverse events, mostly mild; none led to study discontinuation. There were no clinically significant findings in physical examination, vital signs, or laboratory assessment. In the pooled BOS161721 population, four subjects (8.5%) tested antidrug antibody-positive predose, and seven (14.9%) postdose. Absolute CD4+ lymphocyte count remained normal throughout follow-up. BOS161721 administered subcutaneously was absorbed slowly, with a median time to maximum concentration (Tmax ) of 144 hours across doses (range 1-15 days) and a mean apparent terminal elimination half-life of 80-87 days for doses ≥ 30 mg. Area under the concentration-time curve from time zero to infinity (AUC0-inf ) and maximum observed concentration (Cmax ) were linear across doses > 10 mg. Subcutaneous bioavailability was 64%. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) decreased dose-dependently with threshold characteristics at doses of ≥ 10 mg. Downregulation in BATF, IL6, LAG3, and SOCS3 genes caused by IL-21 stimulation was reversed dose-dependently. BOS161721 was well-tolerated across doses, suppressed IL-21-induced pSTAT3 dose-dependently, and reversed downregulation of genes critical to tolerance induction and T-cell exhaustion induced by IL-21. Further clinical studies are ongoing in patients with systemic lupus erythematosus, in which IL-21 has a pathogenetic role.