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In contrast to phosphine oxides and arsine oxides, which are common and exist as stable monomeric species featuring the corresponding pnictoryl functional group (Pn=O/Pn+–O−; Pn = P, As), stibine oxides are generally polymeric, and the properties of the unperturbed stiboryl group (Sb=O/Sb+–O−) remain unexplored. We now report the isolation of the monomeric stibine oxide, Dipp3SbO (where Dipp = 2,6-diisopropylphenyl). Spectroscopic, crystallographic and computational studies provide insight into the nature of the Sb=O/Sb+–O− bond. Moreover, isolation of Dipp3SbO allows the chemistry of the stiboryl group to be explored. Here we show that Dipp3SbO can act as a Brønsted base, a hydrogen-bond acceptor and a transition-metal ligand, in addition engaging in 1,2-addition, O-for-F2 exchange and O-atom transfer. In all cases, the reactivity of Dipp3SbO differed from that of the lighter congeners Dipp3AsO and Dipp3PO.

We report the high-capacity and selective uptake of Cr(VI) from water using the coordination polymer silver bipyridine acetate (SBA, [Ag(4,4'-bipy)][CH

Following the seminal theoretical work on the pleated β-sheet published by Pauling and Corey in 1951, the rippled β-sheet was hypothesized by the same authors in 1953. In the pleated β-sheet the interacting β-strands have the same chirality, whereas in the rippled β-sheet the interacting β-strands are mirror-images. Unlike with the pleated β-sheet that is now common textbook knowledge, the rippled β-sheet has been much slower to evolve. Much of the experimental work on rippled sheets came from groups that study aggregating racemic peptide systems over the course of the past decade. This includes MAX1/DMAX hydrogels (Schneider), L/D-KFE8 aggregating systems (Nilsson), and racemic Amyloid β mixtures (Raskatov). Whether a racemic peptide mixture is "ripple-genic" (

Na2B12I12 has many of the properties desired by an X-ray contrast agent but is lethal at the concentrations needed for medical imaging. We demonstrate here that PBS solutions with >50 mM Na2B12I12 induce hemolysis, consistent with the previously reported superchaotropic nature of the anion. The presence of

Neutron wavelength-resolved Laue diffraction experiments permit accurate refinement of the H-atom positions and anisotropic displacement parameters of [Mes3SbOH][O3SPh]. A multipole-based charge density refinement and a topological analysis of the refined electron density were also performed. Hirshfeld atom refinement (HAR) recovers the neutron-determined H-atom parameters, and the quantum-mechanical electron density used in HAR recovers the electron density topology from the refined multipole model. These results confirm that [Mes3SbOH][O3SPh] does indeed feature a hydroxystibonium cation with a nominal Sb-O single bond and not a stibine oxide with an Sb=O/Sb+-O- bond.

Detecting small mammal species for wildlife research and management typically depends on animals deciding to engage with a device, for instance, by entering a trap. While some animals engage and are detected, others do not, and we often lack a mechanistic understanding of what drives these decisions. As trappability can be influenced by traits of personality, personality has high potential to similarly influence detection success for non-capture devices (chew-track cards, tracking tunnels, etc.). We present a conceptual model of the detection process where animal behaviours which are detected by different devices are grouped into tiers based on the degree of intimacy with a device (e.g., approach, interact, enter). Each tier is associated with an increase in the perceived danger of engaging with a device, and an increase in the potential for personality bias. To test this model, we first surveyed 36 populations of free-living black rats (Rattus rattus), a global pest species, to uniquely mark individuals (n = 128) and quantify personality traits. We then filmed rat behaviour at novel tracking tunnels with different risk-reward treatments. As predicted, detection biases were driven by personality, the bias increased with each tier and differed between the risk treatments. Our findings suggest that personality biases are not limited to live-capture traps but are widespread across devices which detect specific animal behaviours. In showing that biases can be predictable, we also show biases can be managed. We recommend that studies involving small mammal sampling report on steps taken to manage a personality-driven bias.

Background: Workplace-based assessment (WBA) is a critical component of competency-based medical education (CBME), though literature on WBA for overnight call is limited. We evaluated a WBA tool completed by supervising subspecialty trainees on paediatric residents during subspecialty overnight call, for usefulness facilitating feedback/coaching in this setting.Methods: Web-based surveys were sent to residents pre- and post-WBA tool implementation monthly for four months (August-December 2018), exploring feedback frequency, Likert-scaled opinions of tool feasibility/usefulness facilitating feedback, and qualitative experiences. Assessor comments were categorized as actionable/non-actionable. Quantitative data was summarized using descriptive statistics. Qualitative data was coded to identify themes. Results: Total response rates averaged 41% (total 25 responses, average five respondents/12 residents on-call each month). Post-implementation (n = 16 responses), a non-sustained trend of increased Medical Expert feedback was observed. Residents were generally divided or disagreed on tool usefulness facilitating feedback and feasibility. Comments contained actionable feedback in < 10% of completed WBAs. Qualitative analysis revealed barriers to tool-facilitated coaching including: feedback quality and setting/environment, role of senior near-peer as assessor, interpersonal burden in encounters, and tool-specific issues.Conclusions: Increasing frequency of WBA tool completion is not sufficient to achieve CBME goals. Factors impacting feedback/coaching within the resident/near-peer dyad must be addressed., Contexte : Tandis que l’évaluation en milieu de travail (EMT) est une composante essentielle de l’éducation médicale fondée sur les compétences (EMFC), il y a peu de recherches sur l’EMT en contexte de garde de nuit. Nous avons étudié un formulaire d’évaluation en milieu de travail rempli par des résidents en surspécialité supervisant des résidents en pédiatrie pendant la garde de nuit en surspécialité, afin de déterminer s’il facilite la rétroaction avec coaching dans ce contexte.Méthodes : Des questionnaires en ligne ont été envoyés aux résidents avant la mise en œuvre de l’outil d’EMT et à partir de celle-ci, tous les mois pendant quatre mois (d’août à décembre 2018). Ils exploraient la fréquence des rétroactions, les opinions des participants, exprimées sur une échelle de Likert, sur le caractère pratique et l’utilité de l’outil comme facilitateur de la rétroaction et leurs expériences qualitatives. Les commentaires des évaluateurs ont été catégorisés comme étant exploitables ou non exploitables. Les données quantitatives ont été résumées à l’aide de statistiques descriptives. Les données qualitatives ont été codées pour identifier les thèmes.Résultats : Le taux de réponse total était en moyenne de 41 % (total de 25 réponses, moyenne de 5 répondants/12 résidents de garde chaque mois). Après l’introduction de l’outil (n = 16 réponses), une tendance non soutenue à l’augmentation des commentaires des experts médicaux a été observée. Les résidents étaient généralement partagés ou en désaccord quant au caractère pratique de l’outil et à sa capacité à faciliter la rétroaction. Les commentaires contenaient des informations exploitables dans moins de 10 % des EMT remplies. L’analyse qualitative a révélé les obstacles suivants au fonctionnement de l’outil comme facilitateur du coaching : la qualité des commentaires et l’environnement, le rôle du presque pair senior en tant qu’évaluateur, la tension lors des rencontres de coaching et les problèmes spécifiques à l’outil.Conclusion : Pour atteindre les objectifs de l’EMFC, il ne suffit pas de remplir plus souvent l’outil d’EMT. Les facteurs qui influencent la rétroaction avec coaching au sein de la dyade résident-presque pair doivent également être pris en compte.

Herein we report an investigation into the synthesis, metalation, and functionalization of bis-pocket porphyrins using the Suzuki-Miyaura cross-coupling reaction. Steric limitations to accessing bis-pocket porphyrins were overcome by using this Pd-catalyzed C-C-bond-forming strategy to introduce steric bulk

The rippled β-sheet is a peptidic structural motif related to but distinct from the pleated β-sheet. Both motifs were predicted in the 1950s by Pauling and Corey. The pleated β-sheet was since observed in countless proteins and peptides and is considered common textbook knowledge. Conversely, the rippled β-sheet only gained a meaningful experimental foundation in the past decade, and the first crystal structural study of rippled β-sheets was published as recently as this year. Noteworthy, the crystallized assembly stopped at the rippled β-dimer stage. It did not form the extended, periodic rippled β-sheet layer topography hypothesized by Pauling and Corey, thus calling the validity of their prediction into question. NMR work conducted since moreover shows that certain model peptides rather form pleated and not rippled β-sheets in solution. To determine whether the periodic rippled β-sheet layer configuration is viable, the field urgently needs crystal structures. Here we report on crystal structures of two racemic and one quasi-racemic aggregating peptide systems, all of which yield periodic rippled antiparallel β-sheet layers that are in excellent agreement with the predictions by Pauling and Corey. Our study establishes the rippled β-sheet layer configuration as a motif with general features and opens the road to structure-based design of unique supramolecular architectures.

Context Wildlife surveys often rely on a single live-capture technique to sample animal populations. Yet, animal personality (e.g. bold vs shy) can drive heterogeneity in capture probability, leading to biased sampling during live-capture trapping surveys. Aims We tested whether a personality-related capture bias is similar between two live-capture techniques, or whether techniques with different capture mechanisms are biased towards certain spectrums of personality. Methods We compared two live-capture techniques commonly used for surveying lizards, namely, noosing and pitfall traps. Techniques were deployed several days apart to survey populations of a desert-dwelling agamid, the military dragon, and we used outdoor open-field arenas to test for personality traits relating to boldness, activity and exploration. Key results We found that noosing and pitfall traps sampled distinctly different spectrums of personality, with no individuals being captured by both techniques. Unexpectedly, noosing, which involved people approaching dragons to capture them, was biased towards shyer individuals that stayed close to shelter. In contrast, pitfall traps, which were generally set in open areas, were biased towards capturing individuals that moved further from shelter. Conclusions We demonstrated that different live-capture techniques can be biased towards different spectrums of personality. We attribute the relationship between personality and technique to an interaction between the capture mechanisms of each technique and individual perceptions of risk and microhabitat use. Implications To overcome biased and selective sampling and target individuals along a broad spectrum of personality, surveys should use complementary techniques that vary in their capture mechanisms.

Tracheal intubation of a patient with COVID-19 is a high-risk procedure for not only the patient, but all healthcare workers involved, leading to an understandable degree of staff anxiety. We used simulation to help train airway managers to intubate patients with COVID-19. Based on action cards developed by our department, we designed a series of scenarios to simulate airway management during the COVID-19 pandemic. Teams were asked to perform a rapid sequence induction with tracheal intubation. We designed in situ scenarios with low-fidelity manikins that could be set up in operating theatres across multiple sites. Over a period of 4 weeks, 101 consultant anaesthetists, 58 anaesthetic trainees and 30 operating department practitioners received intubation training. These members made up the airway response team of our hospital. 30 emergency department doctors also received training in anticipation of further COVID-19 surges leading to the possibility of overwhelmed services. Simulation-based training was an invaluable tool for our hospital to rapidly upskill medical professionals during the first wave of the COVID-19 pandemic. We have used feedback and additional guidelines to improve our scenarios to retrain staff during subsequent waves.

Pentaphenylantimony (SbPh5) has been previously crystallized in either a square pyramidal or trigonal bipyramidal geometry. Investigation of the solution-state structure of SbPh5 has been hampered by the extreme fluxionality of this compound, but previous vibrational spectroscopic studies concluded that it maintains a square pyramidal geometry in solution. This non-VSEPR-compliant geometry, which is also assumed by BiPh5 in the solid state, stands in contrast to the trigonal bipyramidal geometries of PPh5 and AsPh5. A range of phenomena have been invoked to explain this discrepancy, most notably, the increased importance of relativistic effects as group 15 is descended. We present crystallographic, spectroscopic, and computational data revealing that SbPh5 in fact assumes the VSEPR-compliant trigonal bipyramidal geometry in solution. In particular, Sb X-ray absorption spectroscopy (XAS) was used to obtain geometry-sensitive spectra that do not suffer from the slow spectroscopic time scale that has prevented NMR studies from elucidating the structure of this fluxional molecule. Sb K-edge and LIII-edge XAS spectra of crystalline solids featuring SbPh5 in either a square pyramidal (nonsolvate) or trigonal bipyramidal (cyclohexane hemisolvate or THF hemisolvate) form were compared to spectra of SbPh5 in solution. The solution-state spectra agree with those from solids containing trigonal bipyramidal SbPh5. The most diagnostic spectroscopic feature was the distribution of intensity in the Sb LIII pre-edge features. These distributions were rationalized using time-dependent density functional theory calculations that take into account spin-orbit coupling. Our use of Sb XAS not only resolves a long-standing physical inorganic question but also demonstrates more widely the utility of XAS in establishing the structures of fluxional main-group compounds. This conclusion was further supported by solid- and solution-state Raman data. Finally, we note that the present high-resolution diffraction data allow τ for nonsolvated SbPh5 to be revised to 0.216.

Background Tracheal intubation for patients with COVID-19 is required for invasive mechanical ventilation. The authors sought to describe practice for emergency intubation, estimate success rates and complications, and determine variation in practice and outcomes between high-income and low- and middle-income countries. The authors hypothesized that successful emergency airway management in patients with COVID-19 is associated with geographical and procedural factors. Methods The authors performed a prospective observational cohort study between March 23, 2020, and October 24, 2020, which included 4,476 episodes of emergency tracheal intubation performed by 1,722 clinicians from 607 institutions across 32 countries in patients with suspected or confirmed COVID-19 requiring mechanical ventilation. The authors investigated associations between intubation and operator characteristics, and the primary outcome of first-attempt success. Results Successful first-attempt tracheal intubation was achieved in 4,017/4,476 (89.7%) episodes, while 23 of 4,476 (0.5%) episodes required four or more attempts. Ten emergency surgical airways were reported—an approximate incidence of 1 in 450 (10 of 4,476). Failed intubation (defined as emergency surgical airway, four or more attempts, or a supraglottic airway as the final device) occurred in approximately 1 of 120 episodes (36 of 4,476). Successful first attempt was more likely during rapid sequence induction versus non–rapid sequence induction (adjusted odds ratio, 1.89 [95% CI, 1.49 to 2.39]; P < 0.001), when operators used powered air-purifying respirators versus nonpowered respirators (adjusted odds ratio, 1.60 [95% CI, 1.16 to 2.20]; P = 0.006), and when performed by operators with more COVID-19 intubations recorded (adjusted odds ratio, 1.03 for each additional previous intubation [95% CI, 1.01 to 1.06]; P = 0.015). Intubations performed in low- or middle-income countries were less likely to be successful at first attempt than in high-income countries (adjusted odds ratio, 0.57 [95% CI, 0.41 to 0.79]; P = 0.001). Conclusions The authors report rates of failed tracheal intubation and emergency surgical airway in patients with COVID-19 requiring emergency airway management, and identified factors associated with increased success. Risks of tracheal intubation failure and success should be considered when managing COVID-19. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

A compact two-port feeding circuit that supports a dielectric resonator (DR) element is presented for applications requiring polarization diversity. The L-band structure consists of a cylindrical DR that can generate right-handed circular polarization (RHCP), left-handed circular polarization (LHCP), and linearly polarized radiation. The DR dimensions have been optimized considering a relative dielectric constant of $\epsilon _{r}\,\,=$ 27, and the entire structure (the circuit and DR) has dimensions of 9 cm $\times 9$ cm $\times 2$ cm (or about $0.3\,\,\lambda _{0} \times 0.3\,\,\lambda _{0} \times 0.07\,\,\lambda _{0}$ at the lower operational frequency range). Radiation by the DR originates from four orthogonal HE ${_{11\delta }}$ modes that are excited by four radial slots etched out of the ground plane (all underneath the DR) printed on top of an FR-4 substrate. Each of these four slots is unconventionally driven by two 50- $\Omega $ microstrip lines, and all four radial slots conform to the shape of the top cylindrical DR element. Polarization diversity is achieved with this DR and circuit system (DRCS) arrangement, mainly by the design of its fully integrated and planar circuit, which routes power to the eight microstrip lines for DR excitation. This FR-4 printed circuit board (PCB) feeding system consists of two meandered Wilkinson power dividers, two 180° delay lines, and four surface mount 90° hybrid couplers. The complete DRCS is compact in size, is broadband (more than 40%), and offers the advantage of requiring only two external ports, one for LHCP the other for RHCP, while an external phase shifter and a combiner are needed for linearly polarized radiation.

We report the first total synthesis of an antimycobacterial natural product oxazinin A that takes advantage of a multi-component cascade reaction of anthranilic acid and a precursor polyketide containing an aldehyde. The route utilized for the synthesis of the pseudodimeric oxazinin A validates a previously proposed biosynthetic mechanism, invoking a non-enzymatic pathway to the complex molecule. We found a 76 : 10 : 9 : 5 ratio of oxazinin diastereomers from the synthetic cascade, which is an identical match to that found in the fermentation media from the fungus Eurotiomycetes 110162. Further investigation of the non-enzymatic formation of oxazinin A using

Attempts to investigate the properties and reactivity of the stiboryl moiety (R3Sb+-O- or R3Sb[double bond, length as m-dash]O), as in monomeric stibine oxides free of interaction with Lewis acids/bases, led us to conclude that this functional group remains undiscovered. X-ray crystallographic, computational, and spectroscopic data indicate that previously proposed H-bonded stibine oxide adducts Mes3SbOHO3SR are in fact hydroxystibonium salts [Mes3SbOH][RSO3].

The provision of a safe and healthy workplace is one of the highest responsibilities of both employers and employees. Alongside the ethical aspects, a safe workplace also has a strong correlation to the financial aspects of business performance. In general the journey towards safer workplaces has been neither rapid nor without challenges. However improvements in standards, processes, education, regulations and technology have collectively resulted in strong progress over time. Industry 4.0 promises a significant step-change in industrial operations including improvements to productivity, efficiency, quality and cost. This imminent industrial revolution also has the potential to automate and simplify many aspects of safety and risk management. To date the safety related research and work within Industry 4.0 has largely been developed/proposed in isolated functions and from a ‘technical solution’ perspective with a heavy emphasis on automated monitoring. However safety performance is related to things like human behaviour, psychology and safety culture. This paper highlights the potential of this trajectory to undermine existing safety culture. Key recommendations around a more coherent anthropocentric approach are included. Contemporary estimates for projected market spend on Industry 4.0 vary but are typically in excess of US$150 billion by around 2026. This is all in pursuit of improved performance. If the safety components are not implemented in a manner that retains and supports safety culture then a consequential impact on safety performance could likely impact on other performance measures, which would be the opposite intent of Industry 4.0.

Results are presented for nonlinear equilibrium solutions of the Navier–Stokes equations in the boundary layer set up by a flat plate started impulsively from rest. The solutions take the form of a wave–roll–streak interaction, which takes place in a layer located at the edge of the boundary layer. This extends previous results for similar nonlinear equilibrium solutions in steady 2D boundary layers. The results are derived asymptotically and then compared to numerical results obtained by marching the reduced boundary-region disturbance equations forward in time. It is concluded that the previously found canonical free-stream coherent structures in steady boundary layers can be embedded in unbounded, unsteady shear flows.

Despite the notoriously poor membrane permeability of peptides in general, many cyclic peptide natural products show high passive membrane permeability and potently inhibit a variety of “undruggable” intracellular targets. A major impediment to designing cyclic peptides with good permeability is the high desolvation energy associated with the peptide backbone amide NH groups. Strategies for mitigating the deleterious effect of the backbone NH group on permeability include N-methylation, steric occlusion, and the formation of intramolecular hydrogen bonds with backbone carbonyl oxygens, while there have been relatively few studies on the use of polar side chains to sequester backbone NH groups. We investigated the ability of N,N-pyrrolidinyl glutamine (Pye), whose side chain contains a powerful hydrogen bond accepting C=O amide group but no hydrogen bond donors, to sequester exposed backbone NH groups in a series of cyclic hexapeptide diastereomers. Analyses of partition coefficients, lipophilic permeability efficiencies (LPE), artificial and cell-based permeability assays revealed that specific Leu-to-Pye substitutions conferred dramatic improvements in aqueous solubility and permeability in a scaffold- and position-dependent manner. Introduction of the Pye residue thus offers a complementary tool, alongside traditional approaches, for improving membrane permeability and solubility in cyclic peptides.

Arsenic trioxide (ATO) is an approved therapy for the treatment of acute promyelocytic leukemia, but the extension of arsenic-based therapies to other types of malignancies, notably tumor-forming cancers, has been slow. Nanodelivery vehicles offer a means of effectively delivering ATO to tumors. Very recently, there has been a series of developments in the formulation of arsenic-based nanomedicines that are not simply loaded with ATO. Realgar nanoparticles are comprised of molecular As

Na

Neutron wavelength-resolved Laue diffraction experiments permit accurate refinement of the H-atom positions and anisotropic displacement parameters of [Mes

Ferric complexes of triscatechol siderophores may assume one of two enantiomeric configurations at the iron site. Chirality is known to be important in the iron uptake process, however an understanding of the molecular features directing stereospecific coordination remains ambiguous. Synthesis of the full suite of (DHBL/DLysL/DSer)3 macrolactone diastereomers, which includes the siderophore cyclic trichrysobactin (CTC), enables the effects that the chirality of Lys and Ser residues exert on the configuration of the Fe(iii) complex to be defined. Computationally optimized geometries indicate that the Λ/Δ configurational preferences are set by steric interactions between the Lys sidechains and the peptide backbone. The ability of each (DHBL/DLysL/DSer)3 diastereomer to form a stable Fe(iii) complex prompted a genomic search for biosynthetic gene clusters (BGCs) encoding the synthesis of these diastereomers in microbes. The genome of the plant pathogen Dickeya chrysanthemi EC16 was sequenced and the genes responsible for the biosynthesis of CTC were identified. A related but distinct BGC was identified in the genome of the opportunistic pathogen Yersinia frederiksenii ATCC 33641; isolation of the siderophore from Y. frederiksenii ATCC 33641, named frederiksenibactin (FSB), revealed the triscatechol oligoester, linear-(DHBLLysLSer)3. Circular dichroism (CD) spectroscopy establishes that Fe(iii)–CTC and Fe(iii)–FSB are formed in opposite enantiomeric configuration, consistent with the results of the ferric complexes of the cyclic (DHBL/DLysL/DSer)3 diastereomers., Synthesis and genome mining leverage access to diastereomers of the siderophore cyclic trichrysobactin. Computational modeling and CD spectroscopy address effects that ligand-based stereochemistry exerts on the configuration at Fe(iii).

Our interest in C–F bond activation prompted an investigation of the reactions of PhC(O)CF3 with a superbasic proazaphosphatrane (Verkade's base) and a corresponding FLP. The reaction of PhC(O)CF3 with P(MeNCH2CH2)3N in a 2 : 1 ratio generates [FP(NMeCH2CH2)3N][PhC(O)CF2COCF3Ph]. While this salt was not isolable, the anion could be derivatized to allow the isolation of [PhC(O)CF2C(OSiMe2tBu)CF3Ph], 1. To further probe this C–F bond activation, the FLP P(MeNCH2CH2)3N/BPh3 was allowed to react with PhC(O)CF3, which afforded the salt [PhC(CF2)OP(MeNCH2CH2)3N][FBPh3], 2. Insights into the mechanism of the reaction of the proazaphosphatrane with PhC(O)CF3 have emerged from the reactivity of 2 and these have been augmented by DFT computations. Salt 2 could be readily converted to the triflate derivative 3, which was a viable synthon for further C–F bond reactivity. Sequential reaction with Na[HBEt3] afforded the salts [PhC(CF(H))OP(MeNCH2CH2)3N][O3SCF3], 4 and [PhC(CH2)OP(MeNCH2CH2)3N][O3SCF3], 5. Interestingly, the formation of 5 contrasts with the formation of [HP(MeNCH2CH2)3N][PhC(CH2)OB(C6F5)3], 6 observed following the reaction of the FLP P(MeNCH2CH2)3N/B(C6F5)3 with PhC(O)Me. Thus these differing FLP protocols provide avenues to salts containing either an enolate derived cation or anion.

During metastasis, tumor cells need to adapt to their dynamic microenvironment and modify their mechanical properties in response to both chemical and mechanical stimulation. Physical interactions occur between cancer cells and the surrounding matrix including cell movements and cell shape alterations through the process of mechanotransduction. The latter describes the translation of external mechanical cues into intracellular biochemical signaling. Reorganization of both the cytoskeleton and the extracellular matrix (ECM) plays a critical role in these spreading steps. Migrating tumor cells show increased motility in order to cross the tumor microenvironment, migrate through ECM and reach the bloodstream to the metastatic site. There are specific factors affecting these processes, as well as the survival of circulating tumor cells (CTC) in the blood flow until they finally invade the secondary tissue to form metastasis. This review aims to study the mechanisms of metastasis from a biomechanical perspective and investigate cell migration, with a focus on the alterations in the cytoskeleton through this journey and the effect of biologic fluids on metastasis. Understanding of the biophysical mechanisms that promote tumor metastasis may contribute successful therapeutic approaches in the fight against cancer.

Attempts to investigate the properties and reactivity of the stiboryl moiety (R

BACKGROUND Prebaiting is a technique involving early deployment of 'unarmed' devices (e.g. baits and traps) to increase efficacy of wildlife management. Although commonly used, the mechanisms by which prebaiting works are poorly understood. We propose three mechanisms by which prebaiting may increase device interaction probabilities; (1) overcoming neophobia towards novel devices, (2) a 'trickle in' effect increasing time for animals to encounter devices; and (3) social information transfer about rewards associated with devices. We conducted a survey of 100 articles to understand how prebaiting has been used. We then tested our proposed prebaiting mechanisms using a global pest (black rats, Rattus rattus) examining how uniquely marked free-living rats responded to a common yet novel monitoring technique (tracking tunnels). RESULTS No studies in our dataset tested how prebaiting functioned. Most studies (61%) did not propose a mechanism for prebaiting, but overcoming neophobia was most commonly mentioned. We only found partial support for the overcoming neophobia hypothesis in our field test. We found the dominant mechanism operating in our system to be the 'trickle in' effect with the proportion of individuals visiting the device increasing over time. We found no support for social information transfer as a mechanism of prebaiting. CONCLUSION Applying a mechanistic understanding of how prebaiting functions will improve the efficacy of management devices. Our results suggest that prebaiting allows time for more rats to encounter a device, hence surveys in our system would benefit from long prebaiting periods. © 2021 Society of Chemical Industry.

A variety of methods are available to investigate the bonding in inorganic compounds. In contrast to wavefunction-based analyses, topological analysis of the electron density affords the advantage of analyzing a physical observable: the electron density. Classical topological analyses of bonding interactions within the atoms in molecules framework typically involve location of a bond path between two atoms and evaluation of a range of real-space functions at the (3, -1) critical point in the electron density that exists on that bond path. We show here that counter-intuitive trends are obtained from the analysis of the electron density (ρ), the Laplacian (∇2ρ), and ellipticity (e) at the O-E (3, -1) critical points in the coupled-cluster singles doubles electron densities of a series of compounds featuring a range of oxygen-pnictogen bond types: EO+, HEO, H2EOH, H3EOH+, and H3EO (where E = N, P, As, Sb, or Bi). If, instead, these real-space functions are evaluated along the length of the bond path, the discrepancies in the trends are resolved. We show that robust results are also obtained using electron densities from less computationally demanding density functional theory calculations. The increased computational efficiency allowed us to also investigate organic derivatives of these oxygen-pnictogen-bonded compounds and observe that the trends hold in these instances as well. We anticipate that these results will be of use to inorganic chemists engaged in the synthesis and evaluation of novel bonding interactions, particularly those involving heavy main-group elements.

Pest species control operations are most effective if every individual in a population is targeted. Yet, individual personality drives variation in animal responses to devices such as traps and baits. Failing to account for differences in behavior during control operations may drive a selective removal, resulting in residual animals with biased expressions of personality. If these biased traits are passed onto offspring, control operations would become increasingly problematic. To test if biased trait expressions in founding populations are passed onto offspring, we quantified personality traits in wild-caught house mice (Mus musculus) and created founder populations selected for biased (High, Low) or Intermediate expressions of Activity. We released the behaviorally biased populations into outdoor yards to breed to the F1 generation, and ten weeks later, removed the mice and quantified the personality traits of the offspring. Despite the strong personality bias in founder populations, we observed no transgenerational transfer of personality and detected no personality bias in the F1 generation. Our results provide reassuring evidence that a single intensive control operation which selects for survivors with a personality bias is unlikely to lead to a recovering population inherently more difficult to eradicate, at least for house mice.

For over a decade, the Frustrated Lewis Pair (FLP) concept has helped to extend the frontiers of main-group chemistry. The present-day maturity of the field, coupled with recent research developments highlighting the continuity between FLP chemistry and classical Lewis acid–base chemistry, suggests that FLP chemistry should be introduced into the mainstream undergraduate chemistry curriculum. Herein is described the experience of a pilot project to incorporate FLP chemistry into the undergraduate main-group inorganic chemistry course at the University of California, Santa Cruz. The presentation of the material, which stresses the thermodynamic-based continuity that links classical Lewis acid–base chemistry and FLP chemistry, also suggested that coverage of the FLP material might provide a means of solidifying fundamental concepts from chemical thermodynamics from earlier courses. Preliminary quantitative and qualitative data have been acquired that support this hypothesis.

Detecting small mammal species for wildlife research and management typically depends on animals deciding to engage with a device, for instance, by entering a trap. While some animals engage and are detected, others do not, and we often lack a mechanistic understanding of what drives these decisions. As trappability can be influenced by traits of personality, personality has high potential to similarly influence detection success for non-capture devices (chew-track cards, tracking tunnels, etc.). We present a conceptual model of the detection process where animal behaviours which are detected by different devices are grouped into tiers based on the degree of intimacy with a device (e.g., approach, interact, enter). Each tier is associated with an increase in the perceived danger of engaging with a device, and an increase in the potential for personality bias. To test this model, we first surveyed 36 populations of free-living black rats (Rattus rattus), a global pest species, to uniquely mark individuals (n = 128) and quantify personality traits. We then filmed rat behaviour at novel tracking tunnels with different risk-reward treatments. As predicted, detection biases were driven by personality, the bias increased with each tier and differed between the risk treatments. Our findings suggest that personality biases are not limited to live-capture traps but are widespread across devices which detect specific animal behaviours. In showing that biases can be predictable, we also show biases can be managed. We recommend that studies involving small mammal sampling report on steps taken to manage a personality-driven bias.

Molecular symmetry plays an important role in many areas of chemistry, and students are generally taught to identify intramolecular symmetries at the undergraduate level. Intermolecular symmetry, the symmetry among groups of molecules, is of great importance in topics such as X-ray crystallography, but it receives substantially less attention. Even when familiar with such symmetries as translations, screw rotations, and glide reflections, students rarely obtain the same level of proficiency in identifying these symmetries via inspection as they do with the proper and improper rotations involved in point group symmetry. We describe a tool designed to scaffold the student’s ability to mentally manipulate molecules and identify the presence and nature of intermolecular symmetry. The tool consists of an algorithm that the student follows to generate centroids between atoms in putatively symmetry-related molecules. The easily recognized patterns formed by the centroids provide key information about the presence and nature of any intermolecular symmetry relating the molecules. The theoretical basis for the patterns formed by the centroids is provided along with worked examples, an example problem set, and a prescription for generating new exercises.

Dubiety exists over whether clinical symptoms of schizophrenia can be distinguished from affective psychosis, the assumption being that absence of a “point of rarity” indicates lack of nosological distinction, based on prior group-level analyses. Advanced machine learning techniques, using unsupervised (hierarchical clustering) and supervised (regularized logistic regression algorithm and nested-cross-validation) were applied to a dataset of 202 patients with functional psychosis (schizophrenia n = 120, affective psychosis, n = 82). Patients were initially assessed with the Present State Examination (PSE), and followed up 2.5 years later, when DSM III diagnoses were applied (independent of initial PSE). Based on PSE syndromes, unsupervised learning discriminated depressive (approximately unbiased probability, AUP = 0.92) and mania/psychosis (AUP = 0.94) clusters. The mania/psychosis cluster further split into two groups - a mania (AUP = 0.84) and a psychosis cluster (AUP = 0.88). Supervised machine learning classified schizophrenia or affective psychosis with 83.66% (95% CI = 77.83% to 88.48%) accuracy. Area under the ROC curve (AUROC) was 89.14%. True positive rate for schizophrenia was 88.24% (95%CI = 81.05–93.42%) and affective psychosis 77.11% (95%CI = 66.58–85.62). Classification accuracy and AUROC remained high when PSE syndromes corresponding to affective symptoms (those that corresponded to the depressive and mania clusters) were removed. PSE syndromes, based on clinical symptoms, therefore discriminated between schizophrenia and affective psychosis, suggesting validity to these diagnostic constructs.

Proazaphosphatranes, also known as Verkade’s superbases, are among the strongest nonionic bases available. Their extreme basicity derives in part from their ability to form a P–N transannulation up...

Objective Subunit-specific positive allosteric modulators (PAMs) of gamma-aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs selective for β2/3-subunit containing GABA-A receptors (β2/3-selective PAMs) that are nonbenzodiazepine site-mediated and do not show an α-subunit isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for sedation, cognitive impairment, and tolerance. In this study, we used three novel β2/3-selective PAMs (2-261, 2-262, and 10029) with differential β2/3-subunit potency to identify the role of β2/3-selective receptor isoforms in limbic epileptogenesis. Methods Experimental epileptogenesis was induced in mice by daily hippocampus stimulations until each mouse showed generalized (stage 5) seizures. Patch-clamp electrophysiology was used to record GABA-gated currents. Brain levels of β2/3-selective PAMs were determined for mechanistic correlations. Results Treatment with the β2/3-selective PAMs 2-261 (30 mg/kg), 2-262 (10 mg/kg), and 10029 (30 mg/kg), 30 min prior to stimulations, significantly suppressed the rate of development of kindled seizure activity without affecting the afterdischarge (AD) signal, indicating their disease-modifying activity. The β2/3-selective agents suppressed chemical epileptogenesis in the pentylenetetrazol model. Test doses of these agents were devoid of acute antiseizure activity in the kindling model. Conclusion These findings demonstrate that β2/3-selective PAMs can moderately retard experimental epileptogenesis, indicating the protective role of β2/3-subunit GABA-A receptor isoforms in the development of epilepsy.

B(C6 F5 )3 and P(MeNCH2 CH2 )3 N form a classical Lewis adduct, (C6 F5 )3 BP(MeNCH2 CH2 )3 N. Although (C6 F5 )3 BP(MeNCH2 CH2 )3 N does not exhibit spectroscopic evidence of dissociation into its constituent acid and base, products of frustrated Lewis pair (FLP) addition reactions are seen with PhNCO, PhCH2 N3 , PhNSO, and CO2 . Computational studies show that thermal access to the dissociated acid and base permits FLP reactivity to proceed. These results demonstrate that FLP reactivity extends across the entire continuum of equilibria governing Lewis acid-base adducts.

The electrophilic phosphonium cation (EPC) salt [(3,5-(CF3)2C6H3)3PF][B(C6F5)4] (2) is prepared via oxidation of the precursor phosphine with XeF2 and subsequent abstraction of fluoride with [Et3Si(tol)][B(C6F5)4]. The Lewis acidity of 2 is evaluated by experimental and computational methods and by preliminary catalysis testing. Exchange reactions of 2 and [(C6F5)3PF][B(C6F5)4] with their respective difluorophosphoranes are studied by 2D 19F–19F NOESY/EXSY and selective 1D 19F NMR exchange spectroscopy (SEXSY) experiments affording comparative rates of fluoride exchange. Collectively, although these data show that 2 is less Lewis acidic than [(C6F5)3PF][B(C6F5)4], the improved access to the P center of 2 provides a kinetic acceleration for fluoride exchange and catalysis where the transition states are more sterically demanding.

Diphenyldiazomethane reacts with HB(C6 F5 )2 and B(C6 F5 )3 , resulting in 1,1-hydroboration and adduct formation, respectively. The hydroboration proceeds via a concerted reaction involving initial formation of the Lewis adduct Ph2 CN2 BH(C6 F5 )2 . The highly sensitive adduct Ph2 CN2 (B(C6 F5 )3 ) liberates N2 and generates Ph2 CB(C6 F5 )3 . DFT computations reveal that formation of Ph2 CN2 B(C6 F5 )3 from carbene, N2 , and borane is thermodynamically favourable, suggesting steric frustration could preclude carbene-borane adduct formation and affect FLP-N2 capture.

Autism spectrum disorder (ASD) is associated with two core symptoms (social communication deficits and stereotyped repetitive behaviors) in addition to a number of comorbidities. There are no FDA-approved drugs for the core symptoms and the changes that underlie these behaviors are not fully understood. One hypothesis is an imbalance of the excitation (E)/inhibition (I) ratio with excessive E and diminished I occurring in specific neuronal circuits. Data suggests that both gamma-aminobutyric acidA (GABAA) and α7 nicotinic acetylcholine receptors (nAChRs) significantly impact E/I. BTBR T+tf/J (BTBR) mice are a model that display an autism-like phenotype with impaired social interaction and stereotyped behavior. A β2/3-subunit containing GABAA receptor (GABAAR) subtype selective positive allosteric modulator (PAM), 2-261, and an α7 nAChR subtype selective PAM, AVL-3288, were tested in social approach and repetitive self-grooming paradigms. 2-261 was active in the social approach but not the self-grooming paradigm, whereas AVL-3288 was active in both. Neither compound impaired locomotor activity. Modulating α7 nAChRs alone may be sufficient to correct these behavioral and cognitive deficits. GABAergic and nicotinic compounds are already in various stages of clinical testing for treatment of the core symptoms and comorbidities associated with ASD. Our findings and those of others suggest that compounds that have selective activities at GABAAR subtypes and the α7 nAChR may address not only the core symptoms, but many of the associated comorbidities as well and warrant further investigation in other models of ASD.

Background Accumulating evidence for the co-occurrence Autism spectrum disorder (ASD) and schizotypal personality disorder (SPD) at both the diagnostic and symptom/trait levels raises important questions about the nature of their association and the effect of their co-occurrence on the individual’s phenotype and functional outcome. It has been recommend that informing etiological and phenotypic overlaps between ASD and schizophrenia spectrum disorders (SSD) would require the utilization of a dual-diagnosis cohort compared with two control groups, each singly diagnosed with ASD or SSD, and that the development of a multidimensional model for understanding the relationship between these two spectra would require cohorts to be described not solely by diagnosis, but also by using dimensional measures that cut across diagnostic boundaries. Research comparing adults with ASD and SPD, as well as the impact of their co-occurrence on outcomes is extremely limited. To fill in this gap, we investigated executive functioning in terms of response inhibition and sustained attention, candidate endophenotypes of both conditions, in adults with ASD, SPD, comorbid ASD and SPD, and neurotypical adults using both categorical and dimensional approaches. Methods A total of 88 adults (Mean Age ± SD = 37.54 ± 10.17): ASD (n = 26; m/f = 20/6); SPD (n = 20; m/f = 14/6); comorbid ASD and SPD (n=9; m/f =6/3) and neurotypicals (n=33; m/f =23/10) completed the Sustained Attention to Response Task (SART) in both its fixed and random forms. Individuals with ASD had a DSM-IV diagnosis of either autism or Asperger Syndrome and met ASD cut-offs on the Autism Diagnostic Observational Schedule-Generic (ADOS-G). All individuals with SPD met DSM-IV criteria for SPD using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). Individuals in the comorbid group met criteria for both ASD (determined by DSM-IV and the ADOS) and SPD (determined by the SCID-II). In addition, in both the clinical and healthy participants, positive and autistic symptom severity were assessed with the positive subscale of the Positive and Negative Syndrome Scale (PANSSpos) and the PANSS Autism Severity Score (PAUSS), respectively. Results Controlling for full scale IQ, working memory and medication dosage, group analyses revealed that the comorbid group committed fewer omission errors than the ASD group on the fixed SART, and fewer omission errors than the ASD and SPD groups on the random SART. The individual difference analyses revealed that the PANSSpos and PAUSS interactively reduced omission errors in both the fixed and random SARTs, as well as increased d’ scores, indicative of improved overall performance. Discussion Concurrent elevated levels of autistic and positive psychotic symptoms seem to be associated with improved sustained attention abilities. We propose that sustaining and switching attention may represent two poles of irregularities across the autism and schizotypal spectra, which appear to converge in a compensatory manner in the comorbid group. Our findings highlight the importance of investigating the concurrent effect of ASD and SPD at both the symptom and diagnostic levels, and the potential benefit of this research approach to understanding the underlying mechanisms of seemingly overlapping phenotypes.

Background and aims There is an ever-increasing number of blocks available within the armamentarium of regional anaesthetists. It is a common for such specialists to be called upon to teach with a particular regional technique. We have aimed to collate some of the free-access, high quality training provisions into an Alexa ‘Regional Skill’ to aid teaching. Methods Alexa is speech-to-text software allowing voice interaction with devices. Amazon have released a rich developer environment alongside Alexa allowing developers to create their own ‘skills’ – programmes that respond to a user’s voice command and return customised pictures and videos. The user can invoke the device by saying ‘Alexa, open Regional Wizard’. This opens a launch screen, allowing users to ask questions relating to regional anaesthesia, such as how to perform a particular block, or the anatomy of a particular body area. This skill was coded through an Amazon Web Service (AWS) developer account in JavaScript Object Notation and Node.js runtime environment which handles the request all within the AWS developer environment. Results We have developed an Alexa-enabled regional teaching device for use with an Amazon Echo Show device, which could be used by clinicians to help teach regional blocks. The skill has a number of supported requests including video footage, examples including serratus plane, adductor canal and supraclavicular blocks. Schematic anatomical diagrams are also supported. Conclusions We have developed what we believe to be the world’s first medical Alexa regional training device, which could be utilised within a theatre environment to aid the delivery of regional anaesthesia techniques.

A microfluidic strategy has been used for the time- and labour-efficient evaluation of the relative efficiency and thermodynamic parameters of CO2 binding by three Lewis acid/base combinations, where efficiency is based on the amount of CO2 taken up per binding unit in solution. Neither tBu3P nor B(C6F5)3 were independently effective at CO2 capture, and the combination of the imidazolin-2-ylidenamino-substituted phosphine (NIiPr)3P and B(C6F5)3 was equally ineffective. Nonetheless, an archetypal frustrated Lewis pair (FLP) comprised of tBu3P and B(C6F5)3 was shown to bind CO2 more efficiently than either the FLP derived from tetramethylpiperidine (TMP) and B(C6F5)3 or the highly basic phosphine (NIiPr)3P. Moreover, the proposed microfluidic platform was used to elucidate the thermodynamic parameters for these reactions.