An Exploration of Spatial Visualization Skills: Investigating Students' Use of 3D Models in Science Problems during Think-Aloud Interviews.

Effective spatial visualization and reasoning skills are often credited for students' success in science and engineering courses. However, students enrolled in these science courses are not always exposed to or trained properly on the best ways to utilize models to aid in their learning. Improving spatial visualization techniques with 3D models, such as molecular and DNA modeling kits, is often suggested to facilitate students' ability to conceptualize compounds in two and three dimensions. Here, we investigate what techniques students use to conceptualize 2D representations of various biomolecules with the use of 3D models by interviewing undergraduate students from various natural science and engineering disciplines in task-based, think-aloud sessions. After scoring and analyzing the participant data we explored some of the techniques used among successful scoring participants, including the use of informal models to transition between 2D and 3D. Additional techniques used by students who were able to successfully conceptualize 3D images included starting with smaller, granular details to inductively make conclusions when thinking between two and three dimensions. We find that (1) students who anchor their thinking in 3D models show a deeper level of understanding in initially solving science problems successfully, and (2) proper 3D model use and spatial visualization techniques may improve students' abilities to accurately visualize 2D and 3D representations of molecules in science courses. Our results demonstrate that implementing spatial visualization training to teach students how to effectively use 3D models may improve students' problem-solving techniques in science curricula.

Escaping the cohort of concern: in vitro experimental evidence supports non-mutagenicity of N-nitroso-hydrochlorothiazide.

In recent years, nitrosamine impurities in pharmaceuticals have been subject to intense regulatory scrutiny, with nitrosamine drug substance-related impurities (NDSRIs) treated as cohort of concern impurities, regardless of predicted mutagenic potential. Here, we describe a case study of the NDSRI N-nitroso-hydrochlorothiazide (NO-HCTZ), which was positive in the bacterial reverse mutation (Ames) test but is unstable under the test conditions, generating formaldehyde among other products. The mutagenic profile of NO-HCTZ was inconsistent with that expected of a mutagenic nitrosamine, exhibiting mutagenicity in the absence of metabolic activation, and instead aligned well with that of formaldehyde. To assess further, a modified Ames system including glutathione (3.3 mg/plate) to remove formaldehyde was developed. Strains used were S. typhimurium TA98, TA100, TA1535, and TA1537, and E. coli WP2 uvrA/pKM101. In this system, formaldehyde levels were considerably lower, with a concomitant increase in levels of S-(hydroxymethyl)glutathione (the adduct formed between glutathione and formaldehyde). Upon retesting NO-HCTZ in the modified system (1.6-5000 µg/plate), a clear decrease in the mutagenic response was observed in the strains in which NO-HCTZ was mutagenic in the original system (TA98, TA100, and WP2 uvrA/pKM101), indicating that formaldehyde drives the response, not NO-HCTZ. In strain TA1535, an increase in revertant colonies was observed in the modified system, likely due to a thiatriazine degradation product formed from NO-HCTZ under Ames test conditions. Overall, these data support a non-mutagenic designation for NO-HCTZ and demonstrate the value of further investigation when a positive Ames result does not align with the expected profile.

Modulating the guest binding ability within mixed-coordination geometry [Pd(µ-L)4RuCl2]2+ and [Pd(µ-L)4Pt]4+ cage architectures.

Heterobimetallic cages built from Pd and either octahedral Ru or square-planar Pt moieties and bridged by ligands with H bonding-accepting or -donating properties are reported. They showed stimulus-responsive dis- and reassembly, while guest binding was found to be dependent on the complementary properties of the guest to the host in terms of charge, size and H bonding properties.

Towards building blocks for metallosupramolecular structures: non-symmetrically-functionalised ferrocenyl compounds.

Metallosupramolecular architectures formed from metal ions and bridging ligands are increasing in popularity due to their range of applications and ease of self-assembly. Many are able to readily change their shape and/or function in response to an external stimulus and have the ability to encapsulate guest molecules within their internal cavities. Ferrocenyl groups (Fc) have been incorporated previously within the bridging ligands of metallosupramolecular structures due to their ideal attributes brought about by the structural and rotational flexiblity of the two cyclopentadienyl (Cp) rings coordinated to the Fe(II) centre. However, the majority of these Fc-based structures contain symmetrically substituted Cp rings. We report the synthesis and characterisation of non-symmetrically functionalised Fc-based ligands incorporating both N,N' and NHC-donor groups chosen for their differing coordination properties. Both substituents were designed to coordinate to a single metal centre with the dissimilar coordination properties of each donor group facilitating stimulus-induced dissociation/association of one of the substituents as an opening/closing mechanism. Preliminary investigations into the coordination of these Fc-based ligands to a [Ru(η6-p-cymene)]2+ moiety indicated complexation through a mixture of either a bi- or tridentate fashion, as alluded by 1H NMR spectroscopy and mass spectrometry. Density functional theory (DFT) calculations revealed the Fc-based ligands adopt a syn conformation driven by H-bonding and π-interactions between the two Cp substituents, which facilitate coordination of both donor groups towards the metal centre.

Iridium Complexes with Bidentate Pyridinylidene/N-Amidate Ligands for Transfer Hydrogenation Catalysis.

A series of iridium pentamethylcyclopentadienyl (Cp*) complexes, [Cp*Ir(κ2-RLp/m)Cl], that contain the strongly coordinating bidentate ligands RLp/m were synthesized. The donor groups of the bidentate ligands were an N-amidate and either a para-pyridinylidene remote N-heterocyclic carbene (RLp) or a meta-pyridinylidene remote N-heterocyclic carbene (RLm). For each type of bidentate ligand, a set of iridium complexes was synthesized, which differed only according to the substituents (R) on the phenyl ring associated with the amidate group. The iridium complexes were all fully characterized and molecular structures were obtained by single-crystal X-ray diffraction studies for representative examples. The complexes were found to be good precatalysts in iso-propanol for the transfer hydrogenation of benzaldehyde to give benzyl alcohol. The catalytic activity correlated with the Hammett σm/p parameters of the phenyl ring substituents, with more electron-donating substituents leading to increased catalytic activity. In all cases, the meta-pyridinylidene complexes, [Cp*Ir(κ2-RLm)Cl], performed better than the corresponding para analogues, [Cp*Ir(κ2-RLp)Cl].

Patient Perception of Cough in Interstitial Lung Disease; Impact of Cough Hypersensitivity.

INTRODUCTION: Cough is common in interstitial lung disease (ILD) and is associated with disease progression, yet its mechanisms are understudied. We investigated cough hypersensitivity features and impact in ILD. METHODS: Participants with ILD and cough (n = 195) completed a multiple choice and free text questionnaire on cough sensations/triggers and impacts. RESULTS: The majority of participants were male (54%), aged > 65 (64%), with idiopathic pulmonary fibrosis (IPF, 75%). Common cough triggers were body position (74%), physical activity (72%), and talking (62%). Common laryngeal sensations were globus (43%), and itch/tickle (42%). Cough impacted everyday life in 55%, and all activities in 31%, causing exhaustion (59%), social embarrassment (70%), urinary incontinence (46% females), and syncope/pre-syncope (12%). The total number of cough-provoking sensations/triggers correlated with impacts; ρ = 0.73, p < 0.001. CONCLUSION: Cough hypersensitivity symptoms are prevalent in ILD and detrimentally affect quality of life. Further studies investigating mechanisms of cough hypersensitivity and targeted pharmacotherapy are warranted.

Constructing analogies: Developing critical thinking through a collaborative task.

Analogies are used to make abstract topics meaningful and more easily comprehensible to learners. Incorporating simple analogies into STEM classrooms is a fairly common practice, but the analogies are typically generated and explained by the instructor for the learners. We hypothesize that challenging learners to create complex, extended analogies themselves can promote integration of content knowledge and development of critical thinking skills, which are essential for deep learning, but are challenging to teach. In this qualitative study, college biology students (n = 30) were asked to construct a complex analogy about the flow of genetic information using a familiar item. One week later, participants constructed a second analogy about the same topic, but this time using a more challenging item. Twenty participants worked on the challenging analogy in pairs, while the other 10 worked alone. Analysis of the 50 interviews resulted in a novel-scoring scheme, which measured both content knowledge (understanding of biology terms) and critical thinking (alignment of relationships between elements of the analogy). Most participants improved slightly due to practice, but they improved dramatically when working with a partner. The biggest gains were seen in critical thinking, not content knowledge. Having students construct complex, sophisticated analogies in pairs is a high-impact practice that can help students develop their critical thinking skills, which are crucial in academic and professional settings. The discussion between partners likely requires students to justify their explanations and critique their partner's explanations, which are characteristics of critical thinking.

A dynamic covalent approach to [PtnL2n]2n+ cages.

A dynamic covalent approach was exploited to generate a family of homometallic [PtnL2n]2n+ cage (predominantly [Pt2L4]4+ systems) architectures. The family of platinum(II) architectures were characterized using 1H nuclear magnetic resonance (NMR) and diffusion ordered spectroscopy (DOSY), electrospray ionization mass spectrometry (ESI-MS) and the molecular structures of two cages were determined by X-ray crystallography.

Exploiting reduced-symmetry ligands with pyridyl and imidazole donors to construct a second-generation stimuli-responsive heterobimetallic [PdPtL4]4+ cage.

A new sequential metalation strategy that enables the assembly of a new more robust reduced symmetry heterobimetallic [PdPtL4]4+ cage C is reported. By exploiting a low-symmetry ditopic ligand (L) that features imidazole and pyridine donor units we were able to selectively form a [Pt(L)4]2+ "open-cage" complex. When this was treated with Pd(ii) ions the cage C assembled. 1H and DOSY nuclear magnetic resonance (NMR) spectroscopy and electrospray ionisation mass spectrometry (ESIMS) data were consistent with the quantitative formation of the cage and the heterobimetallic structure was confirmed by single crystal X-ray crystallography. The cage C was shown to bind anionic guest molecules. NMR studies suggested that these guests interacted with the cavity of the cage in a specific orientation and this was confirmed for the mesylate ion (MsO-) : C host-guest adduct using X-ray crystallography. In addition, the system was shown to be stimulus-responsive and could be opened and closed on demand when treated with appropriate stimuli. If a guest molecule was bound within the cage, the opening and closing was accompanied by the release and re-uptake of the guest molecule.

An Iron Macrocyclic Complex Containing Four "Hybrid" Pyridinium Amidate/Amidate N-Donors as a Catalyst for Oxidations with Hydrogen Peroxide.

The macrocyclic proligand [H4 L][OTf]2 , which contains four carboxamide functions and two conjugated pyridinium groups, is easily deprotonated by the weak base sodium acetate to give the corresponding neutral proligand [H2 L]. Metallation of [H2 L] with iron(II) chloride proceeds rapidly to form the macrocyclic complex, [FeIII Cl(L)]. This is an effective catalyst for the oxidation of the organic dye orange II by hydrogen peroxide in aqueous solution, and the kinetic parameters for this reaction have been determined. In striking contrast to an analogous iron-TAML complex that contains two phenyl groups in place of the two pyridinium groups, [FeIII Cl(L)] is a very active oxidation catalyst at pH 7 and is also highly stable towards acid-promoted demetallation at pH 5 or above. The results show that the two pyridinium groups bring greatly enhanced catalytic properties to [FeIII Cl(L)].

Visual Literacy of Molecular Biology Revealed through a Card-Sorting Task.

Visual literacy, which is the ability to effectively identify, interpret, evaluate, use, and create images and visual media, is an important aspect of science literacy. As molecular processes are not directly observable, researchers and educators rely on visual representations (e.g., drawings) to communicate ideas in biology. How learners interpret and organize those numerous diagrams is related to their underlying knowledge about biology and their skills in visual literacy. Furthermore, it is not always obvious how and why learners interpret diagrams in the way they do (especially if their interpretations are unexpected), as it is not possible to "see" inside the minds of learners and directly observe the inner workings of their brains. Hence, tools that allow for the investigation of visual literacy are needed. Here, we present a novel card-sorting task based on visual literacy skills to investigate how learners interpret and think about DNA-based concepts. We quantified differences in performance between groups of varying expertise and in pre- and postcourse settings using percentages of expected card pairings and edit distance to a perfect sort. Overall, we found that biology experts organized the visual representations based on deep conceptual features, while biology learners (novices) more often organized based on surface features, such as color and style. We also found that students performed better on the task after a course in which molecular biology concepts were taught, suggesting the activity is a useful and valid tool for measuring knowledge. We have provided the cards to the community for use as a classroom activity, as an assessment instrument, and/or as a useful research tool to probe student ideas about molecular biology.

Diffuse and concentrated nitrogen sewage pollution in island environments with differing treatment systems.

Macroalgae is an under-utilised tool as a bioindicator of anthropogenic nitrogen loading to the coastal environment in the UK. This study compared two island systems-Jersey (Channel Islands) and St Mary's (Isles of Scilly) to assess how differing sewerage infrastructure affects nitrogen loading. A total of 831 macroalgae samples of Fucus vesiculosus and Ulva sp. were analysed for nitrogen isotopes (δ15N). Elevated δ15N values were recorded for Jersey (> 9‰) in St Aubin's Bay-caused by the outflow of the Bellozanne Sewerage Treatment Works (STW). δ15N isoplots maps indicate low diffusion of nitrogen out of St Aubin's Bay. St Mary's produced a varied δ15N isoplot map in comparison. δ15N was typically lower and is attributed to a smaller population and inefficient STW. Outflow of sewage/effluent at Morning Point, Hugh Town and Old Town produced elevated δ15N values in comparison to the island average. St Mary's inefficient sewerage treatment and reliance on septic tanks/soakaways complicates δ15N interpretation although it still indicates that nitrogen pollution is an island-wide issue. Future sewerage development and upgrades on islands are required to prevent similar effluent environmental issues as recorded in St Aubin's Bay. This study advocates the use of macroalgae as a bioindicator of nitrogen effluent in the marine environment.

Ferrocene-Derived Palladium(II)-Based Metallosupramolecular Structures: Synthesis, Guest Interaction, and Stimulus-Responsiveness Studies.

Using ferrocene-based ligand systems, a series of heterobimetallic architectures of the general formula [PdmLn]x+ were designed with the aim of installing an opening and closing mechanism that would allow the release and binding of guest molecules. Palladium complex formation was achieved through coordination to pyridyl groups, and using 2-, 3-, and 4-pyridyl derivatives provided access to defined PdL, PdL2, and Pd2L4 structures, respectively. The supramolecular complexes were characterized using nuclear magnetic resonance (NMR) and infrared spectroscopy, mass spectrometry, and elemental analysis, and for some examples density functional theory calculations and single-crystal X-ray diffraction analysis. 1H NMR spectroscopy was used to investigate disassembly and reassembly of the metallosupramolecular structures. The former was induced by cleavage of the relatively labile Pd-Npyridyl bonds with the introduction of the competing ligands N,N'-dimethylaminopyridine (DMAP) and Cl- (using tetrabutylammonium chloride) to yield [Pd(DMAP)4]2+ and [PdCl4]2-, respectively. The process was found to be reversible for several of the heterodimetallic compounds, with the addition of H+ or Ag+ triggering complex reassembly. Guest binding studies with several architectures revealed interactions with the anionic guests p-toluenesulfonate and octyl sulfate, but not with neutral molecules. Furthermore, the release of guests was reversibly induced with Cl- ions as a stimulus.

Hydrazone- and imine-containing [PdPtL4]4+ cages: a comparative study of the stability and host-guest chemistry.

A new [PdPtL4]4+ heterobimetallic cage containing hydrazone linkages has been synthesised using the sub-component self-assembly approach. 1H and DOSY nuclear magnetic resonance (NMR) spectroscopy and electrospray ionisation mass spectrometry (ESIMS) data were consistent with the formation of the [PdPtL4]4+ architecture. The cage was stimulus-responsive and could be partially disassembled and reassembled by the addition of dimethylaminopyridine (DMAP) and p-tolenesulfonic acid (TsOH), respectively. Additionally, the stability of the hydrazone cage against hydrolysis in the presence of water and nucleophilic decomposition in the presence of guest molecules was compared to a previously synthesised imine-containing [PdPtL4]4+ cage. It was established that the hydrazone linkage was more resistant to hydrolysis. Furthermore, the host-guest (HG) chemistry with a series of drug and drug-like molecules was examined. The hydrazone cage was shown to interact with cisplatin while the smaller imine cage was shown to interact with 5-fluorouracil and oxaliplatin in CD3CN. No HG interactions were observed in the more polar d6-DMSO. In vitro antiproliferative activity studies demonstrated both cages were active against the cancer cell lines tested and displayed half-maximal inhibitory (IC50) values in the range of 25-35 µM. Most [PdPtL4]4+-drug mixtures tested had higher IC50 values than the hosts. However, the [PdPtL4]4+ cages, and [PdPtL4]4+:drug mixtures were less cytotoxic than the well established anticancer drugs cisplatin, oxaliplatin and 5-fluorouracil.

Postoperative atrial fibrillation following non-cardiac surgery: Predictors and risk of mortality.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a major complication that follows both cardiac and non-cardiac procedures. Many studies have explored POAF after cardiac procedures, however POAF following non-cardiac procedures has been understudied. METHODS: National Inpatient Sample database was utilized to conduct a retrospective study of hospitalizations with diagnosis of POAF following non-cardiac procedures between 2010 and 2015. RESULTS: 294,112 patients met the inclusion criteria. Advanced age, male gender, colonic resections, coagulopathy, fluid and electrolyte disorders and history of congestive heart failure are major predictors of POAF and in-hospital mortality. Race, type of insurance, income quartile and weekend admissions are independent determinants of mortality following POAF. CONCLUSIONS: Development of POAF and mortality is dependent upon a wide range of factors not limited to age and medical comorbidities. Although a patient may be at an increased risk for POAF this does not mean they are at an increased risk for mortality.

The DNA Landscape: Development and Application of a New Framework for Visual Communication about DNA.

Learning molecular biology involves using visual representations to communicate ideas about largely unobservable biological processes and molecules. Genes and gene expression cannot be directly visualized, but students are expected to learn and understand these and related concepts. Theoretically, textbook illustrations should help learners master such concepts, but how are genes and other DNA-linked concepts illustrated for learners? We examined all DNA-related images found in 12 undergraduate biology textbooks to better understand what biology students encounter when learning concepts related to DNA. Our analysis revealed a wide array of DNA images that were used to design a new visual framework, the DNA Landscape, which we applied to more than 2000 images from common introductory and advanced biology textbooks. All DNA illustrations could be placed on the landscape framework, but certain positions were more common than others. We mapped figures about "gene expression" and "meiosis" onto the landscape framework to explore how these challenging topics are illustrated for learners, aligning these outcomes with the research literature to showcase how the overuse of certain representations may hinder, instead of help, learning. The DNA Landscape is a tool to promote research on visual literacy and to guide new learning activities for molecular biology.

Quantification and composition of pharmaceutical waste in New Zealand.

This study aimed to quantify the amount of pharmaceutical waste produced in New Zealand, and determine the composition of pharmaceutical waste from community pharmacies in Auckland, New Zealand. Pharmaceutical waste collected in New Zealand is increasing, peaking at 542 tonne in 2019. Pharmaceutical waste collected from hospitals and pharmacies in Auckland increased by more than fourfold from 2016 to 2020. An audit of the types of pharmaceutical waste collected from community pharmacies revealed that the most common classes of drugs identified in this waste stream belonged to the nervous system, cardiovascular system and alimentary tract, and metabolism. Following examination of the contents of 12 pharmaceutical waste bins, 475 different pharmaceutical products were identified, highlighting the breadth of drugs in this waste stream. A range of dosage forms and hence materials were identified, which could present challenges for future waste treatment approaches. Hazardous drugs were identified including cytotoxic compounds, which should go into a separate waste stream for incineration. There is a need for similar data to be collected from multiple sites to fully appreciate the magnitude and composition of pharmaceutical waste. This will allow for the suitability of current practices for managing this hazardous waste stream to be evaluated.

Heterotrimetallic Double Cavity Cages: Syntheses and Selective Guest Binding.

A strategy for the generation of heterotrimetallic double cavity (DC) cages [Pdn Ptm L4 ]6+ (DC1: n=1, m=2; and DC2: n=2, m=1) is reported. The DC cages were generated by combining an inert platinum(II) tetrapyridylaldehyde complex with a suitably substituted pyridylamine and PdII ions. 1 H and DOSY nuclear magnetic resonance spectroscopy (NMR) and electrospray ionization mass spectrometry (ESIMS) data were consistent with the formation of the DC architectures. DC1 and DC2 were shown to interact with several different guest molecules. The structure of DC1, which features two identical cavities, binding two 2,6-diaminoanthraquinone (DAQ) guest molecules was determined by single-crystal X-ray crystallography. In addition, DC1 was shown to bind two molecules of 5-fluorouracil (5-FU) in a statistical (non-cooperative) manner. In contrast, DC2, which features two different cage cavities, was found to interact with two different guests, 5-FU and cisplatin, selectively.

Synthetic Strategy Towards Heterodimetallic Half-Sandwich Complexes Based on a Symmetric Ditopic Ligand.

Multimetallic complexes have been shown in several examples to possess greater anticancer activity than their monometallic counterparts. The increased activity has been attributed to altered modes of action. We herein report the synthesis of a series of heterodimetallic compounds based on a ditopic ligand featuring 2-pyridylimine chelating motifs and organometallic half-sandwich moieties. The complexes were characterized by a combination of 1H NMR spectroscopy, electrospray ionization mass spectrometry, elemental analysis and single crystal X-ray diffraction. Investigations into the stability of representative complexes in DMSO-d 6 and 10% DMSO-d 6 /D2O revealed the occurrence of solvent-chlorido ligand exchange. Proliferation assays in four human cancer cell lines showed that the Os-Rh complex possessed minimal activity, while all other complexes were inactive.

Tailoring interfacial effect in multilayers with Dzyaloshinskii-Moriya interaction by helium ion irradiation.

We show a method to control magnetic interfacial effects in multilayers with Dzyaloshinskii-Moriya interaction (DMI) using helium (He[Formula: see text]) ion irradiation. We report results from SQUID magnetometry, ferromagnetic resonance as well as Brillouin light scattering results on multilayers with DMI as a function of irradiation fluence to study the effect of irradiation on the magnetic properties of the multilayers. Our results show clear evidence of the He[Formula: see text] irradiation effects on the magnetic properties which is consistent with interface modification due to the effects of the He[Formula: see text] irradiation. This external degree of freedom offers promising perspectives to further improve the control of magnetic skyrmions in multilayers, that could push them towards integration in future technologies.