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If you were a candidate in an election, would you prefer more support from voters or less? Put another way: would you prefer that your campaign staff persuade more voters to vote for you, or fewer? These questions seem silly, because of course you would want more support from voters. Surprisingly, when using certain voting methods it is actually possible for more voter support to produce a worse result for a candidate; such an outcome is a type of monotonicity paradox. In [1], we searched for various types of monotonicity paradoxes in 1079 single-transferable vote (STV) elections from a database of Scottish local government elections. The purpose of this article is to present in detail two of the most interesting elections revealed by our search. These two elections are arguably the most paradox-riddled real-world political ranked choice elections ever documented, perhaps rivalled only by four single-winner examples from the United States: the 2009 mayoral election in Burlington, Vermont ([2, 3]); a 2021 city council race in Minneapolis, Minnesota [4]; the 2022 Special Election for US House in Alaska [5]; and the 2022 District 4 School Director election in Oakland, California [6]. The first election we present is the 2017 council election in the Buckie Ward of the Moray Council Area, which demonstrated the most extreme instance of a committee size monotonicity paradox ever observed in an actual election. The second election is the 2012 council election in the Steòrnabhagh a Tuath Ward of the Nah-Eileanan Siar Council Area, which demonstrated upward and downward monotonicity paradoxes, as well as a no-show paradox. To contextualise these elections, as part of our discussion we indicate how often these kinds of paradoxes occur in Scottish local government elections.

Molecular hinges are ubiquitous in both natural and artificial supramolecular systems. A major challenge to date, however, has been simultaneously achieving high thermodynamic and kinetic stability. Here, we employ host-enhanced intramolecular charge-transfer interactions to mediate entropy-favored complexation between a flexible AB2-type guest and a macrocyclic host, forming a new type of molecular hinge with an ultrahigh picomolar binding affinity (Ka> 1012M–1). This entropy-promoted hinge modulates photoisomerization, exhibiting a substantial preference for the E-isomer, which is further demonstrated to mirror the natural retinal-opsin cycle, promoting the sensitization of visible light. This work unveils an efficient approach to exploit entropy-dominant architectures for the design of hierarchical molecular systems.

The use of single-molecule microscopy is introduced as a method to quantify the photophysical properties of supramolecular complexes rapidly at ultra low concentrations (<1 nM), previously inaccessible. Using a model supramolecular system based on the host–guest complexation of cucurbit[n]uril (CB[n]) macrocycles together with a fluorescent guest (Ant910Me), we probe fluorescent CB[n] host–guest complexes in the single molecule regime. We show quantification and differentiation of host–guest photophysics and stoichiometries, both in aqueous media and noninvasively in hydrogel, by thresholding detected photons. This methodology has wide reaching implications in aiding the design of next-generation materials with programmed and controlled properties.

The methods of single transferable vote (STV) and sequential ranked-choice voting (RCV) are different methods for electing a set of winners in multiwinner elections. STV is a classical voting method that has been widely used internationally for many years. By contrast, sequential RCV has rarely been used, and only recently has seen an increase in usage as several cities in Utah have adopted the method to elect city council members. We use Monte Carlo simulations and a large database of real-world ranked-choice elections to investigate the behavior of sequential RCV by comparing it to STV. Our general finding is that sequential RCV often produces different winner sets than STV. Furthermore, sequential RCV is best understood as a majoritarian method which will not produce proportional results, often at the expense of minority interests.

ABSTRACTPolicy makers increasingly call on higher education to prepare learners for challenges such as global health emergencies or ecological crises. These can be understood as ‘wicked problems’, which are unbounded, complex and resist simplistic definition. Wicked problems involve stakeholders with incompatible value positions and attempted solutions can result in unforeseen outcomes. How academics stay committed to teaching about such challenging topics – despite the many difficulties of contemporary higher education – is an under-researched area. In this study, we interviewed academics who were deeply engaged with teaching about wicked problems. We drew on the concepts of landscapes of practice, boundary work and academic identities to make sense of the teachers’ persistence and practices in this space. We conclude with advice for policy makers on how to support academics in this work.

Pyridinium electrolytes are promising candidates for flow-battery-based energy storage1–4. However, the mechanisms underlying both their charge–discharge processes and overall cycling stability remain poorly understood. Here we probe the redox behaviour of pyridinium electrolytes under representative flow battery conditions, offering insights into air tolerance of batteries containing these electrolytes while providing a universal physico-chemical descriptor of their reversibility. Leveraging a synthetic library of extended bispyridinium compounds, we track their performance over a wide range of potentials and identify the singlet–triplet free energy gap as a descriptor that successfully predicts the onset of previously unidentified capacity fade mechanisms. Using coupled operando nuclear magnetic resonance and electron paramagnetic resonance spectroscopies5,6, we explain the redox behaviour of these electrolytes and determine the presence of two distinct regimes (narrow and wide energy gaps) of electrochemical performance. In both regimes, we tie capacity fade to the formation of free radical species, and further show that π-dimerization plays a decisive role in suppressing reactivity between these radicals and trace impurities such as dissolved oxygen. Our findings stand in direct contrast to prevailing views surrounding the role of π-dimers in redox flow batteries1,4,7–11and enable us to efficiently mitigate capacity fade from oxygen even on prolonged (days) exposure to air. These insights pave the way to new electrolyte systems, in which reactivity of reduced species is controlled by their propensity for intra- and intermolecular pairing of free radicals, enabling operation in air.

BIKE TESTS Moto? The bigger 19-inch front and 16-inch rear wheels gave my son, Gavin, the room we were looking for so that he could literally grow into the bike. We had to make some modifications to the controls, suspension and ride height of the bike to fit his needs initially. [Extracted from the article]

ABSTRACT:The wood-poppy (Stylophorum diphyllum (Michaux) Nuttall [Papaveraceae]) is listed as endangered under Canada's Species at Risk Act. Five extant populations are in Canada. One potential recovery strategy for S. diphyllum is to augment existing populations and (or) establish new populations via conservation translocation. While seeds are sold in the nursery trade, few studies have been published on ex situ germination and propagation. Predictions are that Canadian populations are genetically distinct from US populations, but no studies have tested for phenotypic differences between plants from these sources. We collected, stratified, and sowed seeds from 2 of the native Canadian populations and 3 commercial seed companies and grew them in a common garden. We achieved a germination rate of 53% for seed from Canadian populations and 44% for commercial seeds following 2 mo stratification at 25 °C (77 °F) and 2 mo at 4 °C (39 °F). Plants from 1 Canadian population grew faster, produced more leaves, differed in leaf and seed morphology, and had fewer trichomes than the plants of commercial origin. These results show that S. diphyllum can be propagated successfully from Canadian seed sources and that Canadian S. diphyllum populations are likely phenotypically distinct from commercial stock. Our findings will inform the development of a translocation strategy and set the stage for genetic analysis of these populations.

ABSTRACTOptical coherence tomography (OCT) is a non-invasive imaging method that can be used to study the surface features and subsurface structures of delicate cultural heritage objects. However, the field of view of OCT severely limits the system’s scanning area. Previously, we have presented a hybrid scanning platform combined with an imaging stitching algorithm to achieve macroscopic OCT (macro-OCT) imaging. This paper further demonstrates the potential applications of the OCT data by rendering 3D volumetric data into standard virtual reality (VR), augmented reality (AR), and 3D printing formats. The 3D model can be 3D printed or interactively displayed through various platforms such as VR and AR headsets, smartphones, and web pages. The high-resolution 3D models obtained from the macro-OCT system can potentially improve the experience of accessing artworks online and assist individuals with visual impairments to study art through tactile feedback.

Understanding how human milk impacts growth requires valid analytical methods for quantifying the composition. Lactose, the most abundant constituent in human milk and a predominant source of energy, is often assessed using methods borrowed from the bovine dairy industry. However, the carbohydrate matrices of bovine and human milk are quite different, especially as they relate to human milk oligosaccharides (HMOs), each with a terminal lactose unit that may influence analytical methods.

Cancer and cardiovascular disease are two of the leading causes of global mortality and morbidity. Medical research has generated powerful lifesaving treatments for patients with cancer; however, such treatments may sometimes be at the expense of the patient’s myocardium, leading to heart failure. Anti-cancer drugs, including anthracyclines, can result in deleterious cardiac effects, significantly impacting patients’ functional capacity, mental well-being, and quality of life. Recognizing this, recent international guidelines and expert papers published recommendations on risk stratification and care delivery, including that of cardio-oncology services. This review will summarize key evidence with a focus on anthracycline therapy, providing clinical guidance for the non-oncology professional caring for a patient with cancer and heart failure.

Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer.

This target product profile (TPP) highlights the minimal and optimal characteristics for ex-vivo and in-vivo cell and gene therapy-based products aimed at achieving an HIV cure (ie, durable antiretroviral-free viral control). The need for an effective, safe, scalable, affordable, accessible, and acceptable cure for HIV infection remains a major global priority. The possibilities for cell and gene therapy-based products for an HIV cure are rapidly expanding. In a multi-stakeholder consensus process of clinical experts and civil society, including representatives from low-income and middle-income countries, participants generally agreed on the optimal targets, whereas consensus on the minimal targets was not reached on every parameter. There was less agreement on the minimal targets for ex-vivo than in-vivo therapies given the complexity of ex-vivo interventions. The TTP is planned to be updated at regular intervals. Building a TTP, such as this one, is an important process for stakeholder engagement and aligning ambitions for the development of products that are acceptable to both clinicians and civil society.

We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients’ overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

AbstractThis article gives an algorithm that will build an apportionment diagram for any apportionment method when there are three states. We then provide several images that are produced by the algorithm and discuss what these images can reveal about the given apportionment method.

AimsA robust immunohistochemistry (IHC) assay was developed to detect lymphocyte-activation gene 3 (LAG-3) expression by immune cells (ICs) in tumour tissues. LAG-3 is an immuno-oncology target with demonstrable clinical benefit, and there is a need for a standardised, well-characterised assay to measure its expression. This study aims to describe LAG-3 scoring criteria and present the specificity, sensitivity, analytical precision and reproducibility of this assay.MethodsThe specificity of the assay was investigated by antigen competition and with LAG3knockout cell lines. A melanin pigment removal procedure was implemented to prevent melanin interference in IHC interpretation. Formalin-fixed paraffin-embedded (FFPE) human melanoma samples with a range of LAG-3 expression levels were used to assess the sensitivity and analytical precision of the assay with a ≥1% cut-off to determine LAG-3 positivity. Interobserver and intraobserver reproducibility were evaluated with 60 samples in intralaboratory studies and 70 samples in interlaboratory studies.ResultsThe LAG-3 IHC method demonstrated performance suitable for analysis of LAG-3 IC expression in clinical melanoma samples. The pretreatment step effectively removed melanin pigment that could interfere with interpretation. LAG-3 antigen competition and analysis of LAG3knockout cell lines indicated that the 17B4 antibody clone binds specifically to LAG-3. The intrarun repeatability, interday, interinstrument, interoperator and inter-reagent lot reproducibility demonstrated a high scoring concordance (>95%). The interobserver and intraobserver reproducibility and overall interlaboratory and intralaboratory reproducibility also showed high scoring concordance (>90%).ConclusionsWe have demonstrated that the assay reliably assesses LAG-3 expression in FFPE human melanoma samples by IHC.

Focused ultrasound (FUS) peripheral neuromodulation has been linked to nerve displacement caused by the acoustic radiation force; however, the roles of cavitation and temperature accumulation on nerve modulation are less clear, as are the relationships between these three mechanisms of action. Temperature directly changes tissue stiffness and viscosity. Viscoelastic properties have been shown to affect cavitation thresholds in both theoretical and ex vivo models, but the direct effect of temperature on cavitation has not been investigated in vivo. Here, cavitation and tissue displacement were simultaneously mapped in response to baseline tissue temperatures of either 30 °C or 38 °C during sciatic nerve sonication in mice. In each mouse, the sciatic nerve was repeatedly sonicated at 1.1-MHz, 4-MPa peak-negative pressure, 5-ms pulse duration, and either 15- or 30-Hz pulse repetition frequency (PRF) for 10 s at each tissue temperature. Cavitation increased by 1.8–4.5 dB at a tissue temperature of 38 °C compared to 30 °C, as measured both by passive cavitation images and cavitation doses. Tissue displacement also increased by 1.3– $1.8 \mu \text{m}$ at baseline temperatures of 38 °C compared to 30 °C. Histological findings indicated small increases in red blood cell extravasation in the 38 °C baseline temperature condition compared to 30 °C at both PRFs. A strong positive correlation was found between the inertial cavitation dose and displacement imaging noise, indicating the potential ability of displacement imaging to simultaneously detect inertial cavitation in vivo. Overall, tissue temperature was found to modulate both in vivo cavitation and tissue displacement, and thus, both tissue temperature and cavitation can be monitored during FUS to ensure both safety and efficiency.

This article characterizes and evaluates the development of an accredited, in-house, faculty-based teaching recognition scheme aimed at supporting clinicians and academics to achieve Advance HE Fellowship recognition. The scheme takes 6 to 24 months to complete and forms part of an institution-wide scheme. The evaluation covered 44 months, collecting data on participation rates across the school and 21 semi-structured interviews across 16 staff participants. We describe the outcomes measured alongside key perceived benefits and challenges to support the implementation of similar schemes elsewhere. Across 130 academic staff, there was 61% engagement. In interviews, 11 participants characterized benefits in terms of changes to their teaching, such as adopting new strategies for differing class sizes, and highlighted the benefit of accessible and context-specific development opportunities designed specifically for STEMM (science, technology, engineering, mathematics, and medicine) practitioners and clinicians. Motivations for participating were mainly intrinsic (69%), with international professional recognition also featured (61%, n= 10). Of the 23 participants who withdrew, the largest subgroup (39%) withdrew because they had left the institution, and 35% withdrew because of a lack of time, which encompassed a range of issues. We outline recommendations for implementing similar schemes including protected time, accessible development opportunities, and support for mentors.

Sandra McCunevolunteered at her local animal shelter aged 13 and, fascinated by dog and cat behaviour, she went on to become an RVN and then a leading researcher in the field of human‐animal interactions.

Background: Recent decades have seen many advances in policy and legislation that support the development of drugs used by neonates, infants, children, and young people. This review summarizes the characteristics and performance of networks capable of conducting studies needed to meet regulatory requirements and make advances in pediatric drug development. Methods: Description of network goals and capabilities by network leaders. Results: In the United States, Europe, Japan, and Canada, clinical research networks have been organized to meet the needs of biopharmaceutical and academic sponsors for timely access to high-quality sites, as well as to provide advice about drug development with regard to strategic and operational feasibility. Each network addresses the specificities of its context while working toward shared principles including standards and timelines; alignment of goals and processes, while not disturbing arrangements for conducting trials that work well; wide geographic coverage; all age groups and pediatric conditions; sources of funding; sites that compete on performance; performance monitoring for benchmarking, and opportunities to optimize the allocation of resources; and education and training for network members. Facilitation in interactions among these networks is based on a single point-of-contact for each; similar approaches to strategic and operational feasibility assessment, and site selection; and collaborative approaches to education and training. Conclusion: Within five years, clinical research networks will support the needs of biopharmaceutical and publicly funded pediatric drug development through locally appropriate and globally interoperable approaches.

We examined the impact of language on addiction stigma when using postmodified nouns versus premodified nouns. Use of postmodified nouns was associated with less authoritarian stigmatizing attitudes and higher benevolence than those who received the version with premodified nouns.

The favorable outcomes with immunotherapy for mesothelioma were somewhat unexpected because this tumor has a low tumor mutation burden which has been associated with benefit in other cancers. Because chromosomal rearrangements are common in mesothelioma and have neoantigenic potential, we sought to determine whether they are associated with survival in patients treated with immunotherapy.

ABSTRACTOver the past two decades, monarch butterfly populations have been declining. This decline has been partly attributed to the extensive loss of breeding habitat through the reduction of common milkweed (Asclepias syriaca, the larval host plant) through herbicides. While the decline of milkweed has been well documented in the US, less is known about its decline in Canada. To take a first step in quantifying its potential decline, we compared roadside milkweed abundance at sites around Ottawa, Ontario, Canada in 2018, to a county-wide estimate of milkweed abundance in 1943 and 1944. We also evaluated the effect of roadside characteristics on milkweed abundance at these sites. Current milkweed density in the Ottawa region is 33–86% lower than it was 75 years ago. We found milkweed at 67% of our 100 sites and found less milkweed at sites with a higher number of lanes in the road adjacent to the roadside. Interestingly, mowing indices were not significant predictors of milkweed abundance. Here we document the first quantitative evidence for milkweed decline over the past 75 years in Canada, which has likely contributed to the decline of breeding monarchs in Canada.

Supramolecular polymer networks are non-covalently crosslinked soft materials that exhibit unique mechanical features such as self-healing, high toughness and stretchability. Previous studies have focused on optimizing such properties using fast-dissociative crosslinks (that is, for an aqueous system, dissociation rate constant kd> 10 s−1). Herein, we describe non-covalent crosslinkers with slow, tuneable dissociation kinetics (kd< 1 s−1) that enable high compressibility to supramolecular polymer networks. The resultant glass-like supramolecular networks have compressive strengths up to 100 MPa with no fracture, even when compressed at 93% strain over 12 cycles of compression and relaxation. Notably, these networks show a fast, room-temperature self-recovery (< 120 s), which may be useful for the design of high-performance soft materials. Retarding the dissociation kinetics of non-covalent crosslinks through structural control enables access of such glass-like supramolecular materials, holding substantial promise in applications including soft robotics, tissue engineering and wearable bioelectronics.