Human verifications: Computable with truth values outside logic.

Cognitive scientists treat verification as a computation in which descriptions that match the relevant situation are true, but otherwise false. The claim is controversial: The logician Gödel and the physicist Penrose have argued that human verifications are not computable. In contrast, the theory of mental models treats verification as computable, but the two truth values of standard logics, true and false, as insufficient. Three online experiments (n = 208) examined participants' verifications of disjunctive assertions about a location of an individual or a journey, such as: 'You arrived at Exeter or Perth'. The results showed that their verifications depended on observation of a match with one of the locations but also on the status of other locations (Experiment 1). Likewise, when they reached one destination and the alternative one was impossible, their use of the truth value: could be true and could be false increased (Experiment 2). And, when they reached one destination and the only alternative one was possible, they used the truth value, true and it couldn't have been false, and when the alternative one was impossible, they used the truth value: true but it could have been false (Experiment 3). These truth values and those for falsity embody counterfactuals. We implemented a computer program that constructs models of disjunctions, represents possible destinations, and verifies the disjunctions using the truth values in our experiments. Whether an awareness of a verification's outcome is computable remains an open question.

Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

How people think about the truth of hypothetical impossibilities.

People can think about hypothetical impossibilities and a curious observation is that some impossible conditionals seem true and others do not. Four experiments test the proposal that people think about impossibilities just as they do possibilities, by attempting to construct a consistent simulation of the impossible conjecture with its suggested outcome, informed by their knowledge of the real world. The results show that participants judge some impossible conditionals true with one outcome, for example, "if people were made of steel, they would not bruise easily" and false with the opposite outcome, "if people were made of steel they would bruise easily", and others false with either outcome, for example, "if houses were made of spaghetti, their engines would (not) be noisy". However, they can sometimes judge impossible conditionals true with either outcome, for example, "if Plato were identical to Socrates, he would (not) have a small nose", or "if sheep and wolves were alike, they would (not) eat grass". The results were observed for judgments about what could be true (Experiments 1 and 4), judgments of degrees of truth (Experiment 2), and judgments of what is true (Experiment 3). The results rule out the idea that people evaluate the truth of a hypothetical impossibility by relying on cognitive processes that compare the probability of each conditional to its counterpart with the opposite outcome.

Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series.

BACKGROUND: Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. METHODS: International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. FINDINGS: Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28-40; range 19-84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1-200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. INTERPRETATION: The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. FUNDING: None.

How people reason with counterfactual and causal explanations for Artificial Intelligence decisions in familiar and unfamiliar domains.

Few empirical studies have examined how people understand counterfactual explanations for other people's decisions, for example, "if you had asked for a lower amount, your loan application would have been approved". Yet many current Artificial Intelligence (AI) decision support systems rely on counterfactual explanations to improve human understanding and trust. We compared counterfactual explanations to causal ones, i.e., "because you asked for a high amount, your loan application was not approved", for an AI's decisions in a familiar domain (alcohol and driving) and an unfamiliar one (chemical safety) in four experiments (n = 731). Participants were shown inputs to an AI system, its decisions, and an explanation for each decision; they attempted to predict the AI's decisions, or to make their own decisions. Participants judged counterfactual explanations more helpful than causal ones, but counterfactuals did not improve the accuracy of their predictions of the AI's decisions more than causals (Experiment 1). However, counterfactuals improved the accuracy of participants' own decisions more than causals (Experiment 2). When the AI's decisions were correct (Experiments 1 and 2), participants considered explanations more helpful and made more accurate judgements in the familiar domain than in the unfamiliar one; but when the AI's decisions were incorrect, they considered explanations less helpful and made fewer accurate judgements in the familiar domain than the unfamiliar one, whether they predicted the AI's decisions (Experiment 3a) or made their own decisions (Experiment 3b). The results corroborate the proposal that counterfactuals provide richer information than causals, because their mental representation includes more possibilities.

Cognitive processes in imaginative moral shifts: How judgments of morally unacceptable actions change.

How do people come to consider a morally unacceptable action, such as "a passenger in an airplane does not want to sit next to a Muslim passenger and so he tells the stewardess the passenger must be moved to another seat", to be less unacceptable? We propose they tend to imagine counterfactual alternatives about how things could have been different that transform the unacceptable action to be less unacceptable. Five experiments identify the cognitive processes underlying this imaginative moral shift: an action is judged less unacceptable when people imagine circumstances in which it would have been moral. The effect occurs for immediate counterfactuals and reflective ones, but is greater when participants create an immediate counterfactual first, and diminished when they create a reflective one first. The effect also occurs for unreasonable actions. We discuss the implications for alternative theories of the mental representations and cognitive processes underlying moral judgments.

Possibilities and the parallel meanings of factual and counterfactual conditionals.

The mental model theory postulates that the meanings of conditionals are based on possibilities. Indicative conditionals-such as "If he is injured tomorrow, then he will take some leave"-have a factual interpretation that can be paraphrased as It is possible, and remains so, that he is injured tomorrow, and in that case certain that he takes some leave. Subjunctive conditionals, such as, "If he were injured tomorrow, then he would take some leave," have a prefactual interpretation that has the same paraphrase. But when context makes clear that his injury will not occur, the subjunctive has a counterfactual paraphrase, with the first clause: It was once possible, but does not remain so, that he will be injured tomorrow. Three experiments corroborated these predictions for participants' selections of paraphrases in their native Spanish, for epistemic and deontic conditionals, for those referring to past and to future events, and for those with then clauses referring to what may or must happen. These results are contrary to normal modal logics. They are also contrary to theories based on probabilities, which are inapplicable to deontic conditionals, such as, "If you have a ticket, then you must enter the show."

FOXO3 is involved in the tumor necrosis factor-driven inflammatory response in fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLS) are major contributors to joint inflammation in rheumatoid arthritis (RA). Forkhead box O 3 (FOXO3) perturbations in immune cells are increasingly linked to RA pathogenesis. Here, we show that FOXO3 is distinctly inactivated/phosphorylated in the FLS of rheumatoid synovitis. In vitro, stimulation of FLS with tumor necrosis factor-alpha α (TNFα) induced a rapid and sustained inactivation of FOXO3. mRNA profiling revealed that the inactivation of FOXO3 is important for the sustained pro-inflammatory interferon response to TNFα (CXCL9, CXCL10, CXCL11, and TNFSF18). Mechanistically, our studies demonstrate that the inactivation of FOXO3 results from TNF-induced downregulation of phosphoinositide-3-kinase-interacting protein 1 (PIK3IP1). Thus, we identified FOXO3 and its modulator PIK3IP1 as a critical regulatory circuit for the inflammatory response of the resident mesenchymal cells to TNFα and contribute insight into how the synovial tissue brings about chronic inflammation that is driven by TNFα.

Targeted inhibition of Janus kinases abates interfon gamma-induced invasive behaviour of fibroblast-like synoviocytes.

Objectives: The aim was to explore the function of the T-cell cytokine IFNγ for mesenchymal tissue remodelling in RA and to determine whether IFNγ signalling controls the invasive potential of fibroblast-like synoviocytes (FLS). Methods: To assess architectural responses, FLS were cultured in three-dimensional micromasses. FLS motility was analysed in migration and invasion assays. Signalling events relevant to cellular motility were defined by western blots. Baricitinib and small interfering RNA pools were used to suppress Janus kinase (JAK) functions. Results: Histological analyses of micromasses revealed unique effects of IFNγ on FLS shape and tissue organization. This was consistent with accelerated migration upon IFNγ stimulation. Given that cell shape and cell motility are under the control of the focal adhesion kinase (FAK), we next analysed its activity. Indeed, IFNγ stimulation induced the phosphorylation of FAK-Y925, a phosphosite implicated in FAK-mediated cell migration. Small interfering RNA knockdown of JAK2, but not JAK1, substantially abrogated FAK activation by IFNγ. Correspondingly, IFNγ-induced FAK activation and invasion of FLS was abrogated by the JAK inhibitor, baricitinib. Conclusion: Our study contributes insight into the synovial response to IFNγ and reveals JAK2 as a potential therapeutic target for FLS-mediated joint destruction in arthritis, especially in RA.

Counterfactual Thought.

People spontaneously create counterfactual alternatives to reality when they think "if only" or "what if" and imagine how the past could have been different. The mind computes counterfactuals for many reasons. Counterfactuals explain the past and prepare for the future, they implicate various relations including causal ones, and they affect intentions and decisions. They modulate emotions such as regret and relief, and they support moral judgments such as blame. The loss of the ability to imagine alternatives as a result of injuries to the prefrontal cortex is devastating. The basic cognitive processes that compute counterfactuals mutate aspects of the mental representation of reality to create an imagined alternative, and they compare alternative representations. The ability to create counterfactuals develops throughout childhood and contributes to reasoning about other people's beliefs, including their false beliefs. Knowledge affects the plausibility of a counterfactual through the semantic and pragmatic modulation of the mental representation of alternative possibilities.

Switching Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide Fumarate (TAF) in Hepatitis B/HIV Co-Infection: A Feasibility Study.

PURPOSE: Tenofovir alafenamide (TAF) delivers the active metabolite more efficiently to target cells compared with tenofovir disoproxil fumarate (TDF). Recent studies suggest that TAF is efficacious in treatment naïve individuals who are co-infected with HBV/HIV and may have superior effects on HBV e antigen (HBeAg) seroconversion in this setting. The primary objective of this study was to explore the feasibility of switching from TDF to TAF in HBV/HIV co-infection. METHODS: In this single-arm, multicenter, open-label study, we recruited patients (n = 20) who were on stable TDF-based antiviral therapy for at least 12 months. All participants had undetectable HIV RNA and HBV DNA levels at the time of screening and were converted to a TAF-based treatment regimen (TAF + emtricitabine + third agent) for 48 weeks. FINDINGS: Twenty-seven individuals were invited to take part in the screening process; 3 met the exclusion criteria and a further 4 withdrew consent prior to enrolment. The remaining participants were predominantly male (70%), non-cirrhotic (95%) and of Afro-Caribbean ethnicity (60%). All were co-infected with HIV-1 and established on long-term antiretroviral treatment prior to enrolment (median 6.5 years). No adverse events related to the study drug were observed, and most patients (89.5%) maintained undetectable HIV RNA and HBV DNA throughout the follow-up period. IMPLICATIONS: Switching from TDF to TAF in HBV/HIV co-infection was safe, well tolerated and maintained virological suppression in most patients. Additional studies are needed to confirm these findings in larger cohorts and explore other endpoints.

Social learning in Cartilaginous fish (stingrays Potamotrygon falkneri).

Social learning is considered one of the hallmarks of cognition. Observers learn from demonstrators that a particular behavior pattern leads to a specific consequence or outcome, which may be either positive or negative. In the last few years, social learning has been studied in a variety of taxa including birds and bony fish. To date, there are few studies demonstrating learning processes in cartilaginous fish. Our study shows that the cartilaginous fish freshwater stingrays (Potamotrygon falkneri) are capable of social learning and isolates the processes involved. Using a task that required animals to learn to remove a food reward from a tube, we found that observers needed significantly (P < 0.01) fewer trials to learn to extract the reward than demonstrators. Furthermore, observers immediately showed a significantly (P < 0.05) higher frequency of the most efficient "suck and undulation" strategy exhibited by the experienced demonstrators, suggesting imitation. Shedding light on social learning processes in cartilaginous fish advances the systematic comparison of cognition between aquatic and terrestrial vertebrates and helps unravel the evolutionary origins of social cognition.

The compatibility heuristic in non-categorical hypothetical reasoning: inferences between conditionals and disjunctions.

A new theory explains how people make hypothetical inferences from a premise consistent with several alternatives to a conclusion consistent with several alternatives. The key proposal is that people rely on a heuristic that identifies compatible possibilities. It is tested in 7 experiments that examine inferences between conditionals and disjunctions. Participants accepted inferences between conditionals and inclusive disjunctions when a compatible possibility was immediately available, in their binary judgments that a conclusion followed or not (Experiment 1a) and ternary judgments that included it was not possible to know (Experiment 1b). The compatibility effect was amplified when compatible possibilities were more readily available, e.g., for 'A only if B' conditionals (Experiment 2). It was eliminated when compatible possibilities were not available, e.g., for 'if and only if A B' bi-conditionals and exclusive disjunctions (Experiment 3). The compatibility heuristic occurs even for inferences based on implicit negation e.g., 'A or B, therefore if C D' (Experiment 4), and between universals 'All A's are B's' and disjunctions (Experiment 5a) and universals and conditionals (Experiment 5b). The implications of the results for alternative theories of the cognitive processes underlying hypothetical deductions are discussed.

Acute Charcot arthropathy as a first presentation of type 2 diabetes mellitus.

Charcot arthropathy in people with diabetes is generally seen when diabetes has been well established, and therefore it is not routinely considered as a differential diagnosis in people presenting with erythematous and oedematous joints in primary care. We present two cases of acute Charcot arthropathy as a first presentation of type 2 diabetes mellitus. The first case describes a man in his 70s, who presented with a 5-week history of right foot pain, treated initially in the community as cellulitis. A diagnosis of acute Charcot arthropathy was made in the emergency department following review by the orthopaedic and podiatry department. The second case describes a woman in her 40s who presented with a 2-week history of ankle pain. Charcot arthropathy is associated with significant morbidity and mortality, and these cases highlight the importance of including Charcot arthropathy in the differential diagnosis when people present with atypical joint swelling.

COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2.

Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18-75. Methods: A phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 µg then 10 µg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 216 healthy individuals (median age 51 years) received 1.0 µg followed by 10.0 µg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18-75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 µg dose with a ≥0.5log10 increase in 71% (22/31). Interpretation: Encapsulated saRNA was well tolerated and immunogenic in adults aged 18-75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 µg followed by 10.0 µg. Boosting of S IgG antibodies was observed with a single 1.0 µg injection in those with pre-existing immune responses. Funding: Grants and gifts from the Medical Research Council UKRI (MC_PC_19076), the National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth.

The consistency of disjunctive assertions.

In two experiments, we established a new phenomenon in reasoning from disjunctions of the grammatical form either A or else B, where A and B are clauses. When individuals have to assess whether pairs of assertions can be true at the same time, they tend to focus on the truth of each clause of an exclusive disjunction (and ignore the concurrent falsity of the other clause). Hence, they succumb to illusions of consistency and of inconsistency with pairs consisting of a disjunction and a conjunction (Experiment 1), and with simpler problems consisting of pairs of disjunctions, such as eIther there is a pie or else there is a cake and Either there isn't a pie or else there is a cake (Experiment 2), that appear to be consistent with one another, but in fact are not. These results corroborate the theory that reasoning depends on envisaging models of possibilities.

Similarities and differences in understanding negative and affirmative counterfactuals and causal assertions: Evidence from eye-tracking.

Two eye-tracking experiments compared affirmative and negative counterfactuals, "if she had (not) arrived early, she would (not) have bought roses" and affirmative and negative causal assertions, "Because she arrived (did not arrive) early, she bought (did not buy) roses." When participants heard a counterfactual, they looked on screen at words corresponding to its conjecture ("roses"), and its presupposed facts ("no roses"), whereas for a causal assertion, they looked only at words corresponding to the facts. For counterfactuals, they looked at the conjecture first, and later the presupposed facts, and at the latter more than the former. The effect was more pronounced for negative counterfactuals than affirmative ones because the negative counterfactual's presupposed facts identify a specific item ("she bought roses"), whereas the affirmative counterfactual's presupposed facts do not ("she did not buy roses"). Hence, when participants were given a binary context, "she did not know whether to buy roses or carnations," they looked primarily at the presupposed facts for both sorts of counterfactuals. We discuss the implications for theories of negation, the dual meaning of counterfactuals, and their relation to causal assertions.

Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.

BACKGROUND: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. METHODS: In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. FINDINGS: Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. INTERPRETATION: Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. FUNDING: None.

Fluorosomes: a convenient new reagent to detect and block multivalent and complex receptor-ligand interactions.

We describe for the first time fluorescent virus-like particles decorated with biologically active mono- and multisubunit immune receptors of choice and the basic application of such fluorosomes (FSs) to visualize and target immune receptor-ligand interactions. For that purpose, human embryonic kidney (HEK)-293 cells were stably transfected with Moloney murine leukemia virus (MoMLV) matrix protein (MA) GFP fusion constructs. To produce FSs, interleukins (ILs), IL-receptors (IL-Rs), and costimulatory molecules were fused to the glycosyl phosphatidyl inositol anchor acceptor sequence of CD16b and coexpressed along with MoMLV group-specific antigen-polymerase (gag-pol) in MA::GFP(+) HEK-293 cells. We show that IL-2 decorated but not control-decorated FSs specifically identify normal and malignant IL-2 receptor-positive (IL-2R(+)) lymphocytes by flow cytometry. In addition to cytokines and costimulatory molecules, FSs were also successfully decorated with the heterotrimeric IL-2Rs, allowing identification of IL-2(+) target cells. Specificity of binding was proven by complete inhibition with nonlabeled, soluble ligands. Moreover, IL-2R FSs efficiently neutralized soluble IL-2 and thus induced unresponsiveness of T cells receiving full activation stimuli via T-cell antigen receptor and CD28. FSs are technically simple, multivalent tools for assessing and blocking mono- and multisubunit immune receptor-ligand interactions with natural constituents in a plasma membrane context.