Logical Equivalences, Homomorphism Indistinguishability, and Forbidden Minors

Two graphs $G$ and $H$ are homomorphism indistinguishable over a class of graphs $\mathcal{F}$ if for all graphs $F \in \mathcal{F}$ the number of homomorphisms from $F$ to $G$ is equal to the number of homomorphisms from $F$ to $H$. Many natural equivalence relations comparing graphs such as (quantum) isomorphism, spectral, and logical equivalences can be characterised as homomorphism indistinguishability relations over certain graph classes. Abstracting from the wealth of such instances, we show in this paper that equivalences w.r.t. any self-complementarity logic admitting a characterisation as homomorphism indistinguishability relation can be characterised by homomorphism indistinguishability over a minor-closed graph class. Self-complementarity is a mild property satisfied by most well-studied logics. This result follows from a correspondence between closure properties of a graph class and preservation properties of its homomorphism indistinguishability relation. Furthermore, we classify all graph classes which are in a sense finite (essentially profinite) and satisfy the maximality condition of being homomorphism distinguishing closed, i.e. adding any graph to the class strictly refines its homomorphism indistinguishability relation. Thereby, we answer various question raised by Roberson (2022) on general properties of the homomorphism distinguishing closure.Comment: 26 pages, 1 figure, 1 tabl

Weisfeiler--Leman and Graph Spectra

We devise a hierarchy of spectral graph invariants, generalising the adjacency spectra and Laplacian spectra, which are commensurate in power with the hierarchy of combinatorial graph invariants generated by the Weisfeiler--Leman (WL) algorithm. More precisely, we provide a spectral characterisation of $k$-WL indistinguishability after $d$ iterations, for $k,d \in \mathbb{N}$. Most of the well-known spectral graph invariants such as adjacency or Laplacian spectra lie in the regime between 1-WL and 2-WL. We show that individualising one vertex plus running 1-WL is already more powerful than all such spectral invariants in terms of their ability to distinguish non-isomorphic graphs. Building on this result, we resolve an open problem of F\"urer (2010) about spectral invariants and strengthen a result due to Godsil (1981) about commute distances

Lasserre Hierarchy for Graph Isomorphism and Homomorphism Indistinguishability

We show that feasibility of the t^th level of the Lasserre semidefinite programming hierarchy for graph isomorphism can be expressed as a homomorphism indistinguishability relation. In other words, we define a class ?_t of graphs such that graphs G and H are not distinguished by the t^th level of the Lasserre hierarchy if and only if they admit the same number of homomorphisms from any graph in ?_t. By analysing the treewidth of graphs in ?_t we prove that the 3t^th level of Sherali-Adams linear programming hierarchy is as strong as the t^th level of Lasserre. Moreover, we show that this is best possible in the sense that 3t cannot be lowered to 3t-1 for any t. The same result holds for the Lasserre hierarchy with non-negativity constraints, which we similarly characterise in terms of homomorphism indistinguishability over a family ?_t^+ of graphs. Additionally, we give characterisations of level-t Lasserre with non-negativity constraints in terms of logical equivalence and via a graph colouring algorithm akin to the Weisfeiler-Leman algorithm. This provides a polynomial time algorithm for determining if two given graphs are distinguished by the t^th level of the Lasserre hierarchy with non-negativity constraints

Limitations of Game Comonads via Homomorphism Indistinguishability

Abramsky, Dawar, and Wang (2017) introduced the pebbling comonad for k-variable counting logic and thereby initiated a line of work that imports category theoretic machinery to finite model theory. Such game comonads have been developed for various logics, yielding characterisations of logical equivalences in terms of isomorphisms in the associated co-Kleisli category. We show a first limitation of this approach by studying linear-algebraic logic, which is strictly more expressive than first-order counting logic and whose k-variable logical equivalence relations are known as invertible-map equivalences (IM). We show that there exists no finite-rank comonad on the category of graphs whose co-Kleisli isomorphisms characterise IM-equivalence, answering a question of \'O Conghaile and Dawar (CSL 2021). We obtain this result by ruling out a characterisation of IM-equivalence in terms of homomorphism indistinguishability and employing the Lov\'asz-type theorems for game comonads established by Dawar, Jakl, and Reggio (2021). Two graphs are homomorphism indistinguishable over a graph class if they admit the same number of homomorphisms from every graph in the class. The IM-equivalences cannot be characterised in this way, neither when counting homomorphisms in the natural numbers, nor in any finite prime field.Comment: Minor corrections in Section

Homomorphism Tensors and Linear Equations

Lov\'asz (1967) showed that two graphs $G$ and $H$ are isomorphic if and only if they are homomorphism indistinguishable over the class of all graphs, i.e. for every graph $F$, the number of homomorphisms from $F$ to $G$ equals the number of homomorphisms from $F$ to $H$. Recently, homomorphism indistinguishability over restricted classes of graphs such as bounded treewidth, bounded treedepth and planar graphs, has emerged as a surprisingly powerful framework for capturing diverse equivalence relations on graphs arising from logical equivalence and algebraic equation systems. In this paper, we provide a unified algebraic framework for such results by examining the linear-algebraic and representation-theoretic structure of tensors counting homomorphisms from labelled graphs. The existence of certain linear transformations between such homomorphism tensor subspaces can be interpreted both as homomorphism indistinguishability over a graph class and as feasibility of an equational system. Following this framework, we obtain characterisations of homomorphism indistinguishability over two natural graph classes, namely trees of bounded degree and graphs of bounded pathwidth, answering a question of Dell et al. (2018).Comment: 33 pages, accepted for ICALP 202

The Complexity of Homomorphism Reconstructibility

Representing graphs by their homomorphism counts has led to the beautiful theory of homomorphism indistinguishability in recent years. Moreover, homomorphism counts have promising applications in database theory and machine learning, where one would like to answer queries or classify graphs solely based on the representation of a graph $G$ as a finite vector of homomorphism counts from some fixed finite set of graphs to $G$. We study the computational complexity of the arguably most fundamental computational problem associated to these representations, the homomorphism reconstructability problem: given a finite sequence of graphs and a corresponding vector of natural numbers, decide whether there exists a graph $G$ that realises the given vector as the homomorphism counts from the given graphs. We show that this problem yields a natural example of an \mathsf{NP}^{#\mathsf{P}}-hard problem, which still can be $\mathsf{NP}$-hard when restricted to a fixed number of input graphs of bounded treewidth and a fixed input vector of natural numbers, or alternatively, when restricted to a finite input set of graphs. We further show that, when restricted to a finite input set of graphs and given an upper bound on the order of the graph $G$ as additional input, the problem cannot be $\mathsf{NP}$-hard unless $\mathsf{P} = \mathsf{NP}$. For this regime, we obtain partial positive results. We also investigate the problem's parameterised complexity and provide fpt-algorithms for the case that a single graph is given and that multiple graphs of the same order with subgraph instead of homomorphism counts are given

The impact of growth promoters on muscle growth and the potential consequences for meat quality

To meet the demands of increased global meat consumption, animal production systems will have to become more efficient, or at least maintain the current efficiency utilizing feed ingredients that are not also used for human consumption. Use of growth promoters is a potential option for increasing production animal feed efficiency and increased muscle growth. The objective of this manuscript is to describe the mechanisms by which the growth promoters, beta-adrenergic agonists and growth hormone, mediate their effects, with specific consideration of the aspects which have implications for meat quality.The work described in this manuscript was supported by a BBSRC LINK Zoetis grant, number BB/J005320/1, as well as a BBSRC CASE PhD studentship awarded to David Brown and Krystal Hemmings and a PhD scholarship awarded to Molebeledi HD Mareko by the Botswana College of Agricultur

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570