Cohomological Donaldson-Thomas theory of a quiver with potential and quantum enveloping algebras

This paper concerns the cohomological aspects of Donaldson-Thomas theory for Jacobi algebras and the associated cohomological Hall algebra, introduced by Kontsevich and Soibelman. We prove the Hodge-theoretic categorification of the integrality conjecture and the wall crossing formula, and furthermore realise the isomorphism in both of these theorems as Poincar\'e-Birkhoff-Witt isomorphisms for the associated cohomological Hall algebra. We do this by defining a perverse filtration on the cohomological Hall algebra, a result of the "hidden properness" of the semisimplification map from the moduli stack of semistable representations of the Jacobi algebra to the coarse moduli space of polystable representations. This enables us to construct a degeneration of the cohomological Hall algebra, for generic stability condition and fixed slope, to a free supercommutative algebra generated by a mixed Hodge structure categorifying the BPS invariants. As a corollary of this construction we furthermore obtain a Lie algebra structure on this mixed Hodge structure - the Lie algebra of BPS invariants - for which the entire cohomological Hall algebra can be seen as the positive part of a Yangian-type quantum group.Comment: v5 final version, 64 pages, to appear in Invent. Math. Many thanks to the anonymous referee for helpful suggestion

Rethinking 'risk' and self-management for chronic illness

Self-management for chronic illness is a current high profile UK healthcare policy. Policy and clinical recommendations relating to chronic illnesses are framed within a language of lifestyle risk management. This article argues the enactment of risk within current UK self-management policy is intimately related to neo-liberal ideology and is geared towards population governance. The approach that dominates policy perspectives to ‘risk' management is critiqued for positioning people as rational subjects who calculate risk probabilities and act upon them. Furthermore this perspective fails to understand the lay person's construction and enactment of risk, their agenda and contextual needs when living with chronic illness. Of everyday relevance to lay people is the management of risk and uncertainty relating to social roles and obligations, the emotions involved when encountering the risk and uncertainty in chronic illness, and the challenges posed by social structural factors and social environments that have to be managed. Thus, clinical enactments of self-management policy would benefit from taking a more holistic view to patient need and seek to avoid solely communicating lifestyle risk factors to be self-managed

Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme

For a quantitative understanding of the process of adaptation, we need to understand its “raw material,” that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75–189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a Fréchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Une intervention en ligne de soutien à la décision pour faciliter la communication patient-médecin en lien avec le traitement du cancer de la prostate

Objectif : Mesurer les préférences et les valeurs des hommes nouvellement diagnostiqués d’un cancer de la prostate (CP) au moyen d’une technologie en ligne de soutien à la décision—l’intervention de soutien à la prise de décision en lien avec le cancer de la prostate (ISPD-CP). Méthodologie : Les comportements de recherche d’information sur la santé, les facteurs ayant une influence sur la décision thérapeutique, le contrôle décisionnel et la préférence thérapeutique ont été enregistrés par le programme d’ISPD‑CP avant la consultation thérapeutique. Chaque patient a reçu une fiche sommaire des préférences (FSP) à utiliser lors des discussions thérapeutiques. Nous avons mesuré les degrés de contrôle décisionnel et de conflit décisionnel avant et après la prise de décision thérapeutique (PDT), ainsi que la satisfaction des patients après la PDT. Résultats : Quarante-neuf hommes ont suivi le programme d’ISPD-CP avant leur discussion thérapeutique. Parmi eux, 61 % ont montré leur FSP à leur(s) médecin(s) lors des discussions thérapeutiques. La plupart des patients (63 %) voulaient avoir accès à des renseignements approfondis ou détaillés. Les quatre facteurs qui influaient le plus sur les décisions thérapeutiques des patients étaient les suivants : l’impact du traitement sur la survie, sur la fonction urinaire et sur la fonction intestinale, et la recommandation du médecin quant au traitement le plus indiqué. Les patients ont signalé un degré de satisfaction élevé par rapport à leur décision thérapeutique et par rapport à leur participation au processus décisionnel. Les niveaux de conflit décisionnel étaient considérablement plus faibles (p < 0,001) après la PDT, et les hommes ont signalé avoir joué un rôle considérablement plus actif dans le processus décisionnel que ce qu’ils avaient originalement souhaité (p = 0,038). Conclusions : Les résultats semblent indiquer que l’ISPD-CP peut être un outil utile pour aider les patients à cerner et communiquer leurs valeurs et préférences aux médecins dans le cadre des discussions thérapeutiques

Masculinities and patient perspectives of communication about active surveillance for prostate cancer

Objective: The purpose of this study is to describe connections between masculinities and patient perspectives of active surveillance (AS) related communication with male physicians. Method: An interpretive descriptive qualitative design was used to explore patient physician communication from the perspectives of 25 men on AS. In-depth, semistructured interviews were recorded, transcribed verbatim, and coded. Key concepts were described and a masculinities gender framework guided analyses of patients' perspectives. Results: Patient physician communication of diagnosis, treatment options, and specificities of AS featured prominently within participants' interviews. Most participants reported brevity in patient physician communication amid accepting the physician's communication style and recommendations. Participants' accounts suggested "therapeutic" communications as contingent on positioning physicians as authoritative and assigning them control, while patients were stoic in accepting AS. However, some participants reported being confused about their diagnosis details and specific AS protocols, and resisted traditional physician patient hierarchies, desiring more collaborative decision-making processes. In this regard communications emerged as "threat," in that participants lacked and/or lost confidence in their physician and were uncertain and anxious about the legitimacy of AS. These findings were interpreted within a gender framework, showing how patients drew on an array of masculine ideals, including stoicism, denying illness, and respecting expertise in different ways. Conclusions: Our novel findings illuminate complexities of men's perspectives about patient physician communication in AS, and offer insights about how masculinities influence what can be understood as potentially helpful and unhelpful communication among this emergent patient population

The self-management of uncertainty among men undertaking active surveillance for low-risk prostate cancer

Asymptomatic men with low-risk, early-stage prostate cancer are eligible for active surveillance (AS), which offers a means to monitor the cancer while delaying treatment. However, AS operates within a unique set of circumstances that advocate monitoring, rather than immediate treatment, and men's health practices are central to coping with the inherent uncertainty of living with an untreated cancer. A qualitative study was completed to describe the range of men's self-management strategies used to overcome AS-related uncertainty. The study findings reveal two strategies. First, positioning prostate cancer as benign through stoicism and solitary discourses were common to men intent on "living a normal life." Second, men committed to "doing something extra" complemented AS protocols, and often collaborated with their wives to focus on diet as an adjunct therapy. Although most participants exhibited typical men's health practices, it is clear that tailored AS psychosocial interventions will benefit men and their families