Interleukin-15 and high-intensity exercise: relationship with inflammation, body composition and fitness in cancer survivors.

Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti-oncogenic effects of exercise were associated with the exercise-mediated release of myokines such as interleukin (IL)-15. However, no study has quantified the acute IL-15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n = 14) completed a single bout of high-intensity interval exercise (HIIE) [4×4 min at 85-95% heart rate (HR) peak, 3 min at 50-70% HR peak] before and after 7 months of three times weekly high-intensity interval training (HIIT) on a cycle ergometer. At each time point venous blood was sampled before and immediately after HIIE to assess the acute myokine (IL-15, IL-6, IL-10, IL-1ra) responses. Markers of inflammation, cardiorespiratory fitness and measures of body composition were obtained at baseline and 7 months. An acute bout of HIIE resulted in a significant increase in IL-15 concentrations (pre-intervention: 113%; P = 0.013, post-intervention: 102%; P = 0.005). Post-exercise IL-15 concentrations were associated with all other post-exercise myokine concentrations, lean mass (P = 0.031), visceral adipose tissue (P = 0.039) and absolute V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ peak (P = 0.032). There was no significant effect of 7 months of HIIT on pre- or post-HIIE IL-15 concentrations (P > 0.05). This study demonstrates HIIE is a sufficient stimulus to increase circulating IL-15 and other myokines including IL-6, IL-10 and IL-1ra which may be clinically relevant in the anti-oncogenic effect of exercise and repetitive exposure to these effects may contribute to the positive relationship between exercise and cancer recurrence. KEY POINTS: Exercise has been demonstrated to reduce the risk of cancer recurrence. Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth, mediated by exercise-induced myokines (IL-6 and IL-15). High-intensity interval exercise significantly increased myokines associated with the anti-oncogenic effect of exercise and the magnitude of response was associated with lean mass, but training did not appear to influence this response. Given IL-15 has been implicated in the anti-oncogenic effect of exercise and is being explored as an immunotherapy agent, high-intensity interval exercise may improve outcomes for people living beyond cancer through IL-15-mediated pathways. Interventions that increase lean mass may also enhance this response.

Impact of preoperative body mass index on long-term survival, quality of life, and functional outcomes after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: Results from the UK National Cohort.

BACKGROUND: Previous studies have demonstrated the safety of pulmonary endarterectomy (PEA) across body mass index (BMI) strata. However, long-term survival and patient-reported outcome measures by BMI strata remain unknown. We examined the impact of preoperative BMI on long-term survival, QOL, and functional outcomes for patients undergoing PEA for chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Retrospective review of 2,004 patients from the UK National Cohort between 2007 and 2021 undergoing PEA for CTEPH (mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance >160 dynes). Patients were stratified into BMI<20, 20 to 29, 30 to 39, 40 to 49, and 50+. All-cause mortality was the primary outcome measure. Secondary outcome measures were 3- to 6-month postoperative hemodynamics, 6-minute walk distance (6MWD), New York Heart Association (NYHA) class, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) scores. RESULTS: Hemodynamics and 6MWD at 3 to 6 months were similar across BMI strata. Patients with BMI 50+ reported the highest incidence of postoperative NYHA III/IV limitation (53.3%, p < 0.001) and the highest residual symptom burden by CAMPHOR (p < 0.001). Five-year survival was lowest in patients with BMI 50+ (70.2%) and BMI<20 (73.4%), while highest in BMI 30 to 39 (88.2%, p = 0.008). Ten-year Kaplan-Meier estimates predicted the lowest survival in BMI 50+ and BMI<20. CONCLUSIONS: PEA remains safe and effective for all patients regardless of BMI. Despite similar hemodynamic outcomes, patients with BMI 50+ are at the greatest risk of long-term all-cause mortality, and patients with BMI 50+ experience residual symptomatic limitation.

Pulmonary Thromboendarterectomy: The Potentially Curative Treatment of Choice for Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a consequence of unresolved organized thromboembolic obstruction of the pulmonary arteries, which can cause pulmonary hypertension (PH) and right heart failure (RVF). Due to its subtle signs, it is challenging to determine its exact incidence and prevalence. Furthermore, CTEPH may also present without any prior venous thromboembolic (VTE) history, contributing to underdiagnosis and undertreatment. Diagnosis requires a high degree of suspicion and is ruled out by a normal V/Q scintigraphy. Additional imaging by CT and/or conventional angiography, as well as right heart catheterization are required to confirm CTEPH and formulate treatment plans. Pulmonary thromboendarterectomy (PTE) is the treatment of choice for eligible patients and can be potentially curative. PTE has a low mortality rate of 1-2% at expert centers and offers excellent long-term survival. Furthermore, recent advances in the techniques allow distal endarterectomy with comparable outcomes. There are alternative treatment options available for those who may not be operable or have prohibitive risks, providing some benefit. However, CTEPH is a progressive disease with low long-term survival rates if left untreated. Given excellent short and long-term outcomes of surgery, as well as the benefits seen with other treatment modalities in non-candidate patients, it is crucial that precapillary PH and CTEPH are ruled out in any patient with dyspnea of unexplained etiology. These patients should be referred to expert centers where accurate operability assessment, and appropriate treatment strategies can be offered by a multidisciplinary team.

V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins.

Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2000 known snake venom toxins. Indeed, by identifying similarities (i.e., conserved epitopes) across these different toxins, it is possible to design cross-reactive treatments, such as broadly-neutralising antibodies, that target these similarities. Therefore, in this project, we built an automated pipeline that generates sequence and structural distance matrices and homology trees across all available snake venom toxin sequences and structures. To facilitate analysis, we also developed a user-friendly and high-throughput visualisation tool, coined "Venom TOxin CluStering" (V-ToCs). This tool allows researchers to easily investigate sequence and structure patterns in snake venom toxins for a wide array of purposes, such as elucidating toxin evolution, and will also hopefully help guide the discovery and development of increasingly broadly-neutralising antivenoms in the near future.

Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy.

BACKGROUND: The European Chronic Thromboembolic Pulmonary Hypertension registry (CTEPH), conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. METHODS: Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. RESULTS: Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Oof patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes/(s·cm-5). During an observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non-vitamin K oral anticoagulants (P=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. CONCLUSIONS: This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. REGISTRATION: URL https://clinicaltrials.gov; Unique identifier: NCT02656238.

Perspective on the health value of carbohydrate-rich foods: glycemic index and load; fiber and whole grains.

BACKGROUND: For over 45 y increasingly comprehensive food tables of glycemic index (GI) and glycemic load (GL) have been published in the American Journal of Clinical Nutrition to determine the GI and GL values of diets. Recently the WHO based on a 2019 series of meta-analyses concluded that increases in dietary fiber and whole grains but not reduction in GI or GL warranted recommendations for chronic disease reduction. METHODS AND RESULTS: We therefore provide a perspective on the current evidence that indicates that GI and GL are also determinants of risk of chronic disease outcomes. We are also concerned with the term dietary fiber used in the singular when there are many dietary fibers that may differ in their physiological effects. Furthermore, the term "whole grains" that refers to "whole grain flour" limits the exploration of "intact" grains that are low GI and have useful physiological effects. CONCLUSION: We conclude that all these determinants of the health values of carbohydrate-rich foods should be used in combination to assess the health value of carbohydrate-rich foods.

The Portfolio Diet and HbA1c in Adults Living with Type 2 Diabetes Mellitus: A Patient-Level Pooled Analysis of Two Randomized Dietary Trials.

(1) Background: The Portfolio Diet, a dietary pattern of cholesterol-lowering foods, is also rich in low glycemic index (GI) foods. While strong evidence supports clinically meaningful reductions in cholesterol, evidence on the relationship between the Portfolio Diet and diabetes management is lacking. (2) Objective: To evaluate the relationship between the Portfolio Diet and glycated hemoglobin (HbA1c) as a determinant of glycemic control among adults living with type 2 diabetes mellitus (T2DM). (3) Methods: Patient-level data was pooled from two randomized dietary trials of low glycemic index interventions compared to high cereal fibre control diets in adults living with T2DM where HbA1c was collected (clinicaltrials.gov identifiers: NCT00438698, NCT00438698). Dietary exposure was assessed using weighed 7-day diet records. Adherence to the Portfolio Diet and its pillars (nuts and seeds, plant protein, viscous fibre, plant sterols, monounsaturated fatty acid [MUFA] oils) was determined using the validated clinical Portfolio Diet Score (c-PDS). Multiple linear regression was used to assess the association between change in the c-PDS and change in HbA1c over 6-months with covariate adjustments. (4) Results: A total of 267 participants, predominantly White (67%) and male (63%), were included, with a mean ± standard error age of 62 ± 0.5 years, baseline BMI of 30.2 ± 0.3 kg/m2, HbA1c of 7.08 ± 0.03%, and a c-PDS of 4.1 ± 0.3 points out of 25. Change in the c-PDS was significantly associated with a change in HbA1c (ß: -0.04% per point, 95% CI: -0.07, -0.02, p = 0.001). A 7.5-point (30%) increase in the c-PDS was associated with a 0.3% reduction in HbA1c. Of the individual pillars, a 1-point change in nut and seeds intake (ß: -0.07%, 95% CI: -0.12, -0.02, p = 0.009) or in plant protein intake (ß: -0.11%, 95% CI: -0.18, -0.03, p = 0.009) was associated with a change in HbA1c. Further analysis of plant protein intake revealed that an increase in dietary pulse intake, a particularly low-GI food, was significantly associated with a reduction in HbA1c (ß: -0.24% per 1-cup points cooked pulses (226 g) or 2 c-PDS points, 95% CI: -0.45, -0.03, p = 0.028). (5) Conclusions: Among adults living with T2DM, the Portfolio Diet was associated with lower HbA1c over a 6-month period, predominantly driven by two pillars: nuts and seeds and plant protein, particularly dietary pulses. These data have implications for including the Portfolio Diet in dietary recommendations for glycemic control in T2DM. A trial demonstrating the direct causal effect of the Portfolio Diet in a diverse group is warranted.

Ligand engineering of tetra N-heterocyclic carbenes for boosting catalytic aziridination.

A comprehensive computational study on the underlying reactivity of iron tetra-NHC complexes for C2 + N1 aziridination catalysis is presented. A library of 18 unique iron tetra-NHC complexes was constructed, and a computational screening was performed on the reaction barriers associated with the rate-determining step (formation of an open chain radical intermediate). Thermodynamic barriers were computed along with a variety of steric and electronic properties, including the percentage of buried volume, orbital energies and ETS-NOCV analysis, which were used to identify key characteristics related to reactivity. The analysis performed in this study successfully identified key differences in tetracarbenes, such as linking groups (BMe2 or CH2) and the identity of the NHC groups (imidazole, imidazoline or benzimidazole) in terms of sterics, electronics and thermodynamics. Additionally, we have proposed two reaction pathways based on electronic structure arguments for the formation of the key open-chain radical intermediate. The first reaction pathway proceeds through a σ-hole channel where the Fe(IV)-imide intermediate evolves into Fe(III)-imidyl radical through electron donation into the antibonding σ* orbital, while the second involves a Fe(III)-imidyl radical formed through a π-hole channel (donation into π*). These pathways are consistent with the isoelectronic iron(IV)-oxo species for hydrogen atom abstraction mechanisms and they can be used as descriptors of the rate-determining step of the aziridination reaction.

Factors associated with long-term opioid use among patients with axial spondyloarthritis or psoriatic arthritis who initiated opioids.

OBJECTIVE: Up to one in five patients with axial spondyloarthritis (AxSpA) or psoriatic arthritis (PsA) newly initiated on opioids transition to long-term use within the first year. This study aimed to investigate individual factors associated with long-term opioid use among opioid new users with AxSpA/PsA. METHODS: Adult patients with AxSpA/PsA and without prior cancer who initiated opioids between 2006-2021 were included from Clinical Practice Research Datalink Gold, a national UK primary care database. Long-term opioid use was defined as having ≥3 opioid prescriptions issued within 90 days, or ≥ 90 days of opioid supply, in the first year of follow-up. Individual factors assessed included sociodemographic, lifestyle factors, medication use and comorbidities. A mixed-effects logistic regression model with patient-level random intercept was used to examine the association of individual characteristics with the odds of long-term opioid use. RESULTS: In total 10 300 opioid initiations were identified from 8,212 patients (3037 AxSpA; 5175 PsA). The following factors were associated with long-term opioid use: being a current smoker (OR : 1.62; 95%CI : 1.38,1.90), substance use disorder (OR : 2.34, 95%CI : 1.05,5.21), history of suicide/self-harm (OR : 1.84; 95%CI : 1.13,2.99), co-existing fibromyalgia (OR : 1.62; 95%CI : 1.11,2.37), higher Charlson Comorbidity Index (OR : 3.61; 95%CI : 1.69,7.71 for high scores), high MME/day at initiation (OR : 1.03; 95%CI : 1.02,1.03) and gabapentinoid (OR : 2.35; 95%CI : 1.75,3.16) and antidepressant use (OR : 1.69; 95%CI : 1.45,1.98). CONCLUSIONS: In AxSpA/PsA patients requiring pain relief, awareness of lifestyle, sociodemographic and prescribing characteristics associated with higher risk of long-term opioid use can prompt timely interventions such as structured medication reviews and smoking cessation to promote safer prescribing and better patient outcomes.

Simulation model to assess the validity of the clinical portfolio diet score used in the PortfolioDiet.app for dietary self-tracking: a secondary analysis of a randomized controlled trial in hyperlipidemic adults.

Introduction: The Portfolio Diet combines cholesterol-lowering plant foods for the management of cardiovascular disease risk. However, the translation of this dietary approach into clinical practice necessitates a user-friendly method for patients to autonomously monitor their adherence. Objective: This study aimed to develop and validate the clinical-Portfolio Diet Score (c-PDS) as a food-based metric to facilitate self-tracking of the Portfolio Diet. Methods: Using a simulation model to estimate the c-PDS, the validity was assessed in a secondary analysis of a completed trial of the Portfolio Diet in 98 participants with hyperlipidemia over 6 months. Concurrent and predictive validity of the estimated c-PDS were assessed against the reference measure (weighed 7-day diet records) and concomitant changes in LDL-C from baseline to 6 months. Bland-Altman analysis was used to assess the limits of agreement between the two methods. Results: The c-PDS was positively correlated with dietary adherence as measured using the 7-day diet records (r = 0.94, p < 0.001). The c-PDS was negatively correlated with change in LDL-C (r = -0.43, p < 0.001) with a 1-point increase in the c-PDS being associated with a - 0.04 mmol/L (CI:-0.06,-0.03; p < 0.001) or a 1.09% reduction in LDL-C. Visual evaluation of the Bland-Altman plots showed reasonable agreement. Conclusion: These findings indicate good validity of the c-PDS for primary prevention in adults with hyperlipidemia. The predictive validity findings have informed the goals and messaging within the PortfolioDiet.app, a digital health application for delivering the Portfolio Diet. Future research will assess the effectiveness of the intended combination of the c-PDS and the PortfolioDiet.app in supporting behavior change.

Intranasal Linguatula serrata (tongue worm) in canids and vulpids can be detected using computed tomography.

Linguatula serrata ("tongue worm") is a zoonotic intranasal parasite found globally in wild dogs, free-ranging dogs, some domestic dogs, and vulpids. Since there are no sensitive tests currently available, infections are underdiagnosed. This is a pilot observational prospective study aimed at determining whether nasal linguatulosis can be diagnosed using CT. The secondary aims were to evaluate radiography, rhinoscopy, and nasal egg swabs as methods in the diagnosis of tongue worms. Fifty-four wild canids and three vulpids euthanased by gunshot were sourced from pest-control officers. Cadaver heads were subjected to helical CT examination, nasal-swabbed for tongue worm eggs, and necropsied. Radiographs and rhinoscopy were performed on cadavers suspected to be infected based on preliminary CT examination. Tongue worms were retrieved at necropsy in 25 dogs and one fox. CT findings in animals with no nasal cavity ballistic damage were reviewed in six infected dogs and one infected fox. Adult female tongue worms were identified in 4 of 6 dogs and 1 of 1 fox as long, tubular, slightly heterogeneously attenuating structures in the mid to caudal nasal cavities. They were not clearly visible in CT scans when surrounded by nasal fluid, and small parasites (male and immature females) were not discernible. Radiographic findings were mild and nonspecific. One tongue worm was detected in 1 of 12 dogs examined rhinoscopically. Tongue worm eggs were found in swabs from 7 of 25 dogs. While small tongue worms could not be detected with CT, CT proved to be a useful diagnostic method for visualizing adult female tongue worms.

Tuning N-heterocyclic carbene wingtips to form electrochemically stable adlayers on metals.

Self-assembled monolayers (SAMs) are employed in electrochemical biosensors to passivate and functionalize electrode surfaces. These monolayers prevent the occurrence of undesired electrochemical reactions and act as scaffolds for coupling bioaffinity reagents. Thiols are the most common adlayer used for this application; however, the thiol-gold bond is susceptible to competitive displacement by naturally occurring solvated thiols in biological fluids, as well as to desorption under continuous voltage interrogation. To overcome these issues, N-heterocyclic carbene (NHC) monolayers have been proposed as an alternative for electrochemical biosensor applications due to the strong carbon-gold bond. To maximize the effectiveness of NHCs for SAMs, a thorough understanding of both the steric effects of wingtip substituents and NHC precursor type to the passivation of electrode surfaces is required. In this study, five different NHC wingtips as well as two kinds of NHC precursors were evaluated. The best performing NHC adlayers can be cycled continuously for four days (over 30 000 voltammetric cycles) without appreciably desorbing from the electrode surface. Benchmark thiol monolayers, in contrast, rapidly desorb after only twelve hours. Investigations also show NHC adlayer formation on other biosensor-relevant electrodes such as platinum and palladium.

Chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary hypertension is a complication of pulmonary embolism and a treatable cause of pulmonary hypertension. The pathology is a unique combination of mechanical obstruction due to failure of clot resolution, and a variable degree of microvascular disease, that both contribute to pulmonary vascular resistance. Accordingly, multiple treatments have been developed to target the disease components. However, accurate diagnosis is often delayed. Evaluation includes high-quality imaging modalities, necessary for disease confirmation and for appropriate treatment planning. All patients with chronic thromboembolic pulmonary disease, and especially those with pulmonary hypertension, should be referred to expert centres for multidisciplinary team decision on treatment. The first decision remains assessment of operability, and the best improvement in symptoms and survival is achieved by the mechanical therapies, pulmonary endarterectomy and balloon pulmonary angioplasty. With the advances in multimodal therapies, excellent outcomes can be achieved with 3-year survival of >90%.

Adherence to a Cholesterol-Lowering Diet and the Risk of Pancreatic Cancer: A Case-Control Study.

BACKGROUND: Pancreatic cancer risk has been associated with increased serum cholesterol level, which is in turn partially influenced by diet. This study aimed at evaluating the association between pancreatic cancer risk and the adherence to a plant-based cholesterol-lowering diet. METHODS: Data were derived from an Italian case-control study including 258 pancreatic cancer patients and 551 controls. The cholesterol-lowering diet score was based on seven components: high intakes of (i) non-cellulosic polysaccharides (a proxy of viscous fibers), (ii) monounsaturated fatty acids, (iii) legumes, and (iv) seeds/corn oils (a proxy of phytosterols); and low intakes of (v) saturated fatty acids, (vi) dietary cholesterol, and (vii) food with a high glycemic index. The score was calculated adding one point for each fulfilled component, thus ranging from zero (no adherence) to seven (complete adherence). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated through the logistic regression model. RESULTS: Scores 5-7 were associated with reduced cancer risk (OR = 0.30; 95% CI: 0.18-0.52) compared to scores 0-2. CONCLUSIONS: Adherence to a plant-based cholesterol-lowering diet was associated with a reduced risk of pancreatic cancer.

Introducing the UK Antimicrobial Registry (UKAR) study: providing real world data on new antimicrobials to support antimicrobial stewardship and tackle antimicrobial resistance.

The UK Antimicrobial Registry (UKAR) has been developed to capture data on real world usage of antimicrobial agents with an initial focus on those used to treat drug-resistant infections. Several industry partners have committed support for the study, which is included in the National Institute for Health and Care Research (NIHR) portfolio in England with similar arrangements in the three devolved UK nations. The two antimicrobials in the National Institute for Health and Care Excellence (NICE) subscription model pilot (cefiderocol and ceftazidime/avibactam) are included in the UKAR and future expansion of work in this area is planned. This model decouples payment from usage by using a fixed annual fee. The study will provide information on the characteristics of patients receiving study drugs, the infections being treated, treatment effectiveness and adverse events. UKAR potentially provides a novel resource of enduring value to support healthcare in the UK and more widely and contribute to AMR National Action Plan goals for optimal use of antimicrobials.

Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data.

BACKGROUND: Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. METHODS: 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. RESULTS: Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p < 0.001). Phenogroup membership significantly improved survival prediction compared to conventional factors. Phenogroups were not predictive of hospitalisation for HF. CONCLUSIONS: Applying unsupervised machine learning to routinely collected electronic health record data identified phenogroups with distinct clinical characteristics and unique survival profiles.

Ground-Based Pyrethroid Adulticides Reduce Mosquitoes But Not Nontarget Insects in Central Florida.

As stewards of public and environmental health, mosquito control agencies are rightfully concerned about impacts on nontarget organisms. This study examined the impact of a modern, pyrethroid based ground adulticide program using ultra-low volume applications in a metropolitan county in central Florida. Nontarget insects and mosquitoes were collected in a before-after control-impact design at 21 sites over 1.5 years. While mosquitoes were reduced, we found no evidence for reduction of nontarget insects, regardless of taxon. Night-flying Lepidoptera may experience greater risk than other nontarget taxa, but overall effects of adulticide missions on this group were low and inconsistent. Instead, meteorology, habitat, and phenology dominate patterns of nontarget abundance. Mosquito reduction was more clearly observed and corrected post-mission reduction was consistent with results expected in complex urban and suburban treatment zones.

Nanotubes of a Different Kind: Stoichiometry and Geometry of the Orange II/γ-Cyclodextrin Complex in Water.

Orange II (O-II), a water-soluble ionic azo dye, aggregates and eventually forms needle-like crystals at concentrations greater than 0.15 M. However, when equimolar amounts of γ-cyclodextrin (γ-CD) are added to solutions containing O-II at 0.025 M or higher, the solution's appearance rapidly changes presenting a viscous, birefringent liquid, a lyotropic liquid crystalline solution. Birefringence is absent when viewing aqueous solutions of only O-II or γ-CD at concentrations greater than 0.03 M. Using ultraviolet-visible (UV-vis) and fluorescence spectroscopy, coupled with conductivity measurements, we postulate a structure for the basic "building block" of the self-assembly that eventually gives rise to a rodlike superstructure, leading to the formation of a lyotropic liquid crystalline phase.