Constructing Turing complete Euler flows in dimension 3.

Can every physical system simulate any Turing machine? This is a classical problem that is intimately connected with the undecidability of certain physical phenomena. Concerning fluid flows, Moore [C. Moore, Nonlinearity 4, 199 (1991)] asked if hydrodynamics is capable of performing computations. More recently, Tao launched a program based on the Turing completeness of the Euler equations to address the blow-up problem in the Navier-Stokes equations. In this direction, the undecidability of some physical systems has been studied in recent years, from the quantum gap problem to quantum-field theories. To the best of our knowledge, the existence of undecidable particle paths of three-dimensional fluid flows has remained an elusive open problem since Moore's works in the early 1990s. In this article, we construct a Turing complete stationary Euler flow on a Riemannian [Formula: see text] and speculate on its implications concerning Tao's approach to the blow-up problem in the Navier-Stokes equations.

Maintaining the Region of the Americas free of polio: best practices for incident management support teams.

The Pan American Health Organization (PAHO) and its Member States have been leading the efforts to eradicate wild poliovirus in the Region of Americas since smallpox's successful elimination in 1971. The region became the first to be certified free of wild poliovirus in 1994. However, in July 2022, an unvaccinated patient with no recent travel history was diagnosed with poliomyelitis in the United States of America. In response to the emergence of a circulating vaccine-derived poliovirus in the United States, PAHO established the Polio Incident Management Support Team. This team has been coordinating response efforts, focusing on: coordination, planning, and monitoring; risk communication and community engagement; surveillance and case investigation; vaccination; and rapid response. In this paper, we identified and documented best practices observed following establishment of the Incident Management Support Team (September 2022-2023) through a comprehensive review and analysis of various data sources and country-specific data from the polio surveillance dashboard. The aim was to share these best practices, highlighting technical support and implementation of polio measures by Member States. Despite several challenges, the Americas region remains polio-free. Polio risk is declining, with a July 2023 assessment showing fewer countries at medium, high, and very high risk. This progress reflects improved immunization coverage, surveillance, containment, health determinants, and outbreak preparedness and response. The PAHO Polio Incident Management Support Team has played a key role in supporting these efforts.

La Organización Panamericana de la Salud (OPS) y sus Estados Miembros han liderado los esfuerzos para erradicar el poliovirus salvaje en la Región de las Américas desde la eliminación exitosa de la viruela en 1971. En 1994, la Región fue la primera en obtener la certificación de libre del poliovirus salvaje. Sin embargo, en julio del 2022, se diagnosticó poliomielitis a un paciente de Estados Unidos de América no vacunado y sin antecedentes de viajes recientes. Para responder a la aparición de un poliovirus circulante derivado de la vacuna en ese país, la OPS creó el equipo de apoyo a la gestión de incidentes de poliomielitis. Este equipo ha asumido la coordinación de los esfuerzos de respuesta y se ha centrado en la coordinación, la planificación y seguimiento; la comunicación de riesgos y la participación de la comunidad; la vigilancia e investigación de casos; la vacunación; y la respuesta rápida. En este artículo, se determinan y documentan las mejores prácticas observadas después de la creación del equipo de apoyo a la gestión de incidentes (septiembre del 2022-2023) mediante una revisión y un análisis pormenorizados de datos procedentes de diversas fuentes y de datos específicos de los países del panel de vigilancia de la poliomielitis. El objetivo fue poner en común estas mejores prácticas y resaltar el apoyo técnico y la aplicación de medidas contra la poliomielitis por parte de los Estados Miembros. A pesar de los diversos desafíos, la Región de las Américas se mantiene libre de poliomielitis. El riesgo de esta enfermedad es cada vez menor, y la evaluación de julio del 2023 muestra una disminución del número de países con un riesgo medio, alto o muy alto. Este progreso refleja la mejora de la cobertura de inmunización, la vigilancia, la contención, los determinantes de la salud y la preparación y respuesta ante brotes. El equipo de apoyo a la gestión de incidentes relacionados con la poliomielitis de la OPS ha desempeñado un papel fundamental para brindar apoyo a estas iniciativas.

Desde a eliminação bem-sucedida da varíola em 1971, a Organização Pan-Americana da Saúde (OPAS) e seus Estados Membros têm estado à frente de iniciativas para erradicar o poliovírus selvagem na Região das Américas. Em 1994, a região foi a primeira do mundo a ser certificada como livre do poliovírus selvagem. Entretanto, em julho de 2022, um paciente não vacinado e sem histórico de viagens recentes foi diagnosticado com poliomielite nos Estados Unidos da América. Em resposta ao surgimento de um poliovírus derivado de vacina circulante nos Estados Unidos, a OPAS criou a Equipe de Apoio à Gestão de Incidentes de Poliomielite. A equipe vem administrando os esforços de resposta, concentrando-se em: coordenação, planejamento e monitoramento; comunicação de risco e envolvimento da comunidade; vigilância e investigação de casos; vacinação; e resposta rápida. Neste documento, identificamos e documentamos as melhores práticas observadas após a criação da Equipe de Apoio à Gestão de Incidentes (setembro de 2022 a 2023) por meio de uma revisão e análise abrangentes de diversas fontes de dados e dados específicos de cada país fornecidos por meio do painel de vigilância da poliomielite. O objetivo foi compartilhar essas melhores práticas, destacando o apoio técnico e a implementação de medidas contra a poliomielite pelos Estados Membros. Apesar de vários desafios, a Região das Américas continua livre da poliomielite. Um levantamento de julho de 2023 demonstrou que o risco da poliomielite vem diminuindo, com menos países com risco médio, alto ou muito alto. Essa evolução é resultado de melhoras na cobertura vacinal, vigilância, contenção, preparação, determinantes de saúde e resposta a surtos. A Equipe de Apoio à Gestão de Incidentes de Poliomielite da OPAS foi fundamental para apoiar esses esforços.

Analysis of prognostic factors of failure in perineal urethrostomy.

PURPOSE: To identify prognostic factors of failure in patients undergoing perineal urethrostomy (PU) with Blandy technique, with inverted U-shaped perineal flap. METHODS: This is a retrospective study of PU of non-oncological causes (2001-2017). Data of age, BMI, history of diabetes mellitus, etiology of urethral stricture, type of stricture, previous surgeries, dilatation and suprapubic catheter were collected. Failure was defined as the need for any instrumentation after surgery. Variables were analyzed by Cox regression and Kaplan-Meier curves were used for survival analysis. RESULTS: A total of 115 PU were performed. Median age was 61 years (IQR 53-68) and BMI 27.9 (IQR 25-30.9). The most frequent etiologies were: lichen sclerosus (30.4%), iatrogenic (27%), and idiopathic (25.7%). 62.6% had panurethral stricture. There were no complications in 73%. Clavien I complications occurred in 25.2%, Clavien II in 0.9% and Clavien IVa in 0.9%. The overall success rate was 51.3% with a median follow-up of 71 months. In the last 8 years, it was 75%. In the multivariate analysis, we found that age (p = 0.01), BMI (p = 0.01), date of surgery (p = 0.01), and suprapubic catheter (p = 0.003) were predictive variables. The voiding satisfaction rate was 88.7%. CONCLUSIONS: PU with Blandy technique is a surgery with low morbidity. During the entire study period, it had a failure rate of 48.7% but the failure rate decreased to 25% over the last 8 years. Age, BMI, date of surgery and suprapubic catheter are the most important prognostic factor of failure.

Impact of diabetes in patients waiting for invasive cardiac procedures during COVID-19 pandemic.

BACKGROUND: During COVID-19 pandemic, elective invasive cardiac procedures (ICP) have been frequently cancelled or postponed. Consequences may be more evident in patients with diabetes. OBJECTIVES: The objective was to identify the peculiarities of patients with DM among those in whom ICP were cancelled or postponed due to the COVID-19 pandemic, as well as to identify subgroups in which the influence of DM has higher impact on the clinical outcome. METHODS: We included 2,158 patients in whom an elective ICP was cancelled or postponed during COVID-19 pandemic in 37 hospitals in Spain. Among them, 700 (32.4%) were diabetics. Patients with and without diabetes were compared. RESULTS: Patients with diabetes were older and had a higher prevalence of other cardiovascular risk factors, previous cardiovascular history and co-morbidities. Diabetics had a higher mortality (3.0% vs. 1.0%; p = 0.001) and cardiovascular mortality (1.9% vs. 0.4%; p = 0.001). Differences were especially important in patients with valvular heart disease (mortality 6.9% vs 1.7% [p < 0.001] and cardiovascular mortality 4.9% vs 0.9% [p = 0.002] in patients with and without diabetes, respectively). In the multivariable analysis, diabetes remained as an independent risk factor both for overall and cardiovascular mortality. No significant interaction was found with other clinical variables. CONCLUSION: Among patients in whom an elective invasive cardiac procedure is cancelled or postponed during COVID-19 pandemic, mortality and cardiovascular mortality is higher in patients with diabetes, irrespectively on other clinical conditions. These procedures should not be cancelled in patients with diabetes.

Consequences of canceling elective invasive cardiac procedures during Covid-19 outbreak.

BACKGROUND: During COVID-19 pandemic in Spain, elective procedures were canceled or postponed, mainly due to health care systems overwhelming. OBJECTIVE: The objective of this study was to evaluate the consequences of interrupting invasive procedures in patients with chronic cardiac diseases due to the COVID-19 outbreak in Spain. METHODS: The study population is comprised of 2,158 patients that were pending on elective cardiac invasive procedures in 37 hospitals in Spain on the 14th of March 2020, when a state of alarm and subsequent lockdown was declared in Spain due to the COVID-19 pandemic. These patients were followed-up until April 31th. RESULTS: Out of the 2,158 patients, 36 (1.7%) died. Mortality was significantly higher in patients pending on structural procedures (4.5% vs. 0.8%, respectively; p < .001), in those >80 year-old (5.1% vs. 0.7%, p < .001), and in presence of diabetes (2.7% vs. 0.9%, p = .001), hypertension (2.0% vs. 0.6%, p = .014), hypercholesterolemia (2.0% vs. 0.9%, p = .026) [Correction added on December 23, 2020, after first online publication: as per Dr. Moreno's request changes in p-values were made after original publication in Abstract.], chronic renal failure (6.0% vs. 1.2%, p < .001), NYHA > II (3.8% vs. 1.2%, p = .001), and CCS > II (4.2% vs. 1.4%, p = .013), whereas was it was significantly lower in smokers (0.5% vs. 1.9%, p = .013). Multivariable analysis identified age > 80, diabetes, renal failure and CCS > II as independent predictors for mortality. CONCLUSION: Mortality at 45 days during COVID-19 outbreak in patients with chronic cardiovascular diseases included in a waiting list due to cancellation of invasive elective procedures was 1.7%. Some clinical characteristics may be of help in patient selection for being promptly treated when similar situations happen in the future.

Helicity is the only integral invariant of volume-preserving transformations.

We prove that any regular integral invariant of volume-preserving transformations is equivalent to the helicity. Specifically, given a functional I defined on exact divergence-free vector fields of class C(1) on a compact 3-manifold that is associated with a well-behaved integral kernel, we prove that I is invariant under arbitrary volume-preserving diffeomorphisms if and only if it is a function of the helicity.

Bleeding Risk of Antithrombotic Treatment in Patients on Hemodialysis.

BACKGROUND: The risk-benefit of antithrombotic treatment (ATT) has not been established in patients on dialysis. Our objective was to determine the influence of ATT on the risk of hemorrhage in patients on hemodialysis. METHODS: We included patients who began dialysis between 2003 and 2007. We determined the rates of fatal bleeding or bleeding leading to hospitalization or transfusion. RESULTS: Two hundred twenty-one patients were included. Over the follow-up period (45.5 ± 34 months), there were 76 hemorrhages in 52 patients. There were 10 fatal bleedings. The annual incidence of patients presenting with hemorrhagia was 6.2%. Bleeding occurred in 5.2% of those being treated with aspirin, 7% with acenocumarol, 12.3% with clopidogrel, 15.2% with aspirin + clopidogrel, 45.9% with anticoagulants + antiplatelets, 49.6% with low-molecular-weight heparin, and 3.9% without ATT. On multivariate analysis, masculine gender [hazard ratio (HR): 2.421; 95% confidence interval (CI), 1.261-4.650; P = 0.003], treatment with dicumarins (HR: 2.406; 95% CI, 1.013-5.718; P = 0.047), treatment with clopidogrel (HR: 2.697; 95% CI, 1.440-5.051; P = 0.002), and treatment with low-molecular-weight heparin (HR: 21.463; 95% CI, 9.067-50.806; P = 0.001) were independent predictors of bleeding. CONCLUSIONS: ATT increases the risk of bleeding in patients on hemodialysis. The incidence of hemorrhage varies with the type of antithrombotics used.

Resection of the Intramural Portion of the Distal Ureter during Transurethral Resection of Bladder Tumors: Predictive Factors for Secondary Stenosis and Development of Upper Urinary Tract Recurrence.

PURPOSE: We analyzed the incidence of and predictive factors for ureteral stenosis and recurrent upper urinary tract urothelial carcinoma after resection of tumors located in the intramural portion of the distal ureter. MATERIALS AND METHODS: We retrospectively analyzed the records of 2,317 patients who underwent transurethral resection of bladder tumor for nonmuscle invasive bladder cancer, including 112 (4.83%) with tumors involving the intramural portion of the distal ureter. Multivariate Cox regression analysis was done to determine predictive factors for ureteral stenosis and recurrent urinary tract urothelial carcinoma. RESULTS: At a mean followup of 56 months 17 patients (15.2%) presented with recurrent upper urinary tract urothelial carcinoma and ureteral stenosis had developed in 13 (11.6%). On univariate analysis previous recurrences were associated with both events. On multivariate analysis tumor size 1.5 cm or greater (HR 4.521, p = 0.023) and T1 tumor stage (HR 8.525, p = 0.005) were independent predictive factors for stenosis. Stage T1 in the bladder (HR 7.253, p = 0.001) and carcinoma in situ in the intramural portion of the distal ureter (HR 6.850, p = 0.005) increased the risk of recurrent upper urinary tract urothelial carcinoma. The main study limitation was the lack of information on vesicoureteral reflux due to the retrospective design. CONCLUSIONS: Involvement of the intramural portion of the distal ureter is uncommon. In patients with nonmuscle invasive bladder cancer and involvement of the intramural portion of the distal ureter a stage T1 tumor and a tumor size 1.5 cm or greater are independent predictive factors for distal ureteral stenosis. Moreover, stage T1 and carcinoma in situ in the intramural portion of the distal ureter significantly increase the risk of recurrent upper urinary tract urothelial carcinoma. The urinary tract should be more closely followed in this patient subgroup.

Acute Renal Failure Secondary to Rhabdomyolysis as a Complication of Major Urological Surgery: The Experience of a High-Volume Urological Center.

OBJECTIVE: The aim of this study was to determine the incidence of acute renal failure secondary to rhabdomyolysis (ARFSR) as a complication of major urological surgery (MUS), as well as to describe the clinical characteristics and identify possible risk and protective factors. SUBJECTS AND METHODS: Cases of ARFSR due to MUS between January 1997 and August 2011 were identified using the institutional database. The incidence was estimated and the clinical characteristics were analyzed using simple scatterplot graphs to identify possible risk and protective factors. RESULTS: In this period, 14,337 MUS procedures were performed, in which 4 cases suffered from ARFSR (the incidence rate was 0.03%). The incidence rates after radical cystectomy and urethroplasty were 0.26% (3/1,175 cases) and 0.15% (1/651 cases), respectively. No case of rhabdomyolysis was reported among the patients who underwent other major surgical procedures. Two patients required dialysis, and all 4 patients recovered to their baseline renal function at an average of 11 days (7-17) with the appropriate treatment. Male gender, younger age, lower ASA score, prolonged operative time, high body mass index, elevated preoperative serum creatinine and estimated blood loss were possible risk factors for developing ARFSR due to MUS. We found that a higher intraoperative administered volume was a possible protective factor. The operative position and type of surgery seemed to play minor roles. Early diagnosis and treatment possibly leads to an improved outcome. CONCLUSION: In our study, ARFSR due to MUS was a rare entity and had a good prognosis. It was more frequent as a complication of radical cystectomy. Further studies are required to confirm our findings.

Sudden death in incident dialysis patients.

BACKGROUND: Sudden death (SD) constitutes one of the principal causes of death and is an important problem in healthcare provision. Cardiovascular diseases have a high prevalence in dialysis patients and constitute the principal cause of death. We sought to analyze retrospectively the incidence of SD in patients commencing dialysis and the factors related to its presence. METHODS: We evaluated all the patients who began dialysis in our center between 1/11/2003 and 15/9/2007, and who were followed up until death, transplant, or study completion on 31/12/2012. We determined the presence of SD according to the following criteria: SD at 24 h (SD 24H): unexpected death occurring in the 24 h following the start of symptoms, or when the patient was found dead and had been seen alive 24 h earlier; SD at 1 h (SD 1H): death witnessed as occurring in the first hour following the start of symptoms. RESULTS: We evaluated 285 patients, mean age 65.67 ± 15.7 years. In a follow-up of 39.9 ± 34.2 months (947.6 patient-years of follow-up) 168 died (59%), 28 (10%) patients presented SD 24H (2.9/100 patient-years), and 16 (6%) patients presented SD 1H (1.7/100 patient-years). In the multivariate analysis, having had a myocardial infarction or having had electrocardiographic abnormalities (Q wave, negative T wave, subendocardial lesion or QRS >120 ms) were the principal independent predictors of SD 24H (OR 7.83; 95% CI 2.20-27.86; p = 0.001) and of SD 1H (OR 13.43; 95% CI 1.56-115.42; p = 0.018). CONCLUSIONS: SD on dialysis is very frequent. Two groups can be identified easily, with risk profiles clearly differentiated.

Establishing priorities to strengthen National Immunization Technical Advisory Groups in Latin America and the Caribbean.

Following the COVID-19 pandemic, the Americas faced a significant decline in vaccination coverage as well as increased vaccine hesitancy. The objective of this paper is to summarize the challenges and opportunities outlined by the National Immunization Technical Advisory Groups (NITAGs) in Latin America and the Caribbean (LAC) and prioritize targeted interventions. The exploratory survey included open-ended questions on two primary components: challenges, and opportunities. Free-text comments presented by each NITAG were collated and classified using indicators and sub-indicators of the NITAG Maturity Assessment Tool (NMAT). Opportunities were classified thematically, and priority actions were generated from the responses. All 21 NITAGs in LAC, representing 40 countries, 76 % of which have been active for over a decade, responded to the survey. The most common challenges were establishment and composition (62 %), integration into policymaking (62 %), resources and secretariat (52 %), and stakeholder recognition (48 %). The distribution of responses was seen across the whole sample and did not suggest a more pronounced need in relation to year of establishment. Opportunities included maximizing the Regional NITAG Network of the Americas (RNA) to facilitate collaboration, information sharing, visibility, and communication; existing global, regional, and systemic analyses; the World Health Organization/Pan American Health Organization (WHO/PAHO) templates for standard operating procedures; twinning programs with mature NITAGs; and NITAGs in governance structures. Action plans were outlined to formalize the establishment of NITAGs and broaden their composition; strengthen decision-making and access to data resources; and enhance the credibility of evidence-based recommendations and their uptake by policymakers and the public. NITAG challenges are not unique to LAC. NITAGs have outlined a short-term prioritized action plan which is critical to enhancing NITAG value and importance in countries.

Tying knots in light fields.

We construct analytically, a new family of null solutions to Maxwell's equations in free space whose field lines encode all torus knots and links. The evolution of these null fields, analogous to a compressible flow along the Poynting vector that is shear free, preserves the topology of the knots and links. Our approach combines the construction of null fields with complex polynomials on S3. We examine and illustrate the geometry and evolution of the solutions, making manifest the structure of nested knotted tori filled by the field lines.

Seasonal influenza vaccination in the Americas: Progress and challenges during the COVID-19 pandemic.

BACKGROUND: Vaccination is one of the most effective measures to prevent influenza illness and its complications; influenza vaccination remained important during the COVID-19 pandemic to prevent additional burden on health systems strained by COVID-19 demand. OBJECTIVES: We describe policies, coverage, and progress of seasonal influenza vaccination programs in the Americas during 2019-2021 and discuss challenges in monitoring and maintaining influenza vaccination coverage among target groups during the COVID-19 pandemic. METHODS: We used data on influenza vaccination policies and vaccination coverage reported by countries/territories via the electronic Joint Reporting Form on Immunization (eJRF) for 2019-2021. We also summarized country vaccination strategies shared with PAHO. RESULTS: As of 2021, 39 (89 %) out of 44 reporting countries/territories in the Americas had policies for seasonal influenza vaccination. Countries/territories adapted health services and immunization delivery strategies using innovative approaches, such as new vaccination sites and expanded schedules, to ensure continuation of influenza vaccination during the COVID-19 pandemic. However, among countries/territories that reported data to eJRF in both 2019 and 2021, median coverage decreased; the percentage point decrease was 21 % (IQR = 0-38 %; n = 13) for healthcare workers, 10 % (IQR = -1.5-38 %; n = 12) for older adults, 21 % (IQR = 5-31 %; n = 13) for pregnant women, 13 % (IQR = 4.8-20.8 %; n = 8) for persons with chronic diseases, and 9 % (IQR = 3-27 %; n = 15) for children. CONCLUSIONS: Countries/territories in the Americas successfully adapted influenza vaccination delivery to continue vaccination services during the COVID-19 pandemic; however, reported influenza vaccination coverage decreased from 2019 to 2021. Reversing declines in vaccination will necessitate strategic approaches that prioritize sustainable vaccination programs across the life course. Efforts should be made to improve the completeness and quality of administrative coverage data. Lessons learned from COVID-19 vaccination, such as the rapid development of electronic vaccination registries and digital certificates, might facilitate advances in coverage estimation.

Effectiveness of COVID-19 vaccines against hospitalisation in Latin America during three pandemic waves, 2021-2022: a test-negative case-control design.

Background: Vaccine effectiveness (VE) is essential to monitor the performance of vaccines and generate strategic information to guide decision making. We pooled data from six Latin American countries to estimate the effectiveness of COVID-19 vaccines in preventing laboratory-confirmed SARS-CoV-2 hospitalisation during three different pandemic waves from February 2021 to September 2022. Methods: We used a test-negative case-control design in hospitalised adults in Chile, Costa Rica, Ecuador, Guatemala, Paraguay, and Uruguay. We estimated adjusted VE by age group (18-64 and ≥65 years), vaccine type and product for primary series vaccination and booster vaccination and by time since last dose during the Omicron variant dominant period. We used mixed effects logistic regression models adjusting for sex, age, week of onset of symptom onset and pre-existing conditions with country fit as a random effect term. Findings: We included 15,241 severe acute respiratory infection (SARI) patients in the analysis. Among adults 18-64 years, VE estimates for primary series vaccination during pre-Delta and Delta periods ranged by product from 66.5% to 95.1% and from 33.5% to 88.2% for older adults. During the Omicron period, VE estimates for primary series were lower and decreased by time since last vaccination, but VE increased to between 26.4% and 57.4% when a booster was administered. Interpretation: mRNA and viral vector vaccines presented higher VE for both primary series and booster. While VE decreased over time, protection against severe COVID-19-associated hospitalisation increased when booster doses were administered. Vaccination with additional doses should be recommended, particularly for persons at increased risk of developing severe COVID-19. Funding: This work was supported by a grant from the U.S. Centers for Disease Control and Prevention (CDC) through cooperative agreements with the Pan American Health Organization/World Health Organization.

End-of-season influenza vaccine effectiveness during the Southern Hemisphere 2022 influenza season - Chile, Paraguay, and Uruguay.

OBJECTIVES: This study estimated the 2022 end-of-season influenza vaccine effectiveness (VE) against severe acute respiratory illness (SARI) hospitalization in Chile, Paraguay, and Uruguay. METHODS: We pooled surveillance data from SARI cases in 18 sentinel surveillance hospitals in Chile (n = 9), Paraguay (n = 2), and Uruguay (n = 7) from March 16-November 30, 2022. VE was estimated using a test-negative design and logistic regression models adjusted for country, age, sex, presence of ≥1 comorbidity, and week of illness onset. VE estimates were stratified by influenza virus type and subtype (when available) and influenza vaccine target population, categorized as children, individuals with comorbidities, and older adults, defined per countries' national immunization policies. RESULTS: Among the 3147 SARI cases, there were 382 (12.1%) influenza test-positive case patients; 328 (85.9%) influenza case patients were in Chile, 33 (8.6%) were in Paraguay, and 21 (5.5%) were in Uruguay. In all countries, the predominant subtype was influenza A(H3N2) (92.6% of influenza cases). Adjusted VE against any influenza-associated SARI hospitalization was 33.8% (95% confidence interval: 15.3%, 48.2%); VE against influenza A(H3N2)-associated SARI hospitalization was 30.4% (95% confidence interval: 10.1%, 46.0%). VE estimates were similar across target populations. CONCLUSION: During the 2022 influenza season, influenza vaccination reduced the odds of hospitalization among those vaccinated by one-third. Health officials should encourage influenza vaccination in accordance with national recommendations.

Computational identification of gene over-expression targets for metabolic engineering of taxadiene production.

Taxadiene is the first dedicated intermediate in the biosynthetic pathway of the anticancer compound Taxol. Recent studies have taken advantage of heterologous hosts to produce taxadiene and other isoprenoid compounds, and such ventures now offer research opportunities that take advantage of the engineering tools associated with the surrogate host. In this study, metabolic engineering was applied in the context of over-expression targets predicted to improve taxadiene production. Identified targets included genes both within and outside of the isoprenoid precursor pathway. These targets were then tested for experimental over-expression in a heterologous Escherichia coli host designed to support isoprenoid biosynthesis. Results confirmed the computationally predicted improvements and indicated a synergy between targets within the expected isoprenoid precursor pathway and those outside this pathway. The presented algorithm is broadly applicable to other host systems and/or product choices.

Analysis of heterologous taxadiene production in K- and B-derived Escherichia coli.

Taxa-4(5),11(12)-diene is the first dedicated intermediate in the metabolic pathway responsible for synthesizing the anticancer compound Taxol. In this study, the heterologous production of taxadiene was established in and analyzed between K- and B-derived Escherichia coli strains. First, recombinant parameters associated with precursor metabolism (the upstream methylerythritol phosphate (MEP) pathway) and taxadiene biosynthesis (the downstream pathway) were varied to probe the effect different promoters and cellular backgrounds have on taxadiene production. Specifically, upstream MEP pathway genes responsible for the taxadiene precursors, dimethylallyl diphosphate and isopentenyl diphosphate, were tested with an inducible T7 promoter system within K and B E. coli strains. Whereas, inducible T7, Trc, and T5 promoters were tested with the plasmid-borne geranylgeranyl diphosphate synthase and taxadiene synthase genes responsible for the downstream pathway. The K-derivative produced taxadiene roughly 2.5-fold higher than the B-derivative. A transcriptomics study revealed significant differences in pyruvate metabolism between the K and B strains, providing insight into the differences observed in taxadiene biosynthesis and targets for future metabolic engineering efforts. Next, the effect of temperature on cell growth and taxadiene production was analyzed in these two strains, revealing similar phenotypes between the two with 22°C as the optimal production temperature. Lastly, the effect of indole on cell growth was investigated between the two strains, showing that the K-derivative demonstrated greater growth inhibition compared to the B-derivative.