Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications

Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa – 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios “bioidênticos” “manipulados”, e a ‘modulação hormonal’ não são recomendados pela falta de evidência científica de sua eficácia e segurança

Updated cardiovascular prevention guideline of the Brazilian Society of Cardiology: 2019

Sem informação113478788

Enhanced Data Return from Lunar Farside using RF-Optical TT and C

Science return and high bandwidth communications are key issues to support the foreseen endeavours on spaceflights to the Moon and beyond. For a given mass, power consumption and volume, laser communications can offer an increase in TM bandwidth over classical RF technology allowing for a variety of new options, specifically to missions that require very large distances, such as to the Moon and even beyond. This increase in TM data rate allows for more raw scientific data to be sent back to Earth where data processing can be performed on ground. Enhanced sensing techniques could be used that generate more science data and access during flight could be faster. This paper presents an overview of proof of concept test results obtained for optical telemetry return in a field test campaign together with ESA in October 2007. Based on the results obtained, a sample mission is outlined that shows an optical relay on a HALO trajectory at lunar farside, using an integrated RF-optical TT&C transponder concept

Metapopulation and network models for plant and human infections

Plant pests and diseases infiltrate countries via international trade. Domestic trade moves the pest far beyond the point of entry, making eradication efforts challenging. Understanding the risks and control strategies surrounding trade is vital in mitigating the damage from invasions. While attention has been given to the structure of the international trade network, little is known about the within-UK network structure due to unregistered plant movement and limited data availability. We address this gap by constructing a directed and weighted network, using sales data from four plant nurseries. We find that nurseries specialise sales towards one of the four customer groups (commercial, consumer, nursery, retailer). This allows us to group nodes into classes differing by sales patterns, with trade volumes and customer numbers highly variable within and between classes. Using centrality measures, we identify nodes at higher risk of transmitting pests or diseases. We find that edge weights significantly affect node centrality, emphasising the importance of trade volumes in similar network models. Node centrality is robust to small changes in market structure, and customers’ contribution to network structure is minimal. We extend our network model to a compartmental metapopulation Susceptible-Infected framework and investigate the effect of different seedings, compare inspection strategies and conduct a cost-benefit analysis. Our results demonstrate that disease spread faster when originating in a nursery that primarily sells to other nurseries. We find the utility of inspecting consignments depends on the frequency of inspecting nursery stock. Finally, we identify inspection efficacy regions when nurseries benefit from more frequent inspections, considering cost. From our analysis of network structure, trade, and disease dynamics, this research provides guidance for targeted surveillance, intervention, and control to mitigate the spread of plant pests and diseases. We further use network and metapopulation methods to model the spread of COVID-19 in care homes.Plant pests and diseases infiltrate countries via international trade. Domestic trade moves the pest far beyond the point of entry, making eradication efforts challenging. Understanding the risks and control strategies surrounding trade is vital in mitigating the damage from invasions. While attention has been given to the structure of the international trade network, little is known about the within-UK network structure due to unregistered plant movement and limited data availability. We address this gap by constructing a directed and weighted network, using sales data from four plant nurseries. We find that nurseries specialise sales towards one of the four customer groups (commercial, consumer, nursery, retailer). This allows us to group nodes into classes differing by sales patterns, with trade volumes and customer numbers highly variable within and between classes. Using centrality measures, we identify nodes at higher risk of transmitting pests or diseases. We find that edge weights significantly affect node centrality, emphasising the importance of trade volumes in similar network models. Node centrality is robust to small changes in market structure, and customers’ contribution to network structure is minimal. We extend our network model to a compartmental metapopulation Susceptible-Infected framework and investigate the effect of different seedings, compare inspection strategies and conduct a cost-benefit analysis. Our results demonstrate that disease spread faster when originating in a nursery that primarily sells to other nurseries. We find the utility of inspecting consignments depends on the frequency of inspecting nursery stock. Finally, we identify inspection efficacy regions when nurseries benefit from more frequent inspections, considering cost. From our analysis of network structure, trade, and disease dynamics, this research provides guidance for targeted surveillance, intervention, and control to mitigate the spread of plant pests and diseases. We further use network and metapopulation methods to model the spread of COVID-19 in care homes

The social courts system of the German Democratic Republic

The social courts of the German Democratic Republic consisted of disputes commissions (based at the workplace) and arbitration commissions (based in the community and in certain cooperatives). They had their origins partly in Soviet models of lay justice and partly in the old German institution of the Schiedsmann (arbitrator). They had advisory and conciliatory functions, but also heard a wide range of employment and disciplinary matters, minor civil disputes and petty crime. Hearings took place in public before elected lay judges ("members"), usually outside working hours. Proceedings were relatively informal and were conducted on inquisitorial rather than adversarial principles and without representation by lawyers. Orders could be made imposing "educational measures" which aimed to educate deviant individuals to socialist standards of behaviour. In addition, recommendations could be made for the elimination of the causes of conflict in society. Decisions (which could be enforced) were subject to appeal to the state courts at the instance of the parties or the procuracy. The social courts were an important manifestation of the communist organizational principle of "democratic centralism" whereby centrally planned aims were realized locally through elected agencies. Although described as "social" they were an integral part of the slate system of administration of justice. They aimed to build socialism by educating people to socialist principles, by attacking the root causes of lawlessness in society and by involving the people in dispensing justice as well as safeguarding individual rights. They disciplined rather than punished. They were abolished after unification with the Federal Republic of Germany in 1990 but were replaced by arbitration committees, a limited, if unsuccessful, continuation of the tradition that occurred only because of the lack of judges and legally qualified personnel in the East

Lord Bathurst’s Gift: The Genesis of the Golden Thread, being the Early History of Cross-Border Insolvency and the Theory of Universalism, with particular reference to the original Solomons v. Ross case papers of 1764

The genesis of the golden thread of modified universalism in cross-border insolvency cases has been said to be the seminal 1764 judgment of Lord Bathurst in Solomons v. Ross. From the highest courts in the land to the most authoritative commentators, it has become an axiom that the concept of reciprocity between national courts in insolvency matters traces its roots to the Court of Chancery hearing a dispute between a London trader, Ross, and an insolvent Dutch company’s representative, Solomons. Using primary source material from the National Archive this article challenges this proposition and argues that (1) Lord Mansfield’s earlier judgments in Raynard v. Chase (1756) and in Robinson v. Bland (1760) are in fact the genesis of the golden thread, and that (2) Lord Mansfield influenced the then Mr Justice Bathurst in coming to his decision in Solomons v. Ross (1763) either directly, or because of the approach adopted in Raynard v. Chase (1756) and Robinson v. Bland (1760)

The Suspension of Debt Obligations and Bankruptcy Laws during World War I and World War II: Lessons for Private Law during the Corona Pandemic from previous national crises

On 28 March 2020, the Insolvency Service announced the government was placing before Parliament what are presumed to be temporary reforms to the insolvency law to help companies through the current economic crisis caused by the corona pandemic. The reforms that have so far been highlighted are a moratorium on the ability to present or pursue winding-up petitions and the suspension of the law on wrongful trading. These emergency moves are not without precedent. This article examines a range of measures that were introduced during the First and Second World Wars that were designed to respond to the unusual circumstances caused by a global crisis. The effect of these measures, e.g. the Liabilities (War-Time Adjustment) Act 1941, was to postpone debtors’ liabilities but not to eliminate them. This article demonstrates that these measures went some way towards meeting their objective of saving small businesses from bankruptcy