Time to review the role of surrogate endpoints in health policy: state of the art and the way forward

The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. However, market access and coverage decisions are often based on surrogate endpoints, biomarkers, or intermediate endpoints, which aim to substitute and predict patient-relevant outcomes that are unavailable due to methodological, financial, or practical constraints. We provide a summary of the current use of surrogate endpoints in healthcare policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policy makers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and healthcare systems

Caracterização da cadeia produtiva da carne ovina em Tauá (CE).

Resumo: O presente artigo apresenta a descrição analítica da cadeia produtiva da carne ovina no município de Tauá (CE). A ovinocultura de corte é uma atividade em fase de desenvolvimento e consolidação em diversos locais no Brasil, no entanto ainda enfrenta desafios que precisam ser superados. Dentre os principais entraves para a sua consolidação está a predominância da informalidade nas atividades de abate e de processamento dos ovinos. A caracterização da cadeia produtiva foi realizada por meio de aplicação de questionários junto a 336 produtores rurais criadores de ovinos no município e pela realização de entrevistas com roteiro semiestruturado com sete atravessadores e marchantes que atuam comprando e vendendo ovinos vivos e carne ovina no município. Foram mapeadas as transações realizadas pelos produtores rurais e os principais canais de comercialização por eles utilizados. Constatou-se que 16,7% dos produtores realizam o abate de ovinos com o intuito de comercializar a carne produzida, enquanto 83,3% costumam vender os ovinos vivos para os atravessadores ou para os marchantes. Os produtores rurais são responsáveis pelo abate de 9,9% dos ovinos produzidos e comercializados no município de Tauá, indicando que a maior parte dos abates não inspecionados é realizada por agentes localizados nos estágios pós-porteira da cadeia produtiva da ovinocultura de corte. [Characteristics of lamb meat production chain in Tauá (CE)]. Abstract: This paper presents an analytical description of the production chain of lamb meat in the municipality of Tauá (CE). The production of lamb meat is an activity under a development process and consolidation in several locations of Brazil, but still faces challenges that must be overcome. Among the main obstacles to their consolidation there is the prevalence of informality in the activities of lamb slaughtering. The characterization of the production chain was performed by applying questionnaires from 336 lamb farmers in the municipality, and conducting semi-structured interviews with seven butchers and middlemen that act buying and selling live lamb and lamb meat in the city. It were mapped the transactions carried out by the farmers and the main marketing channels used by them. It was found that 16.7% of producers perform the lamb slaughter on the farm in order to sell the produced meat, while 83.3% usually sell live for middlemen or for the butchers. The farmers are responsible for the slaughter of 9.9% lamb produced and marketed in the municipality of Tauá. This indicates that most of the non-inspected slaughters are performed by agents located in the off-farm stages of this production chain

The effectiveness of social group work remedial model with reality therapy approach on social adjustment of people improved from addiction

The current research aimed to study the effectiveness of social group work remedial model with reality therapy approach on social adjustment of people improved from addiction.The study to quasi-experimental method with pre-test and post-test design on two groups (control and intervention) with one-month follow-up. The statistical population of the study all participants in the self-help group Rahpooyan Rahaei Tehran Branch after the initial leave of abuse. Everyone were assessed in term of social adjustment. Then, 30 people whose social adjustment score was lower than other people in this group and had the criteria to be studied, were randomly divided into two equal groups of control (n = 15) and experimental (n = 15). The experimental group was education in 8 sessions of reality therapy intervention according to the remedial model of social group work. During this period, the control group did not receive any intervention. After completing all sessions and complete training, post-test (Wiseman and Pickel social adjustment questionnaire) was performed on two groups. Descriptive and inferential statistics (analysis of covariance) were used to analyze the data.The results showed that there was a significant difference between intervention and control groups regarding the social adjustment and its dimensions. The scores were increased in intervention group after intervention and in follow-up.In conclusion, social group work remedial model with reality therapy approach has a significant positive effect on social adjustment of improved from addiction.Keywords: social adjustment, improved from addiction, reality therapy approach, social group work remedial mode

Coupled Growth and Division of Model Protocell Membranes

The generation of synthetic forms of cellular life requires solutions to the problem of how biological processes such as cyclic growth and division could emerge from purely physical and chemical systems. Small unilamellar fatty acid vesicles grow when fed with fatty acid micelles and can be forced to divide by extrusion, but this artificial division process results in significant loss of protocell contents during each division cycle. Here we describe a simple and efficient pathway for model protocell membrane growth and division. The growth of large multilamellar fatty acid vesicles fed with fatty acid micelles, in a solution where solute permeation across the membranes is slow, results in the transformation of initially spherical vesicles into long thread-like vesicles, a process driven by the transient imbalance between surface area and volume growth. Modest shear forces are then sufficient to cause the thread-like vesicles to divide into multiple daughter vesicles without loss of internal contents. In an environment of gentle shear, protocell growth and division are thus coupled processes. We show that model protocells can proceed through multiple cycles of reproduction. Encapsulated RNA molecules, representing a primitive genome, are distributed to the daughter vesicles. Our observations bring us closer to the laboratory synthesis of a complete protocell consisting of a self-replicating genome and a self-replicating membrane compartment. In addition, the robustness and simplicity of this pathway suggests that similar processes might have occurred under the prebiotic conditions of the early Earth.Exobiology Program (U.S.) (Grant EXB02- 0031-0018)United States. National Aeronautics and Space Administration (Exobiology Program) (Grant EXB02-0031-0018)Howard Hughes Medical Institute (Investigator

A functional calcium-transporting ATPase encoded by chlorella viruses

Calcium-transporting ATPases (Ca2+ pumps) are major players in maintaining calcium homeostasis in the cell and have been detected in all cellular organisms. Here, we report the identification of two putative Ca2+ pumps, M535L and C785L, encoded by chlorella viruses MT325 and AR158, respectively, and the functional characterization of M535L. Phylogenetic and sequence analyses place the viral proteins in group IIB of P-type ATPases even though they lack a typical feature of this class, a calmodulin-binding domain. A Ca2+ pump gene is present in 45 of 47 viruses tested and is transcribed during virus infection. Complementation analysis of the triple yeast mutant K616 confirmed that M535L transports calcium ions and, unusually for group IIB pumps, also manganese ions. In vitro assays show basal ATPase activity. This activity is inhibited by vanadate, but, unlike that of other Ca2+ pumps, is not significantly stimulated by either calcium or manganese. The enzyme forms a 32P-phosphorylated intermediate, which is inhibited by vanadate and not stimulated by the transported substrate Ca2+, thus confirming the peculiar properties of this viral pump. To our knowledge this is the first report of a functional P-type Ca2+-transporting ATPase encoded by a virus

Development of a digital research assistant for the management of patients\u2019 enrollment in oncology clinical trials within a research hospital

Clinical trials in cancer treatment are imperative in enhancing patients\u2019 survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients\u2019 accrual in clinical trials. We developed a specific platform, called \u201cDigital Research Assistant\u201d (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients\u2019 records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients\u2019 records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient\u2019s data and clinical trial\u2019s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis