Testosterone, signal coloration, and signal color perception in male zebra finch contests.

Many animals use assessment signals to resolve contests over limited resources while minimizing the costs of those contests. The carotenoid-based orange to red bills of male zebra finches (Taeniopygia guttata) are thought to function as assessment signals in male-male contests, but behavioral analyses relating contest behaviors and outcomes to bill coloration have yielded mixed results. We examined the relationship between bill color and contests while incorporating measurements of color perception and testosterone (T) production, for an integrative view of aggressive signal behavior, production, and perception. We assayed the T production capabilities of 12 males in response to a gonadotropin-releasing hormone (GnRH) challenge. We then quantified the initiation, escalation, and outcome of over 400 contests in the group, and measured bill color using calibrated photography. Finally, because signal perception can influence signal function, we tested how males perceive variation in bill coloration, asking if males exhibit categorical perception of bill color, as has been shown recently in female zebra finches. The data suggest that males with greater T production capabilities than their rivals were more likely to initiate contests against those rivals, while males with redder bills than their rivals were more likely to win contests. Males exhibited categorical color perception, but individual variation in the effect of categorical perception on color discrimination abilities did not predict any aspects of contest behavior or outcomes. Our results are consistent with the hypotheses that T plays a role in zebra finch contests and that bill coloration functions as an aggressive signal. We suggest future approaches, based on animal contest theory, for how links among signals, perception, and assessment can be tested.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Evaluating testosterone as a phenotypic integrator: From tissues to individuals to species.

Hormones have the potential to bring about rapid phenotypic change; however, they are highly conserved over millions of years of evolution. Here, we examine the evolution of hormone-mediated phenotypes, and the extent to which regulation is achieved via independence or integration of the many components of endocrine systems. We focus on the sex steroid testosterone (T), its cognate receptor (androgen receptor) and related endocrine components. We pose predictions about the mechanisms underlying phenotypic integration, including coordinated sensitivity to T within and among tissues and along the HPG axis. We then assess these predictions with case studies from wild birds, asking whether gene expression related to androgenic signaling naturally co-varies among individuals in ways that would promote phenotypic integration. Finally, we review how mechanisms of integration and independence vary over developmental or evolutionary time, and we find limited support for integration.

Measurement and validation of frailty as a predictor of outcomes in women undergoing major gynaecological surgery.

OBJECTIVE: Frailty is the loss of physical or mental reserve that impairs function, often in the absence of a defined comorbidity. Our aim was to determine whether a modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing hysterectomy. DESIGN: Retrospective cohort study. SETTING: Hospitals across the USA participating in the National Surgical Quality Improvement Program (NSQIP). SAMPLE: Patients who underwent hysterectomy from 2008 to 2012. METHODS: An mFI was calculated using 11 variables in NSQIP. The associations between mFI and morbidity and mortality were assessed. Model fit statistics (c-statistics) were utilised to evaluate the ability of mFI to distinguish outcomes. MAIN OUTCOME MEASURE: Wound infection, severe complications and mortality. RESULTS: A total of 66 105 patients were identified. Wound complications increased from 2.4% in patients with an mFI of zero to 4.8% in those with mFI ≥ 0.5 (P < 0.0001). Similarly, severe complications increased from 0.98% to 7.3% (P < 0.0001), overall complications rose from 3.7% to 14.5% (P < 0.0001) and mortality increased from 0.06% to 3.2% (P < 0.0001) for patients with a frailty index of zero compared with those with an index of ≥ 0.5. Versus chance, the goodness-of-fit c-statistics suggested that mFI increases the ability to detect wound complications by 11.4%, severe complications by 22.0% and overall complications by 11.0%. CONCLUSIONS: The mFI is easily reproducible from routinely collected clinical data and predictive of outcomes in patients undergoing hysterectomy. Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery. TWEETABLE ABSTRACT: Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery.

Transformações recentes da indústria farmacêutica: um exame da experiência mundial e brasileira no século XXI / Recent changes in the pharmaceutical industry: a survey of worldwide and Brazilian experience in the 21st century

O artigo discute as características e tendências da indústria farmacêutica mundial e brasileira no século XXI, suas transformações e tendências setoriais, e seus atores. Foram utilizadas a pesquisa qualitativa e a técnica de análise documental, que permitiram verificar que, no início do século XX, a indústria farmacêutica mundial apresentava estrutura homogênea e oferta reduzida de seus produtos. Após a Segunda Guerra Mundial, houve fortalecimento da produção de medicamentos baseados na síntese química e diversificação da oferta e demanda por medicamentos. O mercado farmacêutico passou da competição mais ampla para uma de caráter oligopólico. Nos anos 1990, o portfólio dessas indústrias ampliou-se para áreas de saúde animal, produtos de higiene/cuidado pessoal e de nutrição/dietética. Na década de 2000, a indústria farmacêutica mundial intensificou esse processo, e devido à expiração das patentes dos medicamentos, se concentrou no segmento dos genéricos, adquirindo empresas nos mercados emergentes. O setor farmacêutico brasileiro seguiu os moldes da indústria farmacêutica mundial e passou a investir na produção de medicamentos genéricos, fitoterápicos e no avanço dos biotecnológicos, com o apoio financeiro público do BNDES. Esse contexto continua a exigir avanços na inovação em saúde, e reclama da regulação sanitária o enfrentamento dos desafios advindos dessa grande transformação. Cabe destacar os desafios relativos aos custos dos medicamentos e de seus fortes impactos sobre os sistemas de saúde, em especial aqueles de caráter mais inclusivo...

This article discusses the characteristics and trends of the global and Brazilian pharmaceutical industry in the 21st century, its transformations and industry trends, and its actors. Qualitative research and the technique of document analysis allowed us to check that in early 20th century, the global pharmaceutical industry was characterized by homogeneous structure and reduced supply of products. After the Second World War, there was strengthening of the production of medicines based on chemical synthesis and diversification of supply and demand for drugs. The pharmaceutical market has shifted from broader competition for one of oligopolistic character. In the 1990s, these industries' portfolio expanded to areas of animal health, hygiene / personal care and nutrition / dietetics. In the 2000s, the global pharmaceutical industry intensified this process, and due to the expiration of patents on medicines, focused on the generic segment, acquiring companies in emerging markets. The Brazilian pharmaceutical industry followed the lines of the global pharmaceutical industry and started to invest in the production of generic medicines, herbal and advancement of biotechnology, with public financial support of the BNDES. This context continues to demand advances in health innovation, and demands of the health regulation to face the challenges arising from this great transformation. It is worth mentioning the challenges relating to costs of drugs and their strong impact on health systems, particularly those of more inclusive character...

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.

Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology.

Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of pre-eclampsia have yet to be fully elucidated. However, it is evident that this is a complex disorder involving multiple organ systems, and by using integrative approaches, enormous progress has been made towards understanding the pathophysiology of pre-eclampsia. Growing evidence supports the concept that the placenta plays a central role in the pathogenesis of pre-eclampsia and that reduced uteroplacental perfusion, which develops as a result of abnormal cytotrophoblast invasion of spiral arterioles, triggers the cascade of events leading to the maternal disorder. Placental ischaemia leads to release of soluble placental factors, many of which are classified as anti-angiogenic or pro-inflammatory. Once these ischaemic placental factors reach the maternal circulation, they cause widespread activation and dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin-1 and superoxide, increased vascular sensitivity to angiotensin II and decreased formation of vasodilators such as nitric oxide. This review highlights these links between placental ischaemia, maternal endothelial activation and renal dysfunction in the pathogenesis of hypertension in pre-eclampsia.

Dusty starburst galaxies in the early Universe as revealed by gravitational lensing.

In the past decade, our understanding of galaxy evolution has been revolutionized by the discovery that luminous, dusty starburst galaxies were 1,000 times more abundant in the early Universe than at present. It has, however, been difficult to measure the complete redshift distribution of these objects, especially at the highest redshifts (z > 4). Here we report a redshift survey at a wavelength of three millimetres, targeting carbon monoxide line emission from the star-forming molecular gas in the direction of extraordinarily bright millimetre-wave-selected sources. High-resolution imaging demonstrates that these sources are strongly gravitationally lensed by foreground galaxies. We detect spectral lines in 23 out of 26 sources and multiple lines in 12 of those 23 sources, from which we obtain robust, unambiguous redshifts. At least 10 of the sources are found to lie at z > 4, indicating that the fraction of dusty starburst galaxies at high redshifts is greater than previously thought. Models of lens geometries in the sample indicate that the background objects are ultra-luminous infrared galaxies, powered by extreme bursts of star formation.

Frequency multiplexed superconducting quantum interference device readout of large bolometer arrays for cosmic microwave background measurements.

A technological milestone for experiments employing transition edge sensor bolometers operating at sub-Kelvin temperature is the deployment of detector arrays with 100s-1000s of bolometers. One key technology for such arrays is readout multiplexing: the ability to read out many sensors simultaneously on the same set of wires. This paper describes a frequency-domain multiplexed readout system which has been developed for and deployed on the APEX-SZ and South Pole Telescope millimeter wavelength receivers. In this system, the detector array is divided into modules of seven detectors, and each bolometer within the module is biased with a unique ∼MHz sinusoidal carrier such that the individual bolometer signals are well separated in frequency space. The currents from all bolometers in a module are summed together and pre-amplified with superconducting quantum interference devices operating at 4 K. Room temperature electronics demodulate the carriers to recover the bolometer signals, which are digitized separately and stored to disk. This readout system contributes little noise relative to the detectors themselves, is remarkably insensitive to unwanted microphonic excitations, and provides a technology pathway to multiplexing larger numbers of sensors.

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies.

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

A regulação em saúde no Brasil: um breve exame das décadas de 1999 a 2008 / Health regulation in Brazil: a brief survey of the decade from 1999 to 2008

Este artigo discute a experiência brasileira de regulação em saúde no período de 1999 a 2008. Buscou-se compreender as interfaces do processo de regulação em saúde no Brasil, sobretudo com o setor farmacêutico, identificando, historicamente, os atores e contextos referentes a esse processo. A pesquisa baseou-se na revisão bibliográfica e no levantamento das resoluções da diretoria colegiada da Agência Nacional de Vigilância Sanitária. Esse levantamento permitiu identificar a concentração dessas resoluções nas subáreas: medicamentos, recursos humanos e alimentos. No tocante à subárea medicamentos, a concentração se deu em três descritores: registro de medicamentos, boas práticas e substâncias sujeitas a controle especial. Além de fazer uma síntese histórica da evolução da vigilância sanitária brasileira, o artigo focalizou os aspectos regulatórios da Agência Nacional de Vigilância Sanitária e sua relação com a indústria farmacêutica. Portanto, o texto pautou-se pela pretensão de dar resposta à seguinte questão: será que a experiência de regulação da Agência Nacional de Vigilância Sanitária está apta a enfrentar o cenário adverso gerado pela nova crise mundial, especialmente no que se refere ao setor farmacêutico? A principal conclusão do trabalho é de que, apesar dos muitos desafios a serem superados pela Agência Nacional de Vigilância Sanitária no Brasil contemporâneo, a experiência de regulação avançou bastante nesta década. Uma conclusão adicional é que esses avanços constituíram, para o setor farmacêutico, uma proteção face ao quadro adverso gerado pela crise mundial.

This paper discusses the Brazilian experience of health regulation from 1999 to 2008. It aims to understand the interfaces of the regulatory process in health in Brazil, particularly the pharmaceutical industry, seeking to identify, historically, the actors and contexts relating to the proceedings. The research was based on literature review and survey of the resolutions of the Board of the National Health Surveillance Agency. This survey identified the concentration of these resolutions in the following areas: drugs, human resources and food. Regarding drugs, emphasis was placed in three key words: drug registration, practices and substances subject to special control. In addition to a brief history of the evolution of Brazilian health surveillance, this paper focused on the regulatory aspects of the National Health Surveillance Agency and its relationship with the pharmaceutical industry. Therefore, the text was guided by the desire to answer the following question: is the experience of regulation of the National Health Surveillance Agency able to cope with the adverse scenario created by the world crisis, especially with regard to the pharmaceutical industry? The main conclusion of this study is that despite the many challenges to be overcome by the National Sanitary Surveillance Agency in Brazil today, the experience of regulation has made good progress in this decade. A further finding is that these developments were, for the pharmaceutical industry, a protection against the adverse situation created by the global crisis.

Cuidados de longa duração para idosos: um novo risco para os sistemas de seguridade social

Publicação nº 1371 da série 'Texto para Discussão' do IPEA. Analisa o processo de envelhecimento populacional e o surgimento da demanda por cuidados de longa duração no âmbito dos sistemas de seguridade social. Aborda a legislação de proteção aos idosos brasileiros e a situação dos idosos em termos socioeconômicos e familiares.

Cuidados de longa duração para idosos: um novo risco para os sistemas de seguridade social / Texto para Discussão (TD) 1371: Cuidados de longa duração para idosos: um novo risco para os sistemas de seguridade social

Analisa o processo de envelhecimento populacional e o surgimento da demanda por cuidados de longa duração no âmbito dos sistemas de seguridade social. Ressalta as experiências de três países desenvolvidos, com processos de envelhecimento já bastante avançados: Alemanha, Dinamarca e Estados Unidos. Aborda a legislação de proteção aos idosos brasileiros. Analisa a situação dos idosos, tanto em termos socioeconômicos e familiares quanto ao atendimento pretendido pelas políticas sociais vigentes.

Os marcos legais das políticas de medicamentos no Brasil contemporâneo (1990-2006) / The legal landmarks of the drugs policies in contemporary Brazil (1990-2006)

O presente trabalho tem como objeto o processo de reorientação da assistência farmacêutica levada a termo no Brasil a partir da Lei 8.080 de 1990. Essa lei é o primeiro marco legal de um processo que gerou distintas legislações relativas à assistência farmacêutica no âmbito do SUS. O objetivo principal do trabalho foi levantar, sistematizar e nalisar os principais documentos e propostas que promoveram a reorientação da assistência farmacêutica desde 1990 até o presente. O foco do trabalho foi a elaboração, em 1998, da Política Nacional de Medicamentos (PNM), seus antecedentes Central de Medicamentos – (CEME) – Decreto 68.806/71 e a Lei 6.360/76 relativa às ações de vigilância sanitária, bem como a crescente edição de legislações voltadas para a sua efetiva implantação: a criação da Agência Nacional de Vigilância Sanitária – (ANVISA) (1999); a Lei 9.787, conhecida como a Lei dos Genéricos (1999), e a Política Nacional de Assistência Farmacêutica (2004). O trabalho apresenta uma periodização da trajetória das políticas de medicamentos no Brasil contemporâneo e procura assinalar algumas das características desse processo. Entre essas características figura o caráter abrangente dessas legislações, bem como a insuficiente articulação entre estas no sentido de promover a consolidação de uma nova cultura de medicamentos no país. Este trabalho não se limitou a construir uma visão retrospectiva do processo de reorientação da assistência farmacêutica em curso no Brasil contemporâneo, mas procurou buscar alguns elementos para a formação de uma visão prospectiva - na qual estudos avaliativos ganham importância estratégica – das ações no campo da assistência farmacêutica.

The present work focuses on the process of the reorientation of pharmaceutical assistance introduced in Brazil with Law 8,080 of 1990. This law is the first legal landmark of a process that created distinct legal provisions concerning pharmaceutical assistance in the setting of SUS (the Unified National Health System). The main purpose of the study was identifying, systematizing and analyzing the principal documents and proposals that promoted the reorientation of pharmaceutical assistance from 1990 to today. The focus of the work was the elaboration, in 1998, of the National Drug Policy, its antecedents Central for Drugs - (CEME) - Decree 68,806/71 and Law 6,360/76 relative to public health surveillance activities, as well as the increasing number of legislative provisions focused on its effective implementation: establishment: the creation of the National Health Surveillance Agency - (ANVISA) (1999); Law 9,787, known as the Generic Drug Law (1999) and the National Pharmaceutical Assistance Policy (2004). The study presents a timeline of the trajectory of drug policy in Brazil today and seeks to highlight some of the characteristics of this process. Among these characteristics there is the all-inclusive nature of these pieces of legislation as well as the insufficient coordination between them that would promote the consolidation of a new medication culture in the country. This work was not limited to a retrospective view of the reorientation process of pharmaceutical assistance in practice today in Brazil, but it tried to find some elements for the formation of a prospective vision, in which evaluation studies become an important strategy in the policies of pharmaceutical assistance.

Os marcos legais das políticas de medicamentos no Brasil contemponâneo (1990-2006) / The legal landmarks of the drugs policies in contemporany Brazil (1990-2006)

Tem como objetivo o processo de reorientação da assistência farmacêutica levada a termo no Brasil a partir da Lei 8.080 de 1990. Essa lei é o primeiro marco legal de um processo que gerou distintas legislações relativas à assistência farmacêutica no âmbito do SUS. O objetivo principal do trabalho foi levantar, sistematizar e analisar os principais documentos e propostas que promoveram a reorientação da assistência farmacêutica desde 1990 até o presente. (AU)

A saúde no Brasil dos tucanos: quo vadis? / The health in the Brazil

Percorre uma trajetória de análise que se inicia com um plano geral sobre a crise da saúde no Brasil contemporâneo e com a discussão de alguns dos principais dados, acerca da realidade do SUS. A seguir examina questões centrais da política de saúde brasileira. Finalmente apresenta alguns comentßrios sobre a configuração de um quadro de "tempestade" na saúde brasileira - em seus distintos períodos nos anos 80 e 90. Esse quadro é correlacionado à nova ordem internacional capitalista e suas repercussões no Brasil, na atual situação de crise dos sistemas de atenção à saúde

Recombinant interferon-tau regulates secretion of two bovine endometrial proteins.

Conceptus-derived interferon-tau (IFN-tau) has been implicated in the process of maternal recognition of pregnancy in the bovine. This type I IFN interacts with a uterine receptor complex to elicit secondary maternal responses, one of which is secretion of uterine proteins. We investigated the effects of pregnancy and recombinant (r) bovine (bo) IFN-tau (10(7) antiviral units/mg) on secreted proteins by cultured bovine endometrial explants. Explants were cultured for 24 h with [3H]leucine and dialyzed medium analyzed by one- and two-dimensional SDS polyacrylamide gel electrophoresis (PAGE) and fluorography. In one-dimensional PAGE experiments, endometrium representing early pregnancy (days 16-21) and the estrous cycle (days 16-19) was cultured in the presence of 5 nM rboIFN-tau and showed an increase (two- to five-fold) in secretion of 12- and 28-kD proteins. Further examination of these proteins by using two-dimensional PAGE indicated that the 12-kD protein was basic (pI > or = 7.5), whereas the 28-kD protein was acidic (pI approximately 5.0). Isoelectric focusing in the acidic range revealed that the 28-kD protein was composed of several isoelectric variants (pI 4.5-5.5). Although the functions of these secretory proteins are currently unknown, they serve as useful markers for IFN action and may act as secondary signals to protect the early developing conceptus.