Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study

NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer. Core biopsies at baseline, week 4, and surgery were assessed for biomarker changes. Primary endpoint: change in Ki67 labeling index (LI) from baseline to week 4 determined by automated computer imaging system (ACIS). Secondary endpoints: ER protein expression and function; progesterone receptor (PgR) expression; tumor response; tolerability. ER and PgR were examined retrospectively using the H score method. A total of 211 patients were randomized (fulvestrant 500 mg: n = 109; 250 mg: n = 102). At week 4, fulvestrant 500 mg resulted in greater reduction of Ki67 LI and ER expression versus 250 mg (-78.8 vs. -47.4% [p < 0.0001] and -25.0 vs. -13.5% [p = 0.0002], respectively [ACIS]); PgR suppression was not significantly different (-22.7 vs. -17.6; p = 0.5677). However, H score detected even greater suppression of ER (-50.3 vs. -13.7%; p < 0.0001) and greater PgR suppression (-80.5 vs. -46.3%; p = 0.0018) for fulvestrant 500 versus 250 mg. At week 16, tumor response rates were 22.9 and 20.6% for fulvestrant 500 and 250 mg, respectively, with considerable decline in all markers by both ACIS and H score. No detrimental effects on endometrial thickness or bone markers and no new safety concerns were identified. This provides the first evidence of greater biological activity for fulvestrant 500 versus 250 mg in depleting ER expression, function, and growth.

Research Blogging: Indexing and Registering the Change in Science 2.0

Increasing public interest in science information in a digital and 2.0 science era promotes a dramatically, rapid and deep change in science itself. The emergence and expansion of new technologies and internet-based tools is leading to new means to improve scientific methodology and communication, assessment, promotion and certification. It allows methods of acquisition, manipulation and storage, generating vast quantities of data that can further facilitate the research process. It also improves access to scientific results through information sharing and discussion. Content previously restricted only to specialists is now available to a wider audience. This context requires new management systems to make scientific knowledge more accessible and useable, including new measures to evaluate the reach of scientific information. The new science and research quality measures are strongly related to the new online technologies and services based in social media. Tools such as blogs, social bookmarks and online reference managers, Twitter and others offer alternative, transparent and more comprehensive information about the active interest, usage and reach of scientific publications. Another of these new filters is the Research Blogging platform, which was created in 2007 and now has over 1,230 active blogs, with over 26,960 entries posted about peer-reviewed research on subjects ranging from Anthropology to Zoology. This study takes a closer look at RB, in order to get insights into its contribution to the rapidly changing landscape of scientific communication.

Correlates of change in self-perceived oral health among older adults in Brazil Findings from the Health, Well-Being and Aging Study

Background. Identifying changes in the oral health status of older populations, and their predictors and explanations, is necessary for public health planning. The authors assessed patterns of change in oral health-related quality of life in a large cohort of older adults in Brazil during a five-year period and evaluated associations between baseline characteristics and those changes. Methods. The sample consisted of 747 older people enrolled in a Brazilian cohort study called the Health, Well-Being and Aging (Saude, Bem-estar e Envelhecimento [SABE]) Study. Trained examiners measured participants' self-perceived oral health by using the General Oral Health Assessment Index (GOHAI). The authors calculated changes in the overall GOHAI score and in the scores for each of the GOHAI's three dimensions individually by subtracting the baseline score from the score at follow-up. A positive difference indicated improvement in oral health, a negative difference indicated a decline and a difference of zero indicated no change. Results. The authors found that 48.56 percent of the participants experienced a decline in oral health and 33.48 percent experienced an improvement. Participants with 16 or more missing teeth and eight or more years of education were more likely to have an improvement in total GOHAI score. Deterioration was more likely to occur among those with two or more diseases. Improvement and decline in GOHAI functional scores were related to the number of missing teeth. The authors found no significant model for the change in the psychosocial score, and Self-rated general health was the only variable related to both improvement and decline in pain or discomfort scores. Conclusions. The authors observed a bidirectional change in self-perceived oral health, with deterioration predominating. The strongest predictor of improvement in the total GOHAI score was the number of missing teeth, whereas the number of diseases was the strongest predictor of deterioration. Clinical Implications. Dental professionals and policymakers need to know the directions of change in older adults' oral health to establish treatment priorities and evaluate the impact of services directed at this population.

Land-use and land-cover change in Atlantic Forest landscapes

The Atlantic Forest is one of the most threatened tropical biomes, with much of the standing forest in small (less than 50 ha), disturbed and isolated patches. The pattern of land-use and land-cover change (LULCC) which has resulted in this critical scenario has not yet been fully investigated. Here, we describe the LULCC in three Atlantic Forest fragmented landscapes (Sao Paulo, Brazil) between 1960-1980s and 1980-2000s. The three studied landscapes differ in the current proportion of forest cover, having 10%, 30% and 50% respectively. Between the 1960s and 1980s. forest cover of two landscapes was reduced while the forest cover in the third landscape increased slightly. The opposite trend was observed between the 1980s and 2000s: forest regeneration was greater than deforestation at the landscapes with 10% and 50% of forest cover and, as a consequence, forest cover increased. By contrast, the percentage of forest cover at the landscape with 30% of forest cover was drastically reduced between the 1980s and 2000s. LULCC deviated from a random trajectory, were not constant through time in two study landscapes and were not constant across space in a given time period. This landscape dynamism in single locations over small temporal scales is a key factor to be considered in models of LULCC to accurately simulate future changes for the Atlantic Forest. In general, forest patches became more isolated when deforestation was greater than forest regeneration and became more connected when forest regeneration was greater than deforestation. As a result of the dynamic experienced by the study landscapes, individual forest patches currently consist of a mosaic of different forest age classes which is likely to impact bio-diversity. Furthermore, landscape dynamics suggests the beginning of a forest transition in some Atlantic Forest regions, what could be of great importance for biodiversity conservation due to the potential effects of young secondary forests in reducing forest isolation and maintaining a significant amount of the original biodiversity. (C) 2012 Elsevier B.V. All rights reserved.

Rabies in southeast Brazil: a change in the epidemiological pattern

This epidemiological study was conducted using antigenic and genetic characterisation of rabies virus isolates obtained from different animal species in the southeast of Brazil from 1993 to 2007. An alteration in the epidemiological profile was observed. One hundred two samples were tested using a panel of eight monoclonal antibodies, and 94 were genetically characterised by sequencing the nucleoprotein gene. From 1993 to 1997, antigenic variant 2 (AgV-2), related to a rabies virus maintained in dog populations, was responsible for rabies cases in dogs, cats, cattle and horses. Antigenic variant 3 (AgV-3), associated with Desmodus rotundus, was detected in a few cattle samples from rural areas. From 1998 to 2007, rabies virus was detected in bats and urban pets, and four distinct variants were identified. A nucleotide similarity analysis resulted in two primary groups comprising the dog and bat antigenic variants and showing the distinct endemic cycles maintained in the different animal species in this region.

Rates of Change in the Visual Field and Optic Disc in Patients with Distinct Patterns of Glaucomatous Optic Disc Damage

Purpose: To investigate the rate of visual field and optic disc change in patients with distinct patterns of glaucomatous optic disc damage. Design: Prospective longitudinal study. Participants: A total of 131 patients with open-angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44) optic disc damage. Methods: Patients were examined every 4 months with standard automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT, Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany) for a period of 4 years. During this time, patients were treated according to a predefined protocol to achieve a target intraocular pressure (IOP). Rates of change were estimated by robust linear regression of visual field mean deviation (MD) and global optic disc neuroretinal rim area with follow-up time. Main Outcome Measures: Rates of change in MD and rim area. Results: Rates of visual field change in patients with focal optic disc damage (mean -0.34, standard deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean - 0.14, SD 0.77 dB/year) and diffuse (mean + 0.01, SD 0.37 dB/year) optic disc damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with focal optic disc damage (mean - 11.70, SD 25.5 x 10(-3) mm(2)/year) were faster than in patients with diffuse (mean -9.16, SD 14.9 x 10(-3) mm(2)/year) and sclerotic (mean -0.45, SD 20.6 x 10(-3) mm(2)/year) optic disc damage, although the differences were not statistically significant (P = 0.11). Absolute IOP reduction from untreated levels was similar among the groups (P = 0.59). Conclusions: Patients with focal optic disc damage had faster rates of visual field change and a tendency toward faster rates of optic disc deterioration when compared with patients with diffuse and sclerotic optic disc damage, despite similar IOP reductions during follow-up. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 294-303 (C) 2012 by the American Academy of Ophthalmology.

Pollination services at risk: Bee habitats will decrease owing to climate change in Brazil

Native bees are important providers of pollination services, but there are cumulative evidences of their decline. Global changes such as habitat losses, invasions of exotic species and climate change have been suggested as the main causes of the decline of pollinators. In this study, the influence of climate change on the distribution of 10 species of Brazilian bees was estimated with species distribution modelling. We used Maxent algorithm (maximum entropy) and two different scenarios, an optimistic and a pessimistic, to the years 2050 and 2080. We also evaluated the percentage reduction of species habitat based on the future scenarios of climate change through Geographic Information System (GIS). Results showed that the total area of suitable habitats decreased for all species but one under the different future scenarios. The greatest reductions in habitat area were found for Melipona bicolor bicolor and Melipona scutellaris, which occur predominantly in areas related originally to Atlantic Moist Forest. The species analysed have been reported to be pollinators of some regional crops and the consequence of their decrease for these crops needs further clarification. (C) 2012 Elsevier B.V. All rights reserved.