A PRESUNÇÃO DE INOCÊNCIA E SEU ALCANCE E APLICAÇÃO A PARTIR DA CONSTITUIÇÃO FEDERAL DE 1988

O presente artigo apresenta como finalidade a busca do alcance e aplicação mais adequados do princípio da presunção de inocência a partir do artigo 5º, inciso LVII, da Constituição Federal que o positivou. A forma de interpretação do citado dispositivo constitucional é decisiva para indicar o modo como o aparelho punitivo se posicionará diante de uma acusação penal. A questão do ônus da prova no processo penal e o postulado “in dubio pro reo”, bem como os significados da presunção de inocência criados historicamente, variam de aplicação conforme a amplitude concedida ao referido preceito constituciona

Late-Glacial to Late-holocene Shifts in Global Precipitation Delta(sup 18)O

Reconstructions of Quaternary climate are often based on the isotopic content of paleo-precipitation preserved in proxy records. While many paleo-precipitation isotope records are available, few studies have synthesized these dispersed records to explore spatial patterns of late-glacial precipitation delta(sup 18)O. Here we present a synthesis of 86 globally distributed groundwater (n 59), cave calcite (n 15) and ice core (n 12) isotope records spanning the late-glacial (defined as 50,000 to 20,000 years ago) to the late-Holocene (within the past 5000 years). We show that precipitation delta(sup 18)O changes from the late-glacial to the late-Holocene range from -7.1% (delta(sup 18)O(late-Holocene) > delta(sup 18)O(late-glacial) to +1.7% (delta(sup 18)O(late-glacial) > delta(sup 18)O(late-Holocene), with the majority (77) of records having lower late-glacial delta(sup 18)O than late-Holocene delta(sup 18)O values. High-magnitude, negative precipitation delta(sup 18)O shifts are common at high latitudes, high altitudes and continental interiors

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

SummaryThe impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators

Groundwater Hydrographs in the Namoi and Gwydir Catchments: An Assessment of Groundwater Level Change

This report presents all groundwater hydrographs from the Namoi and Gwydir catchments.Change in the groundwater levels recorded throughout the Namoi and Gwydir catchments arepresented for two periods: 1985–2015 and 2006–2015.The period 1985–2015 was selected to show long-term change in groundwater levelsbecause from the mid 1980s there was widespread groundwater monitoring throughout the Namoiand Gwydir catchments. Prior to the 1980s, groundwater monitoring was mostly limited to the regionbetween Narrabri and Wee Waa.For the second period we selected 2006 as the starting reference year because this waswhen the Water Sharing Plans commenced in both catchments. The end reference year 2015 wasselected because the 2006–2015 winter-recovered water set provides the most extensive coveragewhen compared to the 2006–2016 or 2006–2017 available data. Maps of the shallow, intermediateand deep portions of the Namoi and Gwydir alluvium show how the groundwater levels throughoutthe catchments have responded since the “millennium drought” and since the introduction of theWater Sharing Plans in 2006

Analysis of environmental isotopes in groundwater to understand the response of a vulnerable coastal aquifer to pumping: Western Port Basin, south-eastern Australia

The response of a multi-layered coastal aquifer in southeast Australia to decades of groundwater pumping, and the groundwater age, flow paths and salinization processes were examined using isotopic tracers. Groundwater radiocarbon and tritium contents decline with distance and depth away from basin margins; however, in the main zone of pumping, radiocarbon activities are generally homogeneous within a given depth horizon. A lack of tritium and low radiocarbon activities (<25 pMC) in groundwater in and around the pumping areas indicate that seasonal recovery of water levels is related to capture of old water with low radioisotope activities, rather than arrival of recently recharged water. Mechanisms facilitating seasonal recovery include release of water from low-permeability layers and horizontal transfer of water from undeveloped parts of the basin. Overall stability in seasonally recovered water levels and salinities for the past three decades indicate that the system has reached a dynamic equilibrium with respect to water balance and salinity, following a major change in flow paths and solute distributions after initial development. Groundwater δ18O, δ2H and chloride contents indicate mixing between fresh meteoric-derived groundwater and marine water at the coast, with the most saline groundwater approximating an 80:20 mixture of fresh to oceanic water

Baselining Lower Namoi Groundwater and Evaluating Pilliga CSG Developments

This report summarises the primary research outcomes and publications produced as part of CRDC project UNSW1601 Baselining Lower Namoi Groundwater and Evaluating Pilliga CSG Developments. There is considerable public apprehension about the expansion of coal seamgas (CSG) production in the Pilliga. To produce the gas from the Permian coal measures, large quantities of co-produced water will be extracted. This water is commonly of poor quality and once it is brought to the surface there are concerns about its treatment, disposal and subsequent use. There are also concerns about the depressurisation impacts on groundwater resources in the Great Artesian Basin and Lower Namoi Alluvium. This projectassessed potential impacts of CSG production in conjunction with ongoing groundwater withdrawals for irrigated agriculture on sustainable access to groundwater for the cotton industry, as well as stock and domestic users.Measurements of the methane content of groundwater undertaken in the USA have demonstrated that methane levels can be an early indicator of connectivity between coal seam gas developments and aquifers used as water supplies (Osborn et al. 2011). To date there are no extensive baseline measurements of methane concentration in the groundwater or the air in the Namoi Catchment that have been placed in the public domain. This projectestablished baseline methane concentrations in the Lower Namoi Alluvial Aquifer and ground-level atmosphere.Since the establishment of the water sharing plans there have been limited studies reviewing how groundwater levels have responded and whether the groundwater quality is being maintained or improved. To assess changes in water quality the hydrogeochemical data collected as part of this study were compared to historical data sets. Graphs of groundwater levels for all groundwater monitoring locations in the Namoi were produced, along with maps highlighting how the groundwater levels have changed for two periods 1985-2015 and 2006-2015.Throughout Australia there are thousands of abandoned legacy wells. These wells may act as pathways of hydraulic connectivity to enable the transfer of water and gas between the coal measures and overlying aquifers. In 2014 and 2016 as part of CRDC project UNSW1401 mobile surveys were undertaken to measure continuously the methane mole fraction in the ground-level atmosphere of the Condamine catchment. Those campaigns mapped the locations of two legacy wells that were leaking methane at concentrations above ignition potential. Those results demonstrated that the issue of legacy wells requires extensive further study, and that in any region where there is potential for legacy wells to exist surveys should be undertaken. To assess if there are any legacy wells of concern in the Lower Namoi three field campaigns were undertaken to measure the methane mole fraction (concentration) in the ground-level atmosphere. These surveys also created a baseline data set to enable future assessments of changing land use and industrial activities