Beyond Rio+20: governance for a green economy

This repository item contains a single issue of the Pardee Center Task Force Reports, a publication series that began publishing in 2009 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future.As an intellectual contribution to the preparations for the 2012 United Nations Conference on Sustainable Development (UNCSD, a.k.a. Rio +20), the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future convened a task force of experts to discuss the role of institutions in the actualization of a green economy in the context of sustainable development. A stellar group of experts from academia, government and civil society convened at the Pardee Center and were asked to outline ideas about what the world has learned about institutions for sustainable development from the past, and what we can propose about the governance challenges and opportunities for the continuous development of a green economy in the future. The Task Force members were encouraged to think big and think bold. They were asked to be innovative in their ideas, and maybe even a little irreverent and provocative. They were charged specifically NOT to come to consensus about specific recommendations, but to present a variety and diversity of views. This report presents their thoughts and ideas

SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr

<p>Abstract</p> <p>Background</p> <p>Heterozygous and homozygous carriers of <it>SCN5A</it>-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death. We hypothesized that some heterozygous carriers may have unequal expression of wild-type and variant alleles and secondarily that predominance of the variant gene copy could further increase risk for sudden death in this population.</p> <p>Methods</p> <p>We quantified allele-specific expression of <it>SCN5A</it>-p.Ser1103Tyr by real-time reverse-transcription polymerase chain reaction (RT-PCR) in heart tissue from heterozygous African-American infants, who died from sudden infant death syndrome (SIDS) or from other causes, to test for allelic expression imbalance.</p> <p>Results</p> <p>We observed significant allelic expression imbalance in 13 of 26 (50%) African-American infant hearts heterozygous for <it>SCN5A</it>-p.Ser1103Tyr, and a significant (p < 0.0001) bimodal distribution of log₂allelic expression ratios. However, <b>t</b>here were no significant differences in the mean log₂allelic expression ratios in hearts of infants dying from SIDS as compared to infants dying from other causes and no significant difference in the proportion of cases with greater expression of the variant allele.</p> <p>Conclusions</p> <p>Our data provide evidence that <it>SCN5A </it>allelic expression imbalance occurs in African-Americans heterozygous for p.Ser1103Tyr, but this phenomenon alone does not appear to be a marker for risk of SIDS.</p

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients

The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator. Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1–18 months, with a median follow-up of 6 months. Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3–18 months) with no in-field failures and were able to obtain encouraging toxicity profiles. Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity

American College of Rheumatology Provisional Criteria for Global Flares in Childhood-Onset Systemic Lupus Erythematosus

Objective: To validate the preliminary criteria of global flare for childhood-onset SLE (cSLE). Methods: Pediatricians experienced in cSLE care (n = 268) rated unique patient profiles; results of standard cSLE laboratory testing and information about the cSLE flare descriptors were presented as follows: global assessment of patient well-being, physician global assessment of disease activity (MD-global), Disease Activity Index score, protein/creatinine ratio (PCR), and erythrocyte sedimentation rate (ESR). Using rater interpretation of the course of cSLE (baseline versus followup as the gold standard), performance (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]) of the preliminary flare criteria was tested. An international consensus conference was held to rank the preliminary flare criteria as per the American College of Rheumatology recommendations and delineate threshold scores for minor, moderate, and major flares. Results: The accuracy of the 2 highest-ranked candidate criteria that consider absolute changes ( 06) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (BILAG) (numeric scoring: A = 12, B = 8, C = 1, and D/E = 0), MD-global, PCR, and ESR were confirmed (both AUC >0.93). For the SLEDAI-based criteria (0.5 7 06SLEDAI + 0.45 7 06PCR + 0.5 7 06MD-global + 0.02 7 06ESR) flare scores 656.4/3.0/0.6 constituted major/moderate/minor flares, respectively. For the BILAG-based algorithm (0.4 7 06BILAG + 0.65 7 06PCR + 0.5 7 06MD-global + 0.02 7 06ESR) flare scores 657.4/3.7/2.2 delineated major/moderator/minor flares, respectively. These threshold values (SLEDAI, BILAG) were all >82% sensitive and specific for capturing flare severity. Conclusion: Provisional criteria for global flares in cSLE are available to identify patients who experienced a flare. These criteria also allow for discrimination of the severity of cSLE exacerbations

State of play and future direction with NOACs: An expert consensus.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are cardiovascular conditions significant in contemporary practice. In both, the use of anticoagulation with vitamin K antagonists (VKAs) has been traditionally used to prevent adverse events. However, VKA therapy is associated with challenges relating to dose maintenance, the need to monitor anticoagulation, and bleeding risks. The non-vitamin K oral anticoagulants (NOACs) are becoming accepted as a clear alternative to VKA therapy for both AF and VTE management. The aim of this paper was to review contemporary evidence on the safety of NOACs in both conditions. A comprehensive literature review was conducted to explore key safety issues and expert consensus was achieved from eight professionals specialised in AF and VTE care. Consensus-based statements were formulated where available evidence was weak or contradictory. The expert statements in this paper form a key overview of the safety of NOACs compared with VKA therapy, and the comparative safety of different NOACs. It is apparent that a detailed patient work-up is required in order to identify and manage individual risk factors for bleeding and thrombosis prior to NOAC therapy. Additional measures, such as dose reductions, may also be used to maintain the safety of NOACs in practice

What is implicit bias?

Research programs in empirical psychology over the past few decades have led scholars to posit implicit biases. This is due to the development of innovative behavioural measures that have revealed aspects of our cognitions which may not be identified on self-report measures requiring individuals to reflect on and report their attitudes and beliefs. But what does it mean to characterise such biases as implicit? Can we satisfactorily articulate the grounds for identifying them as bias? And crucially, what sorts of cognitions are in fact being measured; what mental states or processes underpin such behavioural responses? In this paper, we outline some of the philosophical and empirical issues engaged when attempting to address these three questions. Our aim is to provide a constructive taxonomy of the issues, and how they interrelate. As we will see, any view about what implicit bias is may depend on a range of prior theoretical choices

Measuring Disease Damage and Its Severity in Childhood-Onset Systemic Lupus Erythematosus

Objective: To describe the frequency and types of disease damage occurring with childhood-onset systemic lupus erythematosus (SLE) as measured by the 41-item Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and to assess the SDI's ability to reflect damage severity. Methods: Information for the SDI was prospectively collected from 1,048 childhood-onset SLE patients. For a subset of 559 patients, physician-rated damage severity measured by visual analog scale (MD VAS damage) was also available. Frequency of SDI items and the association between SDI summary scores and MD VAS damage were estimated. Finally, an international consensus conference, using nominal group technique, considered the SDI's capture of childhood-onset SLE\u2013associated damage and its severity. Results: After a mean disease duration of 3.8 years, 44.2% of patients (463 of 1,048) already had an SDI summary score &gt;0 (maximum 14). The most common SDI items scored were proteinuria, scarring alopecia, and cognitive impairment. Although there was a moderately strong association between SDI summary scores and MD VAS damage (Spearman's r = 0.49, P &lt; 0.0001) in patients with damage (SDI summary score &gt;0), mixed-effects analysis showed that only 4 SDI items, each occurring in &lt;2% of patients overall, were significantly associated with MD VAS damage. There was consensus among childhood-onset SLE experts that the SDI in its current form is inadequate for estimating the severity of childhood-onset SLE\u2013associated damage. Conclusion: Disease damage as measured by the SDI is common in childhood-onset SLE, even with relatively short disease durations. Given the shortcomings of the SDI, there is a need to develop new tools to estimate the impact of childhood-onset SLE\u2013associated damage