Ogni Pensiero Vola: the embodied psyche in Terrence Malick's The Tree of Life

The Tree of Lifetouches on embodiment of the soul in an early sequence covering courtship, marriage and the first pregnancy of a young couple. In a delicate formal scene, Mrs O'Brien, nearing full term, treads gently along a river's edge summoning infant souls luminous in white linen. She opens a minute book of life to one of them, preparing his entry through the iron gates that open on embodied life. Presently, the infant soul rises up from his underwater home beyond the reach of conscious awareness: Mrs O'Brien gives birth to her first son, Jack. This is the boy who will eventually become a middle-aged man in crisis. Ravaged then by grief for his long-dead younger brother and his own inability to live at peace with his family or himself, his memories, visions and reflections accumulate in a way that makes him a suffering Hermes for the early twenty-first century. The initiating episode of the infant's birth complements the embodied and affective experiences of those in the audience who accept the film's sensual invitation to steep themselves in the immense scale of its gorgeous sounds and images. They then discover on the pulse that, more than the history of one Texan family, it attempts nothing less than the necessary re-creation of the godhead for the early twenty-first century. Contrary to the rigid medieval dogmas of so many orthodox religions,The Tree of Lifeassures us not of a changeless eternity but rather the sacred and ceaseless metamorphosis of numinous energy

Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential

The tumour microenvironment is believed to be involved in development, growth, metastasis, and therapy resistance of many cancers. Here we show survivin, a member of the inhibitor of apoptosis protein (IAP) family, implicated in apoptosis inhibition and the regulation of mitosis in cancer cells, exists in a novel extracellular pool in tumour cells. Furthermore, we have constructed stable cell lines that provide the extracellular pool with either wild-type survivin (Surv-WT) or the previously described dominant-negative mutant survivin (Surv-T34A), which has proven pro-apoptotic effects in cancer cells but not in normal proliferating cells. Cancer cells grown in conditioned medium (CM) taken from Surv-WT cells absorbed survivin and experienced enhanced protection against genotoxic stresses. These cells also exhibited an increased replicative and metastatic potential, suggesting that survivin in the tumour microenvironment may be directly associated with malignant progression, further supporting survivin's function in tumourigenesis. Alternatively, cancer cells grown in CM taken from the Surv-T34A cells began to apoptose through a caspase-2- and caspase-9-dependent pathway that was further enhanced by the addition of other chemo- and radiotherapeutic modalities. Together our findings suggest a novel microenvironmental function for survivin in the control of cancer aggressiveness and spread, and should result in the genesis of additional cancer treatment modalities

Autoregulation in resistance training : addressing the inconsistencies

Autoregulation is a process that is used to manipulate training based primarily on the measurement of an individual's performance or their perceived capability to perform. Despite being established as a training framework since the 1940s, there has been limited systematic research investigating its broad utility. Instead, researchers have focused on disparate practices that can be considered specific examples of the broader autoregulation training framework. A primary limitation of previous research includes inconsistent use of key terminology (e.g., adaptation, readiness, fatigue, and response) and associated ambiguity of how to implement different autoregulation strategies. Crucially, this ambiguity in terminology and failure to provide a holistic overview of autoregulation limits the synthesis of existing research findings and their dissemination to practitioners working in both performance and health contexts. Therefore, the purpose of the current review was threefold: first, we provide a broad overview of various autoregulation strategies and their development in both research and practice whilst highlighting the inconsistencies in definitions and terminology that currently exist. Second, we present an overarching conceptual framework that can be used to generate operational definitions and contextualise autoregulation within broader training theory. Finally, we show how previous definitions of autoregulation fit within the proposed framework and provide specific examples of how common practices may be viewed, highlighting their individual subtleties

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

The Penobscot River, Maine, USA: a Basin-Scale Approach to Balancing Power Generation and Ecosystem Restoration

Although hydropower is a source of low-carbon energy, without careful consideration and management, dams have the potential to degrade river ecosystems and the goods and services they provide to society. Today, a broad range of hydropower interests and stakeholders are seeking approaches to hydropower development and operation that are more environmentally and socially sustainable. The Penobscot River Restoration Project (\u27the Project\u27) illustrates that basin-scale approaches can provide a broader set of solutions for balancing energy and riverine environmental resources than can be achieved at the scale of individual projects. The Penobscot basin is the largest in Maine and historically supported culturally and economically significant populations of migratory fish. These migratory fish populations declined dramatically following the construction of a series of hydropower dams on the main stem river and major tributaries in the early 20th century. The Project, negotiated between a power company ( PPL Corporation) and a coalition including the Penobscot Indian Nation, resource agencies, and nongovernmental conservation organizations, features the removal of two main stem dams on the lower Penobscot and improved fish passage at the dams that remain. Because of various capacity and/or operational changes, power production will be increased at the remaining dams and total hydropower energy production from the basin will be maintained or increase slightly. The Project is expected to expand considerably the proportion of the basin accessible to migratory fish and contribute to significant increases in fish populations. The Project illustrates that a basin-scale approach can potentially yield more comprehensive solutions for sustainable hydropower than can be achieved at the project scale, and we recommend that such large-scale planning processes can improve the sustainability of both regulatory licensing of existing dams as well as the planning of future dams in regions undergoing the expansion of water-management infrastructur

The effects of strength and conditioning interventions on sprinting performance in team sport athletes: a systematic review and meta-analysis.

Linear sprinting is a key determinant of athletic performance within team sports. The aims of the review were to quantify and compare the effectiveness of popular strength and conditioning (S&C) training modes to improve sprint performance in team sport athletes, with additional focus on potential moderators and the relationships between improvements in physical factors (e.g. strength, power and jump performance) and improvements in sprint performance. Inclusion was restricted to resistance, plyometric, sprint and combined training interventions comprising team sport athletes. Multi-level, Bayesian meta-analysis and meta-regression models conducted with standardised mean difference effect sizes were used to investigate training modes and potential moderators. Weighted regression models conducted on shrunken estimates from initial Bayesian meta-analyses were used to quantify relationships between improvements in physical factors and improvements in sprint performance. Certainty of evidence was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach. Similar improvements in sprint performance were obtained across training modes, with some evidence of the largest effects with resistance training (SMD_(Pre_0.5 )=0.55 [95%CrI:0.36-0.78; very low certainty]). A strong moderating effect of training intensity was identified across all training modes with evidence of greater improvements in sprint performance with high intensity training (β_(Low:High_0.5 )=0.17 [95%CrI:0.01-0.33; very low certainty]). Strong positive relationships were identified between improvements in all physical factors and sprint performance (β_Strength_0.5=0.56 [95%CrI:0.36-0.77; low certainty], β_Power_0.5=0.80 [95%CrI:0.50-1.0; low certainty], β_Jump_0.5=0.78 [95%CrI:0.57-0.97; low certainty]). The findings indicate that focus on developing speed in team sport athletes should be placed on S&C training with high intensities, including the use of resisted sprint training

Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant

Background: Current therapeutic options for advanced pancreatic cancer have been largely disappointing with modest results at best, and though adjuvant therapy remains controversial, most remain in agreement that Gemcitabine should stand as part of any combination study. The inhibitor of apoptosis (IAP) protein Survivin is a key factor in maintaining apoptosis resistance, and its dominant-negative mutant (Survivin-T34A) has been shown to block Survivin, inducing caspase activation and apoptosis. Methods: In this study, exosomes, collected from a melanoma cell line built to harbor a tetracycline-regulated Survivin-T34A, were plated on the pancreatic adenocarcinoma (MIA PaCa-2) cell line. Evaluation of the presence of Survivin-T34A in these exosomes followed by their ability to induce Gemcitabine-potentiative cell killing was the objective of this work. Results: Here we show that exosomes collected in the absence of tetracycline (tet-off) from the engineered melanoma cell do contain Survivin-T34A and when used alone or in combination with Gemcitabine, induced a significant increase in apoptotic cell death when compared to Gemcitabine alone on a variety of pancreatic cancer cell lines. Conclusion: This exosomes/Survivin-T34A study shows that a new delivery method for anticancer proteins within the cancer microenvironment may prove useful in targeting cancers of the pancreas

The Effects of Sprint Interval Training on Physical Performance: A Systematic Review and Meta-Analysis

The present study aimed to synthesize findings from published research and through meta-analysis quantify the effect of sprint interval training (SIT) and potential moderators on physical performance outcomes (categorized as aerobic, anaerobic, mixed aerobic-anaerobic, or muscular force) with healthy adults, in addition to assessing the methodological quality of included studies and the existence of small study effects. Fifty-five studies were included (50% moderate methodological quality, 42% low methodological quality), with 58% comprising an intervention duration of ≤4 weeks and an array of different training protocols. Bayesian’s meta-analysis of standardized mean differences (SMD) identified a medium effect of improved physical performance with SIT (ES0.5 = 0.52; 95% credible intervals [CrI]: 0.42–0.62). Moderator analyses identified overlap between outcome types with the largest effects estimated for anaerobic outcomes (ES0.5 = 0.61; 95% CrI: 0.48–0.75). Moderator effects were identified for intervention duration, sprint length, and number of sprints performed per session, with larger effects obtained for greater values of each moderator. A substantive number of very large effect sizes (41 SMDs > 2) were identified with additional evidence of extensive small study effects. This meta-analysis demonstrates that short-term SIT interventions are effective for developing moderate improvements in physical performance outcomes. However, extensive small study effects, likely influenced by researchers analyzing many outcomes, suggest potential overestimation of reported effects. Future research should analyze fewer a priori selected outcomes and investigate models to progress SIT interventions for longer-term performance improvements