Energy gap in the aetiology of body weight gain and obesity: a challenging concept with a complex evaluation and pitfalls.

The concept of energy gap(s) is useful for understanding the consequence of a small daily, weekly, or monthly positive energy balance and the inconspicuous shift in weight gain ultimately leading to overweight and obesity. Energy gap is a dynamic concept: an initial positive energy gap incurred via an increase in energy intake (or a decrease in physical activity) is not constant, may fade out with time if the initial conditions are maintained, and depends on the 'efficiency' with which the readjustment of the energy imbalance gap occurs with time. The metabolic response to an energy imbalance gap and the magnitude of the energy gap(s) can be estimated by at least two methods, i.e. i) assessment by longitudinal overfeeding studies, imposing (by design) an initial positive energy imbalance gap; ii) retrospective assessment based on epidemiological surveys, whereby the accumulated endogenous energy storage per unit of time is calculated from the change in body weight and body composition. In order to illustrate the difficulty of accurately assessing an energy gap we have used, as an illustrative example, a recent epidemiological study which tracked changes in total energy intake (estimated by gross food availability) and body weight over 3 decades in the US, combined with total energy expenditure prediction from body weight using doubly labelled water data. At the population level, the study attempted to assess the cause of the energy gap purported to be entirely due to increased food intake. Based on an estimate of change in energy intake judged to be more reliable (i.e. in the same study population) and together with calculations of simple energetic indices, our analysis suggests that conclusions about the fundamental causes of obesity development in a population (excess intake vs. low physical activity or both) is clouded by a high level of uncertainty.

Pediatric advance care planning: a systematic review.

BACKGROUND AND OBJECTIVES: Advance care planning (ACP) is increasingly regarded as the gold standard in the care of patients with life-limiting illnesses. Research has focused on adults, but ACP is also being practiced in pediatrics. We conducted a systematic review on empirical literature on pediatric ACP (pACP) to assess current practices, effects, and perspectives of pACP. METHODS: We searched PubMed, BELIT, and PSYCinfo for empirical literature on pACP, published January 1991 through January 2012. Titles, abstracts, and full texts were screened by 3 independent reviewers for studies that met the predefined criteria. The evidence level of the studies was assessed. Relevant study outcomes were retrieved according to predefined questions. RESULTS: We included 5 qualitative and 8 quantitative studies. Only 3 pACP programs were identified, all from the United States. Two of them were informed by adult programs. Major pACP features are discussions between families and care providers, as well as advance directives. A chaplain and other providers may be involved if required. Programs vary in how well they are evaluated; only 1 was studied by using a randomized controlled trial. Preliminary data suggest that pACP can successfully be implemented and is perceived as helpful. It may be emotionally relieving and facilitate communication and decision-making. Major challenges are negative reactions from emergency services, schools, and the community. CONCLUSIONS: There are few systematic pACP programs worldwide and none in Europe. Future research should investigate the needs of all stakeholders. In particular, the perspective of professionals has so far been neglected.

Prise de poids et contraceptifs à progestatifs seuls: plus d'inquiétude que de preuves scientifiques. [Weight gain and progestin-only contraceptives: more concern than evidence].

Weight gain is a side effect often associated with progestin-only contraceptives. A recently published Cochrane review focuses on this issue that has been addressed in only few studies of good quality. Here we discuss the results of this review in the context of three clinical cases. With progestin-only contraceptives the weight gain is less than often thought, especially after six or twelve months of treatment. Some results are rather reassuring, especially those in obese women and during the post-partum period. This should help improve the compliance of women who fear gaining weight with this type of hormonal contraception.

A gain-of-function allele of TPC1 activates oxylipin biogenesis after leaf wounding in Arabidopsis.

Jasmonates, potent lipid mediators of defense gene expression in plants, are rapidly synthesized in response to wounding. These lipid mediators also stimulate their own production via a positive feedback circuit, which depends on both JA synthesis and JA signaling. To date, molecular components regulating the activation of jasmonate biogenesis and its feedback loop have been poorly characterized. We employed a genetic screen capable of detecting the misregulated activity of 13-lipoxygenase, which operates at the entry point of the jasmonate biosynthesis pathway. Leaf extracts from the Arabidopsis fou2 (fatty acid oxygenation upregulated 2) mutant displayed an increased capacity to catalyze the synthesis of lipoxygenase (LOX) metabolites. Quantitative oxylipin analysis identified less than twofold increased jasmonate levels in healthy fou2 leaves compared to wild-type; however, wounded fou2 leaves strongly increased jasmonate biogenesis compared to wounded wild-type. Furthermore, the plants displayed enhanced resistance to the fungus Botrytis cinerea. Higher than wild-type LOX activity and enhanced resistance in the fou2 mutant depend fully on a functional jasmonate response pathway. The fou2 mutant carries a missense mutation in the putative voltage sensor of the Two Pore Channel 1 gene (TPC1), which encodes a Ca(2+)-permeant non-selective cation channel. Patch-clamp analysis of fou2 vacuolar membranes showed faster time-dependent conductivity and activation of the mutated channel at lower membrane potentials than wild-type. The results indicate that cation fluxes exert strong control over the positive feedback loop whereby JA stimulates its own synthesis.

Computer-assisted two-dimensional preoperative planning for total hip arthroplasty: clinical evaluation.

The purpose of this study is to clinically validate a new two-dimensional preoperative planning software for cementless total hip arthroplasty (THA). Manual and two-dimensional computer-assisted planning were compared by an independent observer for each of the 30 patients with osteoarthritis who underwent THA. This study showed that there were no statistical differences between the results of both preoperative plans in terms of stem size and neck length (<1 size) and hip rotation center position (<5 mm). Two-dimensional computer-assisted preoperative planning provided successful results comparable to those using the manual procedure, thereby allowing the surgeon to simulate various stem designs easily.

The real estate markets : Players, institutions and territories

Revealing the parties, the processes and the institutions and, consequently, both the diversity and contingency of the real estate markets, the existing increasing literature emphasises the contemporary numerous links and interdependencies between real estate, land value, planning and town planning policy and even the financial system. This paper is an attempt to understand all the real estate markets, from the most peripheral ones, where the urban rent is the lowest, to the most dense city centres. To gain a better understanding of the real estate market, a process of firstly deconstruction and then reconstruction is used. The process of deconstruction involves identifying various market trends according to property type (principally residential buildings), players and institutions, territorial situations and temporalities based on research conducted in Switzerland. We then developed a meta-synthesis inspired by Fernand Braudel whose works put as much emphasis on day-to-day economic activity as on long-term activity, and on local as well as global issues.

Ideal and reality: do countries adopt and follow recommended procedures in comprehensive multiyear planning guidelines for national immunization programmes?

BACKGROUND: Meticulous steps and procedures are proposed in planning guidelines for the development of comprehensive multiyear plans for national immunization programmes. However, we know very little about whether the real-life experience of those who adopt these guidelines involves following these procedures as expected. Are these steps and procedures followed in practice? We examined the adoption and usage of the guidelines in planning national immunization programmes and assessed whether the recommendations in these guidelines are applied as consistently as intended. METHODS: We gathered information from the national comprehensive multiyear plans developed by 77 low-income countries. For each of the 11 components, we examined how each country applied the four recommended steps of situation analysis, problem prioritization, selection of interventions, and selection of indicators. We then conducted an analysis to determine the patterns of alignment of the comprehensive multiyear plans with those four recommended planning steps. RESULTS: Within the first 3 years following publication of the guidelines, 66 (86%) countries used the tool to develop their comprehensive multiyear plans. The funding conditions attached to the use of these guidelines appeared to influence their rapid adoption and usage. Overall, only 33 (43%) countries fully applied all four recommended planning steps of the guidelines. CONCLUSIONS: Adoption and usage of the guidelines for the development of comprehensive multiyear plans for national immunization programmes were rapid. However, our findings show substantial variation between the proposed planning ideals set out in the guidelines and actual use in practice. A better understanding of factors that influence how recommendations in public health guidelines are applied in practice could contribute to improvements in guidelines design. It could also help adjust strategies used to introduce them into public health programmes, with the ultimate goal of a greater health impact.

Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma.

BACKGROUND: HOX genes are a family of developmental genes that are expressed neither in the developing forebrain nor in the normal brain. Aberrant expression of a HOX-gene dominated stem-cell signature in glioblastoma has been linked with increased resistance to chemo-radiotherapy and sustained proliferation of glioma initiating cells. Here we describe the epigenetic and genetic alterations and their interactions associated with the expression of this signature in glioblastoma. RESULTS: We observe prominent hypermethylation of the HOXA locus 7p15.2 in glioblastoma in contrast to non-tumoral brain. Hypermethylation is associated with a gain of chromosome 7, a hallmark of glioblastoma, and may compensate for tumor-driven enhanced gene dosage as a rescue mechanism by preventing undue gene expression. We identify the CpG island of the HOXA10 alternative promoter that appears to escape hypermethylation in the HOX-high glioblastoma. An additive effect of gene copy gain at 7p15.2 and DNA methylation at key regulatory CpGs in HOXA10 is significantly associated with HOX-signature expression. Additionally, we show concordance between methylation status and presence of active or inactive chromatin marks in glioblastoma-derived spheres that are HOX-high or HOX-low, respectively. CONCLUSIONS: Based on these findings, we propose co-evolution and interaction between gene copy gain, associated with a gain of chromosome 7, and additional epigenetic alterations as key mechanisms triggering a coordinated, but inappropriate, HOX transcriptional program in glioblastoma.

Automatic Segmentation of the Eye in 3D Magnetic Resonance Imaging: A Novel Statistical Shape Model for Treatment Planning of Retinoblastoma.

PURPOSE: Proper delineation of ocular anatomy in 3-dimensional (3D) imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic resonance imaging (MRI) is presently used in clinical practice for diagnosis confirmation and treatment planning for treatment of retinoblastoma in infants, where it serves as a source of information, complementary to the fundus or ultrasonographic imaging. Here we present a framework to fully automatically segment the eye anatomy for MRI based on 3D active shape models (ASM), and we validate the results and present a proof of concept to automatically segment pathological eyes. METHODS AND MATERIALS: Manual and automatic segmentation were performed in 24 images of healthy children's eyes (3.29 ± 2.15 years of age). Imaging was performed using a 3-T MRI scanner. The ASM consists of the lens, the vitreous humor, the sclera, and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens, and the optic nerve, and then aligning the model and fitting it to the patient. We validated our segmentation method by using a leave-one-out cross-validation. The segmentation results were evaluated by measuring the overlap, using the Dice similarity coefficient (DSC) and the mean distance error. RESULTS: We obtained a DSC of 94.90 ± 2.12% for the sclera and the cornea, 94.72 ± 1.89% for the vitreous humor, and 85.16 ± 4.91% for the lens. The mean distance error was 0.26 ± 0.09 mm. The entire process took 14 seconds on average per eye. CONCLUSION: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor, and the lens, using MRI. We additionally present a proof of concept for fully automatically segmenting eye pathology. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.

Tales of the City. Storytelling as a contemporary tool of urban planning and design

Almost thirty years ago, as the social sciences underwent their 'discursive turn', Bernardo Secchi (1984) drew, in what he called the 'urban planning narrative', the attention of planners to the production of myths, turning an activity often seen as primarily technical into one centred around the production of images and ideas. This conception of planning practice gave rise to a powerful current of research in English-speaking countries. Efforts were made to both combine the urban planning narrative with storytelling and to establish storytelling as a prescriptive or descriptive model for planning practice. Thus, just as storytelling is supposed to have led democratic communication off track through a pronounced concern for a good story, storytelling applied to the field of urban production may have led to an increasing preoccupation with staging and showmanship for projects to the detriment of their real inclusion in political debate. It is this possible transformation of the territorial action that will be the focus of the articles collected in this special issue of Articulo - Journal of urban research.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.