Autophagic cell death exists.

The term autophagic cell death (ACD) initially referred to cell death with greatly enhanced autophagy, but is increasingly used to imply a death-mediating role of autophagy, as shown by a protective effect of autophagy inhibition. In addition, many authors require that autophagic cell death must not involve apoptosis or necrosis. Adopting these new and restrictive criteria, and emphasizing their own failure to protect human osteosarcoma cells by autophagy inhibition, the authors of a recent Editor's Corner article in this journal argued for the extreme rarity or nonexistence of autophagic cell death. We here maintain that, even with the more stringent recent criteria, autophagic cell death exists in several situations, some of which were ignored by the Editor's Corner authors. We reject their additional criterion that the autophagy in ACD must be the agent of ultimate cell dismantlement. And we argue that rapidly dividing mammalian cells such as cancer cells are not the most likely situation for finding pure ACD.

Mutual trust and cooperation in the evolutionary hawks-doves game

Using a new dynamical network model of society in which pairwise interactions are weighted according to mutual satisfaction, we show that cooperation is the norm in the hawks-doves game when individuals are allowed to break ties with undesirable neighbors and to make new acquaintances in their extended neighborhood. Moreover, cooperation is robust with respect to rather strong strategy perturbations. We also discuss the empirical structure of the emerging networks, and the reasons that allow cooperators to thrive in the population. Given the metaphorical importance of this game for social interaction, this is an encouraging positive result as standard theory for large mixing populations prescribes that a certain fraction of defectors must always exist at equilibrium.

IRM cardiaque en évolution: de grandes études multicentriques en 2012 [Cardiac MR in development: the large multicenter CMR studies in 2012].

The results of several large multicenter CMR studies were reported in 2012, thus, constantly corroborating the evidence on CMR performance. In this review, we present results of the MR-IMPACT programme and the CE-MARC study, which demonstrated the superiority of perfusion-CMR over gated SPECT for the workup of suspected CAD, the currently available data from the European CMR registry, comprising almost 30,000 patients from 57 participating centers in 15 European countries, and finally, the results of the Advisa-MRI study, which documented the safety of a MRI-compatible pacemaker system. These large trials and others set the basis for the recommendations in the new European guidelines on heart failure to use CMR as a first line method if echocardiographic quality is inadequate or the etiology of heart failure is unclear.

Patient expectations at a multicultural out-patient clinic in Switzerland.

BACKGROUND: Recognizing patient expectation is considered as an important objective for primary care physicians. A number of studies suggest that failure to identify patient expectations can lead to patient dissatisfaction with care, lack of compliance and inappropriate use of medical resources. It has been suggested that identifying patient expectations in multicultural contexts can be especially challenging. OBJECTIVES: The aim of the study was to compare health care expectations of Swiss and immigrant patients attending the out-patient clinic of a Swiss university hospital and to assess physicians' ability to identify their patients' expectations. METHODS: Over a 3-month period, all patients attending the out-patient clinic at a Swiss university hospital were requested to complete pre-consultation surveys. Their physicians were requested to complete post-consultation surveys. Outcome measures were patients' self-rated health, resort to prior home treatment, patients' expectations of the consultation, physicians' perception of their patients' expectations and agreement between patients and physicians. RESULTS: We analysed 343 questionnaires completed by patients prior to their consultation (> 50% immigrants) and 333 questionnaires completed by their physicians after the consultation. Most expectations were shared by all patients. Physicians had inaccurate perceptions of their patients' expectations, regardless of patients' origin. CONCLUSIONS: Our study found no evidence that immigrant patients' expectations differed from those of Swiss patients, nor that physicians had more difficulty identifying expectations of immigrant patients. However, physicians in our study were generally poor at identifying patients' expectations, and therefore inter-group differences may be difficult to detect. Our results point to the need to strengthen physicians' general communication skills which should then serve as a foundation for more specific, cross-cultural communication training.

How important are interview methods and questionnaire designs in research on self-reported juvenile delinquency? An experimental comparison of internet vs. paper-and-pencil questionnaires and different definitions of the reference period

There has been relatively little change over recent decades in the methods used in research on self-reported delinquency. Face-to-face interviews and selfadministered interviews in the classroom are still the predominant alternatives envisaged. New methods have been brought into the picture by recent computer technology, the Internet, and an increasing availability of computer equipment and Internet access in schools. In the autumn of 2004, a controlled experiment was conducted with 1,203 students in Lausanne (Switzerland), where "paper-and-pencil" questionnaires were compared with computer-assisted interviews through the Internet. The experiment included a test of two different definitions of the (same) reference period. After the introductory question ("Did you ever..."), students were asked how many times they had done it (or experienced it), if ever, "over the last 12 months" or "since the October 2003 vacation". Few significant differences were found between the results obtained by the two methods and for the two definitions of the reference period, in the answers concerning victimisation, self-reported delinquency, drug use, failure to respond (missing data). Students were found to be more motivated to respond through the Internet, take less time for filling out the questionnaire, and were apparently more confident of privacy, while the school principals were less reluctant to allow classes to be interviewed through the Internet. The Internet method also involves considerable cost reductions, which is a critical advantage if self-reported delinquency surveys are to become a routinely applied method of evaluation, particularly so in countries with limited resources. On balance, the Internet may be instrumental in making research on self-reported delinquency far more feasible in situations where limited resources so far have prevented its implementation.

A Note on Interviewer Performance Measures in centralised CATI Surveys

Interviewer performance with respect to convincing sample members to participate in surveys is an important dimension of survey quality. However, unlike in CAPI surveys where each sample case 'belongs' to one interviewer, there are hardly any good measures of interview performance for centralised CATI surveys, where even single contacts are assigned to interviewers at random. If more than one interviewer works one sample case, it is not clear how to attribute success or failure to the interviewers involved. In this article, we propose two correlated methods to measure interviewer contact performance in centralised CATI surveys. Their modelling must take complex multilevel clustering effects, which need not be hierarchical, into account. Results are consistent with findings from CAPI data modelling, and we find that when comparing effects with a direct ('naive') measure of interviewer contact results, interviewer random effects are largely underestimated using the naive measure.

Issue review : narrowband mandate and state agency communications systems.

The federal government mandated that all non-federal public safety license holders on the frequencies ranging from 150 to 512 megahertz reduce their operating bandwidth from 25 kilohertz to 12.5 kilohertz. Narrowband channels must update their operating licenses by January 1, 2013. Failure to do so will result in the loss of communication capabilities and fines. This issue review analyzes the impact to state agencies of the federal mandate requiring all two-way radio systems and some paging networks, including those used by public-safety agencies, to meet the new narrowband requirements by January 1, 2013. This issue review does not address the impact to local communications systems.

Surfactant palmitoylmyristoylphosphatidylcholine is a marker for alveolar size during disease.

Two common lung-related complications in the neonate are respiratory distress syndrome, which is associated with a failure to generate low surface tension at the air-liquid interface because of pulmonary surfactant insufficiency, and bronchopulmonary dysplasia (BPD), a chronic lung injury with reduced alveolarization. Surfactant phosphatidylcholine (PC) molecular species composition during alveolarization has not been examined. Mass spectrometry analysis of bronchoalveolar lavage fluid of rodents and humans revealed significant changes in surfactant PC during alveolar development and BPD. In rats, total PC content rose during alveolarization, which was caused by an increase in palmitoylmyristoyl-PC (16:0/14:0PC) concentration. Furthermore, two animal models of BPD exhibited a specific reduction in 16:0/14:0PC content. In humans, 16:0/14:0PC content was specifically decreased in patients with BPD and emphysema compared with patients without alveolar pathology. Palmitoylmyristoyl-PC content increased with increasing intrinsic surfactant curvature, suggesting that it affects surfactant function in the septating lung. The changes in acyl composition of PC were attributed to type II cells producing an altered surfactant during alveolar development. These data are compatible with extracellular surfactant 16:0/14:0PC content being an indicator of alveolar architecture of the lung.

Feasibility Investigation of Segmentally Precast Bridge Piers for Accelerated Construction, TR-556, 2009

An innovative structural system for pier columns was investigated through a series of laboratory experiments. The columns and connections examined were comprised of precast concrete segments to accelerate construction. In addition some of the columns employed unbonded post-tensioning to self-center the columns when subjected to lateral loads and structural fuses to control large lateral deflections, dissipate energy, and expedite repair in the event of a catastrophic loading event. Six cantilever columns with varying component materials and connection details were subjected to a regimen of vertical dead loads and cyclic, quasi-static lateral loads. One column was designed as a control column to represent the behavior of a conventional reinforced concrete column and provide a basis for comparison with the remaining five jointed columns designed with the proposed structural system. After sustaining significant damage, the self-centering, jointed columns were repaired by replacing the structural fuses and retested to failure to investigate the effectiveness of the repair. The experiments identified both effective and unsatisfactory details for the jointed system. Two of the jointed columns demonstrated equivalent lateral strength, greater lateral stiffness, and greater lateral deformation capacity than the control column. The self-centering capability of the jointed columns was clearly demonstrated as well, and the repair technique proved effective as demonstrated by nearly identical pre and post repair behavior. The authors believe the proposed system to be a feasible alternative to conventional pier systems and recommend further development of details.

Temporal changes of an alfalfa succession and related soil physical properties on the Loess Plateau, China

The objective of this work was to investigate the relationship between changes in the plant community and changes in soil physical properties and water availability, during a succession from alfalfa (Medicago sativa L.) to natural vegetation on the Loess Plateau, China. Data from a succession sere spanning 32 years were collated, and vegetative indexes were compared to changes related to soil bulk density and soil water storage. The alfalfa yield increased for approximately 7 years, then it declined and the alfalfa was replaced by a natural community dominated by Stipa bungeana that began to thrive about 10 years after alfalfa seeding. Soil bulk density increased over time, but the deterioration of the alfalfa was mainly ascribed to a severe reduction in soil water storage, which was lowest around the time when degradation commenced. The results indicated that water consumption by alfalfa could be reduced by reducing plant density. The analysis of the data also suggested that soil water recharge could be facilitated by rotating the alfalfa with other crops, natural vegetation, or bare soil.

In-Pavement Pedestrian Flasher Evaluation: Cedar Rapids, Iowa, 2004

Numerous strategies have been experimented with nationwide in an attempt to reduce the overall number of pedestrian-vehicle crashes, especially in instances where improper crossing or failure to yield was the proximate cause of the crash. Some of these measures include overhead signs, flashing warning beacons, advanced crossing signs, more visible pavement markings, in-street “Yield to Pedestrian” signs, and more recently, in-pavement flashing lights. Pedestrian safety has been a key issue for the City of Cedar Rapids, Iowa, in particular at non-controlled intersections and mid-block crossings. In 2002, the city council gave preliminary approval to implement a pedestrian-actuated overhead flasher system in conjunction with an in-pavement flasher system at the intersection of 1st Avenue NE and 4th Street NE in the downtown central business district. This location is uncontrolled and has several elements that can create conflicts between pedestrians, vehicles, and trains that service local industry. This report summarizes the results from a small-scale study completed by CTRE to evaluate the effectiveness of the in-pavement flasher system installed in downtown Cedar Rapids. The installation of in-pavement flashing warning lights at the pedestrian crosswalk at this site has had a net positive effect on the safety characteristics of the location. The results of this study show a marked improvement in motorist compliance with the state law requiring that motorists yield to pedestrians in the crosswalk. The pedestrian and motorist surveys show that both groups felt the in-pavement flashing lights have increased motorist awareness, especially at night. The data indicate the in-pavement flashing warning lights improved the motorists' response to pedestrians in the area, and that the system could be operational throughout summer and winter conditions.

The Schizosaccharomyces pombe cdc14 gene is required for septum formation and can also inhibit nuclear division.

A conditional heat-sensitive mutation in the cdc14 gene of the fission yeast Schizosaccharomyces pombe results in failure to form a septum. Cells become highly elongated and multinucleate as growth and nuclear division continue in the absence of cell division. This article describes the cloning of the cdc14 gene and the identification of its product, a protein of 240 amino acids, p28cdc14. A null allele of the cdc14 gene shows that the gene is essential for septum formation and completion of the cell-division cycle. Overexpression of the gene product, p28cdc14, causes cell-cycle arrest in late G2 before mitosis. Cells leaking past the block activate p34cdc2 kinase and show condensed chromosomes, but the normal rearrangements of the microtubules and microfilaments that are associated with the transition from interphase to mitosis do not occur. Overexpression of p28cdc14 in mutants, in which the timing of mitosis is altered, suggests that these effects may be mediated upstream of the mitotic inhibitor wee1. These data are consistent with the idea that p28cdc14 may play a role in both the initiation of mitosis and septum formation and, by doing so, be part of the mechanism that coordinates these two cell-cycle events.

Detecting, quantifying and adjusting for publication bias in meta-analyses: protocol of a systematic review on methods.

BACKGROUND: Health professionals and policymakers aspire to make healthcare decisions based on the entire relevant research evidence. This, however, can rarely be achieved because a considerable amount of research findings are not published, especially in case of 'negative' results - a phenomenon widely recognized as publication bias. Different methods of detecting, quantifying and adjusting for publication bias in meta-analyses have been described in the literature, such as graphical approaches and formal statistical tests to detect publication bias, and statistical approaches to modify effect sizes to adjust a pooled estimate when the presence of publication bias is suspected. An up-to-date systematic review of the existing methods is lacking. METHODS/DESIGN: The objectives of this systematic review are as follows:âeuro¢ To systematically review methodological articles which focus on non-publication of studies and to describe methods of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses.âeuro¢ To appraise strengths and weaknesses of methods, the resources they require, and the conditions under which the method could be used, based on findings of included studies.We will systematically search Web of Science, Medline, and the Cochrane Library for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses. A dedicated data extraction form is developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article. As this will be a qualitative systematic review, data reporting will involve a descriptive summary. DISCUSSION: Results are expected to be publicly available in mid 2013. This systematic review together with the results of other systematic reviews of the OPEN project (To Overcome Failure to Publish Negative Findings) will serve as a basis for the development of future policies and guidelines regarding the assessment and handling of publication bias in meta-analyses.

c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation.

The activity of adult stem cells is essential to replenish mature cells constantly lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. Here, we provide genetic evidence for an unexpected function of the c-Myc protein in the homeostasis of hematopoietic stem cells (HSCs). Conditional elimination of c-Myc activity in the bone marrow (BM) results in severe cytopenia and accumulation of HSCs in situ. Mutant HSCs self-renew and accumulate due to their failure to initiate normal stem cell differentiation. Impaired differentiation of c-Myc-deficient HSCs is linked to their localization in the differentiation preventative BM niche environment, and correlates with up-regulation of N-cadherin and a number of adhesion receptors, suggesting that release of HSCs from the stem cell niche requires c-Myc activity. Accordingly, enforced c-Myc expression in HSCs represses N-cadherin and integrins leading to loss of self-renewal activity at the expense of differentiation. Endogenous c-Myc is differentially expressed and induced upon differentiation of long-term HSCs. Collectively, our data indicate that c-Myc controls the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSCs and their niche.

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities.

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics.