Optimal control models of the goal-oriented human locomotion

In recent papers it has been suggested that human locomotion may be modeled as an inverse optimal control problem. In this paradigm, the trajectories are assumed to be solutions of an optimal control problem that has to be determined. We discuss the modeling of both the dynamical system and the cost to be minimized, and we analyze the corresponding optimal synthesis. The main results describe the asymptotic behavior of the optimal trajectories as the target point goes to infinity

Condensate cosmology in O'Raifeartaigh models

Flat directions charged under an R-symmetry are a generic feature of O'Raifeartaigh models. Non-topological solitons associated with this symmetry, R-balls, are likely to form through the fragmentation of a condensate, itself created by soft terms induced during inflation. In gravity mediated SUSY breaking R-balls decay to gravitinos, reheating the universe. For gauge mediation R-balls can provide a good dark matter candidate. Alternatively they can decay, either reheating or cooling the universe. Conserved R-symmetry permits decay to gravitinos or gauginos, whereas spontaneously broken R-symmetry results in decay to visible sector gauge bosons.Comment: 29 pages, 5 figures. Comments and references added, accepted for publication in JHE

Barriers and motivators to gaining access to smoking cessation services amongst deprived smokers – a qualitative study

BACKGROUND: Smoking is strongly associated with disadvantage and is an important contributor to inequalities in health. Smoking cessation services have been implemented in the UK targeting disadvantaged smokers, but there is little evidence available on how to design services to attract this priority group. METHODS: We conducted focus groups with 39 smokers aged 21–75 from the most socio-economically deprived areas of Nottingham UK who had made an unsuccessful attempt to quit within the last year without using smoking cessation services, to identify specific barriers or motivators to gaining access to these services. RESULTS: Barriers to use of existing services related to fear of being judged, fear of failure, a perceived lack of knowledge about existing services, a perception that available interventions – particularly Nicotine Replacement Therapy – are expensive and ineffective, and negative media publicity about bupropion. Participants expressed a preference for a personalised, non-judgemental approach combining counselling with affordable, accessible and effective pharmacological therapies; convenient and flexible timing of service delivery, and the possibility of subsidised complementary therapies. CONCLUSION: We conclude that smokers from these deprived areas generally had low awareness of the services available to help them, and misconceptions about their availability and effectiveness. A more personalised approach to promoting services that are non-judgemental, and with free pharmacotherapy and flexible support may encourage more deprived smokers to quit smoking

Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action

The 16S rRNA binding mechanism proposed for the antibacterial action of the tetracyclines does not explain their mechanism of action against non-bacterial pathogens. In addition, several contradictory base pairs have been proposed as their binding sites on the 16S rRNA. This study investigated the binding of minocycline and doxycycline to short double-stranded RNAs (dsRNAs) of random base sequences. These tetracyclines caused a dose-dependent decrease in the fluorescence intensities of 6-carboxyfluorescein (FAM)-labelled dsRNA and ethidium bromide (EtBr)-stained dsRNA, indicating that both drugs bind to dsRNA of random base sequence in a manner that is competitive with the binding of EtBr and other nucleic acid ligands often used as stains. This effect was observable in the presence of Mg2+. The binding of the tetracyclines to dsRNA changed features of the fluorescence emission spectra of the drugs and the CD spectra of the RNA, and inhibited RNase III cleavage of the dsRNA. These results indicate that the double-stranded structures of RNAs may have a more important role in their interaction with the tetracyclines than the specific base pairs, which had hitherto been the subject of much investigation. Given the diverse functions of cellular RNAs, the binding of the tetracyclines to their double-stranded helixes may alter the normal processing and functioning of the various biological processes they regulate. This could help to explain the wide range of action of the tetracyclines against various pathogens and disease condition

An evaluation of POSSUM and P-POSSUM scoring in predicting post-operative mortality in a level 1 critical care setting

Background POSSUM and P-POSSUM are used in the assessment of outcomes in surgical patients. Neither scoring systems’ accuracy has been established where a level 1 critical care facility (level 1 care ward) is available for perioperative care. We compared POSSUM and P-POSSUM predicted with observed mortality on a level 1 care ward. Methods A prospective, observational study was performed between May 2000 and June 2008. POSSUM and P-POSSUM scores were calculated for all postoperative patients who were admitted to the level 1 care ward. Data for post-operative mortality were obtained from hospital records for 2552 episodes of patient care. Observed vs expected mortality was compared using receiver operating characteristic (ROC) curves and the goodness of fit assessed using the Hosmer-Lemeshow equation. Results ROC curves show good discriminative ability between survivors and non-survivors for POSSUM and P-POSSUM. Physiological score had far higher discrimination than operative score. Both models showed poor calibration and poor goodness of fit (Hosmer-Lemeshow). Observed to expected (O:E) mortality ratio for POSSUM and P-POSSUM indicated significantly fewer than expected deaths in all deciles of risk. Conclusions Our data suggest a 30-60% reduction in O:E mortality. We suggest that the use of POSSUM models to predict mortality in patients admitted to level 1 care ward is inappropriate or that a recalibration of POSSUM is required to make it useful in a level 1 care ward setting

Recruiting to a large-scale physical activity randomised controlled trial – experiences with the gift of hindsight

Background: Recruitment issues continue to impact a large number of trials. Sharing recruitment information is vital to support researchers to accurately predict recruitment and to manage the risk of poor recruitment during study design and implementation. The purpose of this paper is to build on the knowledge available to researchers on recruiting to community based trials. Methods: A critical commentary of the recruitment challenges encountered during the ‘Booster’ Study, a randomised controlled trial which investigated the effectiveness of a Motivational Interviewing style intervention on the maintenance of physical activity. An overview of recruitment is provided, as well as strategies employed to recruit prospective participants and possible barriers to recruitment. Results: Two hundred and eighty two people, 47% of the original target, were recruited through mail-outs with secondary recruitment pathways yielding no additional participants. The research team encountered problems re-contacting interested participants and providing study materials in non-English languages. A lower response rate to the mail-out and a greater number of non-contactable participants in the full study compared to the pilot study resulted in a smaller pool of eligible participants from the brief intervention eligible for recruitment into the RCT. Conclusion: Despite utilising widely accepted recruitment strategies and incorporating new recruitment tactics in response to challenges, the ‘Booster’ study failed to randomise a sufficient number of participants. Recruitment to community based, behavioural interventions may face different challenges than trials based in clinical or primary care pathways. Specific challenges posed by the complexity of the study design and problems with staffing and resources were exacerbated by the need to revise upwards the number of mailed invitations as a result of the pilot study. Researchers should ensure study design is facilitative to recruitment and consider the implications of changing recruitment on the operational aspects of the trial. Where possible the impact of new strategies should be measured, and recruitment successes and challenges shared with those planning similar studies. The study was a registered controlled trial (ISRCTN56495859 12 Feb 2009; NCT00836459 03 Feb 2009) KEYWORDS: Recruitment, Physical Activity, mail-outs, BOOSTER, behaviour maintenance

Developmental trajectories of child to adolescent externalizing behavior and adult DSM-IV disorder: results of a 24-year longitudinal study

Objective: Childhood externalizing behavior is found to be relatively persistent. Developmental pathways within types of externalizing behavior have been recognized from childhood to adolescence. We aimed to describe the prediction of adult DSM-IV disorders from developmental trajectories of externalizing behavior over a period of 24 years on a longitudinal multiple birth cohort study of 2,076 children. This has not been examined yet. Methods: Trajectories of the four externalizing behavior types aggression, opposition, property violations, and status violations were determined separately through latent class growth analysis (LCGA) using data of five waves, covering ages 4-18 years. Psychiatric disorders of 1,399 adults were assessed with the CIDI. We used regression analyses to determine the associations between children's trajectories and adults' psychiatric disorders. Results: All externalizing behavior types showed significant associations with disruptive disorder in adulthood. In all antisocial behavior types high-level trajectories showed the highest probability for predicting adult disorders. Particularly the status violations cluster predicted many disorders in adulthood. The trajectories most often predicted disruptive disorders in adulthood, but predicted also anxiety, mood, and substance use disorders. Conclusions: We can conclude that an elevated level of externalizing behavior in childhood has impact on the long-term outcome, regardless of the developmental course of externalizing behavior. Furthermore, different types of externalizing beh

hTID-1 defines a novel regulator of c-Met Receptor signaling in renal cell carcinomas

The c-Met receptor tyrosine kinase (MetR) is frequently overexpressed and constitutively phosphorylated in a number of human malignancies. Activation of the receptor by its ligand, hepatocyte growth factor (HGF), leads to increased cell proliferation, motility, survival and disruption of adherens junctions. In this study, we show that hTid-1, a DNAJ/Hsp40 chaperone, represents a novel modulator of the MetR signaling pathway. hTid-1 is a co-chaperone of the Hsp70 family of proteins, and has been shown to regulate a number of cellular signaling proteins including several involved in tumorigenic and apoptotic pathways. In this study we demonstrate that hTid-1 binds to unphosphorylated MetR and becomes dissociated from the receptor upon HGF stimulation. Overexpression of the short form of hTid-1 (hTid-1S) in 786-0 renal clear cell carcinomas (RCCs) enhances MetR kinase activity leading to an increase in HGF-mediated cell migration with no discernible effect on cell proliferation. By contrast, knockdown of hTid-1 markedly impairs both the onset and amplitude of MetR phosphorylation in response to HGF without altering receptor protein levels. hTid-1-depleted cells display defective migratory properties, coincident with inhibition of ERK/MAP kinase and STAT3 pathways. Taken together, our findings denote hTid-1S as an essential regulatory component of MetR signaling. We propose that the binding of hTid-1S to MetR may stabilize the receptor in a ligand-competent state and this stabilizing function may influence conformational changes that take place during the catalytic cycle that promote kinase activation. Given the prevalence of HGF/MetR pathway activation in human cancers, targeted inhibition of hTid-1 may be a useful therapeutic in the management of MetR-dependent malignancies

The Eye of the Beholder: Youths and Parents Differ on What Matters in Mental Health Services

The goal of this study was to examine the degree to which youths and caregivers attend to different factors in evaluating their experiences with mental health programs. Youth (n = 251) receiving mental health services at community agencies and their caregivers (n = 275) were asked open-ended questions regarding the positive and negative aspects of the services. Qualitative analyses revealed some agreement but also divergence between youth and caregivers regarding the criteria by which services were evaluated and aspects of services that were valued most highly. Youths’ positive comments primarily focused on treatment outcomes while caregivers focused more on characteristics of the program and provider. Youths’ negative comments reflected dissatisfaction with the program, provider, and types of services offered while caregivers expressed dissatisfaction mainly with program characteristics. Results support the importance of assessing both youth and caregivers in attempts to understand the factors used by consumers to evaluate youth mental health services