Differential Geometry for Model Independent Analysis of Images and Other Non-Euclidean Data: Recent Developments

This article provides an exposition of recent methodologies for nonparametric analysis of digital observations on images and other non-Euclidean objects. Fr\'echet means of distributions on metric spaces, such as manifolds and stratified spaces, have played an important role in this endeavor. Apart from theoretical issues of uniqueness of the Fr\'echet minimizer and the asymptotic distribution of the sample Fr\'echet mean under uniqueness, applications to image analysis are highlighted. In addition, nonparametric Bayes theory is brought to bear on the problems of density estimation and classification on manifolds

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Professional identity formation in the transition from medical school to working life:a qualitative study of group-coaching courses for junior doctors

BACKGROUND: The transition from student to medical doctor is challenging and stressful to many junior doctors. To practice with confidence and professionalism the junior doctors have to develop a strong professional identity. Various suggestions on how to facilitate formation of professional identity have been offered including the possible positive effect of group-coaching courses. The purpose of this study was to explore how group-coaching might facilitate professional identity formation among junior doctors in the transition period. METHODS: Group-coaching courses comprising three whole-day sessions and five 2 h sessions during a period of 4 months were offered to junior doctors in the first years after graduation. The purpose was to support the participants’ professional development, ability to relate to patients, relatives and staff and career development. The coaches in this study had a background as health professionals combined with coaching educations. Data was obtained through observations, open-ended questionnaires and interviews. A generic thematic analysis was applied. RESULTS: Forty-five doctors participated in six coaching groups. The three main themes emerging in the sessions were: Adoption to medical culture, career planning, and work/life-balance. The junior doctors found the coaching intervention highly useful in order to cope with these challenges. Furthermore, the group was a forum where the junior doctors could share thoughts and feelings with colleagues without being afraid that this would endanger their professional career. Many found new ways to respond to everyday challenges mainly through a new awareness of patterns of thinking and feeling. CONCLUSIONS: The participants found that the group-coaching course supported their professional identity formation (thinking, feeling and acting as a doctor), adoption to medical culture, career planning and managing a healthy work/life-balance. Further studies in different contexts are recommended as well as studies using other methods to test the results of this qualitative study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12909-016-0684-3) contains supplementary material, which is available to authorized users

The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis

VEGF-A activity is tightly regulated by ligand and receptor availability. Here we investigate the physiological function of heterodimers between VEGF receptor-1 (VEGFR-1; Flt-1) and VEGFR-2 (KDR; Flk-1) (VEGFR(1-2)) in endothelial cells with a synthetic ligand that binds specifically to VEGFR(1-2). The dimeric ligand comprises one VEGFR-2-specific monomer (VEGF-E) and a VEGFR-1-specific monomer (PlGF-1). Here we show that VEGFR(1-2) activation mediates VEGFR phosphorylation, endothelial cell migration, sustained in vitro tube formation and vasorelaxation via the nitric oxide pathway. VEGFR(1-2) activation does not mediate proliferation or elicit endothelial tissue factor production, confirming that these functions are controlled by VEGFR-2 homodimers. We further demonstrate that activation of VEGFR(1-2) inhibits VEGF-A-induced prostacyclin release, phosphorylation of ERK1/2 MAP kinase and mobilization of intracellular calcium from primary endothelial cells. These findings indicate that VEGFR-1 subunits modulate VEGF activity predominantly by forming heterodimer receptors with VEGFR-2 subunits and such heterodimers regulate endothelial cell homeostasis

Motor control or graded activity exercises for chronic low back pain? A randomised controlled trial

Background: Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25-50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient

Fractional Sobolev Metrics on Spaces of Immersed Curves

Motivated by applications in the field of shape analysis, we study reparametrization invariant, fractional order Sobolev-type metrics on the space of smooth regular curves Imm(S1 , R ) and on its Sobolev completions ℐ (S1 , R ). We prove local well-posedness of the geodesic equations both on the Banach manifold ℐ (S1 , R ) and on the Fr´echetmanifold Imm(S1 , R ) provided the order of the metric is greater or equal to one. In addition we show that the -metric induces a strong Riemannian metric on the Banach manifold ℐ (S1 , R ) of the same order , provided > 3 2 . These investigations can be also interpreted as a generalization of the analysis for right invariant metrics on the diffeomorphism group

Mycobacterium tuberculosis Transcriptional Adaptation, Growth Arrest and Dormancy Phenotype Development Is Triggered by Vitamin C

BACKGROUND: Tubercle bacilli are thought to persist in a dormant state during latent tuberculosis (TB) infection. Although little is known about the host factors that induce and maintain Mycobacterium tuberculosis (M. tb) within latent lesions, O(2) depletion, nutrient limitation and acidification are some of the stresses implicated in bacterial dormancy development/growth arrest. Adaptation to hypoxia and exposure to NO/CO is implemented through the DevRS/DosT two-component system which induces the dormancy regulon. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that vitamin C (ascorbic acid/AA) can serve as an additional signal to induce the DevR regulon. Physiological levels of AA scavenge O(2) and rapidly induce the DevR regulon at an estimated O(2) saturation of <30%. The kinetics and magnitude of the response suggests an initial involvement of DosT and a sustained DevS-mediated response during bacterial adaptation to increasing hypoxia. In addition to inducing DevR regulon mechanisms, vitamin C induces the expression of selected genes previously shown to be responsive to low pH and oxidative stress, triggers bacterial growth arrest and promotes dormancy phenotype development in M. tb grown in axenic culture and intracellularly in THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Vitamin C mimics multiple intracellular stresses and has wide-ranging regulatory effects on gene expression and physiology of M. tb which leads to growth arrest and a 'dormant' drug-tolerant phenotype, but in a manner independent of the DevRS/DosT system. The 'AA-dormancy infection model' offers a potential alternative to other models of non-replicating persistence of M. tb and may be useful for investigating host-'dormant' M. tb interactions. Our findings offer a new perspective on the role of nutritional factors in TB and suggest a possible role for vitamin C in TB

Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses

Background: In most high and middle income countries across the world, at least 1:4 women give birth by cesarean section. Rates of labour induction and augmentation are rising steeply; and in some countries up to 50 % of laboring women and newborns are given antibiotics. Governments and international agencies are increasingly concerned about the clinical, economic and psychosocial effects of these interventions. Discussion: There is emerging evidence that certain intrapartum and early neonatal interventions might affect the neonatal immune response in the longer term, and perhaps trans-generationally. Two theories lead the debate in this area. Those aligned with the hygiene (or ‘Old Friends’) hypothesis have examined the effect of gut microbiome colonization secondary to mode of birth and intrapartum/neonatal pharmacological interventions on immune response and epigenetic phenomena. Those working with the EPIIC (Epigenetic Impact of Childbirth) hypothesis are concerned with the effects of eustress and dys-stress on the epigenome, secondary to mode of birth and labour interventions. Summary: This paper examines the current and emerging findings relating to childbirth and atopic/autoimmune disease from the perspective of both theories, and proposes an alliance of research effort. This is likely to accelerate the discovery of important findings arising from both approaches, and to maximize the timely understanding of the longer-term consequences of childbirth practices