Investigating ion-surface collisions with a niobium superconducting tunnel junction detector in a time-of-flight mass spectrometer

The performance of an energy sensitive, niobium superconducting tunnel junction detector is investigated by measuring the pulse height produced by impacting molecular and atomic ions at different kinetic energies. Ions are produced by laser resorption and matrix-assisted laser desorption in a time-of-flight mass spectrometer. Results show that the STJ detector pulse height decreases for increasing molecular ion mass, passes through a minimum at around 2000 Da, and the increases with increasing mass of molecular ions above 2000Da. The detector does not show a decline in sensitivity for high mass ions as is observed with microchannel plate ion detectors. These detector plus height measurements are discussed in terms of several physical mechanisms involved in an ion-surface collision

Potent selective inhibitors of protein kinase C

AbstractA series of potent, selective inhibitors of protein kinase C has been derived from the structural lead provided by the microbial broth products, staurosporine and K252a. Our inhibitors block PCK in intact cells (platelets and T cells), and prevent the proliferation of mononuclear cells in response to interleukin 2 (IL2)

Client and therapist views of contextual factors related to termination from psychotherapy: A comparison between unilateral and mutual terminators

Contextual variables potentially influencing premature termination were examined. Clients (n = 83) and therapists (n = 35) provided parallel data on early working alliance, psychotherapy termination decision (unilateral vs. mutual), clients’ reasons for termination, and barriers to treatment participation. When clients unilaterally ended therapy, therapists were only partially aware of either the extent of clients’ perceived improvements or their dissatisfaction. When termination was mutually determined, there were no differences between client and therapist ratings of termination reasons. Although working alliance and barriers to treatment participation were rated as lower in the context of unilateral termination by clients and therapists, all clients rated the early alliance and barriers to treatment more highly than did therapists. Results have implications for understanding premature termination and suggest future research examining the utility of therapist feedback regarding contextual variables in terms of retaining clients in therapy

Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

A Systemic approach to scoping of factors influencing more sustainable land use in Herefordshire

Defining and putting into practice sustainable land use is a complex, systemic problem. Systems models and techniques were used in a study of Herefordshire to clarify the situation and identify the potential for a more locally focused, learning-based approach to land use. Issues included: (i) uncertainty about the boundary of a 'system of sustainable Herefordshire land use'; (ii) the complexity of economic flows in the county and the absence of some critical data; (iii) the importance of the Herefordshire landscape to tourism and the role of agriculture as a determinant of the state of that landscape; (iv) weakness of the institutional linkage between tourism and agriculture; (v) the current lack of inclusion of many relevant stakeholders in concerted action. Factors favouring a learning approach included a strong local identity, local food-related developments, and educational initiatives. Barriers to such an approach included questions of power and landholding, government policies, and attitudes and skills within organizations. These findings are considered in relation to the wider debate over approaches to sustainability

Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women.

CAPRISA, 2017.Abstract available in pdf

Cognition and bimanual performance in children with unilateral cerebral palsy: Protocol for a multicentre, cross-sectional study

© 2018 The Author(s). Background: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. Methods/Design: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. Discussion: This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy