Can Rachman’s indirect pathways be used to un-learn fear? A prospective paradigm to test whether children’s fears can be reduced using positive information and modelling a non-anxious response

This study investigated whether children’s fears could be un-learned using Rachman’s indirect pathways for learning fear. We hypothesised that positive information and modelling a non-anxious response are effective methods of un-learning fears acquired through verbal information. One hundred and seven children aged 6–8 years received negative information about one animal and no information about another. Fear beliefs and behavioural avoidance were measured. Children were randomised to receive positive verbal information, modelling, or a control task. Fear beliefs and behavioural avoidance were measured again. Positive information and modelling led to lower fear beliefs and behavioural avoidance than the control condition. Positive information was more effective than modelling in reducing fear beliefs and both methods significantly reduced behavioural avoidance. The results support Rachman’s indirect pathways as viable fear un-learning pathways and supports associative learning theories.

Phosphorus loss from agricultural catchments: pathways and implications for management

The contribution non-point P sources make to the total P loading on water bodies in agricultural catchments has not been fully appreciated. Using data derived from plot scale experimental studies, and modelling approaches developed to simulate system behaviour under differing management scenarios, a fuller understanding of the processes controlling P export and transformations along non-point transport pathways can be achieved. One modelling approach which has been successfully applied to large UK catchments (50-350km2 in area) is applied here to a small, 1.5 km2 experimental catchment. The importance of scaling is discussed in the context of how such approaches can extrapolate the results from plot-scale experimental studies to full catchment scale. However, the scope of such models is limited, since they do not at present directly simulate the processes controlling P transport and transformation dynamics. As such, they can only simulate total P export on an annual basis, and are not capable of prediction over shorter time scales. The need for development of process-based models to help answer these questions, and for more comprehensive UK experimental studies is highlighted as a pre-requisite for the development of suitable and sustainable management strategies to reduce non-point P loading on water bodies in agricultural catchments.

Ontology modeling for generation of clinical pathways

Purpose: Increasing costs of health care, fuelled by demand for high quality, cost-effective healthcare has drove hospitals to streamline their patient care delivery systems. One such systematic approach is the adaptation of Clinical Pathways (CP) as a tool to increase the quality of healthcare delivery. However, most organizations still rely on are paper-based pathway guidelines or specifications, which have limitations in process management and as a result can influence patient safety outcomes. In this paper, we present a method for generating clinical pathways based on organizational semiotics by capturing knowledge from syntactic, semantic and pragmatic to social level. Design/methodology/approach: The proposed modeling approach to generation of CPs adopts organizational semiotics and enables the generation of semantically rich representation of CP knowledge. Semantic Analysis Method (SAM) is applied to explicitly represent the semantics of the concepts, their relationships and patterns of behavior in terms of an ontology chart. Norm Analysis Method (NAM) is adopted to identify and formally specify patterns of behavior and rules that govern the actions identified on the ontology chart. Information collected during semantic and norm analysis is integrated to guide the generation of CPs using best practice represented in BPMN thus enabling the automation of CP. Findings: This research confirms the necessity of taking into consideration social aspects in designing information systems and automating CP. The complexity of healthcare processes can be best tackled by analyzing stakeholders, which we treat as social agents, their goals and patterns of action within the agent network. Originality/value: The current modeling methods describe CPs from a structural aspect comprising activities, properties and interrelationships. However, these methods lack a mechanism to describe possible patterns of human behavior and the conditions under which the behavior will occur. To overcome this weakness, a semiotic approach to generation of clinical pathway is introduced. The CP generated from SAM together with norms will enrich the knowledge representation of the domain through ontology modeling, which allows the recognition of human responsibilities and obligations and more importantly, the ultimate power of decision making in exceptional circumstances.

Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways

We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

Building networks to work: an ethnographic study of informal routes into the UK construction industry and pathways for migrant up-skilling

The UK construction industry labour market is characterised by high levels of self-employment, sub-contracting, informality and flexibility. A corollary of this, and a sign of the increasing globalisation of construction, has been an increasing reliance on migrant labour, particularly that from the Eastern European Accession states. Yet, little is known about how their experiences within and outside of work shape their work in the construction sector. In this context better qualitative understandings of the social and communication networks through which migrant workers gain employment, create routes through the sector and develop their role/career are needed. We draw on two examples from a short-term ethnographic study of migrant construction worker employment experiences and practices in the town of Crewe in Cheshire, UK, to demonstrate how informal networks intersect with formal elements of the sector to facilitate both recruitment and up-skilling. Such research knowledge, we argue, offers new evidence of the importance of attending to migrant worker’s own experiences in the development of more transparent recruitment processes.

Oxidised low-density lipoproteins induce rapid platelet activation and shape change through tyrosine kinase and Rho kinase-signaling pathways

Oxidized low-density lipoproteins (oxLDL) generated in the hyperlipidemic state may contribute to unregulated platelet activation during thrombosis. Although the ability of oxLDL to activate platelets is established, the underlying signaling mechanisms remain obscure. Weshow that oxLDL stimulate platelet activation through phosphorylation of the regulatory light chains of the contractile protein myosin IIa (MLC). oxLDL, but not native LDL, induced shape change, spreading, and phosphorylation of MLC (serine 19) through a pathway that was ablated under conditions that blocked CD36 ligation or inhibited Src kinases, suggesting a tyrosine kinase–dependent mechanism. Consistent with this, oxLDL induced tyrosine phosphorylation of a number of proteins including Syk and phospholipase C g2. Inhibition of Syk, Ca21 mobilization, and MLC kinase (MLCK) only partially inhibited MLC phosphorylation, suggesting the presence of a second pathway. oxLDL activated RhoA and RhoA kinase (ROCK) to induce inhibitory phosphorylation of MLC phosphatase (MLCP). Moreover, inhibition of Src kinases prevented the activation of RhoA and ROCK, indicating that oxLDL regulates contractile signaling through a tyrosine kinase–dependent pathway that induces MLC phosphorylation through the dual activation of MLCK and inhibition of MLCP. These data reveal new signaling events downstream of CD36 that are critical in promoting platelet aggregation by oxLDL.

‘Low carbon’ scenarios, roadmaps, transitions and pathways: an overview and discussion

There are a range of studies based in the low carbon arena which use various ‘futures’- based techniques as ways of exploring uncertainties. These techniques range from ‘scenarios’ and ‘roadmaps’ through to ‘transitions’ and ‘pathways’ as well as ‘vision’-based techniques. The overall aim of the paper is therefore to compare and contrast these techniques to develop a simple working typology with the further objective of identifying the implications of this analysis for RETROFIT 2050. Using recent examples of city-based and energy-based studies throughout, the paper compares and contrasts these techniques and finds that the distinctions between them have often been blurred in the field of low carbon. Visions, for example, have been used in both transition theory and futures/Foresight methods, and scenarios have also been used in transition-based studies as well as futures/Foresight studies. Moreover, Foresight techniques which capture expert knowledge and map existing knowledge to develop a set of scenarios and roadmaps which can inform the development of transitions and pathways can not only help potentially overcome any ‘disconnections’ that may exist between the social and the technical lenses in which such future trajectories are mapped, but also promote a strong ‘co-evolutionary’ content.

Temperature-dependent reduction pathways of complexes fac-[Re(CO)3(N-R-imidazole)(1,10-phenanthroline)]+ (R = H, CH3)

Peculiar reduction pathways of the complexes fac-[Re(imH)(CO)3(phen)]+ and fac-[Re(imCH3)(CO)3(phen)]+ (imH = imidazole, imCH3 = N-methylimidazole and phen = 1,10-phenanthroline) have been unravelled by performing combined cyclic voltammetric and in situ IR spectroelectrochemical experiments. In the temperature range of 293–233 K, the initial reduction of the phen ligand in [Re(imH)(CO)3(phen)]+ results in irreversible conversion of the imidazole ligand to 3-imidazolate by a rapid phen•−→ imH intramolecular electron transfer coupled with N H bond cleavage. This process is followed by second phen-localized 1e− reduction producing [ReI(3-im−)(CO)3(phen•−)]−, similar to the analogous 2,2'-bipyridine complex. In contrast to the bpy analogue, the stability of the phen•−-containing complexes is significantly affected by lowering the temperature. At 233 K, a secondary reaction occurs in both [Re(3-im−)(CO)3(phen•−)]− and [Re(imCH3)(CO)3(phen•−)]. The resulting products exhibit v(CO) wavenumbers indistinguishable from those of the parent phen•− complexes; however, their oxidation occurs at a considerably more positive electrode potential. It is proposed that these species are produced by a new C C bond formation between the C(2) site of 3-im− or imCH3 and the C(2) site of the phen•−ligand.

Biodiversity, cultural pathways, and human health: a framework

Direct contact with biodiversity is culturally important in a range of contexts. Many people even join conservation organisations to protect biodiversity that they will never encounter first-hand. Despite this, we have little idea how biodiversity affects people's well-being and health through these cultural pathways. Human health is sensitive to apparently trivial psychological stimuli, negatively affected by the risk of environmental degradation, and positively affected by contact with natural spaces. This suggests that well-being and health should be affected by biodiversity change, but few studies have begun to explore these relationships. Here, we develop a framework for linking biodiversity change with human cultural values, well-being, and health. We argue that better understanding these relations might be profoundly important for biodiversity conservation and public health.

Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.

Experimental confirmation of transformation pathways between inverse double diamond and gyroid cubic phases

A macroscopically oriented double diamond inverse bicontinuous cubic phase (QIID) of the lipid glycerol monooleate is reversibly converted into a gyroid phase (QIIG). The initial QIID phase is prepared in the form of a film coating the inside of a capillary, deposited under flow, which produces a sample uniaxially oriented with a ⟨110⟩ axis parallel to the symmetry axis of the sample. A transformation is induced by replacing the water within the capillary tube with a solution of poly(ethylene glycol), which draws water out of the QIID sample by osmotic stress. This converts the QIID phase into a QIIG phase with two coexisting orientations, with the ⟨100⟩ and ⟨111⟩ axes parallel to the symmetry axis, as demonstrated by small-angle X-ray scattering. The process can then be reversed, to recover the initial orientation of QIID phase. The epitaxial relation between the two oriented mesophases is consistent with topologypreserving geometric pathways that have previously been hypothesized for the transformation. Furthermore, this has implications for the production of macroscopically oriented QIIG phases, in particular with applications as nanomaterial templates.

Propeptide-mediated inhibition of myostatin increases muscle mass through inhibiting proteolytic pathways in aged mice

Mammalian aging is accompanied by a progressive loss of skeletal muscle, a process called sarcopenia. Myostatin, a secreted member of the transforming growth factor-β family of signaling molecules, has been shown to be a potent inhibitor of muscle growth. Here, we examined whether muscle growth could be promoted in aged animals by antagonizing the activity of myostatin through the neutralizing activity of the myostatin propeptide. We show that a single injection of an AAV8 virus expressing the myostatin propeptide induced an increase in whole body weights and all muscles examined within 7 weeks of treatment. Our cellular studies demonstrate that muscle enlargement was due to selective fiber type hypertrophy, which was accompanied by a shift toward a glycolytic phenotype. Our molecular investigations elucidate the mechanism underpinning muscle hypertrophy by showing a decrease in the expression of key genes that control ubiquitin-mediated protein breakdown. Most importantly, we show that the hypertrophic muscle that develops as a consequence of myostatin propeptide in aged mice has normal contractile properties. We suggest that attenuating myostatin signaling could be a very attractive strategy to halt and possibly reverse age-related muscle loss.

The housing pathways of young people in the UK

The authors examine the housing pathways of young people in the UK in the years 1999 to 2008, and consider the changing nature of these pathways in the run up to 2020. They employ a highly innovative methodology, which begins with the identification and description of key drivers likely to affect young people’s housing circumstances in the future. The empirical identification and analysis of housing pathways is then achieved using multiple-sequence analysis and cluster analysis of the British Household Panel Survey, contextualised by qualitative interviews with a large sample of young people. The authors describe how the interactions between the meanings, perceptions, and aspirations of young people, and the opportunities and constraints imposed by the drivers, are having a major impact on young people’s housing pathways, resulting in considerable housing policy challenges, particularly in relation to the private rented sector