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OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.
In the United Kingdom, compliance with guidelines on physical health monitoring of patients prescribed clozapine is poor. Our community team established a ‘clozapine clinic’, led by junior doctors, to monitor the physical health of this population.
The aims of this audit were:
– to ascertain levels of compliance with guidelines on the physical health monitoring of patients taking clozapine;
– to compare the current level of compliance with that prior to the establishment of the clinic.
Eleven standards were drawn from National Institute for Health and Care Excellence guidelines and the Maudsley Prescribing Guidelines in Psychiatry.
Three audit cycles were conducted: two prior to the establishment of the clinic and one after. In each cycle, searches of patient records were conducted and blood results were reviewed. This was supplemented by telephone calls to general practitioners to ensure a complete data set.
Analysis was conducted in Microsoft Excel™ and changes between the cycles were analysed using a two-tailed Z-score.
Each audit cycle included 28–30 patients. In the current cycle compliance levels varied between 66% (annual ECG recording) and 100% (monthly full blood count). The average compliance level was 73% across all standards. This represents an overall improvement on previous audit cycles. Since the clinic was established there has been a statistically significant improvement in compliance with annual monitoring of weight (P = 0.147), body mass index (P = 0.0178), and ECG monitoring (P = 0.0244).
Improvements in the care of a vulnerable population may be achieved through setting clear standards, regular audit, and harnessing the leadership and enthusiasm of junior doctors.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The small-scale fisheries sector in many Pacific islands is facing increasing challenges in relation to resource availability, economic opportunity, and demographic and social pressure. In particular, intensifying cash-oriented livelihood strategies can exacerbate existing vulnerabilities and threaten food security and resource conservation. In this paper the authors develop a bio-economic model and a quantitative measure of resilience in order to explore the interaction between socio-economic and ecological dynamics, and to analyze the potential role that cooperation and collective arrangements can play in this interaction to maintain the viability of the system. Based on the case of the system known as wantok typically found in the Solomon Islands, numerical examples are used to explore the potential gain that cooperation between fishers can bring in terms of subsistence, profitability and ecological performances, as well as the resilience of the whole system to shocks.
Most suicide attempters are referred to community health professionals (CHP) after discharge from emergency department (ED). Thereafter, outpatient treatment engagement (OTE) is often poor. Strengthening it seems likely to reduce the risk of repeat suicidal behaviour.
To identify the predictive factors of OTE.
Multicentre prospective study in true life conducted in adult patients (≥18) in 4 EDs of the Southern Paris region. Patients were referred to CHP. OTE was assessed by telephone calls at 1 and 3 months. OTE at 1 month was defined as having booked 1 appointment; OTE at 3 months as having attended 2 appointments and booked another one.
One hundred and fifty-five patients were assessed at 1 month and 144 at 3 months. OTE at 1 and 3 months was observed in 58% and 51% respectively. A multivariate analysis showed factors significantly predictive of OTE at 1 month: a psychiatric follow-up before the suicide attempt (SA), ≥2 psychiatric interviews during the stay at ED, appointment with CHP booked before discharge from the ED; and at 3 months: college or university education, absence of alcohol intake during the SA, psychiatric follow-up before the SA, appointment with CHP booked before discharge from the ED.
This multicentre prospective study highlights the benefit of booking outpatient appointment before discharge from ED; of allowing patient to benefit from at least two psychiatric interviews; of being particularly cautious with patients who took alcohol concomitantly to their SA, patients with low level of academic achievement and patients without psychiatric follow-up.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
RF-plasma MBE was used to epitaxially grow 4 – 100-nm-thick metallic
β-Nb2N thin films on hexagonal SiC substrates. When the
N/Nb flux ratios are greater than one, the most critical parameter for
high-quality β-Nb2N is the substrate temperature. The X-ray
diffraction (XRD) of films grown between 775 °C and 850 °C
demonstrates pure β-Nb2N phase formation which was also
confirmed by X-ray photoelectron spectroscopy and transmission electron
microscopy measurements. Using the (0002) and (21
1) XRD peaks of a β-Nb2N film grown at 850
°C reveals a 0.68% lattice mismatch to the 6H-SiC substrate. This
suggests that β-Nb2N can be used for high-quality
metal/semiconductor heterostructures that cannot be fabricated at present.
In this chapter we outline and discuss statistical approaches to the analysis of contest data, with an emphasis on testing key predictions and assumptions of the theoretical models described in Chapters 2 and 3. We use examples from an array of animal taxa, including cnidarians, arthropods and chordates, to illustrate these approaches and also the commonality of many key aspects of contest interactions despite the differing life histories and morphologies (including weaponry) of these organisms. We first deal with the analysis of contest outcomes, a useful approach for determining which traits contribute to an individual's resource holding potential (RHP). Here we outline alternative statistical approaches that treat the outcome as either an explanatory (independent) variable or as the response (dependent) variable. In both cases, we treat a single contest as one ‘experimental unit’ and consider ways in which multiple measures taken from the same experimental unit should be accounted for in the analysis. Thus, we introduce paired and repeated measures approaches for contest data and also the calculation of composite measures. We then discuss more complex mixed models, which are particularly useful for dealing with multi-party contests when multiple individuals from the same group occur in more than one observation. Having established what factors influence RHP, one might then ask questions about the roles of information-gathering and decision-making during contests. These questions are prompted by the theoretical models of dyadic contests discussed in Chapters 1 and 2, and we consider the advantages and limitations of using analysis of contest duration to distinguish between ‘mutual-’ and ‘self-assessment’ type contests. An additional tool that we can use to address this question is the analysis of escalation and de-escalation patterns, and we thus shift the focus to within-contest behavioural changes.
The insect order Hymenoptera is speciose, diverse and common. Many wasps, bees and ants are well known for their ability, and propensity, to engage in agonistic interactions via biting and stinging (chemical injection), and may also interact using chemical deposition and volatile chemical release. Such behaviours are often exhibited during acquisition and defence of resources contested either by conspecifics or by allospecific hymenopterans. Here we examine the types of contests engaged in by social and non-social hymenopterans and highlight links between these and further aspects of evolutionary and applied biology. We first consider factors influencing the outcomes of contests between pairs of females over resources for reproduction. Studies of female–female contests in bethylids and several non-aculeate species of parasitoid wasps, especially scelionids, pteromalids and eupelmids, have addressed fundamental causes of the outcomes of contest interactions and have further linked contest behaviour to strategies of patch exploitation, clutch size and parental care. Further, we review links between the study of contest behaviour in parasitoids and their use as agents of biological pest control, particularly in terms of how contest behaviour may constitute intra-guild predation and influence strategic decisions to deploy single or multiple species of natural enemies. We then consider contests between males for access to mates, especially those engaged in by fig wasps and other wasps. Male–male contests are placed in the context of the evolution of alternative male morphs, mating systems, sex ratios and social behaviours. Finally, we return to female–female contests, this time examining them in the more complex context of the social Hymenoptera, in which both between-individuals (intra-colony) and between-group (inter-colony) contests occur.
Bentonite is one of the more safety-critical components of the engineered barrier system in the disposal concepts developed for many types of radioactive waste. It is used due to its favourable properties (including plasticity, swelling capacity, colloid filtration, low hydraulic conductivity, high retardation of key radionuclides) and its stability in relevant geological environments. However, bentonite is unstable under alkaline conditions and this has driven interest in low-alkali cements (leachate pH of 10–11). To build a robust safety case, it is important to have supporting natural analogue data to confirm understanding of the likely long-term performance of bentonite. In Cyprus, the presence of natural bentonite in close proximity to natural alkaline groundwaters permits the zones of potential bentonite/alkaline water reaction to be studied as an analogy of the potential reaction zones in the repository. Here, the results indicate minimal volumetric reaction of bentonite, with production of a palygorskite secondary phase.
The Cyprus Natural Analogue Project was carried out due to the requirement to support ongoing laboratory and modelling efforts on the potential reaction of the bentonite buffer with cementitious leachates in the repository engineered barrier system. Although it is known that the higher pH (12.5–13) leachates from ordinary Portland cement will degrade bentonite, it is unclear if this will also be the case for the lower pH (10–11) leachates typical of low alkali cements. Ongoing laboratory and underground rock laboratory programmes, which are currently investigating this, face the obstacle of slow kinetics and the production of short-lived metastable phases, meaning obtaining unambiguous results may take decades. It was therefore decided to implement a focussed natural analogue study on bentonite/low alkali cement leachate reactions to provide indications of the probable long-term reaction products and reaction pathways to provide feedback on the existing short-term investigations noted above and to ascertain if any critical path research and development needs to be instigated now. The results of the analyses presented here, in this short overview of the project, suggest that there has been very limited alkaline groundwater reaction with the bentonite. This is generally supported by both the geomorphological evidence and the natural decay series data which imply groundwater/rock interaction in the last 105 a.