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The hydrological niche is one of the few below ground spatial environmental niches, which has been shown to structure English floodplain meadows and other European and African herbaceous ecosystems. However, both the relative contribution of hydrological heterogeneity to the structure of English floodplain meadows across spatial scales and the forms of the individual species’ responses to hydrological heterogeneity remain largely unknown. Here, we use a survey database of 2440 evaluation units sampled in 15 English floodplain meadows to dissect the spatial architecture of this metacommunity and describe the relationship between the abundance of individual species and hydrological heterogeneity. Of the tested species, 65% responded to spatial hydrological heterogeneity, with both monotonic and hump-shaped responses. We found that between-site beta-diversity is much stronger than within-site beta-diversity, with between-site scale hydrological variation explaining twice as much variation in community structure as within-site scale. This leads to the conclusion that a conservation strategy of rare plant communities should include not only the preservation of the diversity of local hydrological regimes, but also, specially, the inclusion in the conservation system of as many and environmentally varied local plant communities as possible.

Although most chronic wounds possess an underlying pathology, infectious agents also contribute. In many instances, pathogens exist as biofilms forming clusters surrounded by a secreted extracellular substance. We hypothesized that compounds secreted by biofilm bacteria may inhibit normal wound healing events including cell proliferation and migration. Conditioned media from two common bacterial species associated with chronic skin wounds and chronic tympanic membrane perforations, Staphylococcus aureus and Pseudomonas aeruginosa , were evaluated for their capacity to affect keratinocyte proliferation and migration. Additionally, proteomic analysis was performed to identify proteins within the biofilm conditioned media that may contribute to these observed effects. Biofilm conditioned media from both species inhibited proliferation in human tympanic membrane derived keratinocytes, whereas only biofilm conditioned media from S. aureus inhibited migration. Human epidermal keratinocytes were found to be more sensitive to the effects of the conditioned media resulting in high levels of cell death. Heat treatment and microfiltration suggested that S. aureus activity was due to a protein, while P. aeruginosa activity was more likely due to a small molecule. Proteomic analysis identified several proteins with putative links to delayed wound healing. These include alpha hemolysin, alcohol dehydrogenase, fructose-bisphosphate aldolase, lactate dehydrogenase and epidermal cell differentiation inhibitor.

The time-critical ‘can’t intubate, can’t oxygenate’ [CICO] emergency post-induction of anaesthesia is rare, but one which, should it occur, requires Anaesthetists to perform rapid emergency front of neck access [FONA] to the trachea, restoring oxygenation, and preventing death or brain hypoxia. The UK Difficult Airway Society [DAS] has directed all Anaesthetists to be trained with surgical cricothyroidotomy [SCT] as the primary emergency FONA method, sometimes referred to as ‘Cric’ as a shorthand. We present a longitudinal analysis using a classical approach to Grounded Theory methodology of ten Specialist Trainee Anaesthetists’ data during a 6-month training programme delivered jointly by Anaesthetists and Surgeons. We identified with a critical realist ontology and an objectivist epistemology meaning data interpretation was driven by participants’ narratives and accepted as true accounts of their experience. Our theory comprises three themes: ‘Identity as an Anaesthetist’; ‘The Role of a Temporary Surgeon’; and ‘Training to Reconcile Identities’, whereby training facilitated the psychological transition from a ‘bloodless Doctor’ (Anaesthetist) to becoming a ‘temporary Surgeon’. The training programme enabled Specialist Trainees to move between the role of control and responsibility (Identity as an Anaesthetist), through self-described ‘failure’ and into a role of uncertainty about one’s own confidence and competence (The Role of a Temporary Surgeon), and then return to the Anaesthetist’s role once the airway had been established. Understanding the complexity of an intervention and providing a better insight into the training needs of Anaesthetic trainees, via a Grounded Theory approach, allows us to evaluate training programmes against the recognised technical and non-technical needs of those being trained.

Communities in urban slums face multiple risks to their health. These are shaped by intermediary and structural determinants. Gaining a clear understanding of these determinants is a prerequisite for developing interventions to reduce the health consequences of urban poverty. With 828 million people living in slum conditions, the need to find ways to reduce risks to health has never been greater. In many low income settings, the kitchen is the epicentre of activities and behaviours which either undermine or enhance health. We used qualitative methods of semi-structured interviews, observation and participatory workshops in two slum areas in Kathmandu, Nepal to gain women's perspectives on the health risks they faced in and around their kitchens. Twenty one women were interviewed and four participatory workshops with a total of 69 women were held. The women took photographs of their kitchens to trigger discussions. The main health conditions identified by the women were respiratory disease, gastrointestinal disease and burn injuries. Women clearly understood intermediary (psychosocial, material and behavioural) determinants to these health conditions such as poor ventilation, cooking on open fires, over-crowding, lack of adequate child supervision. Women articulated the stress they experienced and clearly linked this to health conditions such as heart disease and uptake of smoking. They were also able to identify protective factors, particularly social capital. Subsequent analysis highlighted how female headed-households and those with disabilities had to contend with greater risks to health. Women living in slums are very aware of the intermediary determinants-material, behavioural and psycho-social, that increase their vulnerability to ill health. They are also able to identify protective factors, particularly social capital. It is only by understanding the determinants at all levels, not just the behavioural, that we will be able to identify appropriate interventions.

Background There is a lack of rigorous research investigating the factors that influence scar outcome in children. Improved clinical decision-making to reduce the health burden due to post-burn scarring in children will be guided by evidence on risk factors and risk stratification. This study aimed to examine the association between selected patient, injury and clinical factors and the development of raised scar after burn injury. Novel patient factors were investigated including selected immunological co-morbidities (asthma, eczema and diabetes type 1 and type 2) and skin pigmentation (Fitzpatrick skin type). Methods A prospective case-control study was conducted among 186 children who sustained a burn injury in Western Australia. Logistic regression was used to explore the relationship between explanatory variables and a defined outcome measure: scar height measured by a modified Vancouver Scar Scale (mVSS). Results The overall correct prediction rate of the model was 80.6%; 80.9% for children with raised scars (>1 mm) and 80.4% for children without raised scars (≤1 mm). After adjustment for other variables, each 1% increase in % total body surface area (%TBSA) of burn increased the odds of raised scar by 15.8% (95% CI = 4.4–28.5%). Raised scar was also predicted by time to healing of longer than 14 days (OR = 11.621; 95% CI = 3.727–36.234) and multiple surgical procedures (OR = 11.521; 1.994–66.566). Conclusions Greater burn surface area, time to healing of longer than 14 days, and multiple operations are independently associated with raised scar in children after burn injury. Scar prevention strategies should be targeted to children with these risk factors.

In a 'can't intubate, can't oxygenate' scenario, success of emergency front-of-neck access is dependent upon a clinician's skill, competence and confidence to initiate the procedure. Surgical cricothyroidotomy is an important airway skill, as it can be employed as both the primary method of emergency front-of-neck access or as a rescue approach if a needle technique should fail. We designed a collaborative surgical and anaesthetic training package to address perceived anaesthetic reluctance to perform surgical cricothyroidotomy and undertook a pilot study of the package using a mixed-methods approach. The package consisted of three elements: theory teaching, surgical experience and repeated high-fidelity simulation. Ten anaesthetic trainees were trained using the package. Training comprised face-to-face tuition on the 2015 Difficult Airway Society guidelines, the Vortex cognitive aid, manikin-based surgical cricothyroidotomy instruction and surgical experience gained from an elective surgical tracheostomy. A standardised, high-fidelity in situ 'can't intubate, can't oxygenate' simulation was used to assess performance at baseline and at two weeks and six months after training. Participants scored their self-efficacy, underwent qualitative semi-structured interviews and had their performance quantitatively assessed to evaluate this training. Six months following training, participants' performance had improved. They reported significantly increased self-efficacy and demonstrated significantly reduced deliberation time to initiate surgical cricothyroidotomy in the simulated 'can't intubate, can't oxygenate' emergency. Thematic framework analysis of interview transcripts revealed that reluctance to perform surgical cricothyroidotomy was related to fear and anxiety in regard to performing the procedure. These results support wider adoption of collaborative educational training packages, including hands-on surgical teaching, to improve trainees' efficacy and confidence with surgical cricothyroidotomy and front-of-neck access in an emergency 'can't intubate, can't oxygenate' scenario.

Background and objective: Data are sparse on how well the absolute risk approach is implemented in primary healthcare. The aim of this study was to quantify absolute cardiovascular disease (CVD) risk, appropriate use of blood pressure (BP)-lowering and lipid-lowering therapy, and clinical target responses in the Busselton baby boomer population. Methods: This was a cross-sectional study of 5107 people aged 45-69 years (54.6% female) who participated in the 2010-2015 Busselton Healthy Ageing Study. Results: Overall, 16.1% of participants had prior CVD (5.8%) or a high primary CVD risk (10.3%). The frequency of use of a guideline-recommended combination of BP-lowering and lipid-lowering therapy was 46.2% in participants with prior CVD, compared with only 16.8% in those with high primary CVD risk (P <0.001). Among the high-risk participants who were receiving recommended combination therapy, only 42.7% achieved target systolic BP levels and 42.1% achieved target total cholesterol levels. Discussion: These data confirm substantial under-treatment of Australian adults who are at high CVD risk. Enhanced implementation of absolute CVD risk assessment and evidence-based treatment in high-risk adults has potential for substantial health gains.

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.

Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients’ tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a ‘scar-in-a-jar’ model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.

This pilot study investigated oral doxycycline as an adjunct to compression therapy for non-healing venous leg ulcers. Ten patients received doxycycline 20 mg twice daily (low-dose doxycycline) and ten patients received doxycycline 100 mg twice daily (high-dose doxycycline). Utilising a pre-test post-test study design, ulcer area was measured and wound fluid was collected before and after 4 weeks of treatment. In the high-dose doxycycline group, the reduction in median ulcer area was 48% ( p  = 0.1) and there was a significant reduction in wound fluid total matrix metalloprotease-1 ( p  = 0.02). These effects were not observed with low-dose doxycycline. There were no significant changes in wound fluid tumour necrosis factor-α or quantitative bacteriology following treatment with low-dose or high-dose doxycycline. There was no significant relationship between change in ulcer area and matrix metalloprotease-1, -8 or -9 activities in wound fluid at the end of treatment. Median wound fluid doxycycline concentrations after 4 weeks of treatment were 0.2 (0.45 μM) and 2.3 (5.18 μM) in the low-dose and high-dose groups, respectively, which are lower than that previously shown to inhibit matrix metalloproteases and tumour necrosis factor-α. Our study suggests that doxycycline 100 mg twice daily may improve the healing rate of recalcitrant leg ulcers, however the mechanism remains unclear.