VEGF-C is associated with lymphatic status and invasion in oral cancer

Background: Nodal metastasis is a major prognostic indicator for oral squamous cell carcinoma (OSCC) progression. Recently, it has been revealed that lymphangiogenic growth factor VEGF-C and its receptor Flt-4 play an important role for invasion and metastasis in cancer cells. Aim: To examine VEGF-C expression and its correlation with lymphatic status, including the number of lymph vessels and lymphatic invasion, tumour invasion and metastasis in OSCC. Methods: Intratumoural and peritumoural lymphatic vessels were examined using D2-40 in 54 OSCC cases and correlated with VEGF-C expression and clinicopathological findings. The histological pattern of invasion and pathological findings were compared. Results: High expression of VEGF-C was frequently observed in OSCC and was associated with increased number of lymph vessels and lymphatic invasion. VEGF-C was well correlated with invasion pattern and metastasis. Conclusions: Results suggest that VEGF-C may play an important role for lymphangiogenesis and invasion in the metastatic process and can be a strong predicting factor for metastasis of OSCC

A study of lipid profile and glycemic status in patients with chronic kidney disease of unknown etiology in Sri Lanka

Background: Dyslipidemia and impaired glucose tolerance are common complications of chronic kidney disease (CKD) and are responsible for increased cardiovascular risk. Studies on lipid profile and glycemic status in CKD of unknown origin (CKDu) are scarce. The objective of this study was to evaluate the lipid profile and glycemic status of the patients with CKDu and to aid in preventing morbidity and mortality.Methods: The descriptive, cross sectional study was conducted in a rural CKDu endemic area, Girandurukotte.  Data was collected from February 2018 to June 2019. For the diagnosis of CKDu, history and clinical features with supportive biochemical, renal biopsy and radiological evidence were taken as criteria. Blood samples were taken for serum creatinine, lipid profile and HbA1C. Already diagnosed patients with diabetes mellitus and dyslipidemia were excluded.Results: A total of 168 patients within the age range of 32-66 years (mean 50.3±7.7) were participated. There were 106 males (63%) 46.4% were farmers. Majority of the patients (65.5%) had normal body mass index (BMI) (mean 22.9 kg/m2, normal range 18.5-23.5%) followed by overweight (23.5-30 kg/m2) in 55 (32.7%) patients. The prevalence of dyslipidemia in CKDu was found to be 55.9%.  Majority of the abnormality was seen in the HDL group with 68 (40.5%) patients having low HDL cholesterol (mean 44.7 mg/dl, SD=12.3).  There was a significant rise in the serum triglyceride concentration (>150 mg/dl) in 53 (31.5%) (mean 152.4 mg/dl, SD=73.5) and total cholesterol (>200 mg/dl) in 30 (18%) patients (mean 182 mg/dl, SD=36.9). LDL cholesterol abnormality (>130 mg/dl) was seen in only 9 patients (mean 88.7 7658mg/dl, SD=25.4). From the total, 144 (85.7%) patients had abnormal HbA1C levels; 27 (16.1%) patients had HbA1C levels between 5.7% and 6.4% (pre-diabetes), and 117 (69.6%) patients had HbA1C level more than 6.5% (diabetes mellitus). There was no statistically significant association between HbA1C levels and BMI (p=0.29) or HbA1C and lipid abnormalities (p=0.32)Conclusions: The high prevalence of dyslipidemia, pre-diabetes and diabetes mellitus in patients with CKDu may accelerate the progression of chronic kidney disease and increase the risk of cardiovascular disease. Early detection, initiation of appropriate medication and early referral to the expertise will ameliorate morbidity and mortality.

Models and metaphors: complexity theory and through-life management in the built environment

Complexity thinking may have both modelling and metaphorical applications in the through-life management of the built environment. These two distinct approaches are examined and compared. In the first instance, some of the sources of complexity in the design, construction and maintenance of the built environment are identified. The metaphorical use of complexity in management thinking and its application in the built environment are briefly examined. This is followed by an exploration of modelling techniques relevant to built environment concerns. Non-linear and complex mathematical techniques such as fuzzy logic, cellular automata and attractors, may be applicable to their analysis. Existing software tools are identified and examples of successful built environment applications of complexity modelling are given. Some issues that arise include the definition of phenomena in a mathematically usable way, the functionality of available software and the possibility of going beyond representational modelling. Further questions arising from the application of complexity thinking are discussed, including the possibilities for confusion that arise from the use of metaphor. The metaphor of a 'commentary machine' is suggested as a possible way forward and it is suggested that an appropriate linguistic analysis can in certain situations reduce perceived complexity

Support and Assessment for Fall Emergency Referrals (SAFER) 2: a cluster randomised trial and systematic review of clinical effectiveness and cost-effectiveness of new protocols for emergency ambulance paramedics to assess older people following a fall with referral to community-based care when appropriate.

BACKGROUND: Emergency calls are frequently made to ambulance services for older people who have fallen, but ambulance crews often leave patients at the scene without any ongoing care. We evaluated a new clinical protocol which allowed paramedics to assess older people who had fallen and, if appropriate, refer them to community-based falls services. OBJECTIVES: To compare outcomes, processes and costs of care between intervention and control groups; and to understand factors which facilitate or hinder use. DESIGN: Cluster randomised controlled trial. PARTICIPANTS: Participating paramedics at three ambulance services in England and Wales were based at stations randomised to intervention or control arms. Participants were aged 65 years and over, attended by a study paramedic for a fall-related emergency service call, and resident in the trial catchment areas. INTERVENTIONS: Intervention paramedics received a clinical protocol with referral pathway, training and support to change practice. Control paramedics continued practice as normal. OUTCOMES: The primary outcome comprised subsequent emergency health-care contacts (emergency admissions, emergency department attendances, emergency service calls) or death at 1 month and 6 months. Secondary outcomes included pathway of care, ambulance service operational indicators, self-reported outcomes and costs of care. Those assessing outcomes remained blinded to group allocation. RESULTS: Across sites, 3073 eligible patients attended by 105 paramedics from 14 ambulance stations were randomly allocated to the intervention group, and 2841 eligible patients attended by 110 paramedics from 11 stations were randomly allocated to the control group. After excluding dissenting and unmatched patients, 2391 intervention group patients and 2264 control group patients were included in primary outcome analyses. We did not find an effect on our overall primary outcome at 1 month or 6 months. However, further emergency service calls were reduced at both 1 month and 6 months; a smaller proportion of patients had made further emergency service calls at 1 month (18.5% vs. 21.8%) and the rate per patient-day at risk at 6 months was lower in the intervention group (0.013 vs. 0.017). Rate of conveyance to emergency department at index incident was similar between groups. Eight per cent of trial eligible patients in the intervention arm were referred to falls services by attending paramedics, compared with 1% in the control arm. The proportion of patients left at scene without further care was lower in the intervention group than in the control group (22.6% vs. 30.3%). We found no differences in duration of episode of care or job cycle. No adverse events were reported. Mean cost of the intervention was £17.30 per patient. There were no significant differences in mean resource utilisation, utilities at 1 month or 6 months or quality-adjusted life-years. In total, 58 patients, 25 paramedics and 31 stakeholders participated in focus groups or interviews. Patients were very satisfied with assessments carried out by paramedics. Paramedics reported that the intervention had increased their confidence to leave patients at home, but barriers to referral included patients' social situations and autonomy. CONCLUSIONS: Findings indicate that this new pathway may be introduced by ambulance services at modest cost, without risk of harm and with some reductions in further emergency calls. However, we did not find evidence of improved health outcomes or reductions in overall NHS emergency workload. Further research is necessary to understand issues in implementation, the costs and benefits of e-trials and the performance of the modified Falls Efficacy Scale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60481756 and PROSPERO CRD42013006418. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 13. See the NIHR Journals Library website for further project information

Stocks and flows of natural and human-derived capital in ecosystem services

There is growing interest in the role that natural capital plays in underpinning ecosystem services. Yet, there remain differences and inconsistencies in the conceptualisation of capital and ecosystem services and the role that humans play in their delivery. Using worked examples in a stocks and flows systems approach, we show that both natural capital (NC) and human-derived (produced, human, social, cultural, financial) capital (HDC) are necessary to create ecosystem services at many levels. HDC plays a role at three stages of ecosystem service delivery. Firstly, as essential elements of a combined social-ecological system to create a potential ecosystem service. Secondly, through the beneficiaries in shaping the demand for that service. Thirdly, in the form of additional capital required to realise the ecosystem service flow. We show that it is possible, although not always easy, to separately identify how these forms of capital contribute to ecosystem service flow. We discuss how applying a systems approach can help identify critical natural capital and critical human-derived capital to guide sustainable management of the stocks and flows of all forms of capital which underpin provision of multiple ecosystem services. The amount of realised ecosystem service can be managed in several ways: via the NC & HDC which govern the potential service, and via factors which govern both the demand from the beneficiaries, and the efficiency of use of the potential service by those beneficiaries