Statistical distribution of free water surface over a mild bed slope for extreme wavefields

This paper examines the probability density function (PDF) of free water surface elevations in coastal areas. The functional form and properties of PDFs of extreme storms propagating over a mildly sloping bathymetry are investigated. This is facilitated through comparisons between experimental measurements and a wide range of probability models; the latter including both analytical and empirical distributions. The incident wave conditions correspond to realistic storm spectra (JONSWAP) and have been simulated as long random timeseries of 60-hour duration. The length of the records is sufficient to provide an accurate description of distribution tails. Six sea-states with varying offshore steepness have been generated and measured at different cross-shore locations. The cross-shore evolution of the wavefield initially leads to the development of nonlinear harmonics, both at low and high frequencies, and a broadening of the wave spectrum. This is enhanced by wave breaking particularly at shallower water depths or steeper sea-states. These result in rapid deviations from Gaussian theory with respect to the PDFs of surface elevations. Available models are generally successful in capturing nonlinear evolution arising at a second-order of wave steepness but cannot model the probability structure once a significant proportion of waves are breaking. In comparing the deviations between experimental data and model predictions, the best performing model is identified

An experimental study of wave-in-deck loading and its dependence on the properties of the topside structure

This paper concerns the largest and arguably the most threatening wave loading component experienced by a broad range of offshore structures. It arises when an incident wave crest exceeds the elevation of the underside of the deck structure, leading to direct wave-in-deck (WID) loading. The extent of this loading may be limited to the partial submergence of some of the lowermost deck beams, or could involve the large-scale inundation of the entire deck area. Either way, very large loads can arise which must be taken into account when assessing the reliability of the structure. In an earlier contribution Ma and Swan (2020) provided an extensive laboratory study exploring the variation of these loads with the properties of the incident wave. The present paper describes a second stage of this experimental study in which the variation of the WID loads with the properties of the topside structure is addressed. Specifically, it considers the porosity, position and orientation of the topside relative to the incident wave conditions, and seeks to explore both the variations in the maximum load and the loading time–history resulting from these changes. Given the highly transitory nature of a WID loading event, coupled with the fact that the problem is governed by flow conditions at, or very close to, the instantaneous water surface, the loading process is driven by an exchange of momentum from the wave crest to the topside structure. A recently developed WID load model, based on exactly these arguments (Ma and Swan 2020), is used alongside the laboratory data to provide a break-down of the load into its component parts. This provides an enhanced physical understanding of the resulting load time–history. The first part of the study is based upon an idealised generic topside structure, allowing a systematic variation in key parameters, particularly porosity. The second part addresses a realistic topside structure demonstrating the practical relevance of earlier work. Taken together, the analysis clearly establishes the importance of the topside porosity, clarifies the spatial effects associated with the evolution of a large ocean wave beneath the plan area of a structure and explains the unexpected occurrence of impact-type loading on topside structures having a high porosity. Most importantly, the paper highlights those properties of a topside structure which must be incorporated if the WID loads are to be accurately predicted

Wave-in-deck loads: an assessment of present design practice given recent improvements in the description of extreme waves and the nature of the applied loads

This paper contributes to the on-going discussion of how best to calculate the reliability of a fixed offshores structure. This discussion has been driven, in large part, by improved physical understanding of waves arising in realistic design sea-states, with a growing appreciation that many ‘design wave events’ will be breaking, irrespective of water depth. As such, it is increasingly acknowledged that some aspects of present design practice are non-conservative. In re-assessing older structures, the accurate calculation of horizontal wave-in-deck (WID) loads is often the most important and least tractable part. This paper explains the underlying reason, highlights the wider implications for identifying an appropriate design point, and raises fundamental questions in the assumptions underpinning present practice. Specifically, a large laboratory data base of WID events is used to assess the success of available models. These comparisons confirm that recommended practice, including recent updates, consistently under-predict the maximum WID loads on which reliability calculations should be based. In contrast the recently developed Lagrangian Momentum Absorption (LMA) model (Ma and Swan, 2020b), a simple but complete load model that combines fully-nonlinear wave inputs and the openness/porosity of a structure, provides highly accurate predictions. This is achieved without empirical coefficients/calibrations and therefore ideally suited to design/re-assessment applications

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population

Long-term effects of reduced renal mass in humans

Long-term effects of reduced renal mass in humans. The long-term risks of kidney donation have not been well defined. We carried out a meta-analysis of investigations that examined the long-term effects of reduced renal mass in humans. We used multiple linear regression to combine studies and adjust for differences in the duration of follow-up, the reason for reduced renal mass, the type of controls, age and gender. We analyzed 48 studies with 3124 patients and 1703 controls. Unilateral nephrectomy caused a decrement in glomerular filtration rate (-17.1 ml/min; 95% confidence interval -20.2 to -14.0 ml/min) that tended to improve with each 10 years of follow-up (1.4 ml/min/decade; 0.3 to 2.4 ml/min/decade). Patients with single kidneys had small, progressive increases in proteinuria (76 mg/day/decade; 52 to 101 mg/day/decade), but proteinuria was negligible after nephrectomy for trauma or kidney donation. Nephrectomy did not affect the prevalence of hypertension, but there was a small increase in systolic blood pressure (2.4 mm Hg; -0.3 to 5.1 mm Hg, P > 0.05) which rose further with duration of follow-up (1.1 mm Hg/decade; 0.0 to 2.2 mm Hg/decade). Diastolic blood pressure was higher after nephrectomy (3.1 mm Hg; 1.8 to 4.4 mm Hg), but this increment did not change with duration of follow-up. Thus, in normal individuals, unilateral nephrectomy does not cause progressive renal dysfunction, but may be associated with a small increase in blood pressure

Marfan syndrome and pregnancy: maternal and neonatal outcomes

Objective To report outcomes in a recent series of pregnancies in women with Marfan syndrome (MFS). Design Retrospective case note review. Setting Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). Sample Twenty-nine pregnancies in 21 women with MFS between 1995 and 2010. Methods Multidisciplinary review of case records. Main outcome measures Maternal and neonatal mortality and morbidity of patients with MFS and healthy controls. Results There were no maternal deaths. Significant cardiac complications occurred in five pregnancies (17%): one woman experienced a type–A aortic dissection; two women required cardiac surgery within 6 months of delivery; and a further two women developed impaired left ventricular function during the pregnancy. Women with MFS were also more likely to have obstetric complications (OR 3.29, 95% CI 1.30–8.34), the most frequent of which was postpartum haemorrhage (OR 8.46, 95% CI 2.52–28.38). There were no perinatal deaths, although babies born to mothers with MFS were delivered significantly earlier than those born to the control group (median 39 versus 40 weeks of gestation, Mann–Whitney U–test, P = 0.04). These babies were also significantly more likely to be small for gestational age (24% in the MFS group versus 6% in the controls; OR 4.95, 95% CI 1.58–15.55). Conclusions Pregnancy in women with MFS continues to be associated with significant rates of maternal, fetal, and neonatal complications. Effective pre-pregnancy counselling and meticulous surveillance during pregnancy, delivery, and the puerperium by an experienced multidisciplinary team are warranted for women with MFS

Pancreatic transdifferentiation and glucose-regulated production of human insulin in the H4IIE rat liver cell line

© 2016 by the authors. Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone), H4IIE/ND (NeuroD1 gene alone), and H4IIEins/ND (insulin and NeuroD1 genes). The H4IIEins cells did not store insulin; however, H4IIE/ND and H4IIEins/ND cells stored 65.5 ± 5.6 and 1475.4 ± 171.8 pmol/insulin/ 5 × 106 cells, respectively. Additionally, several β cell transcription factors and pancreatic hormones were expressed in both H4IIE/ND and H4IIEins/ND cells. Electron microscopy revealed insulin storage vesicles in the H4IIE/ND and H4IIEins/ND cell lines. Regulated secretion of insulin to glucose (0–20 mmol/L) was seen in the H4IIEins/ND cell line. The H4IIEins/ND cells were transplanted into diabetic immunoincompetent mice, resulting in normalization of blood glucose. This data shows that the expression of NeuroD1 and insulin in liver cells may be a useful strategy for inducing islet neogenesis and reversing diabetes

An efficient method of defining the tail of a crest height distribution

The exceedance probability of wave crest elevation is a critical environmental input for the design/re-assessment of marine structures. With attention often focused on structural reliability, and in some cases survivability, the largest wave crests arising at the smallest exceedance probabilities, said to be located in the tail of a distribution, are of primary interest. This paper explains why present design practice may be non-conservative in the most extreme seas and outlines a new method by which the tail of the distribution can be defined using a relatively small number of deterministic wave events. This avoids the need to explore the entire distribution using very long (and expensive) random wave simulations. The new approach allows both an extension of the distribution to smaller exceedance probabilities and a concentration on the largest most design relevant crest heights. Having demonstrated the success of the proposed method by comparisons to laboratory data, the analysis is extended to include the effective prediction of the associated confidence intervals (CIs). With the highest waves subject to the largest statistical uncertainty, the paper explores the nonlinear changes in CI, demonstrates that these can also be accurately and efficiently defined, and explains how CI may be reduced. The focus of the paper lies in improved design calculations, based upon the nonlinear dynamics of extreme waves in realistic seas

Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells

© 2015 American Society of Gene & Cell Therapy As an alternative to the transplantation of islets, a human liver cell line has been genetically engineered to reverse type 1 diabetes (TID). The initial liver cell line (Huh7ins) commenced secretion of insulin in response to a glucose concentration of 2.5 mmol/l. After transfection of the Huh7ins cells with human islet glucokinase, the resultant Melligen cells secreted insulin in response to glucose within the physiological range; commencing at 4.25 mmol/l. Melligen cells exhibited increased glucokinase enzymatic activity in response to physiological glucose concentrations, as compared with Huh7ins cells. When transplanted into diabetic immunoincompetent mice, Melligen cells restored normoglycemia. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that both cell lines expressed a range of β-cell transcription factors and pancreatic hormones. Exposure of Melligen and Huh7ins cells to proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) affected neither their viability nor their ability to secrete insulin to glucose. Gene expression (microarray and qRT-PCR) analyses indicated the survival of Melligen cells in the presence of known β-cell cytotoxins was associated with the expression of NF-κB and antiapoptotic genes (such as BIRC3). This study describes the successful generation of an artificial β-cell line, which, if encapsulated to avoid allograft rejection, may offer a clinically applicable cure for T1D

Heart or heart-lung transplantation for patients with congenital heart disease in England

BACKGROUND: Increased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England. METHODS: We performed a retrospective analysis of hospital episodes for England for 1997-2015, identifying patients with a CHD code (ICD-10 'Q2xx.x'), who underwent heart or heart-lung transplantation. RESULTS: In total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure. CONCLUSIONS: The current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population