Expanded statistical analysis of squats on the Great Britain (GB) mainline network.

Squat defects are one of the most common rail surface defects. Significant research effort has gone into understand squat defects over the last 10 years which has brought about important developments in the understanding of their initiation mechanism; however, further work is still required to fully understand squat and the best methods to control them. This study considers records of squat defects over a period 9 years, considering 2600 km of track across 8 different routes on the GB mainline network. The analysis separately reviews squats on: plainline, crossings, joints and welds. Results include an overview of the main factors influencing the development of each type of squats, practical methods to immediately reduce and manage squat defects and recommends focus areas for further research to understand squat defects. Results suggest that squats on plainline, crossings, joints and welds, all correlate with different influencing factors; headcheck defects appear to significantly influence the probability of squats and how other factors influence squat development. There is a strong connection between total head wear rate (combined material removal due to traffic and grinding) and squats; 90 % of all squats appear on rail with a headwear rate of <0.2 mm/year. Overall larger section rail (60 kg/m vs 56 kg/m) and harder material (260 Brinell vs 220 Brinell) is significantly less susceptible to squat damage. Track curvature has an influence of squat development, especially in rail with no headcheck cracking, where the tightest curves are significantly more likely to sustain squat damage. The probability of squat at vertical discontinuities, i.e. joints and crossings are significantly more likely as train speed increases. Whilst squats on joints are 1000 time more likely than squats on welds.

Rare lysosomal disease registries: lessons learned over three decades of real-world evidence.

Lysosomal storage disorders (LSD) are rare diseases, caused by inherited deficiencies of lysosomal enzymes/transporters, that affect 1 in 7000 to 1 in 8000 newborns. Individuals with LSDs face long diagnostic journeys during which debilitating and life-threatening events can occur. Clinical trials and classical descriptions of LSDs typically focus on common manifestations, which are not representative of the vast phenotypic heterogeneity encountered in real-world experience. Additionally, recognizing that there was a limited understanding of the natural history, disease progression, and real-world clinical outcomes of rare LSDs, a collaborative partnership was pioneered 30 years ago to address these gaps. The Rare Disease Registries (RDR) (for Gaucher, Fabry, Mucopolysaccharidosis type I, and Pompe), represent the largest observational database for these LSDs. Over the past thirty years, data from the RDRs have helped to inform scientific understanding and the development of comprehensive monitoring and treatment guidelines by creating a framework for data collection and establishing a standard of care, with an overarching goal to improve the quality of life of affected patients. Here, we highlight the history, process, and impact of the RDRs, and discuss the lessons learned and future directions.

Laboratory parameters associated with prolonged hospital length of stay in COVID-19 patients in Johannesburg, South Africa.

BACKGROUND: Coronavirus disease (COVID-19) has imposed unprecedented stressors on South Africa (SA)'s healthcare system. Superimposed on the country's quadruple burden of disease, pandemic-related care further exposes existing inequities. Some of these inequities are specific to hospital-based inpatient services, such as the geographical maldistribution of hospital beds, lack of oxygen supplies and assisted ventilation, and scarcity of trained healthcare workers. Certain high-risk groups, such as individuals with cardiometabolic comorbidity, are likely to develop severe COVID-19 disease requiring hospitalisation with potential for a prolonged length of stay (LoS). It may be helpful for health authorities to identify those at risk for prolonged LoS to facilitate appropriate health systems planning. OBJECTIVES: To identify hospital admission laboratory parameters associated with a hospital stay >14 days in patients with COVID-19 pneumonia. METHODS: A retrospective observational study design was used. Laboratory data were obtained from an SA private laboratory for 642 inpatients with suspected or confirmed COVID-19 pneumonia, comprising 7 months of admission laboratory data from six private hospitals in Johannesburg, Gauteng Province. RESULTS: Of 642 hospital admissions for pneumonia, 497 were confirmed to have COVID-19 infection (reverse transcription-polymerase chain reaction test positive). In the COVID-19-positive group, hospital LoS was prolonged in 35.4% of admissions. Univariate analysis demonstrated an association with the following risk factors for prolonged LoS: older age; male sex; high serum creatinine, sodium (Na), chloride, potassium and urea levels and low estimated glomerular filtration rate; raised white blood cell count, lymphopenia, neutrophilia and an elevated neutrophil-to-lymphocyte ratio (NLR); and elevated levels of D-dimers, interleukin-6 (IL-6), and procalcitonin (PCT). The strongest univariate associations (relative risk (RR) ≥2.0) with a hospital stay >14 days were high Na levels, NRL >18, high PCT levels and IL-6 >40 pg/mL. On multivariable analysis, the following factors remained significantly associated with prolonged LoS: older age (RR 1.015 per year of age; 95% confidence interval (CI) 1.005 - 1.024); hypernatraemia (RR 1.80; 95% CI 1.25 - 2.60); hyperkalaemia (RR 1.61; 95% CI 1.18 - 2.20); and neutrophilia (RR 1.47; 95% CI 1.15 - 1.88). CONCLUSIONS: COVID-19 pandemic preparedness requires hospital-based inpatient care to be prioritised in resource-limited settings, and availability of beds and prompt admissions are essential to ensure good clinical outcomes. In this study of COVID-19 patients admitted with pneumonia, multivariable analysis showed older age, hypernatraemia, hyperkalaemia and neutrophilia to be associated with LoS >14 days. This may assist with healthcare systems planning.

Comparison of clinical and paraclinical characteristics of patients with urge, mixed, and passive fecal incontinence: a systematic literature review.

PURPOSE: Two subgroups of fecal incontinence (FI) are described in literature and used in clinical practice. However, the pertinence of this classification of FI is still unknown as there are no clear established guidelines. To a better understanding, we performed a systematic review to characterize the different types of FI (active, passive, or mixed) on the basis of clinical presentation and complementary explorations. METHODS: This systematic literature review was performed in reference to recommendations for systematic review using PRISMA guidelines without date restriction, until May 2020. This systematic review was performed without temporal limitation using MEDLINE-PubMed, Cochrane Library, and Google Scholar databases. RESULTS: Six hundred nine unique citations were identified from all the databases combined. Of those, 21 studies met the inclusion criteria, with 8 retrospective observational studies and 13 prospective observational studies. There was a lack of homogeneity in definitions of passive and urge (active) FI among studies. Prevalence of passive and urge FI was respectively of 4.0-5.0 and 15.0-35.0%. Clinical characteristics, physical examination, and endoanal imaging were not evaluated in most studies. In anorectal manometry, maximal squeeze pressure was higher in passive FI subgroup in most studies and results regarding maximal resting pressure remain discordant. There seemed to be no difference regarding first sensation volume and maximal tolerable volume among subgroups. A few studies evaluated pudendal terminal nerve motor latency with no difference among subgroups. CONCLUSION: There is a lack of well-conducted prospective studies comparing the different subtypes of FI with validated definitions in both clinical and paraclinical examinations.

Assessing facial recognition after orthognathic surgery at automated border controls in airports.

The aim of this paper was to find out whether orthognathic surgery affects facial recognition at automated border controls in airports, and whether we should recommend that patients update their photographic identification postoperatively. We collected data on all 82 patients who had orthognathic surgery between August 2013 and June 2017. They were contacted by telephone and asked about any difficulties they had encountered when passing through automated or human-operated border controls or when using other forms of photographic identification such as driving licences. All questions were asked with reference to experiences before the operation. A total of 50 patients responded, of which 35 had travelled by aeroplane since their operations. Six of them had had problems passing through passport control (two human-operated and four automated) but after additional security checks had successfully continued their journeys. Four had had bimaxillary surgery, one had had maxillary advancement, and one mandibular advancement. Orthognathic surgery does affect identification at border controls, and most of our patients had had difficulties at automated checks because of the differences between the biometric data within the e-passport chip and the live biometric that was scanned. These findings will enable us to improve the information we give to our patients before operation, but further studies are required to increase the sample size and improve reliability.

Changes in glycaemic control, blood pressure and lipids 5 years following laparoscopic adjustable gastric banding combined with medical care in patients with type 2 diabetes: a longitudinal analysis.

The long-term outcomes of weight loss maintenance induced by laparoscopic adjustable gastric band (LAGB) followed by multidisciplinary medical care in patients with type 2 diabetes mellitus (T2DM) (beyond 3 years) are scarcely reported. Study aims were to determine the longer term metabolic outcomes following LAGB combined with medical care in patients with T2DM. This is a longitudinal analysis of 200 adults with T2DM who had LAGB between 2003 and 2008 and were followed up till 2013 at a single bariatric unit in a tertiary UK centre. A total of 200 patients (age 47 ± 9.7 years; body mass index [BMI] 52.8 ± 9.2 kg m-2 ; glycosylated haemoglobin (HbA1c) 7.9 ± 1.9% [62.8 mmol mol-1 ]; women, n = 123 [61.5%]; insulin treatment, n = 71 [35.5%]) were included. The mean follow-up was 62.0 ± 13.0 months (range 18-84 months). There were significant reductions in body weight (-24.4 ± 12.3% [38 ± 22.7 kg]), HbA1c (-1.4 ± 2.0%), systolic blood pressure [BP] (-11.7 ± 23.5 mmHg), total cholesterol and triglyceride levels. The proportion of patients requiring insulin reduced from 36.2% to 12.3%. The overall band complication rate was 21% (21 patients). LAGB when combined with multidisciplinary medical care significantly improved metabolic outcomes in patients with T2DM independent of diabetes duration, and baseline BMI over 5 years. Diabetes duration and baseline BMI did not predict changes in glycaemic control, BP or lipids following LAGB.

An "all 5 mm ports" technique for laparoscopic day-case anti-reflux surgery: A consecutive case series of 205 patients.

INTRODUCTION: Laparoscopic anti-reflux surgery is conventionally performed using two 10/12 mm ports. While laparoscopic procedures reduce post-operative pain, the use of larger ports invariably increases discomfort and affects cosmesis. We describe a new all 5 mm ports technique for laparoscopic anti-reflux surgery and present a review of our initial experience with this approach. METHODS: All patients undergoing laparoscopic fundoplication over a 35 month period from February 2013 under the care of a single surgeon were included. A Lind laparoscopic fundoplication was performed using an all 5 mm port technique. Data was recorded prospectively on patient demographics, operating surgeon, surgical time, date of discharge, readmissions, complications, need for re-intervention, and reasons for admission. RESULTS: Two hundred and five consecutive patients underwent laparoscopic fundoplication over the study period. The all 5 mm port technique was used in all cases, with conversion to a 12 mm port only once (0.49%). Median operating time was 52 min 185 (90.2%) patients were discharged as day cases. Increasing ASA grade and the presence of a hiatus hernia were associated with the need for overnight stay with admission required in 33% of patients with ASA 3, compared to 4% with ASA 1 (p = 0.001), and 29% of those with a hiatus hernia vs. 5% without (p < 0.001). No port-related complications occurred, and no patients developed recurrence of reflux symptoms. A single patient required mesh repair of a large hiatus hernia. CONCLUSION: The all 5 mm ports approach to laparoscopic anti-reflux surgery is a safe, efficient, and cost-effective technique which facilitates same day discharge and minimises port related complications. National commissioning guidelines in the UK should target quality improvements in anti-reflux surgery based around day-case management. This would improve the service for these patients and culminate in cost savings for the NHS.

Cell and protein compatible 3D bioprinting of mechanically strong constructs for bone repair.

Rapid prototyping of bone tissue engineering constructs often utilizes elevated temperatures, organic solvents and/or UV light for materials processing. These harsh conditions may prevent the incorporation of cells and therapeutic proteins in the fabrication processes. Here we developed a method for using bioprinting to produce constructs from a thermoresponsive microparticulate material based on poly(lactic-co-glycolic acid) at ambient conditions. These constructs could be engineered with yield stresses of up to 1.22 MPa and Young's moduli of up to 57.3 MPa which are within the range of properties of human cancellous bone. Further study showed that protein-releasing microspheres could be incorporated into the bioprinted constructs. The release of the model protein lysozyme from bioprinted constructs was sustainted for a period of 15 days and a high degree of protein activity could be measured up to day 9. This work suggests that bioprinting is a viable route to the production of mechanically strong constructs for bone repair under mild conditions which allow the inclusion of viable cells and active proteins.

Recombinant macrophage targeted enzyme replacement therapy for Gaucher disease in India.

OBJECTIVE: Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease. DESIGN: Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase. SETTING: Five centers from India with experience in treating lysosomal storage disorders. PATIENTS: The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for >6 months. Indications for treatment included symptomatic anemia, thrombo-cytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days. MAIN OUTCOME MEASURES: Hemoglobin, platelet counts, liver and spleen volumes and growth parameters. RESULTS: 22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 10(9)/L (-98.5 x 109 to 145.5 x10(9))/L (P=0.02). The mean (range) increase in weight was 3 kg (-5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static. CONCLUSIONS: This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India.

Long-term outcomes of liver transplantation in type 1 Gaucher disease.

Gaucher disease (GD) is the most prevalent lysosomal storage disorder. Enzyme replacement therapy (ERT) has demonstrable efficacy in reversing clinical and pathological manifestations of GD. We report four patients with GD and severe hepatic impairment who were successfully treated by orthotopic liver transplantation. Liver failure resulted from GD in two patients and due to a comorbidity in two others (HCV and autoimmune chronic active hepatitis). Following successful liver transplantation, patients received long-term ERT. Liver transplantation is a life-saving treatment for end-stage liver disease in patients with Gaucher disease. All four patients have had excellent outcomes from liver transplantation for up to 10 years postprocedure with no evidence of Gaucher-related pathology in the graft.

Seat-belt trauma of the breast in a pregnant woman causing milk-duct injury: a case report and review of the literature.

Injury to the milk-duct following a road traffic accident has not been reported in the literature. This case report describes a 25-year-old postpartum lady with massive swelling of the breast due to milk-duct injury and collection of milk within the breast. We describe the possible mechanism of milk-duct injury, its presentation and management, and also review the literature on seat-belt injury to the breast.

Immunoprophylaxis in asplenic patients.

The asplenic patient is at risk of overwhelming post-splenectomy infection (OPSI) due to encapsulated bacteria, namely pneumococcus, haemophilus influenza B and meningococcal C pathogens. The lifetime risk is 1-2% with the estimated mortality being in the region of 40-70% (Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 2001;7:657-60). Preventative measures include appropriate prophylactic vaccination, long term antibiotics and patient education. Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were first published by the British Committee for Standards in Haematology in 1996, with a revised edition published in 2002. There are a number of permutations of these guidelines published by a number of professional bodies and consequently this has led to variable adherence rates to such guidelines. We review the perioperative administration of prophylactic vaccinations.

HIV-occlusive vascular disease.

OBJECTIVES: To evaluate peripheral arterial occlusive disease in HIV-infected patients regarding clinical presentation and outcome of surgical intervention. DESIGN: Prospective clinical survey. PATIENTS AND METHODS: Routine voluntary testing for HIV/AIDS was performed in all patients presenting to our vascular unit. HIV+ patients were enrolled in a registry and followed up prospectively. RESULTS: We identified 154 HIV+ patients, of whom 91 (59%) presented with occlusive disease. There were 71 males and 20 females with a mean age of 44.2 years. The usual risk factors for atherosclerosis were present, but the incidence was less than reported in the classic atherosclerosis population. More than 90% of the patients presented with advanced stage vascular disease (Fontaine III/IV), which explains the high rate (31.9%) of primary amputation. Eighty-seven patients presented with lower-limb ischaemia, 2 patients with upper-limb ischaemia and 2 patients with symptomatic carotid artery stenosis. Seventy-eight procedures were performed on 72 patients, with a perioperative mortality of 6.95%. The limb salvage rate for femoro-popliteal bypass procedures was poor (36.1%), resulting in a high incidence of secondary amputations and prolonged hospital stay. Long-term mortality for the operated patients was 20% over a mean follow-up period of 15.4 months. Hypo-albuminaemia was found to be an important predictor of outcome. CONCLUSION: Patients presenting with HIV-associated peripheral arterial disease should be carefully selected for intervention, taking into consideration nutritional and immune status, stage of the vascular disease and selecting the appropriate procedure.

Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring.

Enzyme replacement was introduced as treatment for non-neuronopathic Gaucher disease more than 15 years ago. To ensure the best use of this costly ultra-orphan agent, a systematic disease management approach has been proposed by an international panel; this includes the development, by consensus, of achievable treatment goals. Here we critically review these goals and monitoring guidelines and incorporate emerging experience of the disease in the therapeutic era, as well as contemporary clinical research. This review makes recommendations related specifically to the management of pregnancy; the appropriate use of splenectomy and bisphosphonate treatment; the relevance of biochemical markers to disease monitoring; and the use of semi-quantitative methods for assessing bone marrow infiltration. In addition, we identify key areas for development, including the requirement for a validated index of disease severity; the need to correlate widely used biomarkers with long-term disease outcomes, and the desirability of establishing agreed standards for monitoring of bone disease particularly in infants and children with Gaucher disease.

A prospective comparison of secondary interventions and mortality in open and endovascular infrarenal abdominal aortic aneurysm repair.

Endovascular aneurysm repair (EVAR) has provided a safe and effective alternative to the standard open repair of abdominal aortic aneurysms (AAAs). It has, however, been associated with a high requirement for secondary interventions. This prompted us to compare the two procedures with regard to secondary interventions and mortalities. The sample size was 278 patients, of whom 156 had undergone the open operation and 122 had undergone EVAR. The perioperative morbidity and mortality, as well as the major and minor secondary intervention rates, were obtained for these patients. The results suggest that there is no significant difference in secondary interventions and mortality between the two groups, despite the EVAR group being at significantly higher risk.

Laser-ablation rates measured using x-ray laser transmission.

The rate of laser ablation at irradiances of approximately 2 x 10{14} W cm{-2} of solid iron has been measured using the transmission of a neonlike zinc x-ray laser at 21.2 nm through thin iron targets. Ablated iron becomes transparent to the x-ray laser flux, enabling the thickness of unablated material and hence the rate of ablation to be measured from time resolved x-ray laser transmission.

[Therapeutic objectives in Gaucher disease]. / Buts thérapeutiques dans la maladie de Gaucher.

Evidence-based therapeutic goals have been developed by European and North American experts in the field of Gaucher disease (GD, lysosomal acid beta glucosidase deficiency, OMIM 230 800) in an attempt to reverse the entire disease phenotype, improve quality of life and prevent life-threatening complications. Patients with GD usually have maximal clinical benefit when enzyme replacement treatment (ERT) efficiency is administered at the optimal time i.e. generally during the asymptomatic phase of the disease. Currently, imiglucerase is the standard of care for type 1 GD due to its high efficiency at improving bleeding tendencies, anemia, reversing heptosplenomegaly and part of skeletal damages and eliminating bone crises. ERT has also demonstrated a remarkable safety profile with tolerability at 3 years greater than 99%. Treatment of GD is a lifelong treatment that patients should not interrupt without a careful monitoring of the disease evolution.

Opacity measurements of a hot iron plasma using an x-ray laser.

The temporal evolution of the opacity of an iron plasma at high temperature (30-350 eV) and high density (0.001-0.2 g cm-3) has been measured using a nickel-like silver x-ray laser at 13.9 nm. The hot dense iron plasma was created in a thin (50 nm) iron layer buried 80 nm below the surface in a plastic target that was heated using a separate 80 ps pulse of 6-9 J, focused to a 100 microm diameter spot. The experimental opacities are compared with opacities evaluated from plasma conditions predicted using a fluid and atomic physics code.

Phenotype variations in Gaucher disease.

The Gaucher phenotype is very complex and it cannot be simply evaluated on the basis of blood counts or splenomegaly, but by the analysis of all disease compartments. To establish the diagnosis of Gaucher disease, biochemical assay of glucocerebrosidase activity is the most reliable method. However, it can be supplemented by molecular diagnosis, which may be helpful to predict the severity and the rate of progression of clinical manifestations. The genotype-phenotype correlations are very complex with a high inter-individual variability in the severity of clinical manifestations within a same genotype. Genetic modifiers may play an important role in determining the eventual Gaucher phenotype. Despite of some devastating complications, which can arise with advancing age, Gaucher disease worsen progressively in the majority of patients homozygous for the N370S mutation. The analysis of the data of the International Collaborative Gaucher Group registry should provide a better understanding of the natural history of the Gaucher disease.