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Describes a pivotal moment in Los Angeles history, when writers like Raymond Chandler, Nathanael West, and F. Scott Fitzgerald were creating the images and associations--and the mystique--for which the City of Angels is still known. Los Angeles in the 1930s a guide to the contemporary culture, with a brief L.A. history, revisiting the Spanish colonial period, the Mexican period, the brief California Republic, and finally American sovereignty.

Background The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade. As the number of people affected by the disease is expected to grow significantly in coming years, the aim of this study is to evaluate whether the introduction of new processes and medical technologies will enable cataract services to cope with the demand within the NHS funding constraints. Methods We developed a Discrete Event Simulation model representing the cataract services pathways at Leicester Royal Infirmary Hospital. The model was inputted with data from national and local sources as well as from a surgery demand forecasting model developed in the study. The model was verified and validated with the participation of the cataract services clinical and management teams. Results Four scenarios involving increased number of surgeries per half-day surgery theatre slot were simulated. Results indicate that the total number of surgeries per year could be increased by 40% at no extra cost. However, the rate of improvement decreases for increased number of surgeries per half-day surgery theatre slot due to a higher number of cancelled surgeries. Productivity is expected to improve as the total number of doctors and nurses hours will increase by 5 and 12% respectively. However, non-human resources such as pre-surgery rooms and post-surgery recovery chairs are under-utilized across all scenarios. Conclusions Using new processes and medical technologies for cataract surgery is a promising way to deal with the expected higher demand especially as this could be achieved with limited impact on costs. Non-human resources capacity need to be evenly levelled across the surgery pathway to improve their utilisation. The performance of cataract services could be improved by better communication with and proactive management of patients.

Background Advances in the management of retinal diseases have been fast-paced as new treatments become available, resulting in increasing numbers of patients receiving treatment in hospital retinal services. These patients require frequent and long-term follow-up and repeated treatments, resulting in increased pressure on clinical workloads. Due to limited clinic capacity, many National Health Service (NHS) clinics are failing to maintain recommended follow-up intervals for patients receiving care. As such, clear and robust, long term retinal service models are required to assess and respond to the needs of local populations, both currently and in the future. Methods A discrete event simulation (DES) tool was developed to facilitate the improvement of retinal services by identifying efficiencies and cost savings within the pathway of care. For a mid-size hospital in England serving a population of over 500,000, we used 36 months of patient level data in conjunction with statistical forecasting and simulation to predict the impact of making changes within the service. Results A simulation of increased demand and a potential solution of the ‘Treat and Extend’ (T&E) regimen which is reported to result in better outcomes, in combination with virtual clinics which improve quality, effectiveness and productivity and thus increase capacity is presented. Without the virtual clinic, where T&E is implemented along with the current service, we notice a sharp increase in the number of follow-ups, number of Anti-VEGF injections, and utilisation of resources. In the case of combining T&E with virtual clinics, there is a negligible (almost 0%) impact on utilisation of resources. Conclusions Expansion of services to accommodate increasing number of patients seen and treated in retinal services is feasible with service re-organisation. It is inevitable that some form of initial investment is required to implement service expansion through T&E and virtual clinics. However, modelling with DES indicates that such investment is outweighed by cost reductions in the long term as more patients receive optimal treatment and retain vision with better outcomes. The model also shows that the service will experience an average of 10% increase in surplus capacity.

Taxation of Loan Relationships and Derivative Contracts, Tenth Edition, is updated in line with the Finance Act 2015 which brings in significant changes to the loan relation rules.In addition, it includes changes to both UK and International Accounting Standards.

The activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to ultraviolet B (UVB) exposure, both in vitro and in vivo. Geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response which contributes to the development of aging-associated squamous cell carcinoma. Furthermore, our lab and others have reported that geriatric keratinocytes repair UVB-induced DNA damage less efficiently than young adult keratinocytes. Here, we show that IGF-1R activation influences DNA damage repair in UVB-irradiated keratinocytes. Specifically, in the absence of IGF-1R activation, the rate of DNA damage repair following UVB-irradiation was significantly slowed (using immortalized human keratinocytes) or inhibited (using primary human keratinocytes). Furthermore, inhibition of IGF-1R activity in human skin, using either ex vivo explant cultures or in vivo xenograft models, suppressed DNA damage repair. Primary keratinocytes with an inactivated IGF-1R also exhibited lower steady-state levels of nucleotide excision repair mRNAs. These results suggest that deficient UVB-induced DNA repair in geriatric keratinocytes is due in part to silenced IGF-1R activation in geriatric skin and provide a mechanism for how the IGF-1 pathway plays a role in the initiation of squamous cell carcinoma in geriatric patients. •IGF-1R is necessary for optimal repair of UVB-induced DNA damage in keratinocytes.•Novel separation technique allows study specifically in basal layer keratinocytes.•IGF-1R activation enhances the expression of nucleotide excision repair genes.

Squeezed budgets and funding cuts are expected to become a feature of the healthcare landscape in the future, forcing decision makers such as service managers, clinicians and commissioners to find effective ways of allocating scarce resources. This paper discusses the development of a decision support toolkit (DST) that facilitates the improvement of services by identifying cost savings and efficiencies within the pathway of care. With the help of National Health Service and commercial experts, we developed a discrete event simulation model for deep vein thrombosis (DVT) patients and adapted the socio-technical allocation of resources (STAR) approach to answer crucial questions like what sort of interventions should we spend our money on? Where will we get the most value for our investment? How will we explain the choices we have made? The DST enables users to model their own services by working with the DST interface allowing users to specify local DVT services. They can input local estimates, or data of service demands and capacities, thus creating a baseline discrete event simulation model. The user can then compare the baseline with potential changes in the patient pathway in the safety of a virtual environment. By making such changes key decision makers can easily understand the impact on activity, cost, staffing levels, skill-mix, utilisation of resources and, more importantly, it allows them to find the interventions that have the highest benefit to patients and provide best value for money.

TC to Horace Grant, PM: 25 September less, manuscript offered for bid, September 2019, by Byrne Auctioneers of Cheshire UK and brought to the attention of the Carlyle Letters office at Duke University Press by Melvin Schuetz of Armstrong Browning Library, Baylor University, Waco TX. The London Gazette contains a notice for The Court for the Relief of Insolvent Debtors andhtis entry for Saturday, the 4 th day of November 1844: \"Joseph Henry Garnier, late of No. 16, Quickset Road, New-road, Fitzroy-square, Middlesex. For a given amount of worth and welldoing must exist in the matrimonial as in other forms, or it will go bankrupt to a certainty; and surely it is much handier that there be a good stock of capital in that kind on both sides! I am infinitely busy at this time; fretted all to pieces with that miserable Pamphlet work, and with the new nonsense (superadded to so much old) which it involves me in: The MS was then purchased by that library, and Melvin Schuetz identifies the recipient as T. W. Newton (ca. 1822-1902), assistant librarian of the Museum of Practical Geology and Geological Survey, Jermyn Street, London.

IntroductionDecompensated cirrhosis is a major cause of morbidity and mortality in the United Kingdom (UK).1 The development of ascites complicating cirrhosis frequently represents the first manifestation of decompensation, is a hallmark of advanced liver disease and frequently a prelude to other complications. Refractory ascites (RA), characterised by early recurrence after initial paracentesis, is associated with a worse prognosis.2 The objective of the present study was to describe healthcare resource utilisation and costs incurred by cirrhotic patients following presentation to the South West Liver Unit with large volume ascites requiring paracentesis.MethodsA retrospective study using the Hospital Episode Statistics (HES) data from University Hospitals Plymouth was performed. Patients with decompensated cirrhosis and ascites based on liver disease ICD-10 codes (K70-K77) requiring paracentesis (T46) between January-2015 and February-2020 were identified and healthcare resource utilisation/costs assessed over the following 12 months or until Transjugular Intrahepatic Portosystemic Shunt (TIPS) insertion, liver transplant, diagnosis of RA or death. RA was defined by the need for 2 or more paracenteses in a month. The subset of patients who developed RA were followed up for 12 additional months. Outpatient visits, elective and non-elective admissions and mortality were quantified and costed for the overall population and the sub-group who developed RA.ResultsHES data identified a cohort of 524 cirrhotic patients with ascites. Mean age was 61.8 years and 57.8% were male. 12-month mortality was 22.3%. 3489 outpatient visits, 509 elective day cases, 284 elective admissions and 969 non-elective admissions were required. The mean cost per patient was £12,176 per year. A total of 1061 paracenteses were performed during the 12-month follow-up. RA developed in 129 (24.6%) cases. Patients with RA were more likely to require hospitalisation (421 day cases, 421 non-elective and 206 elective admissions), had more outpatient appointments (1693) and a greater requirement for paracenteses (618 procedures) during the subsequent 12 months. This resulted in a greater mean cost per patient (£23,810 per year).ConclusionsThe development of ascites in cirrhotic patients is associated with significant healthcare resource utilisation and high mortality. One in four patients developed refractory ascites within 12 months of first paracentesis and in these patients hospitalisation rates, outpatient appointments and paracentesis more than doubled, with a significant increase in associated cost. Future treatment strategies that can reduce the likelihood of developing RA may help mitigate costs and ease the burden on both health systems and patients.ReferencesSepanlou SG, Safiri S, Bisignano C, et al. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet Gastroenterology & Hepatology 2020;5(3):245–66.Moore KP, Wong F, Gines P, et al. The management of ascites in cirrhosis: report on the consensus conference of the international ascites club. Hepatology 2003;38(1):258–66.

Background The number of people affected by Parkinson’s disease (PD) is increasing in the United Kingdom driven by population ageing. The treatment of the disease is complex, resource intensive and currently there is no known cure to PD. The National Health Service (NHS), the public organisation delivering healthcare in the UK, is under financial pressures. There is a need to find innovative ways to improve the operational and financial performance of treating PD patients. The use of community services is a new and promising way of providing treatment and care to PD patients at reduced cost than hospital care. The aim of this study is to evaluate the potential operational and financial benefits, which could be achieved through increased integration of community services in the delivery of treatment and care to PD patients in the UK without compromising care quality. Methods A Discrete Event Simulation model was developed to represent the PD care structure including patients’ pathways, treatment modes, and the mix of resources required to treat PD patients. The model was parametrised with data from a large NHS Trust in the UK and validated using information from the same trust. Four possible scenarios involving increased use of community services were simulated on the model. Results Shifting more patients with PD from hospital treatment to community services will reduce the number of visits of PD patients to hospitals by about 25% and the number of PD doctors and nurses required to treat these patients by around 32%. Hospital based treatment costs overall should decrease by 26% leading to overall savings of 10% in the total cost of treating PD patients. Conclusions The simulation model was useful in predicting the effects of increased use of community services on the performance of PD care delivery. Treatment policies need to reflect upon and formalise the use of community services and integrate these better in PD care. The advantages of community services need to be effectively shared with PD patients and carers to help inform management choices and care plans.

BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.