A Discrete Event Simulation model to evaluate the treatment pathways of patients with Cataract in the United Kingdom

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.Peer reviewedFinal Published versio

Quantification of radial arterial pulse characteristics change during exercise and recovery

It is physiologically important to understand the arterial pulse waveform characteristics change during exercise and recovery. However, there is a lack of a comprehensive investigation. This study aimed to provide scientific evidence on the arterial pulse characteristics change during exercise and recovery. Sixty-five healthy subjects were studied. The exercise loads were gradually increased from 0 to 125 W for female subjects and to 150 W for male subjects. Radial pulses were digitally recorded during exercise and 4-min recovery. Four parameters were extracted from the raw arterial pulse waveform, including the pulse amplitude, width, pulse peak and dicrotic notch time. Five parameters were extracted from the normalized radial pulse waveform, including the pulse peak and dicrotic notch position, pulse Area, Area1 and Area2 separated by notch point. With increasing loads during exercise, the raw pulse amplitude increased significantly with decreased pulse period, reduced peak and notch time. From the normalized pulses, the pulse Area, pulse Area1 and Area2 decreased, respectively, from 38 ± 4, 61 ± 5 and 23 ± 5 at rest to 34 ± 4, 52 ± 6 and 13 ± 5 at 150-W exercise load. During recovery, an opposite trend was observed. This study quantitatively demonstrated significant changes of radial pulse characteristics during different exercise loads and recovery phases

Specific and individuated death reflection fosters identity integration

Identity integration is the process wherein a person assimilates multiple or conflicting identities (e.g., beliefs, values, needs) into a coherent, unified self-concept. Three experiments examined whether contemplating mortality in a specific and individuated manner (i.e., via the death reflection manipulation) facilitated outcomes indicative of identity integration. Participants in the death reflection condition (vs. control conditions) considered positive and negative life experiences as equally important in shaping their current identity (Experiment 1), regarded self-serving values and other-serving values as equally important life principles (Experiment 2), and were equally motivated to pursue growth-oriented and security-oriented needs (Experiment 3). Death reflection motivates individuals to integrate conflicting aspects of their identity into a coherent self-concept. Given that identity integration is associated with higher well-being, the findings have implications for understanding the psychological benefits of existential contemplation

Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010.

BACKGROUND: Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). METHODS: We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. RESULTS: For 2010, we estimated 1.7 million (uncertainty range: 1.1-2.4 million) cases of neonatal sepsis, 200,000 (21,000-350,000) cases of meningitis, 510,000 cases (150,000-930,000) of pneumonia, and 79,000 cases (70,000-930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19-26%) of survivors, 18,000 (2,700-35,000) cases, and after neonatal tetanus in 16% (6-27%), 4,700 cases (1,700-8,900). CONCLUSION: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Alternative splicing of barley clock genes in response to low temperature:evidence for alternative splicing conservation

Alternative splicing (AS) is a regulated mechanism that generates multiple transcripts from individual genes. It is widespread in eukaryotic genomes and provides an effective way to control gene expression. At low temperatures, AS regulates Arabidopsis clock genes through dynamic changes in the levels of productive mRNAs. We examined AS in barley clock genes to assess whether temperature-dependent AS responses also occur in a monocotyledonous crop species. We identify changes in AS of various barley core clock genes including the barley orthologues of Arabidopsis AtLHY and AtPRR7 which showed the most pronounced AS changes in response to low temperature. The AS events modulate the levels of functional and translatable mRNAs, and potentially protein levels, upon transition to cold. There is some conservation of AS events and/or splicing behaviour of clock genes between Arabidopsis and barley. In addition, novel temperature-dependent AS of the core clock gene HvPPD-H1 (a major determinant of photoperiod response and AtPRR7 orthologue) is conserved in monocots. HvPPD-H1 showed a rapid, temperature-sensitive isoform switch which resulted in changes in abundance of AS variants encoding different protein isoforms. This novel layer of low temperature control of clock gene expression, observed in two very different species, will help our understanding of plant adaptation to different environments and ultimately offer a new range of targets for plant improvement

Predicting survival of de novo metastatic breast cancer in Asian women: Systematic review and validation study

10.1371/journal.pone.0093755PLoS ONE94-POLN

Comparison of the elastic recovery and strain-in-compression of commercial and novel vinyl polysiloxane impression materials incorporating a novel crosslinking agent and a surfactant

This study aims to formulate experimental vinylpolysiloxane (VPS) impression materials and compare their elastic recovery and strain-in-compressions with three commercial VPS materials (Aquasil, Elite, and Extrude). Five experimental materials (Exp), two hydrophobic (Exp-I and II) and three hydrophilic (Exp-III, IV and V) were developed. Exp 1 contained vinyl-terminated poly-dimethyl siloxane and a conventional cross-linking agent (poly methylhydrosiloxane), while Exp- II contained a novel cross-linking agent that is tetra-functional dimethyl-silyl-ortho-silicate (TFDMSOS). Exp III–V (hydrophilic materials) were formulated by incorporating different concentrations of non-ionic surfactant (Rhodasurf CET-2) into Exp II formulation. Measurement of elastic recovery and strain-in-compression for commercial and experimental materials were performed according to ISO4823 standard using the calibrated mechanical testing machine (Tinius Olsen). One-way analysis of variance (one-way ANOVA) and Tukey’s post-hoc (HSD) test were used for statistical analysis and a p-value of ≤ 0.05 was considered significant. Exp-I has statistically similar values to commercial VPS. The Exp-II showed the highest elastic recovery, while % elastic recovery was reduced with the addition of the non-ionic surfactant (Rhodasurf CET-2). The % reduction was directly related to the concentration of Rhodasurf CET-2. In addition, Exp II had significantly higher strain-in-compression values compared to Exp-I and commercial materials. These values were further increased with the addition of a non-ionic surfactant (Rhodasurf CET-2) was added (Exp-III, IV and V)

The prenatal ultrasonographic detection of myelomeningocele in patients referred to Children's Hospital Medical Center: a cross sectional study

BACKGROUND: To find out about the prenatal diagnosis rate of myelomeningocele (MMC) by ultrasound scan in patients referred to the Children's Hospital Medical Center in Tehran, Iran from July 2004 to July 2005. METHODS: We included 140 children born with MMC and who were referred for management, surgery and treatment of complications associated with it. The ultrasound reports were examined. Data on sex, age, location of MMC, time of prenatal ultrasound and the trimester in which the diagnosis was made along with the results of the diagnosis (MMC, hydrocephalus, or both), were collected. RESULTS: Among the studied patients, 136 (97.1%) cases had prenatal ultrasound, amongst those, 58 (42.6%) sonographic evaluations were diagnostic for hydrocephalus and/or MMC. The prenatal ultrasound was positive for MMC in 16 (11.8%), hydrocephalus in 25 (18.4%) and both MMC and hydrocephalus in 17 (12.5%) cases. Among all cases with prenatal diagnosis of MMC, 3.4% were detected in the first, 31% in the second and 65.5% in the third trimester. Thoracic/thoracolumbar lesions were found prenatally in 40% of cases, which is significantly higher than the detection rate of other locations including cervical/cervicothoracic and lumbar/lumbosacral/sacral regions diagnosed only in 0% and 21% of cases respectively. CONCLUSION: There is a large difference between the detection rate of our population (24.3%) compared to others (68%). Pregnant women should have an ultrasound at 20–22 week for detection of congenital anomalies including MMC

MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses

MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, in our previous studies it has been impossible to determine the relative contribution of MyD88-dependent signalling in the CNS compared with the peripheral immune cell compartments. In the present study we addressed this by examining the course of S. aureus infection in MyD88 bone marrow chimaera mice. Interestingly, chimaeras where MyD88 was present in the CNS, but not bone marrow-derived cells, mounted pro-inflammatory mediator expression profiles and neutrophil recruitment equivalent to or exceeding that detected in WT (wild-type) mice. These results implicate CNS MyD88 as essential in eliciting the initial wave of inflammation during the acute response to parenchymal infection. Microarray analysis of infected MyD88 KO compared with WT mice revealed a preponderance of differentially regulated genes involved in apoptotic pathways, suggesting that the extensive tissue damage characteristic of brain abscesses from MyD88 KO mice could result from dysregulated apoptosis. Collectively, the findings of the present study highlight a novel mechanism for CNS-resident cells in initiating a protective innate immune response in the infected brain and, in the absence of MyD88 in this compartment, immunity is compromised