A Review of Reservoir Operation Optimisations: from Traditional Models to Metaheuristic Algorithms.

Reservoir operation optimisation secures benefits, such as optimising energy production while minimising the possibility of flooding, operating costs, and water scarcity, at the lowest possible cost. This paper carries reviews of research on reservoir optimisation models and the consequential challenges of optimally operating reservoir operations. An introductory section is given to the background of reservoir operations and the current concerns on the optimal reservoir operations, for the decision-makers and stakeholders. Next, the review covered the recent ten years (between 2011 and 2021), on the recent research developments in innovation and techniques of reservoir operation optimisation. Further reviews on the conventional techniques that are the traditional methods, linear programming, nonlinear programming, and dynamic programming are discussed. Enhancements to the techniques in improving the drawbacks of the traditional techniques in optimisation of reservoir policies are next explained and evaluated. Recent advances in applying metaheuristics optimisation algorithms beneficial to the reservoir operations are explained, including the advantages and hinderances. A comprehensive tabulated and categorised review according to the classification of reservoir models, evaluation methods, and reservoir systems is given.

Sublingual tofacitinib for alopecia areata: a roll-over pilot clinical trial and analysis of pharmacokinetics.

Tofacitinib is a JAK1/3 inhibitor used off-label to treat alopecia areata (AA). Oral tofacitinib undergoes extensive hepatic metabolism and has numerous drug interactions and a half-life of 3 hours necessitating twice daily dosing. Sublingual delivery bypasses hepatic first-pass metabolism, which may provide pharmacokinetic benefits and reduce gastrointestinal side effects. We investigate sublingual tofacitinib as a novel form of administration in a cohort of treatment-resistant patients. The objective of this work is to assess the efficacy and pharmacokinetics of sublingual tofacitinib in moderate-to-severe AA patients. An open-label, roll-over pilot clinical trial was conducted. Participants were recruited from a preceding trial. All responders (≥50% reduction in Severity of Alopecia Tool [SALT] score, SALT50) in the preceding trial continued on the same treatment (cyclosporine/placebo), whereas nonresponders rolled over to receive open-label sublingual tofacitinib 5 mg twice daily for 12 weeks. Treatment response as reduction in SALT score after 12 weeks (low: 15-29%, medium: 30-49%, good: 50-75%, and high grade: 75-100%) was measured. Pharmacokinetics was analyzed using liquid chromatography tandem mass spectrometry. Eighteen participants completed the trial. Total treatment response to tofacitinib was 37.5%. SALT50 was achieved in 12.5%. The mean improvement in SALT score was 15.57%. Mean maximum plasma concentration was 43.18 ng/ml occurring after 1 hour. Elimination half-life is estimated to be up to 11 hours. An estimated half-life of up to 11 hours may be achieved with sublingual tofacitinib, which is significantly longer than the oral form and may facilitate daily dosing. Larger clinical trials are required to further characterize its pharmacokinetics and efficacy.

Impact of cyclosporin treatment on health-related quality of life of patients with alopecia areata.

INTRODUCTION: Alopecia areata (AA) is a disfiguring disease with substantial psychological burden. No studies explore the efficacy of pharmacotherapy through health-related quality of life (HRQoL) using both disease-specific and generic quality of life (QoL) instruments. We present the first study to elicit health utility from patients with AA and to evaluate the efficacy of cyclosporin in relation to HRQoL using both measures. METHODS: Participants with moderate to severe AA from a placebo-controlled randomized trial investigating cyclosporin were administered the generic preference-based HRQoL instrument, Assessment of Quality of Life-8D (AQoL-8D) and the disease-specific HRQoL instrument, Alopecia Areata Symptom Impact Scale (AASIS). HRQoL was measured at each study visit and compared to baseline. RESULTS: A number of 32 participants were analyzed. The mean health utility was 0.748. At 3 months, the cyclosporin group had trends for greater improvement in HRQoL across 6 of 8 AQoL-8D dimensions and 5 of 7 AASIS symptom domains compared to placebo. HRQoL was lower than Australian population norms across 6 of 8 AQoL-8D dimensions. CONCLUSIONS: Patients with AA had a mean health utility of 0.748. Treatment with cyclosporin 4 mg/kg/d for 3 months resulted in trends for improvement of HRQoL across multiple dimensions in both disease-specific and generic measures. Capsule summary The mean health utility for patients with AA was 0.748. Patients with alopecia areata have impaired health-related quality of life across 6 of 8 AQoL-8D dimensions compared to population norms. Treatment with oral cyclosporin for moderate to severe AA resulted in trends for improvement in QoL across multiple dimensions.

Cyclosporine for moderate-to-severe alopecia areata: A double-blind, randomized, placebo-controlled clinical trial of efficacy and safety.

BACKGROUND: Despite widespread use of steroid-sparing agents, particularly cyclosporine, for treatment of alopecia areata (AA), there are no clinical trials investigating the efficacy of these agents. OBJECTIVE: To evaluate the efficacy of cyclosporine compared with placebo at 3 months in patients aged 18 to 65 years with moderate-to-severe AA. METHODS: A double-blind, randomized, placebo-controlled trial was conducted. Adults aged 18 to 65 years of age with moderate-to-severe AA were randomized in a 1:1 ratio to receive 3 months of cyclosporine (4 mg/kg/d) or matching placebo. Blinded assessments included physical examination, blood biochemistry, photography, quality of life measurements, and efficacy evaluation using Severity of Alopecia Tool score and eyelash and eyebrow assessment scales. RESULTS: The results obtained for 32 participants (16 who received cyclosporine and 16 who received placebo) were analyzed. Compared with the placebo group, the cyclosporine group had a greater proportion of participants achieving at least a 50% reduction in Severity of Alopecia Tool score (31.3% vs 6.3% [P = .07]) and greater proportion of participants achieving a 1-grade improvement in eyelash (18.8% vs 0% [P = .07]) and eyebrow (31.3% vs 0% [P = .02]) scale score. LIMITATIONS: Small sample size and single-institution trial may limit interpretation and generalizability of these results. CONCLUSION: Response approached but did not reach a statistically significant difference between cyclosporine and placebo.

Systemic treatments for alopecia areata: A systematic review.

A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.

Treatment of alopecia areata: An Australian expert consensus statement.

Alopecia areata (AA) severity varies from a single small patch to complete loss of scalp hair, body hair, eyelashes and eyebrows. While 40% of all affected individuals only ever get one patch and will achieve a spontaneous complete durable remission within 6 months, 27% will develop additional patches but still achieve complete durable remission within 12 months and 33% will develop chronic AA. Without systemic treatment, 55% of individuals with chronic AA will have persistent multifocal relapsing and remitting disease, 30% will ultimately develop alopecia totalis and 15% will develop alopecia universalis. The unpredictable course and psychological distress attributable to AA contributes to the illness associated with AA. Numerous topical, intralesional and systemic agents are currently used to treat AA; however, there is a paucity of data evaluating their use, effectiveness and tolerability. Topical therapy, including topical glucocorticosteroids, minoxidil and immunotherapy, can be used in cases of limited disease. There are no universally agreed indications for initiating systemic treatment for AA. Possible indications for systemic treatment include rapid hair loss, extensive disease (≥50% hair loss), chronic disease, severe distress or a combination of these factors. Currently available systemic treatments include glucocorticosteroids, methotrexate, ciclosporin, azathioprine, dapsone, mycophenolate mofetil, tacrolimus and sulfasalazine. The optimal treatment algorithm has not yet been described. The purpose of this consensus statement is to outline a treatment algorithm for AA, including the indications for systemic treatment, appropriate choice of systemic treatment, satisfactory outcome measures and when to discontinue successful or unsuccessful treatment.

Residential NO2 exposure is associated with urgent healthcare use in a thunderstorm asthma cohort.

BACKGROUND: There is increasing interest in the role of traffic-related air pollution (TRAP) in allergic airway diseases. Few studies investigate the relationship between TRAP exposure and acute exacerbations of asthma. OBJECTIVE: The 2016 Melbourne thunderstorm asthma epidemic provided an opportunity to investigate the relationship between proxies of TRAP exposure and asthma exacerbation requiring urgent healthcare in the previous 12 months. METHODS: Current asthmatics who presented to the 3 Emergency Departments of Melbourne's second-largest health service with epidemic thunderstorm asthma in November 2016 were identified and completed a standard questionnaire. Their residential addresses were geocoded and the annual average nitrogen dioxide (NO2) exposure for each patient was assigned using a validated satellite-based land use regression model. Residential distance to the nearest major road was calculated using ArcGIS. Multivariate logistic regression was used to investigate the relationship between each TRAP proxy and healthcare use, adjusting for potential confounders. RESULTS: From 263 thunderstorm asthma patients, 88 patients identified with current asthma were analysed. Those with higher mean annual residential NO2 exposure had greater odds of urgent healthcare use in the previous year (odds ratio [OR], 3.45 per one interquartile-range increase; 95% confidence interval [CI], 1.31-9.10; p = 0.01), however distance from major road (OR, 0.95 per 100-m increase; 95% CI, 0.80-1.13; p = 0.57) and living <200 m from a major road (OR, 1.47; 95% CI, 0.29-7.45; p = 0.64) were not significantly associated. CONCLUSION: In current asthmatics who presented during an epidemic thunderstorm asthma event, greater exposure to residential NO2 was significantly associated with greater odds of asthma exacerbations requiring urgent healthcare in the previous 12 months.

Epidemiology of skin cancer in the mature patient.

Epidermal cancers include keratinocyte cancer, melanocyte cancer, and Merkel cell carcinoma. These cancers account for the vast majority of new cancers diagnosed in Australia, North America, and Europe. Keratinocyte cancer is the most common epidermal cancer and accounts for 7 out of 8 new cancers diagnosed in Australia. Melanoma and Merkel cell carcinoma are less common than keratinocyte carcinoma but are more important causes of mortality in Australia. Keratinocyte cancer has also been demonstrated to be a marker of cancer-prone phenotype. Risk factors for epidermal cancer include intrinsic and environmental factors, in particular exposure to ultraviolet radiation and advanced age. Actinic keratosis has an approximate prevalence of 79% of men and 68% of women between 60 and 69 years of age, and has a low risk of malignant transformation into squamous cell carcinoma. Basal cell carcinoma is the most common malignancy in Caucasians worldwide, with the incidence increasing by 2% per year in Australia. Squamous cell carcinoma is the second most common epidermal cancer, with an incidence of approximately 1035 or 472 per 100,000 person-years in men and women, respectively. Primary risk factors for both basal cell carcinoma and squamous cell carcinoma include light skin color, UV radiation exposure, and chronic immunosuppression. Although the rate of melanoma is increasing, the mortality in Australia is reducing and is currently 9%. The overall incidence of melanoma in Australia is approximately 50 cases per 100,000 persons (62 for men and 40 for women). Keratinocyte carcinoma and melanoma are risk factors for developing further skin cancer and primary malignancy. This contribution reviews the incidence, prevalence, and risk factors associated with the development of epidermal cancer and premalignant epidermal neoplasia.

Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus.

Adult neurogenesis takes place in the brain subventricular zone (SVZ) in the lateral walls of lateral ventricles and subgranular zone (SGZ) in the hippocampal dentate gyrus (HDG), and functions to supply newborn neurons for normal brain functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in the SVZ. This study was designed to determine whether Mn exposure disturbed neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single dose of bromodeoxyuridine (BrdU) at the end of 4-week Mn exposure to label the proliferating cells. Immunostaining and cell counting data showed that BrdU(+) cells in Mn-exposed HDG were about 37% lower than that in the control (p < .05). The majority of BrdU(+) cells were identified as Sox2(+) cells. Another set of adult rats received BrdU injections for 3 consecutive days followed by 2- or 4-week Mn exposure to trace the fate of BrdU-labeled cells in the HDG. The time course studies indicated that Mn exposure significantly reduced the survival rate (54% at 2 weeks and 33% at 4 weeks), as compared with that in the control (80% at 2 weeks and 51% at 4 weeks) (p < .01). A significant time-dependent migration of newborn cells from the SGZ toward the granule cell layer was also observed in both control and Mn-exposed HDG. Triple-stained neuroblasts and mature neurons further revealed that Mn exposure significantly inhibited the differentiation of immature neuroblasts into mature neurons in the HDG. Taken together, these observations suggest that subchronic Mn exposure results in a reduced cell proliferation, diminished survival of adult-born neurons, and inhibited overall neurogenesis in the adult HDG. Impaired adult neurogenesis is likely one of the mechanisms contribute to Mn-induced Parkinsonian disorder.