Thomas Hardy was born in the hamlet of Upper Bockhampton about three miles east of Dorchester in Dorset, England, on 2nd June 1840. Despite a fairly wide education and being an avid reader his ...parents thought it unlikely he would lead a successful scholarly or clerical career and he was apprenticed in 1856, at age 16, to a local architect whose speciality was in church restoration. Hardy's only opportunity to read was in the morning before work between the hours of five and eight. On the back of a failed love affair he moved to London and spent five years working as Arthur Blomfield's assistant architect, also a restorer and designer of churches. Hardy though had become disillusioned with institutionalised forms of Christianity and abandoned any lingering hopes of ordination in the Anglican Church. However, his poetry was now flourishing, although it was still rejected for publication. His novel 'Desperate Remedies', was published anonymously in 1871 and he now resolved to write full time though he was not yet in a position to achieve financial security or literary success. His second novel, 'Under the Greenwood Tree', appeared in 1872 and in 1873 'A Pair of Blue Eyes', the most autobiographical of his works arrived. With 'Far From the Madding Crowd' in 1874, came critical acclaim, public attention and financial success. 1878 saw more of the same with 'The Return of the Native', and the ensuing years saw him rise to ever greater popularity. 'The Mayor of Casterbridge' was published in 1886. In 1891 came 'Tess of the d'Urbervilles'. It only saw publication after extensive alterations to its plot and deleting long passages to lessen the shock to the prudish Victorian audience who were dismayed by the seduction and ruin of a young girl by a rakish aristocrat. His last novel, 'Jude the Obscure', suffered the same fate when it was published in 1895. The uproar so disturbed him that he returned to poetry. In 1898 he had an earlier poetry collection published 'Wessex Poems'Hardy spent the years between 1903 and 1908 writing 'The Dynasts', an epic poem on the Napoleonic Wars.In his twilight years came honours and awards from the great and the good and recognition of his stature as one of the most outstanding of British authors. George V conferred on him the Order of Merit in 1910.In 1924 a new stage production of 'Tess of the d'Urbervilles', was staged. Meanwhile from 1920 to 1927 he worked, in secret, on his autobiography, which was later published after his death as the work of Florence Hardy. Thomas Hardy OM died on the 11th January 1928.
Thomas Hardy was born in the hamlet of Upper Bockhampton about three miles east of Dorchester in Dorset, England, on 2nd June 1840. Despite a fairly wide education and being an avid reader his ...parents thought it unlikely he would lead a successful scholarly or clerical career and he was apprenticed in 1856, at age 16, to a local architect whose speciality was in church restoration. Hardy's only opportunity to read was in the morning before work between the hours of five and eight. On the back of a failed love affair he moved to London and spent five years working as Arthur Blomfield's assistant architect, also a restorer and designer of churches. Hardy though had become disillusioned with institutionalised forms of Christianity and abandoned any lingering hopes of ordination in the Anglican Church. However, his poetry was now flourishing, although it was still rejected for publication. His novel 'Desperate Remedies', was published anonymously in 1871 and he now resolved to write full time though he was not yet in a position to achieve financial security or literary success. His second novel, 'Under the Greenwood Tree', appeared in 1872 and in 1873 'A Pair of Blue Eyes', the most autobiographical of his works arrived. With 'Far From the Madding Crowd' in 1874, came critical acclaim, public attention and financial success. 1878 saw more of the same with 'The Return of the Native', and the ensuing years saw him rise to ever greater popularity. 'The Mayor of Casterbridge' was published in 1886. In 1891 came 'Tess of the d'Urbervilles'. It only saw publication after extensive alterations to its plot and deleting long passages to lessen the shock to the prudish Victorian audience who were dismayed by the seduction and ruin of a young girl by a rakish aristocrat. His last novel, 'Jude the Obscure', suffered the same fate when it was published in 1895. The uproar so disturbed him that he returned to poetry. In 1898 he had an earlier poetry collection published 'Wessex Poems'Hardy spent the years between 1903 and 1908 writing 'The Dynasts', an epic poem on the Napoleonic Wars.In his twilight years came honours and awards from the great and the good and recognition of his stature as one of the most outstanding of British authors. George V conferred on him the Order of Merit in 1910.In 1924 a new stage production of 'Tess of the d'Urbervilles', was staged. Meanwhile from 1920 to 1927 he worked, in secret, on his autobiography, which was later published after his death as the work of Florence Hardy. Thomas Hardy OM died on the 11th January 1928.
Several models for the long-term development of T2DM already exist, focusing on the dynamics of the interaction between glycemia, insulinemia and β-cell mass. Current models consider representative ...(fasting or daily average) glycemia and insulinemia as characterizing the compensation state of the subject at some instant in slow time. This implies that only these representative levels can be followed through time and that the role of fast glycemic oscillations is neglected. An improved model (DPM15) for the long-term progression of T2DM is proposed, introducing separate peripheral and hepatic (liver and kidney) insulin actions. The DPM15 model no longer uses near-equilibrium approximation to separate fast and slow time scales, but rather describes, at each step in slow time, a complete day in the life of the virtual subject in fast time. The model can thus represent both fasting and postprandial glycemic levels and describe the effect of interventions acting on insulin-enhanced tissue glucose disposal or on insulin-inhibited hepatic glucose output, as well as on insulin secretion and β-cell replicating ability. The model can simulate long-term variations of commonly used clinical indices (HOMA-B, HOMA-IR, insulinogenic index) as well as of Oral Glucose Tolerance or Euglycemic Hyperinsulinemic Clamp test results. The model has been calibrated against observational data from the Diabetes Prevention Program study: it shows good adaptation to observations as a function of very plausible values of the parameters describing the effect of such interventions as Placebo, Intensive LifeStyle and Metformin administration.
To determine risk factors and treatment outcomes in dysthyroid optic neuropathy (DON) at a single tertiary ophthalmic centre.
Retrospective audit of DON patients who have received intravenous ...methylprednisolone (IVMP) therapy at Royal Victorian Eye and Ear Hospital, Melbourne, Australia from July 2015 to October 2021.
Study included 24 patients (58% female) with an average age of 59.8 ± 14.7 years at DON diagnosis. Majority (92%) had Graves' hyperthyroidism and 77% had a smoking history. At diagnosis, average visual acuity (VA) of worse eye was LogMAR 0.46, and 48% had relative afferent pupillary defect. Proptosis (89%) and diplopia (73%) were most commonly present at diagnosis. 78% showed predominantly extra-ocular muscle enlargement, and apical crowding (52%) on radiology. 38% (n = 9/24) responded to IVMP alone, 58% (n = 14/24) progressed to surgical orbital decompression. The average total cumulative dose of IVMP during DON treatment was 6.8 ± 1.9 g. 29% required further treatment after IVMP and surgical decompression, 4 (17%) had additional radiotherapy, and three (13%) required immuno-modulatory therapy. Average final VA was LogMAR 0.207, with all patients having inactive TED at final follow-up (mean 1.7 years). In refractory DON cases, 71% retained VA ≥ 6/9 and 48% had DON reversal.
DON patients typically present in late 50s, with a smoking history and predominant extra-ocular muscle enlargement. High-dose IVMP fully resolved DON in only 38%. A considerable proportion required urgent orbital decompression. Most patients retained good vision at final follow-up.
Obesity and diabetes are a progressively more and more deleterious hallmark of modern, well fed societies. In order to study the potential impact of strategies designed to obviate the pathological ...consequences of detrimental lifestyles, a model for the development of Type 2 diabetes geared towards large population simulations would be useful. The present work introduces such a model, representing in simplified fashion the interplay between average glycemia, average insulinemia and functional beta-cell mass, and incorporating the effects of excess food intake or, conversely, of physical activity levels. Qualitative properties of the model are formally established and simulations are shown as examples of its use.
Aims
To evaluate whether treatment with LY2409021, a novel, selective glucagon receptor antagonist, is associated with changes in hepatic fat and other safety variables related to the benefit–risk ...profile for chronic use in patients with type 2 diabetes (T2D).
Methods
Safety and efficacy were assessed in patients with T2D taking metformin and sulphonylurea who were randomized to LY2409021 20 mg (n = 65), placebo (n = 68), or sitagliptin 100 mg (n = 41). Key endpoints included change from baseline to month 6 in hepatic fat fraction (HFF), assessed by magnetic resonance imaging; hepatic aminotransferases; blood pressure; lipid profile; fasting plasma glucose; and glycated haemoglobin (HbA1c).
Results
A significant increase in HFF was seen with LY2409021 vs sitagliptin (least squares LS mean difference 3.72%; P < .001) and placebo (4.44%; P < .001), accompanied by significant elevations in alanine aminotransferase levels with LY2409021 vs sitagliptin (6.8 U/L; P = .039) and vs placebo (10.7 U/L; P < .001). No patients had concomitant elevations in bilirubin levels. LY2409021 treatment showed significant HbA1c reductions vs placebo (LS mean difference −0.77%; P < .001) but not sitagliptin (−0.20%; P = .383). Similar results were observed for fasting plasma glucose. LY2409021 was also associated with significant increases in systolic blood pressure vs sitagliptin (4.9 mm Hg; P = .030) and vs placebo (4.3 mm Hg; P = .029), as well as significant increases in body weight and total cholesterol. All effects of LY2409021 were reversible.
Conclusion
In this cohort of patients with T2D, chronic glucagon receptor antagonism with LY2409021 was associated with glucose‐lowering but also demonstrated increases in hepatic fat, hepatic aminotransferases, and other adverse effects.
Lemierre's syndrome is a triad consisting of oropharyngeal infection, internal jugular vein thrombophlebitis, and systemic embolisation typically involving lung and brain. Orbital involvement in this ...life-threatening condition is rare but potentially blinding and may be an indicator of intracranial involvement. We describe a case of odontogenic Lemierre's syndrome complicated by extensive orbital and intracranial septic venous thrombosis, with optic and cranial neuropathy resulting in monocular blindness and ophthalmoplegia. A multidisciplinary approach with abscess drainage, antibiotic and antithrombotic therapy, and close radiological monitoring was critical for preserving contralateral vision and neurological function.
The popularity of using unmanned aerial vehicles (UAVs) to survey colonial waterbirds has increased in the past decade, but disturbance associated with this bourgeoning technology requires further ...study. Disturbance was investigated by conducting aerial surveys with a consumer-grade quadcopter (DJI Phantom 3), while concurrently recording behavioural reactions on video. Surveys of mixed-species waterbird colonies (1-6 species per colony) were flown in horizontal transects at heights of 122, 91, 61, and 46 m, which is a typical range for collecting aerial imagery and producing high-resolution mosaicked orthophotos of nesting bird sites. An upper limit of 122 m was used due to local regulations prohibiting higher-altitude flights without federal authorization. Behavioural reactions were tallied every minute and a disturbance score was calculated for each sampling period. When compared to control periods, we found no evidence that colony-wide escape (i.e., flight) behaviour increased during drone flights, at any altitude flown. However, disturbance score increased significantly by 53% for surveys at 46 m. Some species were more sensitive to surveys than others. Laughing Gulls, in particular, exhibited a significant (125%) increase in escape behaviour for surveys at 91 m. Our results indicate when used in a capacity to gather high-resolution imagery for estimating breeding pairs, UAV surveys affected some species more than others, but severe reactions did not appear to increase for mixed-species colonies as a whole. Further study on safe operating thresholds is essential, especially at local and regional scales.
Type 2 diabetes pathophysiology is characterized by dysregulated glucagon secretion. LY2409021, a potent, selective small-molecule glucagon receptor antagonist that lowers glucose was evaluated for ...efficacy and safety in patients with type 2 diabetes.
The efficacy (HbA1c and glucose) and safety (serum aminotransferase) of once-daily oral administration of LY2409021 was assessed in two double-blind studies. Phase 2a study patients were randomized to 10, 30, or 60 mg of LY2409021 or placebo for 12 weeks. Phase 2b study patients were randomized to 2.5, 10, or 20 mg LY2409021 or placebo for 24 weeks.
LY2409021 produced reductions in HbA1c that were significantly different from placebo over both 12 and 24 weeks. After 12 weeks, least squares (LS) mean change from baseline in HbA1c was -0.83% (10 mg), -0.65% (30 mg), and -0.66% (60 mg) (all P < 0.05) vs. placebo, 0.11%. After 24 weeks, LS mean change from baseline in HbA1c was -0.45% (2.5 mg), -0.78% (10 mg, P < 0.05), -0.92% (20 mg, P < 0.05), and -0.15% with placebo. Increases in serum aminotransferase, fasting glucagon, and total fasting glucagon-like peptide-1 (GLP-1) were observed; levels returned to baseline after drug washout. Fasting glucose was also lowered with LY2409021 at doses associated with only modest increases in aminotransferases (mean increase in alanine aminotransferase ALT ≤10 units/L). The incidence of hypoglycemia in the LY2409021 groups was not statistically different from placebo.
In patients with type 2 diabetes, glucagon receptor antagonist treatment significantly lowered HbA1c and glucose levels with good overall tolerability and a low risk for hypoglycemia. Modest, reversible increases in serum aminotransferases were observed.
Mergers and acquisitions in shipping Alexandrou, George; Gounopoulos, Dimitrios; Thomas, Hardy M.
Transportation research. Part E, Logistics and transportation review,
January 2014, 2014-1-00, 20140101, Letnik:
61
Journal Article
Recenzirano
Odprti dostop
•First comprehensive study of all shipping mergers.•Acquirers earn abnormal returns of 1.2% and targets 3.3%.•N. American targets and Asian acquirers benefit most.•Cross-border deals create more ...economic value than domestic.•Regulation impacts differently across regions on the marginal propensity to merge.
In this comprehensive study of all shipping mergers and acquisitions from 1984 to 2011 we document that the shareholders of both acquirers and targets realise average abnormal gains of 1.2% and 3.3% respectively and both parties gain more from diversifying than focus-increasing deals. Acquirers gain more when paying with stock, in cross-border deals and from taking over public targets. Targets gain more from cross-border and focus-increasing deals. Regulatory interventions, like the EU repeal of exemption from competition and the US Ocean Shipping Reform Act, affect the marginal merger propensity and this propensity differs significantly across regions.
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