838 research outputs found
Injectivity of sections of convex harmonic mappings and convolution theorems
In the article the authors consider the class of
sense-preserving harmonic functions defined in the unit disk
and normalized so that and , where
and are analytic in the unit disk. In the first part of the article we
present two classes and of
functions from and show that if
and , then the harmonic convolution is a univalent
and close-to-convex harmonic function in the unit disk provided certain
conditions for parameters and are satisfied. In the second
part we study the harmonic sections (partial sums) where , and denote the -th partial sums of
and , respectively. We prove, among others, that if
is a univalent harmonic convex mapping,
then is univalent and close-to-convex in the disk for
, and is also convex in the disk for
and . Moreover, we show that the section of is not convex in the disk but is shown to be convex
in a smaller disk.Comment: 16 pages, 3 figures; To appear in Czechoslovak Mathematical Journa
Ecological succession of a Jurassic shallow-water ichthyosaur fall.
After the discovery of whale fall communities in modern oceans, it has been hypothesized that during the Mesozoic the carcasses of marine reptiles created similar habitats supporting long-lived and specialized animal communities. Here, we report a fully documented ichthyosaur fall community, from a Late Jurassic shelf setting, and reconstruct the ecological succession of its micro- and macrofauna. The early 'mobile-scavenger' and 'enrichment-opportunist' stages were not succeeded by a 'sulphophilic stage' characterized by chemosynthetic molluscs, but instead the bones were colonized by microbial mats that attracted echinoids and other mat-grazing invertebrates. Abundant cemented suspension feeders indicate a well-developed 'reef stage' with prolonged exposure and colonization of the bones prior to final burial, unlike in modern whale falls where organisms such as the ubiquitous bone-eating worm Osedax rapidly destroy the skeleton. Shallow-water ichthyosaur falls thus fulfilled similar ecological roles to shallow whale falls, and did not support specialized chemosynthetic communities
Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety
<p>Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.</p>
<p>Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.</p>
<p>Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.</p>
<p>Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.</p>
Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment
Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized protooncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created a murine transgenic model to target PBF expression to the thyroid gland (PBF-Tg mice) and found that these mice exhibited normal thyroid function, but a striking enlargement of the thyroid gland associated with hyperplastic and macrofollicular lesions. Expression of the sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators of thyrocyte proliferation, along with upregulation of the downstream proliferative marker cyclin D1. We extended and confirmed findings from the mouse model by examining PBF expression in human multinodular goiters (MNG), a hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in human primary thyrocytes was sufficient to increase radioiodine uptake. Together, our findings indicate that overexpression of PBF causes thyroid cell proliferation, macrofollicular lesions, and hyperplasia, as well as repression of the critical therapeutic route for radioiodide uptake
Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis
Increased glucose uptake mediated by glucose
transporters and reliance on glycolysis are common features
of malignant cells. Hypoxia-inducible factor-1α supports the
adaptation of hypoxic cells by inducing genes related to
glucose metabolism. The contribution of glucose transporter
(GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to
tumor behavior and their prognostic value in head and neck
cancers remains unclear. The aim of this study was to examine
the predictive value of GLUT1, GLUT3, and HIF-1α messenger
RNA (mRNA)/protein expression as markers of tumor
aggressiveness and prognosis in laryngeal cancer. The level of
hypoxia/metabolic marker genes was determined in 106 squamous
cell laryngeal cancer (SCC) and 73 noncancerous
matched mucosa (NCM) controls using quantitative realtime
PCR. The related protein levels were analyzed by
Western blot. Positive expression of SLC2A1, SLC2A3, and
HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC
specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer
samples. Higher levels of mRNA/protein for GLUT1 and
HIF-1α were noted in SCC compared to NCM (p<0.05).
SLC2A1 was found to have a positive relationship with grade,
tumor front grading (TFG) score, and depth and mode of
invasion (p<0.05). SLC2A3 was related to grade and invasion
type (p<0.05). There were also relationships of HIF-1α with
pTNM, TFG scale, invasion depth and mode, tumor recurrences,
and overall survival (p<0.05). In addition, more advanced
tumors were found to be more likely to demonstrate
positive expression of these proteins. In conclusion, the
hypoxia/metabolic markers studied could be used as molecular
markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory
fund of the Department of Cytobiochemistry, University of Łódź, Poland
(506/811), and by grant fromtheNational Science Council, Poland (N403
043 32/2326)
Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT
Contains fulltext :
86695.pdf (publisher's version ) (Open Access)Rationale Pharmacokinetics of melatonin in children might differ from that in adults.
Objectives This study aims to establish a dose–response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI).
Methods The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n=72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL.
Results Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (rs=-0.33, p=0.022) and SO (rs=-0.38, p=0.004), whereas clock TOA was correlated with SO shift (r=-0.35, p=0.006) and not with DLMO shift.
Conclusions No dose–response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05–0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime.13 p
The economics of Theocracy
This paper models theocracy as a regime where the clergy in power retains knowledge of the cost of political production but which is potentially incompetent or corrupt. This is contrasted with a secular regime where government is contracted out to a secular ruler, and hence the church loses the possibility to observe costs and creates for itself a hidden-information agency problem. The church is free to choose between regimes – a make-or-buy choice – and we look for the range of environmental parameters that are most conducive to the superiority of theocracy and therefore to its occurrence and persistence, despite its disabilities. Numerical solution of the model indicates that the optimal environment for a theocracy is likely to be one in which the “bad” (high-cost) state is disastrously bad but the probability of its occurrence is not very high. A broad review of the historical evidence yields some suggestive support to the predictions of the model. Finally, the model is shown to be applicable to the make-or-buy-government choices of other groups, such as organized labor and the military
Circadian profiles in young people during the early stages of affective disorder
Although disturbances of the circadian system are strongly linked to affective disorders, no known studies have examined melatonin profiles in young people in early stages of illness. In this study, 44 patients with an affective disorder underwent clinical and neuropsychological assessments. They were then rated by a psychiatrist according to a clinical staging model and were categorized as having an ‘attenuated syndrome' or an ‘established disorder'. During the evening, salivary melatonin was sampled under dim light conditions over an 8-h interval and for each patient, the time of melatonin onset, total area under the curve and phase angle (difference between time of melatonin onset and time of habitual sleep onset) were computed. Results showed that there was no difference in the timing of melatonin onset across illness stages. However, area under the curve analyses showed that those patients with ‘established disorders' had markedly reduced levels of melatonin secretion, and shorter phase angles, relative to those with ‘attenuated syndromes'. These lower levels, in turn, were related to lower subjective sleepiness, and poorer performance on neuropsychological tests of verbal memory. Overall, these results suggest that for patients with established illness, dysfunction of the circadian system relates clearly to functional features and markers of underlying neurobiological change. Although the interpretation of these results would be greatly enhanced by control data, this work has important implications for the early delivery of chronobiological interventions in young people with affective disorders
Circadian function in patients with advanced non-small-cell lung cancer
This study aimed to evaluate whether patients with advanced non-small-cell lung cancer experience disrupted rest–activity daily rhythms, poor sleep quality, weakness, and maintain attributes that are linked to circadian function such as fatigue. This report describes the rest–activity patterns of 33 non-small-cell lung cancer patients who participated in a randomised clinical trial evaluating the benefits of melatonin. Data are reported on circadian function, health-related quality of life (QoL), subjective sleep quality, and anxiety/depression levels prior to randomisation and treatment. Actigraphy data, an objective measure of circadian function, demonstrated that patients' rest–activity circadian function differs significantly from control subjects. Our patients reported poor sleep quality and high levels of fatigue. Ferrans and Powers QoL Index instrument found a high level of dissatisfaction with health-related QoL. Data from the European Organization for Research and Treatment for Cancer reported poor capacity to fulfil the activities of daily living. Patients studied in the hospital during or near chemotherapy had significantly more abnormal circadian function than those studied in the ambulatory setting. Our data indicate that measurement of circadian sleep/activity dynamics should be accomplished in the outpatient/home setting for a minimum of 4–7 circadian cycles to assure that they are most representative of the patients' true condition. We conclude that the daily sleep/activity patterns of patients with advanced lung cancer are disturbed. These are accompanied by marked disruption of QoL and function. These data argue for investigating how much of this poor functioning and QoL are actually caused by this circadian disruption, and, whether behavioural, light-based, and or pharmacologic strategies to correct the circadian/sleep activity patterns can improve function and QoL
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