bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily and seasonal adaptation of the circadian clock requires plasticity of the SCN neuronal network
Authors: Meijer Johanna H. , Michel Stephan , VanderLeest Henk T. , Rohling Jos H. T. 
Published: December 2010

AbstractCircadian rhythms are an essential property of many living organisms, and arise from an internal pacemaker, or clock. In mammals, this clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and generates an intrinsic circadian rhythm that is transmitted to other parts of the CNS. We will review the evidence that basic adaptive functions of the circadian system rely on functional plasticity in the neuronal network organization, and involve a change in phase relation among oscillatory neurons. We will illustrate this for: (i) photic entrainment of the circadian clock to the light–dark cycle; and (ii) seasonal adaptation of the clock to changes in day length. Molecular studies have shown plasticity in the phase relation between the ventral and dorsal SCN during adjustment to a shifted environmental cycle. Seasonal adaptation relies predominantly on plasticity in the phase relation between the rostral and caudal SCN. Electrical activity is integrated in the SCN, and appears to reflect the sum of the differently phased molecular expression patterns. While both photic entrainment and seasonal adaptation arise from a redistribution of SCN oscillatory activity patterns, different neuronal coupling mechanisms are employed, which are reviewed in the present paper.
Pituitary stem /progenitor cells: embryonic players in the adult gland?
Authors: Vankelecom Hugo 
Published: December 2010

AbstractThe pituitary gland represents the endocrine core of the body, and its hormonal output governs many key physiological processes. Because endocrine demands frequently change, the pituitary has to flexibly remodel its hormone‐producing cell compartment. One mechanism of pituitary plasticity may rely on the generation of new hormonal cells from resident stem/progenitor cells. Existence of such ‘master’ cells in the pituitary has in the past repeatedly been postulated. Only recently, however, very plausible candidates have been identified that express stem cell‐associated markers and signalling factors, and display the stem/progenitor cell characteristics of multipotency, efflux capacity (side population phenotype) and niche‐like organization. In other adult tissues, stem cells recapitulate the embryonic developmental path on their course towards mature specialized cells. Interestingly, the pituitary stem/progenitor cell compartment shows prominent expression of transcriptional regulators and signalling factors that play a pivotal role during pituitary embryogenesis. This review summarizes the recent progress in pituitary stem/progenitor cell identification, highlights their potential embryonic phenotype, sketches a tentative stem/progenitor cell model, and discusses further research and challenges. Recognizing and scrutinizing the pituitary stem/progenitor cells as embryonic players in the adult gland may profoundly impact on our still poor understanding of the mechanisms underlying pituitary cell turnover and plasticity.
Functional importance of blood flow dynamics and partial oxygen pressure in the anterior pituitary
Authors: Schaeffer Marie , Hodson David J. , Lafont Chrystel , Mollard Patrice 
Published: December 2010

AbstractThe pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions.
Neuronal plasticity and seasonal reproduction in sheep
Authors: Lehman Michael N. , Ladha Zamin , Coolen Lique M. , Hileman Stanley M. , Connors John M. , Goodman Robert L. 
Published: December 2010

AbstractSeasonal reproduction represents a naturally occurring example of functional plasticity in the adult brain as it reflects changes in neuroendocrine pathways controlling gonadotropin‐releasing hormone (GnRH) secretion and, in particular, the responsiveness of GnRH neurons to estradiol negative feedback. Structural plasticity within this neural circuitry may, in part, be responsible for seasonal switches in the negative feedback control of GnRH secretion that underlie annual reproductive transitions. We review evidence for structural changes in the circuitry responsible for seasonal inhibition of GnRH secretion in sheep. These include changes in synaptic inputs onto GnRH neurons, as well as onto dopamine neurons in the A15 cell group, a nucleus that plays a key role in estradiol negative feedback. We also present preliminary data suggesting a role for neurotrophins and neurotrophin receptors as an early mechanistic step in the plasticity that accompanies seasonal reproductive transitions in sheep. Finally, we review recent evidence suggesting that kisspeptin cells of the arcuate nucleus constitute a critical intermediary in the control of seasonal reproduction. Although a majority of the data for a role of neuronal plasticity in seasonal reproduction has come from the sheep model, the players and principles are likely to have relevance for reproduction in a wide variety of vertebrates, including humans, and in both health and disease.
Simultaneous anti‐angiogenic therapy and single‐fraction radiosurgery in clinically relevant metastases from renal cell carcinoma
Authors: Staehler Michael , Haseke Nicolas , Nuhn Philipp , Tüllmann Cordula , Karl Alexander , Siebels Michael , Stief Christian G. , Wowra Berndt , Muacevic Alexander 
Published: December 2010

Study Type – Therapy (case series)Level of Evidence 4What’s known on the subject? and What does the study add?To date radiation therapy has had no oncological implication in renal cell carcinoma. Its use was limited to palliation in painful bone lesions. Radiation therapy was considered ineffective as renal cell cancer is resistant to the commonly used doses of radiotherapy. Side effects in combination with systemic therapy were not known, but heavy skin toxicities were expected. Only a few cases of combined radiation with systemic therapy were published.This is the only series where consecutive patients have been treated simultaneously with sunitnib and hypo‐fractionated high‐dose radiotherapy. Side effects were similar to those expected with systemic therapy or radiation therapy alone. Oncological results are extremely encouraging.OBJECTIVE• To analyse the safety and efficacy of simultaneous standard anti‐angiogenic therapy and stereotactic radiosurgery (SRS) in patients with spinal and cerebral metastases from renal cell carcinoma.PATIENTS AND METHODS• In all, 106 patients with spinal (n= 55) or cerebral (n= 51) metastatic lesions and an Eastern Cooperative Oncology Group status of 0 or 1 were treated with sorafenib or sunitinib and simultaneous SRS.• The primary endpoint was local control.• Secondary endpoints were toxicity and overall survival.RESULTS• Median follow up was 14.7 months (range 1–42 months). Forty‐five patients were treated with sunitinb and 61 patients with sorafenib. Two patients had asymptomatic tumour haemorrhage after SRS.• No skin toxicity, neurotoxicity or myelopathy occurred after SRS, and SRS did not alter the adverse effects of anti‐angiogenic therapy.• Local tumour control 15 months after SRS was 98% (95% confidence interval 89–99%). The median pain score before SRS was 5 (range 1–8) and was lowered to 0 (range 0–2, P < 0.01) after SRS. There were no treatment‐related deaths or late complications after SRS.• Overall survival was 17.4 months in patients with spinal lesions and 11.1 month in patients with cerebral lesions (P= 0.038).CONCLUSIONS• Simultaneous systemic anti‐angiogenic therapy and SRS for selected patients with renal cell carcinoma who have spinal and cerebral metastases is safe and effective.• Single‐fraction delivery allows for efficacious integration of focal radiation treatment into oncological treatment concepts without additional toxicity.• Further studies are needed to determine the limits of SRS for renal cell carcinoma metastases outside the brain and spine.
Use of fluorescein isothiocyanate‐human serum albumin for the intravesical photodiagnosis of non‐muscle‐invasive bladder cancer: an in vitro study using multicellular spheroids composed of normal human urothelial and urothelial cell carcinoma cell lines
Authors: Roelants Mieke , Van Cleynenbreugel Ben , Van Poppel Hendrik , Lerut Evelyne , de Witte Peter A.M. 
Published: December 2010

OBJECTIVE

To evaluate human serum albumin (HSA), fluorescently labelled with fluorescein isothiocyanate (FITC), as a potential intravesical photodiagnostic method for the early detection of non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

By using multicellular spheroids prepared from normal human urothelial (NHU) cells and from different urothelial cell carcinoma (UCC) cell lines (T24, J82), we simulated three‐dimensionally the normal urothelium and non‐muscle‐invasive UCCs present in the bladder of patients.
The distribution of FITC‐HSA in these spheroids was investigated.

RESULTS

Our data showed that fluorescently labelled albumin is quite evenly dispersed throughout the spheroids. However, in the case of the 10 mg/mL incubations, the fluorescence intensity seems to increase slightly towards the spheroid core.
Using 1 mg/mL, the penetration of FITC‐HSA in T24 differed significantly from the penetration in NHU spheroids, but this was not the case for J82 spheroids.
When the concentration of FITC‐HSA was increased 10‐fold, all UCC spheroids exhibited a significantly different accumulation of FITC‐HSA.

CONCLUSIONS

As spheroids represent a suitable in vitro model for predicting the in vivo behaviour of compounds, our data suggest that FITC‐HSA could be used for the early detection of non‐muscle‐invasive bladder cancer.
Human serum albumin conjugates of new or already available intravesical drugs could be generated to create alternative bladder cancer therapies with increased selectivity.
Multi‐scale Internet traffic forecasting using neural networks and time series methods
Authors: Cortez Paulo , Rio Miguel , Rocha Miguel , Sousa Pedro 
Published: December 2010

AbstractThis article presents three methods to forecast accurately the amount of traffic in TCP/IP based networks: a novel neural network ensemble approach and two important adapted time series methods (ARIMA and Holt‐Winters). In order to assess their accuracy, several experiments were held using real‐world data from two large Internet service providers. In addition, different time scales (5 min, 1 h and 1 day) and distinct forecasting lookaheads were analysed. The experiments with the neural ensemble achieved the best results for 5 min and hourly data, while the Holt‐Winters is the best option for the daily forecasts. This research opens possibilities for the development of more efficient traffic engineering and anomaly detection tools, which will result in financial gains from better network resource management.
Hybrid flowshop scheduling with sequence‐dependent setup times by hybridizing max–min ant system, simulated annealing and variable neighbourhood search
Authors: Behnamian J. , Fatemi Ghomi S. M. T. , Zandieh M. 
Published: December 2010

AbstractThis paper deals with the hybrid flowshop scheduling problems with sequence‐dependent setup times. To minimize the makespan, we propose hybrid metaheuristic approach, which integrates several features from ant colony optimization, simulated annealing and variable neighbourhood search in a new configurable scheduling algorithm. Our proposed algorithms are tuned by means of design of experiments approach. We present computational experiments on standard test problems and compare the results with the several algorithms presented previously. The results illustrate that the hybrid metaheuristic outperforms the other algorithms.
Morphological and genetic differentiation in populations of the dispersal‐limited coco de mer (Lodoicea maldivica): implications for management and conservation
Authors: Fleischer‐Dogley Frauke , Kettle Chris J. , Edwards Peter J. , Ghazoul Jaboury , Määttänen Kirsti , Kaiser‐Bunbury Christopher N. 
Published: December 2010

AbstractAims  Developing plant conservation strategies requires knowledge of ecological and genetic processes underlying population dynamics. We aimed to quantify morphological and genetic differentiation among remnant populations of the iconic coco‐de‐mer palm Lodoicea maldivica. We hypothesized that limited gene flow among widely spaced populations would result in high genetic variation and large phenotypic differences among populations.Location  Islands of Praslin and Curieuse (CU), Seychelles, Indian Ocean.Methods  We conducted an extensive population survey and recorded morphological parameters for 447 Lodoicea in the main populations at Vallée de Mai (VM) and Fond Ferdinand (FF) on Praslin, and on CU. We collected leaf material from 180 trees in these populations for DNA genotyping using amplified fragment length polymorphisms.Results  A total of 16,766 Lodoicea trees were recorded in the three populations (72.6% of Lodoicea on both islands). Lodoicea trees at VM and FF showed similar morphology, but differed in most parameters from those at CU, which were shorter, grew more slowly and produced fewer seeds. Mean overall genetic diversity was 0.337, and percentage of polymorphic loci was 91.1. Genetic diversity of the CU population was lower than that at VM and FF. There was weak genetic differentiation between CU and Praslin populations, but 99% of all genetic diversity was within populations.Main conclusions  Trees on CU differed in growth and morphology from those of the two Praslin populations. These phenotypic differences, however, were not mirrored in the genetic structure of the populations. All populations were relatively genetically diverse with remarkably little differentiation among populations. This suggests that the capacity of Lodoicea to dominate across a range of habitats may be because of high phenotypic plasticity. High genetic connectivity may be maintained through long‐distance wind pollination. Given the uncertainty about the extent of underlying adaptive variation, we recommend that restoration projects avoid transferring seeds between island populations.
Bridging the translation gap – new hopes, new challenges
Authors: Tageja Nishant 
Published: December 2010

AbstractThe complexity of modern biomedical research continues to increase. Research‐to‐practice gaps are now widely pervasive; these widening fissures between the disciplines of research and clinical medicine can only be abridged if the translational processes are methodically backed up by robust methods, many of which are yet to be developed. This primarily relates to the development of biomarkers, biostatistical methods, accelerated human study designs including phase 0 trials and smarter decision‐making tools among other features. This brief review highlights the tribulations that have contributed to the lack of technology transfer including lapses in communication between researchers and practitioners, and related factors in service deliverance such as the health care policies, public awareness, and financing. The paper also underscores the heightened attentiveness about the problem in recent years which has, in turn, paved the road for better opportunities to enable cross‐fertilization of ideas, collaboration across multiple disciplines and centers, training of students, residents and junior researchers, and promotion of practical research goals.
Randomised controlled trial of intermittent photic stimulation for treating amblyopia in older children and adults
Authors: Evans Bruce JW , Yu Charlotte S , Massa Emmanuelle , Mathews Jewlsy E 
Published: December 2010

Citation information: Evans BJW, Yu CS, Massa E & Mathews JE. Randomised controlled trial of intermittent photic stimulation for treating amblyopia in older children and adults. Ophthalmic Physiol Opt 2011, 31, 56–68.AbstractThe treatment of amblyopia is reviewed and it is noted that in addition to conventional ‘passive treatment’ in children with occlusion, it has been argued that ‘active treatment’ may be effective in older children and adults. Intermittent photic stimulation (IPS) is one such active treatment. In Study 1, we report a clinical audit of 21 patients treated with IPS, which demonstrated that the maximum improvement is reached after 6 half hour sessions. Study 2 is a double‐masked randomised controlled trial comparing IPS with a control treatment in 30 participants aged 10–57 years. Using a sensitive staircase measure of visual acuity (VA), the IPS group improved by about one line (p = 0.0053). The mean improvement was significantly greater (unpaired t‐test, p = 0.022) in the IPS group (mean 0.096; S.E.M. 0.029) than in the control group (mean 0.019; S.E.M. 0.022). The improvement occurred in participants with strabismic amblyopia, but not in those with anisometropic amblyopia. Follow up data after about 1 year showed that VA had regressed to pre‐treatment levels. The results are discussed within the context of another development in active amblyopia therapy, perceptual learning. The literature on this therapy reveals improvements in VA of about 2.5 lines in older children and adults with anisometropic amblyopia. It is concluded that perceptual learning is likely a better treatment option than IPS for anisometropic amblyopes, and probably also for strabismic amblyopes although a randomised controlled trial is required. It is noted that the existence of effective treatments for adults does not detract from the need to treat amblyopia in younger children.
An exploration of the initial effects of stereoscopic displays on optometric parameters
Authors: Fortuin Marten F , Lambooij Marc T , IJsselsteijn Wijnand A , Heynderickx Ingrid , Edgar David F , Evans Bruce JW 
Published: December 2010

Citation information: Fortuin MF, Lambooij MT, IJsselsteijn WA, Heynderickx I, Edgar DF & Evans BJW. An exploration of the initial effects of stereoscopic displays on optometric parameters. Ophthalmic Physiol Opt 2011, 31, 33–44.AbstractPurpose:  To compare the effect on optometric variables of reading text presented in 2‐D and 3‐D on two types of stereoscopic display.Methods:  This study measured changes in binocular visual acuity, fixation disparity, aligning prism, heterophoria, horizontal fusional reserves, prism facility and accommodation responses for near of subjects after completing ten consecutive reading tasks of 1 minute each. The tasks consisted of reading words on a polarized two‐view (n = 39) and an auto‐stereoscopic lenticular nine‐view display (n = 19) with the text presented without or with stereoscopic disparity at 3 m. Performance was assessed by measuring reading speed and symptoms were rated by the Convergence Insufficiency Symptom Survey (CISS) questionnaire.Results:  With both types of display, CISS scores at least doubled immediately after subjects viewed the 3‐D text image in an extreme stereoscopic condition compared to the 2‐D condition (p < 0.001), while the mean reading speed slowed (p < 0.001). Mean changes in optometric test variables were not clinically or statistically significant (p values > 0.05). After the 3‐D task one participant showed consistent clinically meaningful decreases in convergent fusional break and recovery points for both displays.Conclusion:  When healthy adult subjects with normal binocular vision viewed text images at 3 m in extreme 3‐D display settings for a short period of time there were no clinically significant mean changes in optometric test variables compared with 2‐D viewing.
Vanishing Optotype acuity: repeatability and effect of the number of alternatives
Authors: Shah Nilpa , Dakin Steven C , Redmond Tony , Anderson Roger S 
Published: December 2010

Citation information: Shah N, Dakin SC, Redmond T & Anderson RS. Vanishing Optotype acuity: repeatability and effect of the number of alternatives. Ophthalmic Physiol Opt 2011, 31, 17–22.AbstractPurpose:  Vanishing Optotype letters have a pseudo high‐pass design so that the mean luminance of the target is the same as the background and the letters thus ‘vanish’ soon after the resolution threshold is reached. We wished to determine the variability of acuity measurements using these letters compared to conventional letters, and in particular how acuity is affected by the number of alternatives available to the subject.Methods:  Acuity was measured using high contrast letters of both conventional and Vanishing Optotype design for three experienced normal subjects. Thresholds were determined for central vision in a forced choice paradigm for two alternatives (2AFC; AU and OQ), 4AFC (AQUO), 6AFC (QUANGO) and 26AFC (whole alphabet) using a QUEST procedure. Three measurements were made for each condition.Results:  Threshold letter size was always larger for the Vanishing Optotypes than conventional letters, although the size of this difference (0.11–0.34 logMAR) depended on the number of alternatives and what they were. The effect of the number of AFC, and the individual letters employed, was smaller for the Vanishing Optotypes, implying that they are more equally legible than conventional optotypes. Variability was also lower for the Vanishing Optotype sets (0.01–0.03 logMAR) than the conventional letter sets (0.03–0.06).Conclusions:  The smaller effect of the number of letter alternatives, combined with more equal discriminability and lower threshold variability, implies that Vanishing Optotypes may be appropriate targets from which to design letter charts to measure small clinical changes in acuity.
Donor return after temporary deferral
Authors: Custer Brian , Schlumpf Karen S. , Wright David , Simon Toby L. , Wilkinson Susan , Ness Paul M. ,   for the NHLBI Retrovirus Epidemiology Donor Study‐II
Published: December 2010

BACKGROUND: The consequences of temporary predonation deferral are unsatisfactorily understood. Studies have found that deferral negatively impacts future donor return. However, the applicability of these findings across centers has not been established.STUDY DESIGN AND METHODS: Using a cohort design, presenting donors with a temporary deferral in 2006 to 2008 in one of six categories (low hematocrit [Hct], blood pressure or pulse, feeling unwell, malaria travel, tattoos or piercing and related exposures, or could not wait or second thoughts) were passively followed for up to a 3‐year period for the time to first return after deferral expiration at six US blood centers. Time‐to‐event methods were used to assess return. We also analyzed which donor characteristics were associated with return using multivariable logistic regression.RESULTS: Of 3.9 million donor presentations, 505,623 resulted in deferral in the six categories. Low Hct was the most common deferral, had the shortest median time to return (time in days when 50% of deferred donors had returned), and had the largest cumulative proportion of donors returning. Deferrals of shorter duration had better return. Longer‐term deferrals (up to 1 year in length) had the lowest cumulative return proportion, which did not exceed 50%. Return was associated with previously identified factors such as repeat donor status, older age, and higher educational attainment regardless of the type of deferral. In addition, return was associated with having been born in the United States and donation at fixed sites.CONCLUSION: The category of temporary deferral influences the likelihood of future return, but the demographic and donation factors associated with return are largely consistent regardless of the deferral.