bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemic features affecting the performance of outbreak detection algorithms
Authors: Kuang Jie , Yang Wei Zhong , Zhou Ding Lun , Li Zhong Jie , Lan Ya Jia
Published: June 2012

Background

Outbreak detection algorithms play an important role in effective automated surveillance. Although many algorithms have been designed to improve the performance of outbreak detection, few published studies have examined how epidemic features of infectious disease impact on the detection performance of algorithms. This study compared the performance of three outbreak detection algorithms stratified by epidemic features of infectious disease and examined the relationship between epidemic features and performance of outbreak detection algorithms.

Methods

Exponentially weighted moving average (EWMA), cumulative sum (CUSUM) and moving percentile method (MPM) algorithms were applied. We inserted simulated outbreaks into notifiable infectious disease data in China Infectious Disease Automated-alert and Response System (CIDARS), and compared the performance of the three algorithms with optimized parameters at a fixed false alarm rate of 5% classified by epidemic features of infectious disease. Multiple linear regression was adopted to analyse the relationship of the algorithms’ sensitivity and timeliness with the epidemic features of infectious diseases.

Results

The MPM had better detection performance than EWMA and CUSUM through all simulated outbreaks, with or without stratification by epidemic features (incubation period, baseline counts and outbreak magnitude). The epidemic features were associated with both sensitivity and timeliness. Compared with long incubation, short incubation had lower probability (β* = −0.13, P < 0.001) but needed shorter time to detect outbreaks (β* = −0.57, P < 0.001). Lower baseline counts were associated with higher probability (β* = −0.20, P < 0.001) and longer time (β* = 0.14, P < 0.001). The larger outbreak magnitude was correlated with higher probability (β* = 0.55, P < 0.001) and shorter time (β* = −0.23, P < 0.001).

Conclusions

The results of this study suggest that the MPM is a prior algorithm for outbreak detection and differences of epidemic features in detection performance should be considered in automatic surveillance practice.
A longitudinal cohort based association study between uric acid level and metabolic syndrome in Chinese Han urban male population
Authors: Zhang Qian , Zhang Chengqi , Song Xinhong , Lin Haiyan , Zhang Dongzhi , Meng Wenjia , Zhang Yongyuan , Zhu Zhenxin , Tang Fang , Liu Longjian , Yang Xiaowei , Xue Fuzhong
Published: June 2012

Background

It has been recently demonstrated that serum uric acid (UA) is associated with metabolic syndrome (MetS) or its related clinical indications based on cross-sectional or prospective cohort studies. Nonetheless, due to the fact that UA level constantly fluctuates from time to time even for the person, using a single measure of UA level at baseline of those studies may not be sufficient for estimating the UA-Mets association.

Methods

To further estimate this time-dependent association, we fitted a generalized estimating equation (GEE) regression model with data from a large-scale 6-year longitudinal study, which included 2222 participants aged > =25 years with an average of 3.5 repeated measures of UA per person in the Health Management Center of Shandong Provincial Hospital, Shandong, China.

Results

After adjusting for other potential confounding factors (i.e., total cholesterol, low-density lipoprotein), it was verified that time-dependent UA level was an independent risk factor for MetS (OR = 1.6920, p < 0.0001). It was found that UA level was positively associated with obesity, hypertension, and dyslipidemia, but was inversely associated with hyperglycemia.

Conclusions

Serum UA level may serve as an important risk factor of MetS. Additionally, our study suggested that UA level be an independent risk factor to obesity, hypertension and dyslipidemia, but a protective factor to hyperglycemia. These findings are concordant with results from other studies on Asian populations, and jointly provide a basis to further develop a risk assessment model for predicting MetS using UA levels and other factors in China.
Development and validation of sunlight exposure measurement questionnaire (SEM-Q) for use in adult population residing in Pakistan
Authors: Humayun Quratulain , Iqbal Romaina , Azam Iqbal , Khan Aysha Habib , Siddiqui Amna Rehana , Baig-Ansari Naila
Published: June 2012

Background

Vitamin D deficiency has been identified as a major public health problem worldwide. Sunlight is the main source of vitamin D and its measurement using dosimeters is expensive and difficult for use in population-based studies. Hence, the aim of this study was to develop and validate questionnaires to assess sunlight exposure in healthy individuals residing in Karachi, Pakistan.

Methods

Two questionnaires with seven important items for sunlight exposure assessment were developed. Fifty four healthy adults were enrolled based on their reported sunlight exposure (high = 17, moderate = 18, low = 19) from Aga Khan University, Karachi. Over four days, study participants were asked to wear a dosimeter between sunrise and sunset and report time spent and activities undertaken in the sun for questionnaire validation. Algorithm for item weightage was created as an average score based on ultraviolet B percentage received. Blood samples were obtained for serum vitamin D.

Results

The mean time (minutes) spent in sun over 4 days (±SD) was 69.5 (±32) for low, 83.5 (±29.7) for moderate and 329 (±115) for high exposure group. The correlation between average time (minutes) spent in sun over 4 days and mean change in absorbance of UV dosimeters for 4 days was 0.60 (p < 0.01). Correlation between average score and vitamin D levels was found to be 0.36 (p = 0.01) for short term questionnaire score, 0.43 (p = 0.01) for long term questionnaire score in summers and 0.48 (p = 0.01) in winters.

Conclusions

The sunlight exposure measurement questionnaires were valid tools for use in large epidemiological studies to quantify sunlight exposure.
Five-year monitoring of a gay-friendly voluntary counselling and testing facility in Switzerland: who got tested and why?
Authors: Gumy Cédric , Jeannin André , Balthasar Hugues , Huissoud Thérèse , Jobin Vincent , Häusermann Michael , Crevoisier Hubert , Sudre Philippe , Dubois-Arber Françoise
Published: June 2012

Background

An increase in new HIV cases among men who have sex with men (MSM) has been reported in Switzerland since 2001. A rapid result HIV testing for MSM through voluntary counselling and testing (VCT) facility (“Checkpoint”) was opened in Geneva in 2005. This gay-friendly facility, the first to open in Switzerland, provides testing for sexually transmitted infections (STI) and rapid result HIV testing and counselling. Our objective was to analyze Checkpoint’s activity over its first five years of activity and its ability to attract at-risk MSM.

Methods

We used routine data collected anonymously about the facility activity (number of clients, number of tests, and test results) and about the characteristics of the clientele (sociodemographic data, sexual risk behaviour, and reasons for testing) from 2005 to 2009.

Results

The yearly number of HIV tests performed increased from 249 in 2005 to 561 in 2009. The annual proportion of positive tests among tests performed varied between 2% and 3%. Among MSM clients, the median annual number of anal intercourse (AI) partners was three. Roughly 30% of all MSM clients had at least one unprotected anal intercourse (UAI) experience in the previous 12 months with a partner of different/unknown HIV status.

The main reason for testing in 2007, 2008, and 2009 was “sexual risk exposure” (~40%), followed by “routine” testing (~30%) and “condom stopping in the beginning of a new steady relationship” (~10%). Clients who came to the facility after a sexual risk exposure, compared to clients who came for "routine testing" or "condom stopping" reasons, had the highest number of AI partners in the previous 12 months, were more likely to have had UAI with a partner of different/unknown HIV status in the previous 12 months (respectively 57.3%, 12.5%, 23.5%), more likely to have had an STI diagnosed in the past (41.6%, 32.2%, 22.9%), and more likely to report recent feelings of sadness or depression (42.6%; 32.8%, 18.5%).

Conclusion

Many of Checkpoint's clients reported elevated sexual risk exposure and risk factors, and the annual proportion of new HIV cases in the facility is stable. This VCT facility attracts the intended population and appears to be a useful tool contributing to the fight against the HIV epidemic among MSM in Switzerland.
Usefulness and acceptability of a standardised orientation and mobility training for partially-sighted older adults using an identification cane
Authors: Ballemans Judith , Zijlstra GA Rixt , van Rens Ger HMB , Schouten Jan SAG , Kempen Gertrudis IJM
Published: June 2012

Background

Orientation and mobility (O&M) training in using an identification (ID) cane is provided to partially-sighted older adults to facilitate independent functioning and participation in the community. Recently, a protocolised standardised O&M-training in the use of the ID cane was developed in The Netherlands. The purpose of this study is to assess the usefulness and acceptability of both the standardised training and the regular training for participants and O&M-trainers in a randomised controlled trial (NCT00946062).

Methods

The standardised O&M-training consists of two structured face-to-face sessions and one telephone follow-up, in which, in addition to the regular training, self-management and behavioural change techniques are applied. Questionnaires and interviews were used to collect data on the training’s usefulness, e.g. the population reached, self-reported benefits or achievements, and acceptability, e.g. the performance of the intervention according to protocol and participants’ exposure to and engagement in the training.

Results

Data was collected from 29 O&M-trainers and 68 participants. Regarding the self-reported benefits, outcomes were comparable for the standardised training and the regular training according the trainers and participants e.g., about 85% of the participants in both groups experienced benefits of the cane and about 70% gained confidence in their capabilities. Participants were actively involved in the standardised training. Nearly 40% of the participants in the standardised training group was not exposed to the training according to protocol regarding the number of sessions scheduled and several intervention elements, such as action planning and contracting.

Conclusions

The standardised and regular O&M-training showed to be useful and mostly acceptable for the partially-sighted older adults and trainers. Yet, a concern is the deviation from the protocol of the standardised O&M-training by the O&M-trainers regarding distinguishing elements such as action planning. Overall, participants appreciated both trainings and reported benefit.
The association of insulin resistance and carotid atherosclerosis with thigh and calf circumference in patients with type 2 diabetes
Authors: Park Jong Suk , Cho Min Ho , Ahn Chul Woo , Kim Kyung Rae , Huh Kap Bum
Published: June 2012

Background

The relationship between body composition parameters such as thigh and calf circumference and insulin resistance or atherosclerosis in type 2 diabetes is poorly understood. The aim of this study was to investigate the relationship between insulin resistance, atherosclerosis, and thigh and calf circumference in patients with type 2 diabetes.

Methods

A total of 4,427 subjects with type 2 diabetes were enrolled in this study. Insulin sensitivity was assessed according the rate constant for plasma glucose disappearance (Kitt) determined via the short insulin tolerance test. Biochemical and anthropometric profiles were measured according to a standardized protocol. Visceral fat thickness and carotid intima media thickness (IMT) were measured by ultrasonography.

Results

Insulin sensitivity index (Kitt) was significantly correlated with weight adjusted thigh and calf circumference. Thigh circumference was inversely associated with IMT in men and women and calf circumference was negatively correlated with IMT in women. Multiple stepwise regression analysis revealed that thigh circumference was independently correlated with insulin sensitivity index (Kitt) and IMT. Furthermore, in multivariate logistic regression analysis, thigh circumference was an independent determinant factor for carotid atherosclerosis in patients with type 2 diabetes even after adjusting for other cardiovascular risk factors.

Conclusions

Thigh and calf circumference were correlated with insulin resistance and carotid atherosclerosis, and thigh circumference was independently associated with insulin resistance and carotid atherosclerosis in patients with type 2 diabetes.
New Agilent platform DNA microarrays for transcriptome analysis of Plasmodium falciparum and Plasmodium berghei for the malaria research community
Authors: Kafsack Björn F C , Painter Heather J , Llinás Manuel
Published: June 2012

Background

DNA microarrays have been a valuable tool in malaria research for over a decade but remain in limited use in part due their relatively high cost, poor availability, and technical difficulty. With the aim of alleviating some of these factors next-generation DNA microarrays for genome-wide transcriptome analysis for both Plasmodium falciparum and Plasmodium berghei using the Agilent 8x15K platform were designed.

Methods

Probe design was adapted from previously published methods and based on the most current transcript predictions available at the time for P. falciparum or P. berghei. Array performance and transcriptome analysis was determined using dye-coupled, aminoallyl-labelled cDNA and streamlined methods for hybridization, washing, and array analysis were developed.

Results

The new array design marks a notable improvement in the number of transcripts covered and average number of probes per transcript. Array performance was excellent across a wide range of transcript abundance, with low inter-array and inter-probe variability for relative abundance measurements and it recapitulated previously observed transcriptional patterns. Additionally, improvements in sensitivity permitted a 20-fold reduction in necessary starting RNA amounts, further reducing experimental costs and widening the range of application.

Conclusions

DNA microarrays utilizing the Agilent 8x15K platform for genome-wide transcript analysis in P. falciparum and P. berghei mark an improvement in coverage and sensitivity, increased availability to the research community, and simplification of the experimental methods.
Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran
Authors: Shekarchizadeh Hajar , Ekhtiari Hamed , Khami Mohammad R , Virtanen Jorma I
Published: June 2012

Background

Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran.

Methods

We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses.

Results

A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction.

Conclusion

Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men.
Application of anodized titanium for enhanced recruitment of endothelial progenitor cells
Authors: Moradi Iman , Behjati Mohaddeseh , Kazemi Mohammad
Published: June 2012

Objectives

To study the efficacy of an effective anodized titanium surface with enhanced attachment of endothelial progenitor cell (EPC).

Background

In-stent restenosis is a major obstacle for vascular patency after catheter-based intravascular interventions. Recently, stents that capture EPCs have been paid attention in order to make a functional endothelialized layer at the site of stent-induced endothelial denudation. Anodized titanium has been shown to enhance stem cell attachment. Anodization is a quick and inexpensive method, which can provide suitable stent surface.

Methods

Surface topography was examined by high-resolution scanning electron microscopy (SEM). Substrates were co-cultured with EPCs at second passage in 24-well culture plates. Evaluation of cell growth, proliferation, viability, surface cytotoxicity and cell adhesion was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and 4,6-diamidino-2-phenylindole dihydrochloride staining. For platelet attachment, platelets added to substrates were evaluated under SEM.

Results

The average MTT values for tissue culture polystyrene plate, unanodized and anodized titanium with nanostructure were equal to 0.49, 0.16 and 0.72, respectively (P < 0.05). The surface had no cytotoxic effects on cells. The average cell attachment results showed that 9,955 ± 461.18, 3,300 ± 197.98 and 11,359 ± 458.10 EPCs were attached per well of tissue culture polystyrene plate, unanodized and anodized titanium surfaces, respectively (P < 0.05).

Conclusions

Anodized titanium surfaces can be potentially applied for devices that need enhanced recruitment of EPCs. This unique property makes these anodized surfaces good and cheap candidates for designing cardiovascular medical devices as endovascular stents.
Heterogeneous nucleation of β-type precipitates on nanoscale Zr-rich particles in a Mg-6Zn-0.5Cu-0.6Zr alloy
Authors: Zhu Hongmei , Sha Gang , Liu Jiangwen , Liu Hongwei , Wu Cuilan , Luo Chengping , Liu Zongwen , Zheng Rongkun , Ringer Simon P
Published: June 2012

Zirconium (Zr) is an important alloying element to Mg-Zn-based alloy system. In this paper, we report the formation of the β-type precipitates on the nanoscale Zr-rich particles in a Mg-6Zn-0.5Cu-0.6Zr alloy during ageing at 180°C. Scanning transmission electron microscopy examinations revealed that the nanoscale Zr-rich [0001]α rods/laths are dominant in the Zr-rich core regions of the as-quenched sample after a solution treatment at 430°C. More significantly, these Zr-rich particles served as favourable sites for heterogeneous nucleation of the Zn-rich β-type phase during subsequent isothermal ageing at 180°C. This research provides a potential route to engineer precipitate microstructure for better strengthening effect in the Zr-containing Mg alloys.
Frequency tracking by method of least squares combined with channel estimation for OFDM over mobile wireless channels
Authors: Yen Rainfield Y , Liu Hong-Yu , Tsai Chia-Sheng
Published: June 2012

To track frequency offset and time-varying channel in orthogonal frequency division multiplexing (OFDM) systems over mobile wireless channels, a common technique is, based on one OFDM training block sample, to apply the maximum-likelihood (ML) algorithm to perform joint frequency tracking and channel estimation employing some adaptive iteration processes. The major drawback of such joint estimation techniques is the local extrema problem arising from the highly nonlinear nature of the log-likelihood function. This makes the joint estimation process very difficult and complicated, and many a time the results are not very satisfactory if the algorithm is not well designed. In this study, rather than using the ML algorithm, we shall apply the method of least squares (LS) for frequency tracking utilizing repeated OFDM training blocks. As will be seen, by using such an LS approach, the frequency offset estimation requires no channel knowledge. The channel state can be estimated separately after the LS frequency offset correction. This not only circumvents the local extrema complication, but also obviates the need for the lengthy adaptive iteration process of joint estimation thus greatly simplifies the entire estimation process. Most importantly, our technique can achieve excellent estimation performance as compared to the usual ML algorithms.
Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa
Authors: Sedlackova Dana , Kopeckova Jana , Papezova Hana , Hainer Vojtech , Kvasnickova Hana , Hill Martin , Nedvidkova Jara
Published: June 2012

Background

The present study investigated plasma levels of gut-brain axis peptides ghrelin, obestatin, NPY and PYY after consumption of a high-carbohydrate (HC) and high-protein (HP) breakfast in patients with anorexia nervosa, bulimia nervosa and in healthy controls. These peptides play an important role in regulation of energy homeostasis and their secretion is disturbed under condition of eating disorders. As various types of consumed macronutrients may induce different plasma hormone responses, so we examined these responses in women patients with eating disorders and compared them with those of healthy controls.

Methods

We examined plasma hormone responses to HC and HP breakfast in patients with AN (n = 14; age: 24.6 ± 1.8 years, BMI: 15.3 ± 0.7), BN (n = 15; age: 23.2 ± 1.7 years, BMI: 20.5 ± 0.9) and healthy controls (n = 14; age: 24.9 ± 1.4 years, BMI: 21.1 ± 0.8). Blood samples were drawn from the cubital vein, the first blood drawn was collected before meal, and then 30, 60, 90, 120 and 150 min after breakfast consumption. Plasma hormone levels were determined by commercially available RIA kits.

Results

Fasting and postprandial plasma obestatin levels were significantly increased in both AN and BN patients, while plasma ghrelin levels were significantly increased in AN patients only. After breakfast consumption, plasma levels of ghrelin and obestatin decreased, although they were still above the range of values of healthy controls. Fasting NPY plasma levels were significantly increased in AN and BN patients and did not change postprandially. Fasting PYY levels were comparable in AN, BN and healthy controls, but postprandially significantly increased after HP breakfast in AN and BN patients. Different reactions to breakfast consumption was found for ghrelin and PYY among investigated groups, while for obestatin and NPY these reactions were similar in all groups.

Conclusions

Significant increase of obestatin and NPY in AN and BN patients may indicate their important role as the markers of eating disorders. Different reactions of ghrelin and PYY to breakfast consumption among groups suggest that role of these hormones in regulation of energy homeostasis can be adjusted in dependence to acute status of eating disorder.
Cryptococcus spp isolated from dust microhabitat in Brazilian libraries
Authors: Leite Diniz P , Amadio Janaina V R S , Martins Evelin R , Simões Sara A A , Yamamoto Ana Caroline A , Leal-Santos Fábio A , Takahara Doracilde T , Hahn Rosane C
Published: June 2012

Background

TheCryptococcusspp is currently composed of encapsulated yeasts of cosmopolitan distribution, including the etiological agents of cryptococcosis. The fungus are found mainly in substrates of animal and plant origin. Human infection occurs through inhalation of spores present in the environment.

Methods

Eighty-four swab collections were performed on dust found on books in three libraries in the city of Cuiabá, state of Mato Grosso, Brazil. The material was seeded in Sabouraud agar and then observed for characteristics compatible with colonies with a creamy to mucous aspect; the material was then isolated in birdseed (Niger) agar and cultivated at a temperature of 37°C for 5 to 7 days. Identification of isolated colonies was performed by microscopic observation in fresh preparations dyed with India ink, additional tests performed on CGB (L-canavanine glycine bromothymol blue), urea broth, and carbohydrate assimilation tests (auxanogram).

Results

Of the 84 samples collected from book dust, 18 (21.4%) were positive forCryptococcusspp totalizing 41 UFC’s. The most frequently isolated species wasC. gattii15 (36.6%); followed byC. terreus,12 (29.3%);C. luteolus4 (9.8%);C. neoformans, andC. uniguttulatus3 (7.3%), andC. albidusandC. humiculuswith 2 (4.6%) of the isolates.

Conclusion

The high biodiversity of the yeasts of theCryptococcusgenus, isolated from different environmental sources in urban areas of Brazil suggests the possibility of individuals whose immune systems have been compromised or even healthy individuals coming into sources of fungal propagules on a daily bases throughout their lives. This study demonstrates the acquisition possible of cryptococcosis infection from dust in libraries.
Unusual primary osseous Hodgkin lymphoma in rib with associated soft tissue mass: a case report and review of literature
Authors: Li Yang , Wang Xiao-bing , Tian Xiao-ying , Li Bin , Li Zhi
Published: June 2012

Hodgkin lymphoma (HL) typically presents as nodal lesion and may involve extranodal sites during the progression of the disease. Primary osseous HL without any lymph node association is extremely rare and only a few such cases have been described in the literature. We present a case of unusual primary HL in rib occurring in a middle-aged female patient. Computed tomography (CT) scan revealed an osteolytic lesion was located at the right second rib and was associated with a large soft tissue mass. There was no regional lymph node involvement. CT scan of neck and abdomen was performed and showed no pathologic findings, particularly no lymphadenopathy and organomegaly could be observed. Histologically, typical binucleated Reed-Sternberg (RS) cells and lacunar cells were scattered in the background of reactive inflammation with infiltration of lymphocytes, histiocytes and eosinophilic granulocytes. By immunohistochemistry, RS cells and lacunar cells were positive for CD15 and CD30 with typical membrane and paranuclear dot-like staining pattern. However, these cells were negative for Epstein-Barr virus detection by in situ hybridization. A diagnosis of primary osseous HL was made. The patient received systemic chemotherapy and local radiotherapy, and was on regular follow-up for 24 months. There was no sign of recurrence of tumor and lymph node or bone marrow involvement. Because there is a possibility of secondary bone involvement by systemic HL, strict histological analysis and thorough radiographic examination are suggested to be necessary for accurately diagnosing this tumor when it presents as a solitary bone lesion.

Virtual slides

The virtual slide(s) for this article can be found here:

http://www.diagnosticpathology.diagnomx.eu/vs/2846916171507084
Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types
Authors: Villegas Rosario , Martin Seanna M , O’Donnell Kelley C , Carrillo Simon A , Sagasti Alvaro , Allende Miguel L
Published: June 2012

Background

Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL) nerve is an ideal model system for live studies of axon degeneration and regeneration.

Results

We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths.

Conclusions

Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes.
An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia
Authors: Pandina Gahan , Kushner Stuart , Karcher Keith , Haas Magali
Published: June 2012

Background

Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia.

Methods

This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE) monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales.

Results

A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7%) subjects completed this study: 209 of the 279 subjects (75%) in the 6-month group and 55 of the 111 subjects (50%) in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects) were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs) were reported by 36 (9%) subjects. The AE profile in this study was qualitatively similar to those of other studies in adult subjects with schizophrenia and in other psychiatric studies of risperidone in pediatric populations.

Conclusions

Risperidone maintenance treatment in adolescents over 6 to 12 months was well tolerated, consistent with related studies in this clinical population, and associated with continued efficacy.

Clinical trials

ClinicalTrials.gov registration number: NCT00246285 http://clinicaltrials.gov/ct2/show/NCT00246285?term=NCT00246285&rank=1
Long-term safety and tolerability of donepezil 23 mg in patients with moderate to severe Alzheimer’s disease
Authors: Tariot Pierre , Salloway Steven , Yardley Jane , Mackell Joan , Moline Margaret
Published: June 2012

Background

Donepezil (23 mg/day) is approved by the US Food and Drug Administration for the treatment of patients with moderate to severe Alzheimer’s disease (AD). Approval was based on results from a 24-week, randomized, double-blind study of patients who were stable on donepezil 10 mg/day and randomized 2:1 to either increase their donepezil dose to 23 mg/day or continue taking 10 mg/day. The objective of this study was to assess the long-term safety and tolerability of donepezil 23 mg/day in patients with moderate to severe AD.

Methods

Patients who completed the double-blind study and were eligible could enroll into a 12-month extension study of open-label donepezil 23 mg/day. Clinic visits took place at open-label baseline and at months 3, 6, 9, and 12. Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs); changes in weight, electrocardiogram, vital signs, and laboratory parameters; and discontinuation due to AEs.

Results

915 double-blind study completers were enrolled in the open-label extension study and 902 comprised the safety population. Mean treatment duration in this study was 10.3 ± 3.5 months. In total, 674 patients (74.7%) reported at least one AE; in 320 of these patients (47.5%) at least one AE was considered to be possibly or probably study drug related. The majority of patients reporting AEs (81.9%) had AEs of mild or moderate severity. There were 268 patients (29.7%) who discontinued early, of which 123 (13.6%) were due to AEs.

Patients increasing donepezil dose from 10 mg/day in the double-blind study to 23 mg/day in the extension study had slightly higher rates of AEs and SAEs than patients who were already receiving 23 mg (78.0% and 16.9% vs 72.8% and 14.0%, respectively). The incidence of new AEs declined rapidly after the first 2 weeks and remained low throughout the duration of the study.

Conclusion

This study shows that long-term treatment with donepezil 23 mg/day is associated with no new safety signals. The elevated incidence of AEs in patients increasing the dose of donepezil from 10 mg/day to 23 mg/day was limited to the initial weeks of the study.
Complete remission after first-line radio-chemotherapy as predictor of survival in extranodal NK/T cell lymphoma
Authors: Chauchet Adrien , Michallet Anne-Sophie , Berger Françoise , Bedgedjian Isabelle , Deconinck Eric , Sebban Catherine , Antal Daciana , Orfeuvre Hubert , Corront Bernadette , Petrella Tony , Hacini Maya , Bouteloup Marie , Salles Gilles , Coiffier Bertrand
Published: June 2012

Background

Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors.

Methods

Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL).

Results

For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 %vs.10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %)versusCT alone (33 %) (p < 0.0001). For early-stage disease, CR rates were 37 % for CT aloneversus100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patientsversus0 % for progressive disease patients (p < 0.01).

Conclusion

Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.
The role of vitamin D in children with recurrent Tonsillopharyngitis
Authors: Yildiz Ismail , Unuvar Emin , Zeybek Umit , Toptas Bahar , Cacina Canan , Toprak Sadık , Kilic Ayse , Aydin Salih
Published: June 2012

Background

The exact etiology of recurrent tonsillopharyngitis in children is not clear. Recurrent tonsillitis in children has multifactorial etiology like most of the diseases in childhood. In this study, our aim was to determine the potential role of vitamin D in recurrent tonsillitis by measuring serum 25-OH vitamin D levels and determining the vitamin D receptor polymorphism among children with recurrent tonsillitis.

Methods

Eighty-four children with recurrent tonsillitis and seventy-one healthy children aging between 2 and 10 years were enrolled in this study. Serum 25-OH vitamin D level was measured with ELISA and vitamin D receptor gene polymorphism (Apa1, Taq 1, Fok1) was determined by PCR. Serum 25-OH vitamin D level below 50 nmol/L was accepted as deficiency. The vitamin D receptor gene polymorphism in each group was compared.

Results

The mean age was 5.6 ± 2.4 and 6.1 ± 2.7 years in study and control group, respectively. The average serum 25-OH vitamin D level was 142.7 ± 68.1 nmol/L in study group and 192.3 ± 56.1 nmol/L in control group. There was significant difference between the groups (p < 0.01). In study group, 4.7% (n = 4) of children had serum 25 OH vitamin D levels below 50 nmol/L. None of the children in control group had serum 25-OH vitamin D level below 50 nmol/L. There was no significant differences in vitamin D receptor gene polymorphisms between groups.

Conclusion

Serum 25-OH vitamin D levels in recurrent tonsillitis group were lower than those in healthy children. But, there was no difference in the incidence of vitamin D receptor gene polymorphism between the two groups.
IFN-γ-independent intraocular tumor rejection is mediated by a macrophage-dependent process that leaves the eye intact
Authors: Coursey Terry G , Chen Peter W , Niederkorn Jerry Y
Published: June 2012

Intraocular tumors can undergo rejection by an IFN-γ-independent process that requires macrophages, leaving the eye in pristine condition.

Intraocular tumors reside in an immune-privileged site, yet in certain circumstances, they can undergo immune rejection. Ocular tumor rejection can follow one of two pathways. One pathway is CD4+ T cell-dependent and culminates in ischemic necrosis of the tumor and phthisis (atrophy) of the eye. A second pathway is also CD4+ T cell-dependent but does not inflict collateral injury to ocular tissues, and the eye is preserved. We isolated two clones of a murine tumor, Ad5E1 that undergo profoundly different forms of immune rejection in the eye. Clone 2.1 tumors undergo an ischemic necrotizing form of rejection that requires IFN-γ, T cells, and ocular macrophages and culminates in destruction of the eye. By contrast, the second clone of Ad5E1, clone 4, undergoes rejection that also requires T cells and ocular macrophages, but leaves the eye in pristine condition (nonphthisical rejection). Here, we demonstrate that nonphthisical tumor rejection of clone 4 tumors is IFN-γ-independent but requires an ocular macrophage population that contains M1 and M2 macrophages. Clone 4 tumor-bearing eyes displayed ten- and 15-fold increases in M2- and M1-associated markers Arg1 and NO2, respectively. This is in sharp contrast to previous results with clone 2.1 tumor rejection, in which M2 markers were undetectable, and the eye was destroyed. These results suggest that the presence of M2 macrophages tempers the immune rejection of intraocular tumors and promotes immune effectors that inflict minimal injury to innocent bystander cells and thereby preserve the integrity and function of the eye.
Multi-functional foot use during running in the zebra-tailed lizard (Callisaurus draconoides)
Authors: Li Chen , Hsieh S. Tonia , Goldman Daniel I.
Published: June 2012

A diversity of animals that run on solid, level, flat, non-slip surfaces appear to bounce on their legs; elastic elements in the limbs can store and return energy during each step. The mechanics and energetics of running in natural terrain, particularly on surfaces that can yield and flow under stress, is less understood. The zebra-tailed lizard (Callisaurus draconoides), a small desert generalist with a large, elongate, tendinous hind foot, runs rapidly across a variety of natural substrates. We use high speed video to obtain detailed three-dimensional running kinematics on solid and granular surfaces to reveal how leg, foot, and substrate mechanics contribute to its high locomotor performance. Running at ~10 body length/s (~1 m/s), the center of mass oscillates like a spring-mass system on both substrates, with only 15% reduction in stride length on the granular surface. On the solid surface, a strut-spring model of the hind limb reveals that the hind foot saves about 40% of the mechanical work needed per step, significant for the lizard's small size. On the granular surface, a penetration force model and hypothesized subsurface foot rotation indicates that the hind foot paddles through fluidized granular medium, and that the energy lost during irreversible deformation of the substrate does not differ from the reduction in the mechanical energy of the center of mass. The upper hind leg muscles must perform three times as much mechanical work on the granular surface as on the solid surface to compensate for the greater energy lost within the foot and to the substrate.
Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes inDrosophila melanogaster
Authors: Lye Jessica C , Richards Christopher D , Dechen Kesang , Paterson David , de Jonge Martin D , Howard Daryl L , Warr Coral G , Burke Richard
Published: June 2012

The heavy metal zinc is an essential component of the human diet and is incorporated as a structural component in up to 10% of all mammalian proteins. The physiological importance of zinc homeostasis at the cellular level and the molecular mechanisms involved in this process have become topics of increasing interest in recent years. We have performed a systematic functional characterization of the majority of the predicted Drosophila Zip (Zinc/iron regulated transporter-related protein) and ZnT genes, using the Gal4-UAS system to carry out both ubiquitous and targeted over expression and suppression studies for thirteen of the seventeen putative zinc transport genes identified to date. We find that six of these thirteen genes may be essential for fly viability and that three of the remaining seven demonstrate over expression phenotypes. Our findings reaffirm the previously proposed function of dZnT63C (CG17723: FBgn005432) as an important zinc efflux protein and indicate that the fly homolog of hZip1, dZip42C.1 (CG9428: FBgn0033096), is a strong zinc importer in Drosophila. By combining over expression of dZip42C.1 with suppression of dZnT63C we were able to produce easily identifiable zinc toxicosis phenotypes which can be rescued or worsened by modifying dietary zinc content. Our findings show that a genetically based zinc toxicosis situation can be therapeutically treated or exacerbated by modifications to the diet, providing a sensitized background for future, more detailed studies of Zip / ZNT function.
Temperature compensation of aerobic capacity and performance in the Antarctic pteropod,Clione antarctica, compared to its northern congener,C. limacina
Authors: Dymowska Agnieszka K. , Manfredi Thomas , Rosenthal Joshua J. C. , Seibel Brad A.
Published: June 2012

In ectotherms living in cold waters, locomotory performance is constrained by a slower generation of the ATP that is needed to fuel muscle contraction. Both polar and temperate pteropods of the genus Clione, however, are able to swim continuously by flapping their parapodia (wings) at comparable frequencies, despite the latitudinal temperature gradient. Therefore, we expected polar species to have increased aerobic capacities in their wing muscles. We investigated muscle and mitochondrial ultrastructure of Clione antarctica from the Southern Ocean (-1.8ºC) and populations of a sister species, Clione limacina, from the Arctic (-0.5-3ºC) and from the N. Atlantic (10ºC). We also measured oxygen consumption and the activity of the mitochondrial enzyme citrate synthase (CS), in isolated wings of the two species. The Antarctic species showed a substantial up-regulation of the density of oxidative muscle fibers, but at the expense of fast-twitch muscle fibers. Mitochondrial capacity was also substantially increased in the Antarctic species, with the cristae surface density (58.2±1.3 µm2/µm3) more than twice that found in temperate species (34.3±0.8 µm2/µm3). Arctic C. limacina was intermediate between these two populations (43.7±0.5 µm2/µm3). The values for cold adapted populations are on par with those found in high-performance vertebrates. As a result of oxidative muscle proliferation, CS activity was 4-fold greater in C. antarctica wings than in temperate C. limacina when measured at a common temperature (20°C). Oxygen consumption of isolated wing preparations was comparable in the two species when measured at their respective habitat temperatures. These findings indicate complete compensation of ATP generation in wing muscles across a 10°C temperature range, which supports similar wing-beat frequencies during locomotion at each species' respective temperature. The elevated capacity in the wing muscles is reflected in whole-animal oxygen consumption and feeding rates.
Technical Note—Branch-and-Price-and-Cut Approach to the Robust Network Design Problem Without Flow Bifurcations
Authors: Lee Chungmok , Lee Kyungsik , Park Kyungchul , Park Sungsoo
Published: June 2012

This paper presents a robust optimization approach to the network design problem under traffic demand uncertainty. We consider the specific case of the network design problem in which there are several alternatives in edge capacity installations and the traffic cannot be split over several paths. A new decomposition approach is proposed that yields a strong LP relaxation and enables traffic demand uncertainty to be addressed efficiently through localization of the uncertainty to each edge of the underlying network. A branch-and-price-and-cut algorithm is subsequently developed and tested on a set of benchmark instances.