bluuebunny/crossref_metadata_2025 huggingface dataset:
THE INFLUENCE OF FOOD ON SIDE EFFECTS AND ABSORPTION OF LITHIUM
Authors: Jeppsson J. , Sjögren J.
Published: January 2014

In a cross‐over study, 24 mmol of lithium sulphate was given as a single dose in slow release tablets to 30 healthy volunteers fasting and after a standardised meal. Comparisons were also made with lithium citrate in slow release tablets and placebo. Postprandial administration of lithium gave practically no side effects, while lithium on an empty stomach gave diarrhoea in about 20 % of the subjects.

The absorption was measured by determination of the amount of lithium excreted in the urine in a group of ten subjects. Lithium was completely absorbed when given after food, but when given on an empty stomach the absorption was lower in some subjects, apparently due to rapid gastrointestinal passage in connection with diarrhoea. Lithium should therefore preferably be administered after meals.
Impaired geranylgeranyltransferase‐I regulation reduces membrane‐associated Rho protein levels in aged mouse brain
Authors: Afshordel Sarah , Wood Wellington Gibson , Igbavboa Urule , Muller Walter E. , Eckert Gunter P.
Published: January 2014

Synaptic impairment rather than neuronal loss may be the leading cause of cognitive dysfunction in brain aging. Certain small Rho‐GTPases are involved in synaptic plasticity, and their dysfunction is associated with brain aging and neurodegeneration. Rho‐GTPases undergo prenylation by attachment of geranylgeranylpyrophosphate (GGPP) catalyzed by GGTase‐I. We examined age‐related changes in the abundance of Rho and Rab proteins in membrane and cytosolic fractions as well as of GGTase‐I in brain tissue of 3‐ and 23‐month‐old C57BL/6 mice. We report a shift in the cellular localization of Rho‐GTPases toward reduced levels of membrane‐associated and enhanced cytosolic levels of those proteins in aged mouse brain as compared with younger mice. The age‐related reduction in membrane‐associated Rho proteins was associated with a reduction in GGTase‐Iβ levels that regulates binding of GGPP to Rho‐GTPases. Proteins prenylated by GGTase‐II were not reduced in aged brain indicating a specific targeting of GGTase‐I in the aged brain. Inhibition of GGTase‐I in vitro modeled the effects of aging we observed in vivo. We demonstrate for the first time a decrease in membrane‐associated Rho proteins in aged brain in association with down‐regulation of GGTase‐Iβ. This down‐regulation could be one of the mechanisms causing age‐related weakening of synaptic plasticity.

image

Rho‐GTPases are geranylgeranylated by transferase GGTase‐I. Their prenylation is essential for their localization in membranes, the site of their activation and function. Despite elevated GGPP levels in brains of aged (23 months) mice compared to younger (3 months) mice as well as in GGTI‐2133‐treated SH‐SY5Y cells, the amount of total (homogenate) Rho‐GTPases (Rac1, RhoA, and Cdc42) was unchanged. Treatment with the GGTaseI‐inhibitor GGTI‐2133 decreased prenylation of Rho‐GTPases in membrane preparations of aged mice and SH‐SY5Y, correlating with the reduction of relative GGTase activity, GGTaseIß protein, and mRNA levels. As Rac1, RhoA, and Cdc42 are associated with synaptogenesis, we examined the synaptic marker proteins GAP43 and synaptophysin. GAP43 and synaptophysin declined in an age‐related manner in the mouse brain and were also reduced in our in vitro model. Faulty regulation of Rho proteins in aged brain is associated with a specific deficit in GGTase‐Iβ, which could contribute to age‐related deficits in neuronal outgrowth.
Reduction of tobacco smoke exposure for pregnant passive smokers using feedback of urinary cotinine test results
Authors: Higashida Yuka , Ohashi Kazutomo
Published: January 2014

Aims

Our objective was to evaluate the level of pregnant women's exposure to tobacco smoke by urinary cotinine testing at prenatal examinations, and to examine the effects of disclosing the results of urinary cotinine tests to pregnant women and their families on their smoking activities.

Methods

A prospective cohort study was conducted, enrolling 420 pregnant women who attended prenatal examinations at five private clinics in Japan. Urinary cotinine testing and a questionnaire survey regarding smoking status were conducted in early, middle, and late pregnancy. Urinary cotinine values were measured semiquantitatively using NicCheck I test strips. The results of each urinary cotinine test were handed to the pregnant woman and shared with her family.

Results

The percentages of urinary cotinine‐positive subjects in middle and late pregnancy were significantly decreased compared with early pregnancy (P < 0.001 each). Among the active smokers, there were no significant differences in the urinary cotinine‐positive rates and the numbers of cigarettes among the three stages. In contrast, the urinary cotinine‐positive rates in the passive smokers in late pregnancy were significantly lower than in early pregnancy (P = 0.045) and those in non‐smokers in middle and late pregnancy were also lower than in early pregnancy (P = 0.001, P < 0.001). The numbers of cigarettes smoked by persons close to the passive smokers in middle and late pregnancy were significantly lower than in early pregnancy (P < 0.001).

Conclusions

The feedback of the urinary cotinine test results at prenatal examinations decreased the level of exposure of pregnant passive smokers and non‐smokers to tobacco smoke.
Therapeutic amnioinfusion for chronic abruption‐oligohydramnios sequence: A possible prevention of the infant respiratory disease
Authors: Morita Ayako , Kondoh Eiji , Kawasaki Kaoru , Fujita Kohei , Mogami Haruta , Minamiguchi Sachiko , Konishi Ikuo
Published: January 2014

Chronic abruption‐oligohydramnios sequence (CAOS), characterized by chronic vaginal bleeding and oligohydramnios, is associated with adverse pregnancy outcomes, including preterm delivery and lung problems in the infant. Fetal lung damage may be induced by not only oligohydramnios but also iron‐induced oxidative stress through chronic aspiration of bloody substances in amniotic fluid. We describe a pregnancy complicated with CAOS that was managed with repeated amnioinfusions. This is the first report showing that amnioinfusions succeeded in a significant reduction in high concentrations of iron, lactose dehydrogenase, and 8‐hydroxy‐2′‐deoxyguanosine, a marker of oxidative DNA damage, in the amniotic fluid complicated by CAOS. The baby, born at 26 weeks' gestation via cesarean, was discharged home without supplemental oxygen 116 days after birth.
Can magnetic resonance imaging at 3.0‐Tesla reliably detect patients with endometriosis? Initial results
Authors: Thomeer Maarten G. , Steensma Anneke B. , van Santbrink Evert J. , Willemssen Francois E. , Wielopolski Piotr A. , Hunink Myriam G. , Spronk Sandra , Laven Joop S. , Krestin Gabriel P.
Published: January 2014

Aim

The aim of this study was to determine whether an optimized 3.0‐Tesla magnetic resonance imaging (MRI) protocol is sensitive and specific enough to detect patients with endometriosis.

Material and Methods

This was a prospective cohort study with consecutive patients. Forty consecutive patients with clinical suspicion of endometriosis underwent 3.0‐Tesla MRI, including a T2‐weighted high‐resolution fast spin echo sequence (spatial resolution = 0.75 × 1.2 × 1.5 mm3) and a 3D T1‐weighted high‐resolution gradient echo sequence (spatial resolution = 0.75 × 1.2 × 2.0 mm3). Two radiologists reviewed the dataset with consensus reading. During laparoscopy, which was used as reference standard, all lesions were characterized according to the revised criteria of the American Fertility Society. Patient‐level and region‐level sensitivities and specificities and lesion‐level sensitivities were calculated.

Results

Patient‐level sensitivity was 42% for stage I (5/12) and 100% for stages II, III and IV (25/25). Patient‐level specificity for all stages was 100% (3/3). The region‐level sensitivity and specificity was 63% and 97%, respectively. The sensitivity per lesion was 61% (90% for deep lesions, 48% for superficial lesions and 100% for endometriomata). The detection rate of obliteration of the cul‐the‐sac was 100% (10/10) with no false positive findings. The interreader agreement was substantial to perfect (kappa = 1 per patient, 0.65 per lesion and 0.71 for obliteration of the cul‐the‐sac).

Conclusions

An optimized 3.0‐Tesla MRI protocol is accurate in detecting stage II to stage IV endometriosis.
Changes in expression of vascular endothelial growth factor D‐related genes in placental mesenchymal dysplasia
Authors: Takahashi Hironori , Matsubara Shigeki , Kuwata Tomoyuki , Saruyama Miyuki , Usui Rie , Ohkuchi Akihide , Takizawa Toshihiro , Suzuki Mitsuaki
Published: January 2014

A recent report indicated that vascular endothelial growth factor (VEGF)‐D, regulating cell proliferation and/or differentiation, may be associated with the development of placental mesenchymal dysplasia (PMD), a disorder characterized by cell proliferation/differentiation. In PMD placenta, we examined the expression of five cell‐proliferation/differentiation‐associated genes, namely, Wnt3a, Wnt5a, β‐catenin, VEGF‐D and Dickkopf‐1 (DKK‐1). In PMD, expressions of Wnt3a, Wnt5a and β‐catenin were decreased, whereas those of VEGF‐D and DKK‐1 were increased. These abnormal expressions suggest a relationship between these genes and PMD pathogenesis/pathophysiology.
Relation between gestational weight gain and pregnancy outcomes
Authors: Sunsaneevithayakul Prasert , Titapant Vitaya , Ruangvutilert Pornpimol , Sutantawibul Anuwat , Phatihattakorn Chayawat , Wataganara Tuangsit , Talungchit Pattarawalai
Published: January 2014

Aim

The aim of this study was to evaluate the effects of gestational weight gain on pregnancy outcomes in pregnant Thai women with different pre‐pregnancy body mass indexes (BMI).

Materials and Methods

A retrospective study was carried out by reviewing 5200 medical records of pregnant women who delivered at the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital during 1 September 2011–1 August 2012. Inclusion criteria were singleton pregnancy with available pre‐pregnant weight and maternal height. Pre‐pregnancy BMI were categorized according to World Health Organization criteria. Pregnancy outcomes of interest were appropriate‐for‐gestational‐age infants. The optimal gestational weight gain for each BMI group was proposed to achieve a high proportion of appropriate‐for‐gestational age infants.

Results

Patients were divided into four groups according to their pre‐pregnancy BMI: underweight (21.3%), normal weight (64.1%), overweight (11.5%), and obese (3.1%). Optimal gestational weight gain ranges for each group were 10–18, 8–16, 6–14 and 4–8 kg, respectively. Our proposed criteria seem to be realistic, with 60% of pregnant Thai women able to adhere to the recommendation, compared to 40.5% adherence to the 2009 Institute of Medicine recommendation. There were no significant complications when following either of the recommendations. Adverse pregnancy outcomes, including large for gestational age, cesarean section, and severe pre‐eclampsia, were significantly decreased in women who complied with our recommendation.

Conclusion

To achieve a high proportion of appropriate‐for‐gestational‐age infants, Thai pregnant women could follow our gestational weight gain recommendation.
Complicated rectovaginal fistula secondary to Bartholin's cyst infection
Authors: Nasser Haydar A. , Mendes Vanessa Marron , Zein Farah , Tanios Bassem Y. , Berjaoui Tarek
Published: January 2014

Rectovaginal fistula formation secondary to Bartholin's cyst is a very rare complication, and to date only three cases were reported in the literature. We report a case of a 32‐year‐old woman who suffered recurrent episodes of Bartholin's cyst infection with subsequent abscess formation that resulted in rectovaginal fistula formation. We treated her initially with transperineal repair; however, the fistulous tract recurred a month later. A laparoscopic colostomy and transperineal repair using biological graft was then performed, with excellent results. The patient underwent reversal of colostomy after 2 months, and remained asymptomatic upon follow‐up 12 months later.
Dietary exposure to polychlorinated biphenyls is associated with increased risk of stroke in women
Authors: Bergkvist C. , Kippler M. , Larsson S. C. , Berglund M. , Glynn A. , Wolk A. , Åkesson A.
Published: January 2014

Objective

The potentially beneficial effects of fish consumption on stroke may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular are proposed to play a role in the aetiology of stroke. The aim of this study was to assess the association between dietary PCB exposure and stroke risk with the intake of long‐chain omega‐3 fish fatty acids and fish consumption.

Design

The prospective population‐based Swedish Mammography Cohort was examined. It was comprised of 34 591 women free of cardiovascular diseases and cancer at baseline in 1997 and followed up for 12 years. Validated estimates of dietary PCB exposure were obtained via a food frequency questionnaire at baseline. Incident cases of stroke were ascertained through register linkage.

Results

During 12 years of follow‐up (397 309 person‐years), there were 2015 incident cases of total stroke (1532 ischaemic strokes, 216 intracerebral haemorrhages, 94 subarachnoid haemorrhages and 173 unspecified strokes). Multivariable‐adjusted relative risks (RR), controlled for known stroke risk factors and fish consumption, were 1.67 [95% confidence interval (CI), 1.29–2.17] for total stroke, 1.61 (95% CI, 1.19–2.17) for ischaemic stroke and 2.80 (95% CI, 1.42–5.55) for haemorrhagic stroke for women in the highest quartile of dietary PCB exposure (median 288 ng day−1) compared with women in the lowest quartile (median 101 ng day−1).

Conclusion

Dietary exposure to PCBs was associated with an increased stroke risk in women, especially haemorrhagic stroke. The results provide important information regarding the risk‐benefit analysis of fish consumption, particularly for cerebrovascular disease prevention.
Approaches to the treatment of some of the troublesome manifestations of sarcoidosis
Authors: Eklund A. , du Bois R. M.
Published: January 2014

Sarcoidosis can be a major therapeutic challenge given its multiplicity of clinical presentations, variable combination of organ involvement and severity, and unpredictable longitudinal behaviour. Six manifestations of sarcoidosis are especially difficult to manage because of (i) an incomplete knowledge of causation – fatigue and small fibre neuropathy, (ii) the rare occurrence in sarcoidosis – intra‐abdominal complications or (iii) the potentially life‐threatening consequences in some patients – neurological disease, pulmonary hypertension and hypercalcaemia. In none of these situations have a prospective, double‐blind, placebo‐controlled trial of any therapy been conducted. Despite this absence of any firm evidence base to support therapeutic recommendations, these six entities can be extremely problematic for the practising clinician. It is for this reason that we have focused in this review on these six disease manifestations and provided a synopsis of each problem together with suggested treatment approaches, based on an analysis of the current literature.
Prevalence of Disc Displacement of Various Severities among Young Preorthodontic Population: A Magnetic Resonance Imaging Study
Authors: Ikeda Kazumi , Kawamura Akira , Ikeda Renie
Published: January 2014

Purpose

There has been no study on the prevalence of disc displacement (DD) of different levels in children and adolescents with adequate sample size using magnetic resonance images (MRIs). This retrospective cross‐sectional study was designed to investigate the relationship between increasing age and the prevalence of DD of various severities in a young preorthodontic population.

Materials and Methods

Of 199 preorthodontic patients aged 6 to 15 years visiting a private orthodontic office for initial examination, 153 patients with signs and symptoms of temporomandibular joint (TMJ) disorders had MRIs of their TMJs taken for further evaluation. Of those, 302 TMJs from 151 patients’ MRIs of diagnostic quality were divided into three age groups (I: 6 to 9, II: 10 to 12, and III: 13 to 15 years). DD of each patient was categorized based on its severity from stage 0 (normal) to stage 4 (total DD without reduction). The distribution of DD stages in each age group was plotted on a line graph and statistically analyzed for intergroup comparison.

Results

A graphical representation of the results clearly demonstrated a trend for higher occurrence of more advanced DD with an increase in age. No gender difference was observed. Statistical analysis showed that DD was significantly more advanced in group II than group I (p < 0.01) and group III than group I (p < 0.01).

Conclusions

The study revealed a high prevalence of DD in the young preorthodontic population and significant increase in the proportion of patients with more advanced stages of DD in older patients.
Comparison of Forelimb and Hindlimb Systolic Blood Pressures and Proteinuria in Healthy Shetland Sheepdogs
Authors: Scansen B.A. , Vitt J. , Chew D.J. , Schober K.E. , Bonagura J.D.
Published: January 2014

Background

The prevalence of systemic hypertension (SHT) in Shetland Sheepdogs has not been reported.

Hypothesis/Objectives

SHTis common in Shetland Sheepdogs and positively correlated with proteinuria. Measurements of forelimb and hindlimb systolic arterial pressure (SAP) are comparable.

Animals

Seventy‐two clinically healthy, client‐owned Shetland Sheepdogs.

Methods

Forelimb and hindlimbSAPwere recorded by Doppler ultrasonography. Proteinuria was quantified by urine dipstick, microalbuminuria, and protein:creatinine ratio (UPC). The relationship ofUPC, anxiety, age, weight, and heart rate with forelimbSAPwas evaluated.

Results

The mean forelimb and hindlimbSAPwere 132 ± 20 and 118 ± 20 mmHg, respectively. TheSAPexceeded 160 mmHg in 9 dogs, suggesting 13% prevalence ofSHT. Four dogs had aUPCabove 0.5; 2 of these had forelimbSAPexceeding 160 mmHg. Correlation of forelimb and hindlimbSAPwas poor (r2 = 0.09;P = .011). Bland–Altman plots revealed substantial bias (−14 mmHg) between limb measurements with clinically unacceptable 95% limits of agreement (−60 to 33 mmHg). There was no correlation between forelimbSAPandUPC(P = .06) or anxiety level (P = .49). Age (P < .0001) and heart rate (P = .038) were significant predictors of forelimbSAP; weight (P = .73) was not.

Conclusions

Prevalence ofSHTwas 13% and not correlated with proteinuria. Forelimb and hindlimbSAPwere poorly correlated; therefore, trends in an individual animal should be monitored using the same measurement site. Additionally, values for DopplerSAPwere determined in Shetland Sheepdogs.
Heterothermy in pouched mammals – a review
Authors: Riek A. , Geiser F.
Published: January 2014

Hibernation and daily torpor (i.e. temporal heterothermy) have been reported in many marsupial species of diverse families and are known to occur in ∼15% of all marsupials, which is a greater proportion than the percentage of heterothermic placentals. Therefore, we aimed to gather data on heterothermy, including minimal body temperature, torpor metabolic rate and torpor bout duration for marsupials, and relate these physiological variables to phylogeny and other physiological traits. Data from published studies on 41 marsupial species were available for the present analysis. Heterothermic marsupials ranged from small species such as planigales weighing 7 g to larger species such as quolls weighing up to 1000 g. We used the marsupial phylogeny to estimate various heterothermic traits where the current dataset was incomplete. The torpor metabolic rate in relation to basal metabolic rate (%) ranged from 5.2 to 62.8% in daily heterotherms and from 2.1 to 5.2% in marsupial hibernators, and was significantly correlated with the minimum body temperature in daily heterotherms (R2 = 0.77, P < 0.001), but not in hibernators (R2 = 0.10, P > 0.05). The mean torpor bout duration ranged from 2 to 15 h in daily heterotherms and from 85 to 342 h in hibernators, and decreased significantly with increasing minimum body temperature in daily heterotherms (R2 = 0.31, P < 0.001), but was not significant in hibernators. Our results show that phylogeny has a significant influence on nearly all analysed individual traits and relationships between traits in daily heterotherms (n = 35), but not in hibernators (n = 6). However, allometric analyses show that many of the physiological parameters scale differently between hibernators and daily heterotherms.
Interpreting ecology and behaviour from the vertebrate fossil track record
Authors: Falkingham P. L.
Published: January 2014

Fossil tracks represent a direct window onto the lives of extinct organisms, being formed and preserved in situ. Because track morphology is determined by limb motion, foot anatomy and substrate consistency, studies of fossil tracks can provide insight into producer, behaviour and palaeoenvironment. However, each determining factor is subject to variation, either continuous or discrete, and this variation may be co‐dependent, making it difficult to correctly interpret a track. In addition to variance from the track‐forming variables, tracks and tracksites are subject to further obfuscation because of time averaging, even before the effects of weathering, erosion and exposure are accounted for. This paper presents a discussion of the factors that may confound interpretation of fossil tracks, trackways and tracksites, and reviews experimental studies that have attempted to elucidate and eliminate these sources of confusion.
Identification of a novel mutation in the CLCN5 gene in a Chinese family with Dent‐1 disease
Authors: Zhang Hao , Wang Chun , Yue Hua , Hu Wei‐Wei , Gu Jie‐Mei , He Jin‐Wei , Fu Wen‐Zhen , Liu Yu‐Juan , Zhang Zeng , Zhang Zhen‐Lin
Published: January 2014

Dent disease comprises a group of X‐linked recessive inherited renal tubular disorders, the symptoms of which include low‐molecular‐weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and progressive renal failure. We sought to characterize the clinical manifestations and to identify the mutations associated with this disease in Chinese patients. In total, 155 DNA samples were collected from one affected individual, four of his family members, and 150 healthy donors. All 12 exons and the exon‐intron boundaries of the CLCN5 gene were amplified and directly sequenced in this Chinese family. The proband demonstrated osteomalacia, which had resulted in more than 10 fractures, LMWP, and renal failure. A single base ‘G’ deletion at nucleotide 246 (c. 246delG) was identified in exon 5 of the CLCN5 gene in this patient, resulting in a frame shift mutation (fsX) that changed the Threonine (Thr) residue in position 83 to Proline (Pro). The proband's mother was found to be a carrier of this mutation. The present study suggests that a novel frameshift mutation (c. 246delG) in exon 5 of the CLCN5 gene is responsible for Dent disease in this case. Our findings also expand the known spectrum of CLCN5 mutations.
Knowledge deficit of patients with stage 1–4 CKD: A focus group study
Authors: Lopez‐Vargas Pamela A , Tong Allison , Phoon Richard KS , Chadban Steven J , Shen Yvonne , Craig Jonathan C
Published: January 2014

Background

Patients with early‐stage chronic kidney disease (CKD) must make lifestyle modifications and adhere to treatment regimens to prevent their progression to end‐stage kidney disease. The aim of this study was to elicit the perspectives of patients with stage 1–4 CKD about their disease, with a specific focus on their information needs in managing and living with CKD and its sequelae.

Methods

Patients with CKD stages 1–4 were purposively sampled from three major hospitals in Sydney, Australia to participate in focus groups. Transcripts were thematically analysed.

Results

From nine focus groups including 38 participants, six major themes were identified: medical attentiveness (shared decision‐making, rapport, indifference and insensitivity); learning self‐management (diet and nutrition, barriers to physical activity, medication safety); contextualizing comorbidities (prominence of CKD, contradictory treatment); prognostic uncertainty (hopelessness, fear of disease progression, disbelief regarding diagnosis); motivation and coping mechanisms (engage in research, pro‐active management, optimism, feeling normal); and knowledge gaps (practical advice, access to information, comprehension of pathology results and CKD diagnosis, education for general practitioners).

Conclusion

Patients capacity to slow the progression of CKD may be limited by their lack of knowledge about the disease, its comorbidities, psychosocial influences and their ability to interact and communicate effectively with their health‐care provider. Support from a multidisciplinary care team, combined with provision of comprehensive, accessible and practical educational resources may enhance patients' ability and motivation to access and adhere to therapeutic and lifestyle interventions to retard progression of CKD.
Risk Factor Selection in Rate Making: EM Adaptive LASSO for Zero‐Inflated Poisson Regression Models
Authors: Tang Yanlin , Xiang Liya , Zhu Zhongyi
Published: January 2014

Risk factor selection is very important in the insurance industry, which helps precise rate making and studying the features of high‐quality insureds. Zero‐inflated data are common in insurance, such as the claim frequency data, and zero‐inflation makes the selection of risk factors quite difficult. In this article, we propose a new risk factor selection approach, EM adaptive LASSO, for a zero‐inflated Poisson regression model, which combines the EM algorithm and adaptive LASSO penalty. Under some regularity conditions, we show that, with probability approaching 1, important factors are selected and the redundant factors are excluded. We investigate the finite sample performance of the proposed method through a simulation study and the analysis of car insurance data from SAS Enterprise Miner database.
The Fokas Method: The Dirichlet to Neumann Map for the Sine‐Gordon Equation
Authors: Hwang Guenbo
Published: January 2014

We study initial boundary value problems for the sine‐Gordon equation on the half‐line via the Fokas method, known as an extension of the inverse scattering transform. The method is based on the simultaneous analysis of both parts of the Lax pair and the global algebraic relation that couples known and unknown boundary values. One of most difficult steps of the method is to characterize the unknown boundary values that appear in the spectral functions. We derive the Dirichlet to Neumann map by using the global relation and the asymptotics of the eigenfunctions. Furthermore, employing perturbation expansion, we present an effective characterizations of the unknown boundary value in terms of the given initial and boundary values, and we then derive the first few terms of the expansions of the Neumann boundary value up to the third order.
Asymptotics of Stirling and Chebyshev‐Stirling Numbers of the Second Kind
Authors: Gawronski Wolfgang , Littlejohn Lance L. , Neuschel Thorsten
Published: January 2014

For the classical Stirling numbers of the second kind, asymptotic formulae are derived in terms of a local central limit theorem. The underlying probabilistic approach also applies to the Chebyshev–Stirling numbers, a special case of the Jacobi–Stirling numbers. Essential features are uniformity properties and the fact that the leading terms of the asymptotics are given explicitly and they contain elementary expressions only. Thereby supplements of the asymptotic analysis of these numbers are established.
A Comparison Between the HeRO Graft and Conventional Arteriovenous Grafts in Hemodialysis Patients
Authors: Nassar George M. , Glickman Marc H. , McLafferty Robert B. , Kevin Croston J. , Zarge Joseph I. , Katzman Howard E. , Peden Eric K. , Lawson Jeffrey H. , Martinez Jeffrey M. , Thackeray Lisa
Published: January 2014

Venous stenosis and occlusion are a major cause of vascular access dysfunction and failure. The HeRO Graft bypasses occlusion and traverses stenosis with outflow directly into the central venous circulation. A randomized, multicenter study was conducted to evaluate the efficacy and safety of the HeRO Graft relative to conventional AV grafts. The design was to enroll 143 patients in a 2:1 randomization ratio between HeRO and conventional AV control groups. Data on 72 subjects (52 HeRO Graft and 20 AV graft controls) were obtained. The HeRO Graft and control cohorts were comparable in baseline characteristics. Adequacy of dialysis, bacteremia rates, and adverse events were consistent between groups. Twelve month Kaplan–Meier estimates for primary and secondary patency rates were 34.8% and 67.6% in the HeRO Graft cohort, and 30.6% and 58.4% in the control cohort. There was no statistical difference in terms of patency between groups. The rates of intervention were 2.2/year for HeRO Graft and 1.6/year for the control (p = 0.100). Median days to loss of secondary patency was 238 for HeRO Graft versus 102 for the control (p = 0.032). The HeRO Graft appears to provide similar patency, adequacy of dialysis, and bacteremia rates to those of conventional AV grafts.
Limit theorems for reflected Ornstein–Uhlenbeck processes
Authors: Huang Gang , Mandjes Michel , Spreij Peter
Published: January 2014

This paper studies one‐dimensional Ornstein–Uhlenbeck (OU) processes, with the distinguishing feature that they are reflected on a single boundary (put at level 0) or two boundaries (put at levels 0 and d > 0). In the literature, they are referred to as reflected OU (ROU) and doubly reflected OU (DROU), respectively. For both cases, we explicitly determine the decay rates of the (transient) probability to reach a given extreme level. The methodology relies on sample‐path large deviations, so that we also identify the associated most likely paths. For DROU, we also consider the ‘idleness process’ Lt and the ‘loss process’ Ut, which are the minimal non‐decreasing processes, which make the OU process remain ≥ 0 and ≤ d, respectively. We derive central limit theorems (CLTs) for Ut and Lt, using techniques from stochastic integration and the martingale CLT.
Optimal number of accrual groups and accrual group sizes in longitudinal trials with discrete‐time survival endpoints
Authors: Safarkhani Maryam , Jolani Shahab , Moerbeek Mirjam
Published: January 2014

In longitudinal trials, the number of accrual groups and their sizes should carefully be chosen to ensure a desired power to detect a specified treatment effect. Methods are proposed to obtain a cost‐effective combination of the number and size of accrual groups that provides high efficiency at minimal cost. We focus on trials where an event occurs at any point in time, but it is recorded on a discrete scale. The Weibull survival function is considered for modeling the underlying time to event. By using a cost function, it is shown that the ratio of the cost of recruiting and treating subjects to the cost of measuring them and also the survival pattern highly influence the optimal combination of the number and size of accrual groups. A maximin approach is further presented to obtain robust designs with respect to poor specification of these modeling parameters. We also show the application of the proposed optimal design methodology using real examples.
Mucoadhesive chitosan films as a potential ocular delivery system for ofloxacin: preliminary in vitro studies
Authors: de Oliveira Fulgêncio Gustavo , Viana Fernando Antônio B. , Silva Rodrigo Otávio S. , Lobato Francisco Carlos F. , Ribeiro Raul R. , Fanca Juçara R. , Byrro Ricardo Martins D. , Faraco André Augusto G. , da Silva Cunha‐Júnior Armando
Published: January 2014

Objective

The objective of the study is to evaluate the physical properties, in vitro release profile, and antibacterial efficiency of chitosan films prepared with ofloxacin.

Procedure

Mucoadhesive films were prepared by means of a casting and solvent evaporation technique performed in a 2 wt% acetic acid solution and distilled water. Physical properties were characterized by release and swelling studies, differential scanning calorimetry (DSC) analysis, and attenuated total reflectance Fourier transformed infrared spectroscopy (ATR‐FTIR) analysis. The in vitro evaluation of the films was performed by inhibiting Staphylococcus aureus and Pseudomonas aeruginosa through activity studies.

Results

Circular ofloxacin‐loaded chitosan‐developed films with 0.3 mg of drug weighed 7 mg were 110 μm thick and 5 mm in diameter. The DSC curve of ofloxacin‐loaded chitosan films suggests an amorphous dispersion of ofloxacin within these films. ATR‐FTIR analysis showed that ofloxacin is indeed present in the matrix film. The drug was released in vitro over a 1‐h period. No statistical difference could be observed between the ofloxacin‐loaded chitosan films and sterile disk soaked for 1 min in 0.3% commercial ofloxacin ophthalmic solution for S. aureus and P. aeruginosa (P = 0.1686, P = 0.1172, respectively).The films presented a significantly larger mean bacterial inhibition zone of S. aureus than did the commercial ciprofloxacin control disk (P = 0.0002) and a significantly larger mean bacterial kill zone of P. aeruginosa than did the commercial enrofloxacin control disk (P < 0.0001).

Conclusions

Ofloxacin was successively incorporated onto chitosan films and was not inactivated during the process of manufacturing, thus preserving antibacterial proprieties.
A Class of Mathematical Models Describing Processes in Spatially Heterogeneous Biofilm Communities
Authors: Sonner Stefanie
Published: January 2014

We present a class of deterministic continuum models for spatially heterogeneous biofilm communities. The prototype is a single-species biofilm growth model, which is formulated as a highly non-linear system of reaction-diffusion equations for the biomass density and the concentration of the growth controlling substrate. While the substrate concentration satisfies a standard semi-linear reaction-diffusion equation the equation for the biomass density comprises two non-linear diffusion effects: a porous medium-type degeneracy and super diffusion. When further biofilm processes are taken into account equations for several substrates and multiple biomass components have to be included in the model. The structure of these multi-component extensions is essentially different from the mono-species case, since the diffusion operator forthe biomass componentsdepends on the total biomass in the system and the equations are strongly coupled. We present the prototype biofilm growth model and give an overview of its multi-component extensions. Moreover, we summarize analytical results that were obtained for these models.
Evaluation of a new commercial Monte Carlo dose calculation algorithm for electron beams
Authors: Vandervoort Eric J. , Tchistiakova Ekaterina , La Russa Daniel J. , Cygler Joanna E.
Published: January 2014

Purpose:

In this report the authors present the validation of a Monte Carlo dose calculation algorithm (XiO EMC from Elekta Software) for electron beams.

Methods:

Calculated and measured dose distributions were compared for homogeneous water phantoms and for a 3D heterogeneous phantom meant to approximate the geometry of a trachea and spine. Comparisons of measurements and calculated data were performed using 2D and 3D gamma index dose comparison metrics.

Results:

Measured outputs agree with calculated values within estimated uncertainties for standard and extended SSDs for open applicators, and for cutouts, with the exception of the 17 MeV electron beam at extended SSD for cutout sizes smaller than 5 × 5 cm2. Good agreement was obtained between calculated and experimental depth dose curves and dose profiles (minimum number of measurements that pass a 2%/2 mm agreement 2D gamma index criteria for any applicator or energy was 97%). Dose calculations in a heterogeneous phantom agree with radiochromic film measurements (>98% of pixels pass a 3 dimensional 3%/2 mm γ‐criteria) provided that the steep dose gradient in the depth direction is considered.

Conclusions:

Clinically acceptable agreement (at the 2%/2 mm level) between the measurements and calculated data for measurements in water are obtained for this dose calculation algorithm. Radiochromic film is a useful tool to evaluate the accuracy of electron MC treatment planning systems in heterogeneous media.
Plan averaging for multicriteria navigation of sliding window IMRT and VMAT
Authors: Craft David , Papp Dávid , Unkelbach Jan
Published: January 2014

Purpose:

To describe a method for combining sliding window plans [intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT)] for use in treatment plan averaging, which is needed for Pareto surface navigation based multicriteria treatment planning.

Methods:

The authors show that by taking an appropriately defined average of leaf trajectories of sliding window plans, the authors obtain a sliding window plan whose fluence map is the exact average of the fluence maps corresponding to the initial plans. In the case of static‐beam IMRT, this also implies that the dose distribution of the averaged plan is the exact dosimetric average of the initial plans. In VMAT delivery, the dose distribution of the averaged plan is a close approximation of the dosimetric average of the initial plans.

Results:

The authors demonstrate the method on three Pareto optimal VMAT plans created for a demanding paraspinal case, where the tumor surrounds the spinal cord. The results show that the leaf averaged plans yield dose distributions that approximate the dosimetric averages of the precomputed Pareto optimal plans well.

Conclusions:

The proposed method enables the navigation of deliverable Pareto optimal plans directly, i.e., interactive multicriteria exploration of deliverable sliding window IMRT and VMAT plans, eliminating the need for a sequencing step after navigation and hence the dose degradation that is caused by such a sequencing step.
Conserved Class of Queen Pheromones Stops Social Insect Workers from Reproducing
Authors: Van Oystaeyen Annette , Oliveira Ricardo Caliari , Holman Luke , van Zweden Jelle S. , Romero Carmen , Oi Cintia A. , d'Ettorre Patrizia , Khalesi Mohammadreza , Billen Johan , Wäckers Felix , Millar Jocelyn G. , Wenseleers Tom
Published: January 2014

Long Live the Queen

Eusociality is often considered to have arisen, at least in part, due to the inclusive fitness that workers gain through helping their queen sister to raise her offspring.

Van Oystaeyen
et al.

(p.
287
; see the Perspective by

Chapuisat

) characterized the sterility-inducing queen pheromone across three distantly related eusocial hymenopterans (a wasp, a bumblebee, and a desert ant) and synthesized data across 69 other species. Queen pheromones appear to be remarkably conserved, which suggests that reproductive manipulation has ancient roots.
Smells Like Queen Since the Cretaceous
Authors: Chapuisat Michel
Published: January 2014

Chemically similar queen pheromones inhibit worker reproduction in ants, wasps, and some bees, suggesting that these pheromones have served to signal fertility for 150 million years.

[Also see Report by

Van Oystaeyen
et al.

]
Frederick Sanger (1918–2013)
Authors: Brenner Sydney
Published: January 2014

Twice awarded the Nobel Prize, a biochemist's work on protein and DNA structure opened the door to modern biomedical science.
Reproducibility
Authors: McNutt Marcia
Published: January 2014

Science advances on a foundation of trusted discoveries. Reproducing an experiment is one important approach that scientists use to gain confidence in their conclusions. Recently, the scientific community was shaken by reports that a troubling proportion of peer-reviewed preclinical studies are not reproducible. Because confidence in results is of paramount importance to the broad scientific community, we are announcing new initiatives to increase confidence in the studies published in
Science
. For preclinical studies (one of the targets of recent concern), we will be adopting recommendations of the U.S. National Institute of Neurological Disorders and Stroke (NINDS) for increasing transparency.
*
Authors will indicate whether there was a pre-experimental plan for data handling (such as how to deal with outliers), whether they conducted a sample size estimation to ensure a sufficient signal-to-noise ratio, whether samples were treated randomly, and whether the experimenter was blind to the conduct of the experiment. These criteria will be included in our author guidelines.
Development and Evaluation of a Blocking Enzyme-Linked Immunosorbent Assay and Virus Neutralization Assay To Detect Antibodies to Viral Hemorrhagic Septicemia Virus
Authors: Wilson Anna , Goldberg Tony , Marcquenski Susan , Olson Wendy , Goetz Frederick , Hershberger Paul , Hart Lucas , Toohey-Kurth Kathy
Published: January 2014

Viral hemorrhagic septicemia virus (VHSV) is a target of surveillance by many state and federal agencies in the United States. Currently, the detection of VHSV relies on virus isolation, which is lethal to fish and indicates only the current infection status. A serological method is required to ascertain prior exposure. Here, we report two serologic tests for VHSV that are nonlethal, rapid, and species independent, a virus neutralization (VN) assay and a blocking enzyme-linked immunosorbent assay (ELISA). The results show that the VN assay had a specificity of 100% and sensitivity of 42.9%; the anti-nucleocapsid-blocking ELISA detected nonneutralizing VHSV antibodies at a specificity of 88.2% and a sensitivity of 96.4%. The VN assay and ELISA are valuable tools for assessing exposure to VHSV.
Live Oral Salmonella enterica Serovar Typhi Vaccines Ty21a and CVD 909 Induce Opsonophagocytic Functional Antibodies in Humans That Cross-React withS. Paratyphi A andS. Paratyphi B
Authors: Wahid Rezwanul , Zafar Shah J. , McArthur Monica A. , Pasetti Marcela F. , Levine Myron M. , Sztein Marcelo B.
Published: January 2014

Live oralSalmonella entericaserovar Typhi vaccine Ty21a induces specific antibodies that cross-react againstSalmonella entericaserovar Paratyphi A andSalmonella entericaserovar Paratyphi B, although their functional role in clearance remains unknown. We utilized anin vitroassay with THP-1 macrophages to compare the phagocytosis and survival ofSalmonellaopsonized with heat-inactivated human sera obtained before and after vaccination with Ty21a or a live oralS. Typhi vaccine, CVD 909. Opsonization with postvaccination sera predominantly increased the phagocytosis ofS. Typhi relative to the corresponding prevaccination sera, and increases were also observed withS. Paratyphi A andS. Paratyphi B, albeit of lower magnitudes. Relative to prevaccination sera, opsonization with the postvaccination sera reduced the survival inside macrophages ofS. Typhi but not ofS. Paratyphi A orS. Paratyphi B. Higher anti-S. Typhi O antigen (lipopolysaccharide [LPS]) IgG, but not IgA, antibody titers correlated significantly with postvaccination increases in opsonophagocytosis. No differences were observed between immunization with four doses of Ty21a or one dose of CVD 909. Ty21a and CVD 909 induced cross-reactive functional antibodies, predominantly againstS. Typhi. IgG anti-LPS antibodies may be important in phagocytic clearance of these organisms. Therefore, measurement of functional antibodies might be important in assessing the immunogenicity of a new generation of typhoid and paratyphoid A vaccines. (The CVD 909 study has been registered at ClinicalTrials.gov under registration no. NCT00326443.)
Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians
Authors: Ogunjimi Benson , Smits Evelien , Heynderickx Steven , Van den Bergh Johan , Bilcke Joke , Jansens Hilde , Malfait Ronald , Ramet Jose , Maecker Holden T. , Cools Nathalie , Beutels Philippe , Van Damme Pierre
Published: January 2014

Reexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-γ)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4+-naive T cells and showed boosting of CD8+effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-γ-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZV-specific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.
Comparison of the
illumi
gene Mycoplasma DNA Amplification Assay and Culture for Detection of Mycoplasma pneumoniae
Authors: Ratliff Amy E. , Duffy Lynn B. , Waites Ken B.
Published: January 2014

A loop-mediated isothermal amplification (LAMP) system, the
illumi
gene Mycoplasma DNA amplification assay (Meridian Bioscience, Inc., Cincinnati, OH) was evaluated to determine its analytical sensitivity, specificity, and clinical application in comparison to historic culture in a collection of archived respiratory specimens. The
illumi
gene limit of detection was ≤88 CFU/reaction for 10
Mycoplasma pneumoniae
reference strains. This assay correctly identified 36
M. pneumoniae
reference strains and clinical isolates from various geographic origins, including both of the main subtypes. No cross-reactions were detected with other mycoplasmas, ureaplasmas, other bacterial species, viruses, yeasts, or human DNA. Among 214 respiratory specimens previously cultured for
M. pneumoniae
, when real-time PCR with bidirectional sequencing of the PCR products was used to resolve discrepancies, the sensitivity was 22 of 22 (100%) and the specificity was 190 of 192 (99%). This commercial LAMP assay is a useful rapid method for detecting
M. pneumoniae
in clinical specimens. Additional prospective clinical trials with direct comparison to culture and PCR are warranted.
Eggerthella lenta Bacteremia Complicated by Spondylodiscitis, Psoas Abscess, and Meningitis
Authors: Gardiner B. J. , Korman T. M. , Junckerstorff R. K.
Published: January 2014

Eggerthella lenta
bacteremia is uncommon and generally associated with abdominal sepsis. The organism and its clinical significance have not been well characterized due to historical difficulties with identification. We report a case of severe infection in a paraplegic man complicated by psoas abscess, osteomyelitis, and meningitis and discuss treatment challenges.