bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of in-patient and out-patient antipsychotic prescriptions in Hong Kong
Authors: Hung Gabriel B. K. , Cheung H. K.
Published: February 2008

Aims and Method

Antipsychotic prescriptions were analysed for a large sample of psychiatric in-patients and out-patients in Hong Kong. Case notes for patients receiving high doses were reviewed and compared with the most recent consensus statement issued by the Royal College of Psychiatrists.

Results

Demographic and prescription data were obtained from 1254 in-patients and 19 986 out-patients. Antipsychotic medications were prescribed to 1129 in-patients and 7520 out-patients, with 9.2% of in-patients and 1.8% of out-patients receiving a high dose. Almost all case notes failed to record the clinical indications for high-dose prescribing or that the patient had been informed. Electrocardiograms were performed in a very small proportion of patients receiving a high dose.

Clinical Implications

Low levels of adherence to established guidelines for high-dose antipsychotic prescription were found in this study, with clinical and medico-legal implications. The results of this study highlight the need for staff education and regular audit of antipsychotic doses in the in-patient and out-patient setting.
Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques
Authors: Adams Sean H. , Stanhope Kimber L. , Grant Ryan W. , Cummings Bethany P. , Havel Peter J.
Published: February 2008

Diurnal patterns of circulating leptin concentrations are attenuated after consumption of fructose-sweetened beverages compared with glucose-sweetened beverages, likely a result of limited postprandial glucose and insulin excursions after fructose. Differences in postprandial exposure of adipose tissue to peripheral circulating fructose and glucose or in adipocyte metabolism of the two sugars may also be involved. Thus, we compared plasma leptin concentrations after 6-h iv infusions of saline, glucose, or fructose (15 mg/kg·min) in overnight-fasted adult rhesus monkeys (n = 9). Despite increases of plasma fructose from undetectable levels to about 2 mm during fructose infusion, plasma leptin concentrations did not increase, and the change of insulin was only about 10% of that seen during glucose infusion. During glucose infusion, plasma leptin was significantly increased above baseline concentrations by 240 min and increased steadily until the final 480-min time point (change in leptin = +2.5 ± 0.9 ng/ml, P < 0.001 vs. saline; percent change in leptin = +55 ± 16%; P < 0.005 vs. saline). Substantial anaerobic metabolism of fructose was suggested by a large increase of steady-state plasma lactate (change in lactate = 1.64 ± 0.15 mm from baseline), which was significantly greater than that during glucose (+0.53 ± 0.14 mm) or saline (−0.51 ± 0.14 mm) infusions (P < 0.001). Therefore, increased adipose exposure to fructose and an active whole-body anaerobic fructose metabolism are not sufficient to increase circulating leptin levels in rhesus monkeys. Thus, additional factors (i.e. limited post-fructose insulin excursions and/or hexose-specific differences in adipocyte metabolism) are likely to underlie disparate effects of fructose and glucose to increase circulating leptin concentrations.
Identification, molecular structure and expression of two cloned serotonin receptors from the pond snail, Helisoma trivolvis
Authors: Mapara Sabeen , Parries Shawn , Quarrington Caitlin , Ahn Kee-Chan , Gallin Warren J. , Goldberg Jeffrey I.
Published: February 2008

Helisoma trivolvis has served as a model system to study the functions of serotonin (5-HT) from cellular, developmental, physiological and behavioural perspectives. To further explore the serotonin system at the molecular level, and to provide experimental knockout tools for future studies, in this study we identified serotonin receptor genes from the H. trivolvis genome, and characterized the molecular structure and expression profile of the serotonin receptor gene products. Degenerate oligonucleotide primers, based on conserved regions of the Lymnaea stagnalis 5-HT1Lym receptor, were used to amplify G protein-coupled biogenic amine receptor sequences from H. trivolvisgenomic cDNA, resulting in the cloning of two putative serotonin receptors. The deduced gene products both appear to be G protein-coupled serotonin receptors, with well-conserved structure in the functional domains and high variability in the vestibule entrance of the receptor protein. Phylogenetic analysis placed these receptors in the 5-HT1 and 5-HT7families of serotonin receptors. They are thus named the 5-HT1Heland 5-HT7Hel receptors, respectively. In situhybridization and immunofluorescence studies revealed that these genes and gene products are expressed most heavily in the ciliated pedal and mantle epithelia of H. trivolvis embryos. In adults, widespread expression occurred in all ganglia and connectives of the central nervous system. Expression of both receptor proteins was localized exclusively to neurites when examined in situ. In contrast, when isolated neurons were grown in culture, 5-HT1Hel and 5-HT7Hel immunoreactivity were located primarily in the cell body. This is the first study to reveal a 5-HT7 receptor in a molluscan species.
The Dedicated Emergency Surgeon: Towards Consultant-Based Acute Surgical Admissions
Authors: Sorelli PG , El-Masry NS , Dawson PM , Theodorou NA
Published: February 2008

INTRODUCTION

The management of an efficient acute surgical service with conflicting pressures of managing elective and emergency work, compounded by waiting list targets and the maximum 4-h wait for patients in accident and emergency poses a significant challenge. We assess the impact of appointing a dedicated emergency surgeon on the delivery of our emergency surgery service.

PATIENTS AND METHODS

A comparative retrospective review was undertaken of all surgical admissions (n = 1622) over a 9-month period (between February and November) in the year before and after (2004 and 2005) the appointment of a dedicated emergency surgeon. The impact on service, training and possible financial consequences of this appointment was assessed.

RESULTS

A total of 798 surgical admissions in 2004 were compared with 824 admissions in 2005 for the 9-month periods of this study. In 2004, 258 patients were operated on compared with 286 in 2005 (NS). There was a significant increase in day-time operating from 57% in 2004 to 74% in 2005 (P < 0.001) and a significant increase in consultant-supervised operations from 14% to 52% (P < 0.001), with a consequent fall in out-of-hours operating (43% to 26%; P < 0.001). In addition, there was a significant increase in early (within 48 h) discharges from 41% to 53% (P < 0.001). The salary of the new appointment is more than offset by the quantifiable savings of approximately £90,000 per annum based on the increased proportion of earlier discharges alone as well as the improved quality of care provided.

CONCLUSIONS

The appointment of a dedicated emergency surgery consultant has resulted in an increase in day-time consultant-supervised operating, shorter hospital stay for emergency admissions, improved training for surgical trainees, as well as providing potential financial savings for the trust.
Mobile Phones, in Combination with a Computer Locator System, Improve the Response Times of Emergency Medical Services in Central London
Authors: Gossage JA , Frith DP , Carrell TWG , Damiani M , Terris J , Burnand KG
Published: February 2008

INTRODUCTION

The aim of this study was to determine whether mobile phones and mobile phone locating devices are associated with improved ambulance response times in central London.

PATIENTS AND METHODS

All calls from the London Ambulance Service database since 1999 were analysed. In addition, 100 consecutive patients completed a questionnaire on mobile phone use whilst attending the St Thomas's Hospital Emergency Department in central London.

RESULTS

Mobile phone use for emergencies in central London has increased from 4007 (5% of total) calls in January 1999 to 21,585 (29%) in August 2004. Ambulance response times for mobile phone calls were reduced after the introduction of the mobile phone locating system (mean 469 s versus 444 s; P = 0.0195). The proportion of mobile phone calls made from mobile phones for life-threatening emergencies was higher after injury than for medical emergencies (41% versus 16%, P = 0.0063). Of patients transported to the accident and emergency department by ambulance, 44% contacted the ambulance service by mobile phone. Three-quarters of calls made from outside the home or work-place were by mobile phone and 72% of patients indicated that it would have taken longer to contact the emergency services if they had not used a mobile.

CONCLUSIONS

Since the introduction of the mobile phone locating system, there has been an improvement in ambulance response times. Mobile locating systems in urban areas across the UK may lead to faster response times and, potentially, improved patient outcomes.
Learning Assessment at Shoulder Surgical Skills Course
Authors: John J , Kuiper JH , Kelly CP
Published: February 2008

INTRODUCTION

Surgical skills courses are an important part of learning during surgical training. The assessments at these courses tend to be subjective and anecdotal. Objective assessment using multiple choice questions (MCQs) quantifies the learning experience for both the organisers and the participants.

MATERIALS AND METHODS

Participants of the open shoulder surgical skills course conducted at The Royal College of Surgeons of England in 2005 and 2006 underwent assessment using MCQs prior to and after the course.

RESULTS

The participants were grouped as non-consultants (14) and consultant orthopaedic surgeons (8). All participants improved after attending the course. The average improvement was 17% (range, 4–43%). We compared the two groups while adjusting for the association between pre-course score and score gain. We found a strong correlation between pre-course score and score gain (r = 0.734; P = 0.001). Adjusted for pre-course score, we found that the score gain (learning) for the non-consultants was slightly larger than for the consultants, but this did not reach statistical significance (P = 0.247).

CONCLUSIONS

All participants had a positive learning experience which did not have a significant correlation to the grade of surgeon.
The Impact of Creutzfeldt–Jakob Disease on Surgical Practice
Authors: Lumley John SP
Published: February 2008

Creutzfeldt–Jakob disease (CJD) is characterised by abnormal prion protein that can replicate and replace nervous tissue, with rapid lethal neurodegenerative consequences. The transmissible nature of CJD has been known for half a century and transmission has occurred through neurosurgical procedures. Variant Creutzfeldt–Jakob disease (vCJD) emerged in 1996, and the presence of abnormal prion in lymphatic tissue extended the number of surgical specialties dealing with infected material; transmission through blood transfusion raised the possibilities of a large carrier pool and spread of epidemic proportion.

The abnormal prion is difficult to remove and this could influence future decontamination programmes. Contaminated instruments must be withdrawn from surgical practice, and this can interfere with the efficient running of a surgical unit and optimal patient care.

There is an urgent need for reliable methods for the detection of abnormal prion, within and outside the body. These will help to clarify the epidemiology of CJD, and to reduce its transmission via blood and tissue. They will also allow determination of the efficacy of new decontamination products in surgical practice, and the value of any treatment of sufferers and carriers of CJD. In the meantime, continued vigilance and informed regulation of all aspects of CJD must remain.
Choline in Whole Blood and Plasma: Sample Preparation and Stability
Authors: Yue Bingfang , Pattison Elizabeth , Roberts William L , Rockwood Alan L , Danne Oliver , Lueders Christian , Möckel Martin
Published: February 2008

Background: Choline is critical for a variety of biological functions and has been investigated as a biomarker for various pathological conditions including acute coronary syndrome.

Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to quantify choline in whole blood and plasma in freshly collected samples prepared with ultrafiltration or protein precipitation. We investigated the effects of preanalytical variables including types of anticoagulants and storage temperature and time.

Results: We observed no significant differences in whole-blood choline concentration in EDTA-anticoagulated vs heparin-anticoagulated samples: mean (SD) difference 0.9% (3.2%), P = 0.80. For plasma, choline concentrations with heparin in 5 of 12 volunteers were >10% higher than with EDTA, P = 0.01. One freeze-thaw cycle led to significant mean (SD) increases in choline concentrations in heparin whole blood, 19.3% (11.4%), P <0.01, and the effect was not significant for other sample types studied (P >0.33). For freshly collected samples stored at ambient temperature, choline concentrations in all types of samples increased with storage time. For EDTA whole blood, EDTA plasma, and heparin plasma, the choline concentration increased for the first 60 min and then stabilized. For heparin whole blood, the choline concentration continued to increase linearly with storage time for >4 h, at which time the choline concentrations were increased by approximately 50%.

Conclusions: Sample collection, storage, and sample preparation procedures are critical for clinical measurements of choline in whole blood and plasma.
Ein hochpräzises Drehmomentmesssystem durch Trägerfrequenz-Messverstärker und Digitaltechnik (A High-Precision Torque Measurement System through Carrier Frequency Amplifier and Digital Technology)
Authors: Kuhn Sven , Schicker Rainer
Published: February 2008

Thema des Beitrags ist die Entwicklung eines berührungslosen Drehmomentmesssystems mit Trägerfrequenzmessverstärker. Die Optimierung des Temperatureinflusses auf das Messsignal durch eine hohe Symmetrie der Messbrücke wird durch die digitale Kompensation von verbleibenden Temperatureinflüssen ergänzt. Die digitale Signalverarbeitung und Übertragung ermöglicht es, die derzeitige hohe Genauigkeit von nicht rotierenden Drehmomentaufnehmern auch im rotierenden Wellenstrang zu erreichen. Der Nutzen dieser Technologie in der Anwendung wird anhand verschiedener Anwendungsbeispiele gezeigt.
Kontur-, Rauheits- und Kraftmesstechnik mit Silizium-Cantileversonden (Shape, Roughness and Force Metrology using Silicon Cantilever Sensors)
Authors: Peiner Erwin , Balke Michael , Doering Lutz , Christ Andreas
Published: February 2008

Es werden piezoresistive Cantileversonden beschrieben, die für die Kontur- und Rauheitsbestimmung an mikroskopischen Bauteilen mit hohem Aspektverhältnis konzipiert sind. Sie sind weiterhin als transferierbare Krafteinstellnormale im Bereich von Nano- bis Millinewton einsetzbar. Als ein Beispiel für dimensionelle Messungen werden Rillen- und Rauheitsnormale sowie Eindrücke von Prüfkörpern zur Härtebestimmung charakterisiert. Der Einsatz von transferierbaren Krafteinstellnormalen zur Weitergabe geringer Kräfte wird vorgestellt. Messergebnisse an handelsüblichen Tastschnittgeräten sowie die Messung von Mikronewton-Kräften an lebenden einzelnen Herzmuskelzellen werden gezeigt.
Undiagnosed Respiratory Viruses in Children
Authors: Arnold John C. , Singh Kumud K. , Spector Stephen A. , Sawyer Mark H.
Published: February 2008

OBJECTIVE. An estimated 12 to 32 million upper respiratory infections occur in young children each year. In addition, 20% to 53% of infants will have ≥1 episode of lower respiratory infection in the first year of life. The current methods of diagnosing respiratory viruses are limited in scope and sensitivity. Polymerase chain reaction is a more sensitive method than antigen detection and is often used for newly discovered viruses. Using polymerase chain reaction, we sought to diagnose adenoviruses, human bocavirus, and human metapneumovirus at our children's hospital.

METHODS. Nasal-swab specimens submitted for antigen detection of respiratory viruses were collected and processed by using polymerase chain reaction to detect adenoviruses, human bocavirus, and human metapneumovirus. Inpatient and emergency department records were reviewed for clinical and demographic data.

RESULTS. Approximately 1500 specimens were collected over 21 months; they contained adenoviruses, human bocavirus, and human metapneumovirus in 5.9%, 5.6%, and 5.2% of children, respectively. Using polymerase chain reaction and antigen detection, a viral agent was identified in as many as 62% of the specimens. Lower respiratory tract disease was present most frequently in patients infected with human metapneumovirus (63%) and least frequently in those infected with adenoviruses (45%). We detected adenoviruses by polymerase chain reaction in 59 patients for whom the antigen-detection test results were negative. A paroxysmal cough led to clinical suspicion of Bordetella pertussis infection in 19% of patients infected with human bocavirus.

CONCLUSIONS. Adenoviruses, human bocavirus, and human metapneumovirus were each present in ∼5% of specimens submitted for respiratory virus rapid testing. The lower respiratory tract was more commonly affected in patients with human bocavirus and human metapneumovirus infections. Adenovirus was often undiagnosed by antigen detection. Other findings included the presence of a pertussis-like illness associated with human bocavirus.
Effect of Computer Order Entry on Prevention of Serious Medication Errors in Hospitalized Children
Authors: Walsh Kathleen E. , Landrigan Christopher P. , Adams William G. , Vinci Robert J. , Chessare John B. , Cooper Maureen R. , Hebert Pamela M. , Schainker Elisabeth G. , McLaughlin Thomas J. , Bauchner Howard
Published: February 2008

OBJECTIVE. Although initial research suggests that computerized physician order entry reduces pediatric medication errors, no comprehensive error surveillance studies have evaluated the effect of computerized physician order entry on children. Our objective was to evaluate comprehensively the effect of computerized physician order entry on the rate of inpatient pediatric medication errors.

METHODS. Using interrupted time-series regression analysis, we reviewed all charts, orders, and incident reports for 40 admissions per month to the NICU, PICU, and inpatient pediatric wards for 7 months before and 9 months after implementation of commercial computerized physician order entry in a general hospital. Nurse data extractors, who were unaware of study objectives, used an established error surveillance method to detect possible errors. Two physicians who were unaware of when the possible error occurred rated each possible error.

RESULTS. In 627 pediatric admissions, with 12 672 medication orders written over 3234 patient-days, 156 medication errors were detected, including 70 nonintercepted serious medication errors (22/1000 patient-days). Twenty-three errors resulted in patient injury (7/1000 patient-days). In time-series analysis, there was a 7% decrease in level of the rates of nonintercepted serious medication errors. There was no change in the rate of injuries as a result of error after computerized physician order entry implementation.

CONCLUSIONS. The rate of nonintercepted serious medication errors in this pediatric population was reduced by 7% after the introduction of a commercial computerized physician order entry system, much less than previously reported for adults, and there was no change in the rate of injuries as a result of error. Several human-machine interface problems, particularly surrounding selection and dosing of pediatric medications, were identified. Additional refinements could lead to greater effects on error rates.
Maternal Microchimerism in Underlying Pathogenesis of Biliary Atresia: Quantification and Phenotypes of Maternal Cells in the Liver
Authors: Muraji Toshihiro , Hosaka Naoki , Irie Naoki , Yoshida Makiko , Imai Yukihiro , Tanaka Kohichi , Takada Yasutsugu , Sakamoto Seisuke , Haga Hironori , Ikehara Susumu
Published: February 2008

OBJECTIVE. The goal was to examine whether microchimerism plays a crucial role in the pathogenesis of biliary atresia; we analyzed the localization of maternal microchimeric cells and their phenotypes.

METHODS. Liver biopsy specimens from 8 male infants with biliary atresia and 6 control subjects with other liver diseases were investigated for maternal chimeric cells and their phenotypes through double-staining fluorescence in situ hybridization and immunohistochemical analyses.

RESULTS. Significantly larger numbers of maternal XX+ cells were found in the portal area and sinusoids of patients with biliary atresia, in comparison with control patients. In phenotypic analyses of XX+ cells, CD8+ T cells, CD45+ cells, and cytokeratin-positive cells were found, and the numbers and proportions among total CD8+ T cells were significantly higher than those in control patients.

CONCLUSIONS. Significantly more maternal chimeric CD8+ T cells in the livers of patients with biliary atresia suggest that maternal immunologic insults represent the underlying pathogenesis in biliary atresia. The findings support the recently postulated mechanisms of alloautoimmune and/or autoalloimmune responses.
Psychotropic Medication Use Among Medicaid-Enrolled Children With Autism Spectrum Disorders
Authors: Mandell David S. , Morales Knashawn H. , Marcus Steven C. , Stahmer Aubyn C. , Doshi Jalpa , Polsky Daniel E.
Published: February 2008

OBJECTIVE. The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use.

METHODS. This cross-sectional study used Medicaid claims for calendar year 2001 from all 50 states and Washington, DC, to examine 60641 children with an autism spectrum disorder diagnosis. Logistic regression with random effects was used to examine the child, county, and state factors associated with psychotropic medication use.

RESULTS. Of the sample, 56% used at least 1 psychotropic medication, 20% of whom were prescribed ≥3 medications concurrently. Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%). Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%). In adjusted analyses, male, older, and white children; those who were in foster care or in the Medicaid disability category; those who received additional psychiatric diagnoses; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs. Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications.

CONCLUSIONS. Psychotropic medication use is common among even very young children with autism spectrum disorders. Factors unrelated to clinical presentation seem highly associated with prescribing practices. Given the limited evidence base, there is an urgent need to assess the risks, benefits, and costs of medication use and understand the local and national policies that affect medication use.
Safety and Immunogenicity of Concurrent Administration of Live Attenuated Influenza Vaccine With Measles-Mumps-Rubella and Varicella Vaccines to Infants 12 to 15 Months of Age
Authors: Nolan Terry , Bernstein David I. , Block Stan L. , Hilty Milo , Keyserling Harry L. , Marchant Colin , Marshall Helen , Richmond Peter , Yogev Ram , Cordova Julie , Cho Iksung , Mendelman Paul M. ,   for the LAIV Study Group
Published: February 2008

OBJECTIVE. This study evaluated the safety, tolerability, and immunogenicity of live attenuated influenza vaccine administered concurrently with measles-mumps-rubella vaccine and varicella vaccine to healthy children 12 to 15 months of age.

METHODS. Children were assigned randomly to receive (1) measles-mumps-rubella vaccine, varicella vaccine, and intranasal placebo on day 0, followed by 1 dose of live attenuated influenza vaccine on days 42 and 72; (2) measles-mumps-rubella, varicella, and live attenuated influenza vaccines on day 0, followed by a second dose of live attenuated influenza vaccine on day 42 and intranasally administered placebo on day 72; or (3) 1 dose of live attenuated influenza vaccine on days 0 and 42, followed by measles-mumps-rubella and varicella vaccines on day 72. Serum samples were collected before vaccination on days 0, 42, and 72. Reactogenicity events and adverse events were collected through day 41 after concurrent vaccinations and through day 10 after administration of live attenuated influenza vaccine or placebo alone.

RESULTS. Among 1245 (99.5%) evaluable children, seroresponse rates and geometric mean titers for measles-mumps-rubella vaccine and varicella vaccine were similar with concurrent administration of live attenuated influenza vaccine or placebo (seroresponse rates of ≥96% for measles-mumps-rubella vaccine and ≥82% for varicella vaccine in both groups). Hemagglutinin-inhibiting antibody geometric mean titers and seroconversion rates to influenza strains in live attenuated influenza virus vaccine were similar after the vaccine was administered alone (seroconversion rates of 98%, 92%, and 44% for H3, B, and H1 strains, respectively) or with measles-mumps-rubella and varicella vaccines (seroconversion rates of 98%, 96%, and 43%). The incidences of reactogenicity events and adverse events were similar among treatment groups.

CONCLUSIONS. Concurrent administration of live attenuated influenza vaccine with measles-mumps-rubella vaccine and varicella vaccine provided equivalent immunogenicity, compared with separate administration, and was well tolerated.
Risk Factors for Developing Apnea After Immunization in the Neonatal Intensive Care Unit
Authors: Klein Nicola P. , Massolo Maria L. , Greene John , Dekker Cornelia L. , Black Steven , Escobar Gabriel J. ,   for the Vaccine Safety Datalink
Published: February 2008

OBJECTIVES. Among hospitalized NICU infants, preimmunization apnea is a well-recognized predictor of postimmunization apnea. However, predictors for postimmunization apnea among NICU infants without preimmunization apnea have not been investigated.

METHODS. Using a large NICU database in the Northern California Kaiser Permanente Medical Care Program, we abstracted NICU charts of infants who were hospitalized for ≥53 days and who were also immunized, capturing preimmunization (24 hours before immunization) and postimmunization (48 hours after immunization) events. We assessed factors associated with postimmunization apnea by using multivariate logistic regression.

RESULTS. Of 16 146 infants admitted to the NICU, 557 received ≥1 vaccine and 497 met the criteria for study entry. All infants with preimmunization apnea (n = 27) and all except 3 infants with postimmunization apnea (n = 65) had gestational ages of <31 weeks. Multivariate analyses revealed preimmunization apnea as the most important predictor of postimmunization apnea, although higher 12-hour Score for Neonatal Acute Physiology II and age of <67 days (mean cohort age) were also associated. Multivariate analysis exclusively among infants without preimmunization apnea similarly found elevated Score for Neonatal Acute Physiology II, age of <67 days, and weight of <2000 g to be associated with postimmunization apnea. Forty-nine infants without preimmunization apnea and with ≥1 apnea predictor were discharged within 48 hours after immunization; 2 were subsequently readmitted because of apnea.

CONCLUSIONS. For infants in the NICU without apnea during the 24 hours immediately before immunization, younger age, smaller size, and more severe illness at birth are important predictors of postimmunization apnea.
Improving Pediatric Dosing Through Pediatric Initiatives: What We Have Learned
Authors: Rodriguez William , Selen Arzu , Avant Debbie , Chaurasia Chandra , Crescenzi Terrie , Gieser Gerlie , Di Giacinto Jennifer , Huang Shiew-Mei , Lee Peter , Mathis Lisa , Murphy Dianne , Murphy Shirley , Roberts Rosemary , Sachs Hari Cheryl , Suarez Sandra , Tandon Veneeta , Uppoor Ramana S.
Published: February 2008

OBJECTIVE. The goal was to review the impact of pediatric drug studies, as measured by the improvement in pediatric dosing and other pertinent information captured in the drug labeling.

METHODS. We reviewed the pediatric studies for 108 products submitted (July 1998 through October 2005) in response to a Food and Drug Administration written request for pediatric studies, and the subsequent labeling changes. We analyzed the dosing modifications and focused on drug clearance as an important parameter influencing pediatric dosing.

RESULTS. The first 108 drugs with new or revised pediatric labeling changes had dosing changes or pharmacokinetic information (n = 23), new safety information (n = 34), information concerning lack of efficacy (n = 19), new pediatric formulations (n = 12), and extended age limits (n = 77). A product might have had ≥1 labeling change. We selected specific examples (n = 16) that illustrate significant differences in pediatric pharmacokinetics.

CONCLUSIONS. Critical changes in drug labeling for pediatric patients illustrate that unique pediatric dosing often is necessary, reflecting growth and maturational stages of pediatric patients. These changes provide evidence that pediatric dosing should not be determined by simply applying weight-based calculations to the adult dose. Drug clearance is highly variable in the pediatric population and is not readily predictable on the basis of adult information.
Increased Concordance of Severe Respiratory Syncytial Virus Infection in Identical Twins
Authors: Thomsen Simon Francis , Stensballe Lone Graff , Skytthe Axel , Kyvik Kirsten Ohm , Backer Vibeke , Bisgaard Hans
Published: February 2008

OBJECTIVE. We estimated differences in the severity of respiratory syncytial virus infection attributable to genetic and environmental factors.

METHODS. Record linkage data on hospitalizations attributable to respiratory syncytial virus infection were gathered on all twins (12346 pairs) born in Denmark between 1994 and 2003. Latent-factor models of genetic and environmental effects were fitted to the observed data by using maximal likelihood methods.

RESULTS. Identical twins resembled each other significantly more than did fraternal twins for respiratory syncytial virus hospitalization (concordance rate: 0.66 vs 0.53), which suggests genetic influences on disease severity. Genetic factors accounted for 16%, family environment for 73%, and nonshared environment for 11% of the individual susceptibility to develop severe respiratory syncytial virus infection.

CONCLUSIONS. The severity of respiratory syncytial virus infection is determined partly by genetic factors. This result should stimulate the search for genetic markers of disease severity.
Cord Blood and Breast Milk Iron Status in Maternal Anemia
Authors: Kumar Ashok , Rai Arun Kumar , Basu Sriparna , Dash Debabrata , Singh Jamuna Saran
Published: February 2008

OBJECTIVES. The purpose of this work was to assess the effect of severe maternal iron-deficiency anemia and nutritional status on cord blood and breast milk iron status.

METHODS. We conducted a prospective observational study over a 6-month period in a teaching hospital in central India. The study population consisted of 55 anemic (hemoglobin: <110 g/L) and 20 healthy nonanemic (hemoglobin: ≥110 g/L) pregnant women who delivered singleton live births at term gestation. We measured hemoglobin, iron, and ferritin levels in paired maternal and cord blood and iron levels in early (day 3 ± 1) and late (day 15 ± 3) transitional milk. Maternal anthropometry, including weight, height, midarm circumference, triceps skinfold thickness, and placental weight, were recorded. The main outcome measure of the study was to find out the relationship of maternal hemoglobin, iron, ferritin, and anthropometry with hemoglobin, iron, and ferritin in cord blood and iron levels in breast milk.

RESULTS. Concentrations of hemoglobin, iron, and ferritin were significantly lower in the cord blood of anemic mothers and showed linear relationships with maternal hemoglobin and ferritin levels. Breast milk iron content was significantly reduced in severely anemic mothers but not in those with mild-to-moderate anemia. Breast milk iron level correlated with maternal hemoglobin and iron levels but not with ferritin levels. Maternal anthropometry had significant correlations with indices of iron nutriture in maternal and cord blood but showed no relationship with breast milk iron content. Placental weight was comparable between anemic and nonanemic mothers.

CONCLUSIONS. Maternal anemia, particularly the severe type, adversely affects cord blood and breast milk iron status. Maternal nutritional status exerts a significant influence on fetal iron status but has little influence on breast milk iron content.
Structure of (001)-, (110)-, and (111)-oriented Pb(Fe1/2Nb1/2)O3 epitaxial thin films on SrRuO3-buffered SrTiO3 substrates
Authors: Yan Li , Li Jiefang , Viehland D.
Published: February 2008

We have studied the lattice structure of variously oriented lead iron niobate (PFN) thin films with thicknesses of 50 < t < 500 nm that were deposited by pulsed laser deposition (PLD). We have identified that (001)-, (110)-, and (111)-oriented PFN thin films have tetragonal, orthorhombic, and rhombohedral phases at room temperature, respectively. The change in phase stability, when deposited on substrates of different orientations, is discussed with respect to the influence of epitaxial stress.
Microstructural and electrochemical characterization of hydroxyapatite-coated Ti6Al4V alloy for medical implants
Authors: Xie Jianhui , Luan Ben Li
Published: February 2008

The in vitro behaviors of the etched, electrochemically anodized, and hydroxyapatite (HA)-coated Ti6Al4V alloys were investigated through microstructural analysis, electrochemical measurements, and immersion tests in the Hank’s solution. A nanometer-scale, bonelike porous structure with a layer of TiO2on top was formed during the anodization process. The surface of the coated substrate was composed of a thin TiO2layer adjacent to the substrate, a thick monolithic HA on the outside, and a composite layer of TiO2and HA in the middle. The anodization significantly improved the stability of the Ti6Al4V alloy in Hank’s solution due to a layer of TiO2formed on the surface. The precoated HA further improved the stability of the Ti6Al4V alloy due to a composite layer of TiO2and HA. The barrier layer of the composite of TiO2and HA was suggested by the capacitive behavior of the HA-coated substrate in the electrochemical impedance spectroscopy. The electrochemical measurements implied a high tendency for the new formation of HA on the precoated HA and the anodized substrates, which was confirmed through the immersion tests. The newly formed HA on the anodized substrate was scattered over the entire surface. The newly formed HA on the HA-precoated surface mingled with the precoated HA, and gradually a new layer of HA was formed on top. These proved the favorable condition of the anodized surface as a prerequisite step for coating HA and the conductive promotion of new HA formation on the precoated surface. The new formation of HA during the immersion might suggest that artificial joints pretreated through anodization and HA coating could induce strong bonding to the bone due to the easy growth of new HA.
Controllable synthesis, characterization, and electrochemical properties of manganese oxide nanoarchitectures
Authors: Zhang Lichun , Kang Liping , Lv Hao , Su Zhikui , Ooi Kenta , Liu Zong-Huai
Published: February 2008

Flowerlike manganese oxide microspheres and cryptomelane-type manganese oxide nanobelts were selectively synthesized by a simple decomposition of KMnO4 under mild hydrothermal conditions without using template or cross-linking reagents. The effect of varying the hydrothermal times and temperatures on the nanostructure, morphology, compositional, and electrochemical properties of the obtained manganese oxides was investigated. X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) studies showed that the flowerlike manganese oxide microspheres could be obtained at relatively low hydrothermal temperatures, while high hydrothermal temperatures were favorable for the formation of cryptomelane-type manganese oxide nanobelts. A morphology and crystalline evolution of the nanostructures was observed as the hydrothermal temperature was increased from 180 to 240 °C. On the basis of changing the temperatures and hydrothermal reaction times, the formation mechanism of cryptomelane-type manganese oxide nanobelts is discussed. Cyclic voltammetry (CV) was used to evaluate the electrochemical properties of the obtained manganese oxide nanostructures, and the results show that the electrochemical properties depend on their shape and crystalline structure. This easily controllable, template-free, and environmentally friendly method has the potential for being used in syntheses of manganese oxide nanomaterials with uniform morphologies and crystal structures.
Enhancement of thermal conductivity in ceramics obtained from a combustion synthesized AlN powder by microwave sintering and reheating
Authors: Chung Shyan-Lung , Hsieh Cheng-Yu , Chang Chih-Wei
Published: February 2008

A combustion-synthesized AlN powder was investigated for use as a starting material in obtaining a high thermal conductivity AlN by microwave sintering followed by microwave reheating under a reducing atmosphere. Microwave sintering was found to proceed very quickly so that a density of 99.5% of theoretical with a thermal conductivity of 165 W/mK was achieved after sintering at 1900 °C for 5 min. The thermal conductivity could be improved by prolonging the soaking time, which is attributed to decreases in both oxygen content and secondary phases by evaporation and sublimation of the secondary phases. The reducing atmosphere was created by adding carbon particles to the AlN packing powder surrounding the specimen. The thermal conductivity could be significantly improved by microwave reheating of the sintered specimen under the reducing atmosphere. This is considered to be due to enhanced removal of the secondary phases by the reducing atmosphere. Sintering under the reducing atmosphere was found to retard densification because of the earlier removal of the secondary phases, thus resulting in a poor densification and a low thermal conductivity.
A microstructure diagram for known bounds in conductivity
Authors: Zhou Shiwei , Li Qing
Published: February 2008

Two important analytical means—theoretical bounds and homogenization techniques—have gained increasing attention and led to substantial progress in material research. Nevertheless, there is a lack of relating material microstructures to an entire theoretical bound and exploring the possibility of generating multiple microstructures for each property value. This paper aims to provide a microstructure diagram in relation to “bound B” constructed by translation and Weiner bounds. The inverse homogenization technique is used to seek for the optimal phase distribution within a base cell model to make the effective conductivity approach the “bound B” in two- or three-phase material cases. The design shows that the “bound B” is exactly attainable for two-phase composites even with single-length-scale microstructures. Although the multiphase translations bounds are well known to be asymptotically attainable on some parts, they still appear too roomy to be attained by single-length-scale composites. Our results showed a certain improvement in the attainability of single-length-scale structural composites when compared with new bounds established by [V. Nesi: Proc. R. Soc. Edinburgh Sect. A125, 1219 (1995)], [V. Cherkaev: Variational Methods for Structural Optimization (Springer Verlag, New York, 2000)], and (N. Albin et al.: Proc. R. Soc. London Ser. A463, 2031 (2007)]. Applicability of the translation bounds to the composites with high-contrast conductivities of phase compositions is also studied in this paper. Finally, we explore the multiple solutions to the optimal microstructures and categorize them into three classes in line with their topological resemblance, namely, spatially identical, unidirectionally identical, and bidirectionally different solutions.
Octyl-β-D-glucopyranoside mediated synthesis of nanocrystalline BaTiO3 using a single-source precursor
Authors: Chaudhary Yatendra S. , Bhatta Umananda M. , Khushalani Deepa
Published: February 2008

A new amphiphile: octyl-β-D-glucopyranoside along with a single-source precursor, barium titanium methoxyethoxide, were used to develop a facile route for synthesis of BaTiO3, via either a hydrolytic or a nonhydrolytic method. The average particle size for the samples was on the order of 20 to 30 nm, while that for the control samples (without the amphiphile) ranged from 100 nm to several microns. The high-resolution transmission electron microscopy (HRTEM) images and selected-area electron- diffraction patterns revealed that these nanoparticles were single crystalline; the Raman active longitudinal optical modes observed in calcined (650 °C) samples at 718 and 304 cm−1 directly indicated the presence of tetragonal domains in an overall cubic lattice structure. Moreover, the one-step nonhydrolytic approach developed for the synthesis of BaTiO3 is fast, and it eliminates tedious steps such as prolonged refluxing and aging. Thermogravimetric and Fourier transform infrared (FTIR) analysis were performed to investigate the role of octyl-β-D-glucopyranoside in the evolution of the perovskite phase, grain size, and morphology. These techniques suggested that van der Waals type of interactions were present between the amphiphile and barium titanium methoxyethoxide oligomers, and in turn they led to the controlled growth of nanoparticles.
Characterization of oxygen and nitrogen rapid thermal annealing processes for ultra-low-k SiCOH films
Authors: Lee Sungwoo , Jung Donggeun , Yang Jaeyoung , Boo Jin-hyo , Kim Hyoungsub , Lee Jaewon , Chae Heeyeop
Published: February 2008

Rapid thermal annealing (RTA) processing under N2 and O2 ambient is suggested and characterized in this work for improvement of SiCOH ultra-low-k (k = 2.4) film properties. Low-k film was deposited by plasma-enhanced chemical vapor deposition (PECVD) with decamethylcyclopentasiloxane and cyclohexane precursors. The PECVD films were treated by RTA processing in N2 and O2 environments at 550 °C for 5 min, and k values of 1.85 and 2.15 were achieved in N2 and O2 environments, respectively. Changes in the k value were correlated with the chemical composition of C–Hx and Si–O related groups determined from the Fourier transform infrared (FTIR) analysis. As the treatment temperature was increased from 300 to 550 °C, the signal intensities of both the CHx and Si–CH3 peaks were markedly decreased. The hardness and modulus of the film processed by RTA have been determined as 0.44 and 3.95 GPa, respectively. Hardness and modulus of RTA-treated films were correlated with D-group [O2Si–(CH3)2] and T-group [O3Si–(CH3)] fractions determined from the FTIR Si–CH3 bending peak. The hardness and modulus improvement in this work is attributed to the increase of oxygen content in (O)x–Si–(CH3)y by rearrangement.
Characterization of Bipotential Epidermal Progenitors Derived from Human Sebaceous Gland: Contrasting Roles of c-Myc and β-Catenin
Authors: Lo Celso Cristina , Berta Melanie A. , Braun Kristin M. , Frye Michaela , Lyle Stephen , Zouboulis Christos C. , Watt Fiona M.
Published: February 2008

The current belief is that the epidermal sebaceous gland (SG) is maintained by unipotent stem cells that are replenished by multipotent stem cells in the hair follicle (HF) bulge. However, sebocytes can be induced by c-Myc (Myc) activation in interfollicular epidermis (IFE), suggesting the existence of bipotential stem cells. We found that every SZ95 immortalized human sebocyte that underwent clonal growth in culture generated progeny that differentiated into both sebocytes and cells expressing involucrin and cornifin, markers of IFE and HF inner root sheath differentiation. The ability to generate involucrin positive cells was also observed in a new human sebocyte line, Seb-E6E7. SZ95 xenografts differentiated into SG and IFE but not HF. SZ95 cells that expressed involucrin had reduced Myc levels; however, this did not correlate with increased expression of the Myc repressor Blimp1, and Blimp1 expression did not distinguish cells undergoing SG, IFE, or HF differentiation in vivo. Overexpression of Myc stimulated sebocyte differentiation, whereas overexpression of β-catenin stimulated involucrin and cornifin expression. In transgenic mice simultaneous activation of Myc and β-catenin revealed mutual antagonism: Myc blocked ectopic HF formation and β-catenin reduced SG differentiation. Overexpression of the Myc target gene Indian hedgehog did not promote sebocyte differentiation in culture and cyclopamine treatment, while reducing proliferation, did not block Myc induced sebocyte differentiation in vivo. Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation.

Disclosure of potential conflicts of interest is found at the end of this article.
Functional Network Reconstruction Reveals Somatic Stemness Genetic Maps and Dedifferentiation-Like Transcriptome Reprogramming Induced by GATA2
Authors: Huang Tse-Shun , Hsieh Jui-Yu , Wu Yu-Hsuan , Jen Chih-Hung , Tsuang Yang-Hwei , Chiou Shih-Hwa , Partanen Jukka , Anderson Heidi , Jaatinen Taina , Yu Yau-Hua , Wang Hsei-Wei
Published: February 2008

Somatic stem cell transplantation holds great promise in regenerative medicine. The best-characterized adult stem cells are mesenchymal stem cells (MSCs), neural stem cells (NSCs), and CD133+ hematopoietic stem cells (HSCs). The applications of HSCs are hampered since these cells are difficult to maintain in an undifferentiated state in vitro. Understanding genes responsible for stem cell properties and their interactions will help on this issue. The construction of stem cell genetic networks will also help to develop rational strategies to revert somatic cells back to a stem-like state. We performed a systemic study on human CD133+ HSCs, NSCs, MSCs, and embryonic stem cells and two different progenies of CD133+ HSCs, microvascular endothelial cells (MVECs) and peripheral blood mononuclear cells. Genes abundant in each or in all three somatic stem cells were identified. We also observed complex genetic networks functioning in postnatal stem cells, in which several genes, such as PTPN11 and DHFR, acted as hubs to maintain the stability and connectivity of the whole genetic network. Eighty-seven HSC genes, including ANGPT1 and GATA2, were independently identified by comparing CD34+CD33−CD38− hematopoietic stem cells with CD34+ precursors and various matured progenies. Introducing GATA2 into MVECs resulted in dedifferentiation-like transcriptome reprogramming, with HSC genes (such as ANGPT1) being up and endothelial genes (such as EPHB2) being down. This study provides a foundation for a more detailed understanding of human somatic stem cells. Expressing the newly discovered stem cell genes in matured cells might lead to a global reversion of somatic transcriptome to a stem-like status.

Disclosure of potential conflicts of interest is found at the end of this article.