bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a multifaceted intervention on documentation of vital signs at triage: A before‐and‐after study
Authors: Gerdtz Marie F , Waite Rebbecca , Vassiliou Theresa , Garbutt Bruce , Prematunga Roshani , Virtue Elizabeth
Published: November 2013

Background

Triage systems provide a centralised safety mechanism where all patients are assessed for clinical urgency at point of entry to the ED.

Objective

The present study aims to evaluate the effect of a multifaceted intervention on triage documentation rates and guideline adherence.

Methods

A before‐and‐after design was used. The intervention involved restructuring the computerised interface, regular audit and feedback and education sessions. The setting was one adult tertiary referral hospital and major trauma centre located in Melbourne, Australia. Participants were triage nurses. Data were collected at five time points for a consecutive sample of one month of presentations.

Results

Over a 15 month period, we sampled 35.8% (24 862/69 395) episodes of triage performed by 122 nurses. Documentation rates for all vital signs progressively increased from baseline. There were significant increases in the proportion of episodes of triage where any vital sign was documented (32.2% vs 82.6%), and where pair and triplet combinations of vital signs were recorded in the triage field (heart rate and respiratory rate: 17.9% vs 64.6%; heart rate, respiratory rate and temperature: 7.0% vs 30.4%). No significant change in guideline adherence was observed after the intervention.

Conclusion

Progressive sustained improvements in vital sign documentation were observed over the study period; however, no such increases were noted in guideline adherence. To facilitate evaluation of guideline adherence, we recommend specific vital sign parameters be included in the Australasian Triage Scale Guideline for all levels of urgency.
Heart Rate Variability and Heart Rate Turbulence in Patients with Hematologic Malignancies Subjected to High‐Dose Chemotherapy in the Course of Hematopoietic Stem Cell Transplantation
Authors: Poręba Małgorzata , Poręba Rafał , Gać Paweł , Usnarska‐Zubkiewicz Lidia , Pilecki Witold , Piotrowicz Ewa , Piotrowicz Ryszard , Rusiecki Leszek , Kuliczkowski Kazimierz , Mazur Grzegorz , Sobieszczańska Małgorzata
Published: November 2013

Background

In hematological malignancies, remissions and cures may be achieved by hematopoietic stem cell transplantation (HSCT) following high‐dose chemotherapy (HDC). Cardiotoxicity of such therapy has not yet been fully elucidated. Noninvasive approaches allowing to evaluate an autonomic control of the heart function include analyses of both heart rate variability (HRV) and heart rate turbulence (HRT).

Methods

In 38 patients with hematological malignancies, 24‐hour electrocardiography Holter monitoring , with HRV and HRT analysis before HSCT (A test) and after HSCT (B test), was performed.

Results

The 24‐hour analysis of HRV demonstrated that SDNN, SDNNi, rMSSD, and pNN50 parameters were significantly lower after HSCT as compared to the results obtained before the transplantation (P < 0.05). For period of diurnal activity and for night hours, SDANN, SDNNi, rMSSD, and pNN50 were significantly lower in B test, as compared to the results of A test (P < 0.05). The analysis of HRT demonstrated that turbulence onset parameter was significantly higher, and turbulence slope parameter was significantly lower in B test, as compared to A test (P < 0.05). The multifactorial stepwise backward regression analysis indicated that administration of cyclophosphamide and carmustine and higher concentrations of blood cholesterol represented risk factors for decreased HRV. Cyclophosphamide and higher triglyceride levels represented independent risk factors for decreased HRT.

Conclusions

In patients with hematopoietic malignancies treated with HSCT, decreased HRV and HRT were observed after chemotherapy and stem cells administration.
The efficiency of cross‐linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light
Authors: Bäckman Anders , Makdoumi Karim , Mortensen Jes , Crafoord Sven
Published: November 2013

Purpose

To determine bacterial eradication using numerous riboflavin concentrations and different ultraviolet light A (UVA) radiant and exposure time in an experimental model.

Methods

Dilutions of Staphylococcus epidermidis were mixed with riboflavin at varying concentrations (0.007–0.09%). Effects on bacterial growth were evaluated after 0, 3, 6, 30 and 60 min of UVA exposure (irradiance 30 and 3 mW/cm2). Standard settings of UVA were compared with high‐power UVA approach. Different fluid thicknesses of the exposed dilutions were also examined to improve the model.

Results

Bacterial eradication (%) was increased after 60 compared with 30 min of UVA exposure for concentrations of 0.03–0.07% but not for 0.09% riboflavin. There was a significant difference between the efficacy between 0.03 and 0.09% and eradication dropped from 80% to 50% (p = 0.01). A correlation could be calculated for the amount of riboflavin at 60 min of UVA and the ability to kill bacteria (p = 0.01). The antibacterial effect was more pronounced when the tested bacterial suspension thickness was reduced. High‐power UVA method was less potent in microbial elimination, eradicating only 60% of bacteria after 6 min versus 97–99% after 60 min in the low‐power setting, compared with respective controls (p = 0.02).

Conclusions

In these in vitro experiments, a longer UVA exposure time in combination with lower riboflavin levels were found to be favourable in killing bacteria as compared to the standard cross‐linking settings. Further studies are needed to evaluate the clinical relevance of these findings.
New Threats to Academic Freedom
Authors: Minerva Francesca
Published: November 2013

Using a specific case as an example, the article argues that the Internet allows dissemination of academic ideas to the general public in ways that can sometimes pose a threat to academic freedom. Since academic freedom is a fundamental element of academia and since it benefits society at large, it is important to safeguard it. Among measures that can be taken in order to achieve this goal, the publication of anonymous research seems to be a good option.
Corticotropin‐releasing factor (CRF) receptor‐1 is involved in cardiac noradrenergic activity observed during naloxone‐precipitated morphine withdrawal
Authors: Martínez‐Laorden Elena , García‐Carmona Juan‐Antonio , Baroja‐Mazo Alberto , Romecín Paola , Atucha Noemí M , Milanés María‐Victoria , Laorden María‐Luisa
Published: November 2013

Background and Purpose

The negative affective states of withdrawal involve the recruitment of brain and peripheral stress circuitry [noradrenergic activity, induction of the hypothalamic–pituitary–adrenocortical (HPA) axis and activation of heat shock proteins (Hsps)]. Corticotropin‐releasing factor (CRF) pathways are important mediators in the negative symptoms of opioid withdrawal. We performed a series of experiments to characterize the role of the CRF1 receptor in the response of stress systems to morphine withdrawal and its effect in the heart using genetically engineered mice lacking functional CRF1 receptors.

Experimental Approach

Wild‐type and CRF1 receptor‐knockout mice were treated with increasing doses of morphine. Precipitated withdrawal was induced by naloxone. Plasma adrenocorticotropic hormone (ACTH) and corticosterone levels, the expression of myocardial Hsp27, Hsp27 phosphorylated at Ser82, membrane (MB)‐ COMT, soluble (S)‐COMT protein and NA turnover were evaluated by RIA, immunoblotting and HPLC.

Key Results

During morphine withdrawal we observed an enhancement of NA turnover in parallel with an increase in mean arterial blood pressure (MAP) and heart rate (HR) in wild‐type mice. In addition, naloxone‐precipitated morphine withdrawal induced an activation of HPA axis and Hsp27. The principal finding of the present study was that plasma ACTH and corticosterone levels, MB‐COMT, S‐COMT, NA turnover, and Hsp27 expression and activation observed during morphine withdrawal were significantly inhibited in the CRF1 receptor‐knockout mice.

Conclusion and Implications

Our results demonstrate that CRF/CRF1 receptor activation may contribute to stress‐induced cardiovascular dysfunction after naloxone‐precipitated morphine withdrawal and suggest that CRF/CRF1 receptor pathways could contribute to cardiovascular disease associated with opioid addiction.
Adult Attachment States of Mind: Measurement Invariance Across Ethnicity and Associations With Maternal Sensitivity
Authors: Haltigan John D. , Leerkes Esther M. , Wong Maria S. , Fortuna Keren , Roisman Glenn I. , Supple Andrew J. , O'Brien Marion , Calkins Susan D. , Plamondon André
Published: November 2013

This study examined the developmental significance of mothers' adult attachment representations assessed prenatally with the Adult Attachment Interview in relation to observed maternal sensitivity at 6 months postpartum in an ethnically diverse sample (N = 131 African American; N = 128 European American). Multiple‐group confirmatory factor analyses provided evidence for partial measurement invariance of a two‐factor dismissing and preoccupied latent structure of adult attachment across the two ethnic groups of women. African American women showed modest elevations on the preoccupied factor relative to European American women. Although the dismissing factor showed an empirically equivalent negative association with maternal sensitivity in both ethnic groups, this effect was reduced to marginal significance when controlling for maternal socioeconomic status.
Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg‐allergic children
Authors: Vazquez‐Ortiz M. , Alvaro M. , Piquer M. , Dominguez O. , Machinena A. , Martín‐Mateos M. A. , Plaza A. M.
Published: November 2013

Background

Oral immunotherapy (OIT) is a promising treatment for food allergy but dose‐related reactions are common.

Objective

To evaluate safety of egg‐OIT. To identify predictors of dose‐related reactions.

Methods

Fifty children aged 5‐18 underwent egg‐OIT after confirming IgE‐mediated egg allergy by double‐blind placebo‐controlled challenge (DBPCFC). All dose‐related reactions over a median period of 18 months on‐OIT (range: 12–28) were registered. Children were retrospectively divided into three subgroups: (1) children who stopped reacting to OIT‐doses over time (RR, Resolved Reactions); (2) children with ongoing dose‐related reactions over the whole period on‐OIT (PR, Persistent Reactions); (3) children who discontinued OIT within induction phase due to frequent reactions not improved by protocol re‐adaptation and medication (ED, Early Discontinuation). Baseline clinical/immunological parameters associated with subgroups were investigated.

Results

Reactions occurred in 7.6% of doses. Adrenaline was required in 26% of children. The three subgroups corresponded to three different safety phenotypes: (1) twenty‐four children (48%, RR) experienced infrequent and mainly mild reactions that resolved over time. None required adrenaline; (2) seventeen children (34%, PR) experienced more frequent and severe ongoing reactions over time; (3) nine children (18%, ED) discontinued OIT due to very frequent and mainly moderate reactions. Early discontinuation was associated with underlying asthma, higher specific IgE (sIgE) and lower threshold at DBPCFC. In contrast, lower sIgE and less severe reactions at DBPCFC were associated with subgroup RR. sIgE showed excellent performance in predicting belonging to subgroup RR. Levels below the optimal cut‐off (ovomucoid‐sIgE 8.85 kU/L) indicated 77% probability of belonging to subgroup RR, whereas levels above it indicated 95% probability of early discontinuation or ongoing reactions over time.

Conclusions and Clinical Relevance

Egg‐OIT involves substantial risks. However, baseline parameters, particularly sIgE, may help identify children in whom the procedure is more likely to be safe. Egg‐OIT safety needs improvement in children with more severe and persistent egg allergy.
Strong correlations between circulating chemerin levels and lipoprotein subfractions in nondiabetic obese and nonobese subjects
Authors: Lőrincz Hajnalka , Katkó Mónika , Harangi Mariann , Somodi Sándor , Gaál Krisztina , Fülöp Péter , Paragh György , Seres Ildikó
Published: November 2013

Objective

Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared with lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear.

Patients and Methods

Fifty nondiabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) subfractions were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint).

Results

We detected significantly higher serum chemerin levels in NDO patients compared with healthy controls (590·1 ± 190·3 ng/ml vs 405 ± 127·1 ng/ml, P < 0·001). A significant positive correlation was found between chemerin and LDL cholesterol levels, while chemerin showed a significant negative correlation with the level of HDL cholesterol. Significant positive correlation was detected between chemerin and the ratio of small dense LDL, while chemerin correlated negatively with the mean LDL size. Also, a significant negative correlation was found between serum chemerin and the ratio of large HDL subfraction, while there were significant positive correlations between chemerin levels and intermediate and small HDL subfraction ratios, respectively.

Conclusion

Chemerin may be involved in the regulation of lipoprotein metabolism in obese patients who do not show apparent abnormalities of glucose metabolism. Early changes in the distribution of the lipoprotein subfractions may contribute to the progression of atherosclerosis, leading to increased cardiovascular risk.
A comprehensive laboratory‐based program for classification of variants of uncertain significance in hereditary cancer genes
Authors: Eggington J.M. , Bowles K.R. , Moyes K. , Manley S. , Esterling L. , Sizemore S. , Rosenthal E. , Theisen A. , Saam J. , Arnell C. , Pruss D. , Bennett J. , Burbidge L.A. , Roa B. , Wenstrup R.J.
Published: November 2013

Genetic testing has the potential to guide the prevention and treatment of disease in a variety of settings, and recent technical advances have greatly increased our ability to acquire large amounts of genetic data. The interpretation of this data remains challenging, as the clinical significance of genetic variation detected in the laboratory is not always clear. Although regulatory agencies and professional societies provide some guidance regarding the classification, reporting, and long‐term follow‐up of variants, few protocols for the implementation of these guidelines have been described. Because the primary aim of clinical testing is to provide results to inform medical management, a variant classification program that offers timely, accurate, confident and cost‐effective interpretation of variants should be an integral component of the laboratory process. Here we describe the components of our laboratory's current variant classification program (VCP), based on 20 years of experience and over one million samples tested, using the BRCA1/2 genes as a model. Our VCP has lowered the percentage of tests in which one or more BRCA1/2 variants of uncertain significance (VUSs) are detected to 2.1% in the absence of a pathogenic mutation, demonstrating how the coordinated application of resources toward classification and reclassification significantly impacts the clinical utility of testing.
A novel de novo point mutation of the OCT‐binding site in the IGF2/H19‐imprinting control region in a Beckwith–Wiedemann syndrome patient
Authors: Higashimoto K. , Jozaki K. , Kosho T. , Matsubara K. , Fuke T. , Yamada D. , Yatsuki H. , Maeda T. , Ohtsuka Y. , Nishioka K. , Joh K. , Koseki H. , Ogata T. , Soejima H.
Published: November 2013

The IGF2/H19‐imprinting control region (ICR1) functions as an insulator to methylation‐sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin‐specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith–Wiedemann syndrome (BWS) or Silver–Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF‐binding site, but also point mutations and a small deletion of the OCT‐binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT‐binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT‐binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT‐binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.
Brånemark Novum® immediate loading rehabilitation of edentulous mandibles: 11‐year retrospective study
Authors: Tealdo Tiziano , Menini Maria , Bevilacqua Marco , Pera Francesco , Capalbo Vanessa , Pera Paolo
Published: November 2013

Objectives

Short‐term results indicated that the Brånemark Novum® protocol (Nobel Biocare AB, Goteborg, Sweden) allowed successful rehabilitation of mandibular edentulism with immediately loaded implants. Yet, long‐term studies are lacking. The aim of the present retrospective study was to report the 11‐year outcomes for patients treated according to this protocol.

Material and methods

Four patients treated according to the Brånemark Novum protocol (Nobel Biocare AB) were followed‐up to evaluate implant and prosthesis cumulative survival rate (CSR), implant stability (RFA), marginal bone loss by periapical radiographs, probing depth (PD), and possible complications. Clinical and radiographic parameters were evaluated immediately after completion of the treatment and 1, 5, and 11 years after loading.

Results

The 11‐year implant and prosthesis CSRs were 100%. Implant stability (RFA values) remained stable over the 11‐year follow‐up. Small bone resorption was found next to distal implants (median 1 mm) after 11 years, while central implants showed greater bone resorption (median 4.5 mm). The PD (mean 3.75 mm at 11 years) grew together with marginal bone loss. One implant complication was detected on a central implant (crater‐form bone destruction), and 10 prosthetic complications (fractures of resin or teeth), 80% of which registered on the same parafunctional patient.

Conclusions

The 11‐year results demonstrated that the Brånemark Novum protocol (Nobel Biocare AB) is a predictable technique with favorable long‐term outcomes. This was a rigid protocol, which could be applied only in patients with specific anatomical characteristics of the lower jaw, but it had the merit of indicating the key factors for full‐arch immediate loading rehabilitations.
The CTSA Mentored Career Development Program: Supporting the Careers of Child Health Investigators
Authors: Byington Carrie L. , Higgins Sarah , Kaskel Fredrick J. , Purucker Mary , Davis Jonathan M. , Smoyer William E.
Published: November 2013

Training translational scientists is a priority of the Clinical and Translational Science Award (CTSA) consortium. Objectives: 1) Describe the landscape of CTSA Mentored Research Career Development Awards (CDA) and 2) evaluate participation and outcomes of child health investigators in these programs. Design: Survey of the CTSA Child Health Oversight Committee (CC‐CHOC) and review of nonresponders' CTSA Websites. Results: Thirty‐two of 53 CC‐CHOC members (60%) responded and all nonresponder Websites were reviewed. Institutions supported 1,166 CDA positions from 2006 to 2011, with 134 awarded to child health investigators (11.5%). Respondents reported a mean of 29.8 KL2 positions (95% CI 17.5–42.2) during their award period, with a mean of 2.8 (95% CI 1.8–3.8) awarded to child health investigators. The proportion of child health awardees varied from 0% to 50% across institutions. We identified 45 subsequent National Institutes of Health (NIH) awards to the 134 child health investigators (34%). Conclusions: The CTSA program contributes substantially to training the next generation of translational investigators. One‐third of child health investigators obtained subsequent NIH awards in the short follow‐up period demonstrating success of the CTSA CDA programs. Child health investigators are represented variably across the consortium. Pediatric institutions can partner with the CTSA program to further support training child health investigators.
Not Fit for Purpose: The Ethical Guidelines of the Indian Council of Medical Research
Authors: Satalkar Priya , Shaw David
Published: November 2013

In 2006, the Indian Council of Medical Research (ICMR) published its ‘Ethical guidelines for Biomedical Research on human participants’. The intention was to translate international ethical standards into locally and culturally appropriate norms and values to help biomedical researchers in India to conduct ethical research and thereby safeguard the interest of human subjects. Unfortunately, it is apparent that the guideline is not fit for purpose. In addition to problems with the structure and clarity of the guidelines, there are several serious omissions and contradictions in the recommendations. In this paper, we take a close look at the two key chapters and highlight some of the striking flaws in this important document. We conclude that ethics committees and national authorities should not lose sight of international ethical standards while incorporating local reality and cultural and social values, as focusing too much on the local context could compromise the safety of human subjects in biomedical research, particularly in India.
The Effects of Industrial Clusters on the Poverty Rate
Authors: Fowler Christopher S. , Kleit Rachel Garshick
Published: November 2013

Industrial clusters are widely understood as a worthwhile target of local economic development resources. Nevertheless, most of the work on cluster development has asserted benefits that accrue to a regional economy as a whole, with little or no focus on specific links between clusters and poverty alleviation. This article seeks to understand the degree to which economic clusters are associated with lower poverty rates. Specifically, using spatial regression analysis techniques, we examine patterns that link clusters to poverty rates while controlling for the presence of other factors that shape the distribution of poverty in the United States. When controlling for other economic and demographic factors in a multivariate framework, the presence of industrial clusters is associated with lower poverty rates. Moreover, regions with a higher share of employment in clusters, and with that employment dispersed across many industries within the same cluster, fare even better than those where employment is concentrated in a single industry. Furthermore, while there is evidence that particular clusters are associated with significantly altered poverty rates, not all of these associations are beneficial.
Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic structural abnormalities
Authors: Lin Jack J. , Siddarth Prabha , Riley Jeffrey D. , Gurbani Suresh G. , Ly Ronald , Yee Victor W. , Levitt Jennifer G. , Toga Arthur W. , Caplan Rochelle
Published: November 2013

Purpose

Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood‐onset epilepsies, suggesting that epilepsy‐related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural–functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes.

Methods

We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent‐completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC.

Key Findings

Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction.

Significance

Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood‐onset epilepsy.
Prognostic factors for subsequent epilepsy in children with febrile seizures
Authors: Pavlidou Efterpi , Panteliadis Christos
Published: November 2013

Objective

Epilepsy following febrile seizures (FS) has been estimated between 2% and 7%. It concerns a prospective study in a large sample of children with a long‐term follow‐up. The aim of this study is to identify the prognostic factors that can lead children with FS to epilepsy.

Methods

Children with a first episode of FS were included. We gathered information about prenatal and perinatal history, family history of FS and epilepsy in first‐ and second degree relatives, age at the time of the initial FS, dates of FS recurrences, focality, duration of the FS and recurrent episodes within the same febrile illness, height and duration of fever prior to the seizure, cause of the fever, and frequency of febrile illnesses. Patients were seen every 4–6 months and also at each recurrence.

Key Findings

A group of 560 children with a first FS met all entry criteria. Epilepsy was recorded at 5.4%. Statistical analysis was performed between children with epilepsy and those with no afebrile seizure. We analyzed FS recurrences in accordance with the occurrence of epilepsy. From the third FS recurrence and beyond, only focality continued to have prognostic value.

Significance

Main prognostic factors for the development of epilepsy after FS are: (1) complex FS that increased the risk for epilepsy 3.6 times, (2) age at onset of FS beyond the third year of life that raised the risk 3.8 times, (3) positive family history of epilepsy 7.3 times, and (4) multiple episodes of FS about 10 times. Focality at the first and the second FS recurrence increased the risk of epilepsy about 9.7 and 11.7 times, respectively. Focality was the only factor that continued to be significant in further FS recurrences. A prognostic profile of each child with FS would be very useful for the follow‐up of these children.
Epilepsy in TSC: Certain etiology does not mean certain prognosis
Authors: Vignoli Aglaia , Briola Francesca La , Turner Katherine , Scornavacca Giulia , Chiesa Valentina , Zambrelli Elena , Piazzini Ada , Savini Miriam Nella , Alfano Rosa Maria , Canevini Maria Paola
Published: November 2013

Purpose

Prevalence and long‐term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial.

Methods

We reviewed the clinical characteristics of patients with TSC who were regularly followed since 2000 at the San Paolo Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts we collected data about age at epilepsy onset, seizure frequency and seizure type, history of infantile spasms (IS), epileptic syndrome, evolution to refractory epilepsy or to seizure freedom and/or medication freedom, electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings, cognitive outcome, and genetic background.

Key Findings

Among the 160 subjects (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure‐free, and 59 (36.9%) had drug‐resistant epilepsy. Most seizure‐free patients had a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their lives. Epilepsy onset in the first year of life with IS and/or focal seizures was characteristic of the drug‐resistant group of patients, as well as cognitive impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients, 4.4%) experienced a seizure only once; all of them had normal cognition.

Significance

Although epilepsy management can be challenging in TSC, more than one third of patients had their seizures controlled: through monotherapy in 56% and by polytherapy in 32%. Moreover, 12% of the patients became seizure‐free and were off medication. Identifying predictive features of epilepsy and cognitive outcome can ensure better management for patients with TSC and delineate genotype–phenotype correlations.
Electroencephalography/functional magnetic resonance imaging responses help predict surgical outcome in focal epilepsy
Authors: An Dongmei , Fahoum Firas , Hall Jeffery , Olivier André , Gotman Jean , Dubeau François
Published: November 2013

Purpose

Simultaneous electroencephalography/functional magnetic resonance imaging (EEG/fMRI) recording can noninvasively map in the whole brain the hemodynamic response following an interictal epileptic discharge. EEG/fMRI is gaining interest as a presurgical evaluation tool. This study aims to determine how hemodynamic responses related to epileptic activity can help predict surgical outcome in patients considered for epilepsy surgery.

Methods

Thirty‐five consecutive patients with focal epilepsy who had significant hemodynamic responses and eventually surgical resection, were studied. The statistical map of hemodynamic responses were generated and coregistered to postoperative anatomic imaging. Patients were classified into four groups defined by the relative relationship between the location of the maximum hemodynamic response and the resection: group 1, fully concordant; group 2, partially concordant; group 3, partially discordant; and group 4, fully discordant. These findings were correlated with surgical outcome with at least 12‐month follow‐up.

Key Findings

Ten patients in group 1 had the maximum t value (t‐max) inside the resection; nine in group 2 had the t‐max outside but close to the resection and the cluster with t‐max overlapped the resection; five in group 3 had the t‐max remote from resection, but with another less significant cluster in the resection; and 11 in group 4 had no response in the resection. The degree of concordance correlated largely with surgical outcome: a good surgical outcome (Engel's class I) was found in 7 of 10 patients of group 1, 4 of 9 of group 2, 3 of 5 of group 3, and only 1 of 11 of group 4. These results indicate that the partially concordant and partially discordant groups are best considered as inconclusive. In contrast, in the fully concordant and fully discordant groups, the sensitivity, specificity, positive predictive value, and negative predictive value were high, 87.5%, 76.9%, 70%, and 90.9%, respectively.

Significance

This study demonstrates that hemodynamic responses related to epileptic activity can help delineate the epileptogenic region. Full concordance between maximum response and surgical resection is indicative of seizure freedom, whereas a resection leaving the maximum response intact is likely to lead to a poor outcome. EEG/fMRI is noninvasive but is limited to patients in whom interictal epileptic discharges can be recorded during the 60–90 min scan.
Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone
Authors: Hussain Shaun A. , Shinnar Shlomo , Kwong Grace , Lerner Jason T. , Matsumoto Joyce H. , Wu Joyce Y. , Shields W. Donald , Sankar Raman
Published: November 2013

Purpose

This study investigated the short‐term response to a standardized hormonal therapy protocol for treatment of infantile spasms.

Methods

Twenty‐seven children with video electroencephalography (EEG)–confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video‐EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m2/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video‐EEG after ACTH therapy.

Key Findings

Sixty‐three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2‐week course with ACTH. Among 27 subjects with median follow‐up of 13.5 months (interquartile range [IQR] 4.8–25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response.

Significance

Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.
Temperature effects on the fidelity of a thermostable HIV‐1 reverse transcriptase
Authors: Álvarez Mar , Menéndez‐Arias Luis
Published: November 2013

Transcriptomics and gene expression analysis are largely dependent of the availability of efficient thermostable reverse transcriptases (RTs). However, the intrinsic fidelity of DNA synthesis catalyzed by retroviral RTs is low. Reported error rates are in the range 1.2 × 10−5–6.7 × 10−4, with oncoretroviral RTs being the most faithful enzymes. Wild‐type HIV‐1 group O (HIV‐1O) RT is a thermostable polymerase that is able to synthesize cDNA at temperatures as high as 70 °C. At 37 °C, its error rate has been estimated at 5.8 × 10−5 in M13mp2 lacZ‐based forward mutation assays. However, at higher temperatures (e.g. 50 and 55 °C), the accuracy of HIV‐1O RT is increased by approximately two‐ to five‐fold. At 55 °C, the HIV‐1O RT error rate (1.3 × 10−5) was similar to that shown by the AffinityScript (Agilent Technologies Inc., La Jolla, CA, USA) RT, a commercially available thermostable murine leukaemia virus RT. At higher temperatures, the increased accuracy of the HIV‐1 enzyme results from a lower base substitution error rate, although it shows a higher tendency to introduce frameshifts. Kinetic studies carried out with model template‐primers suggest minor differences in nucleotide discrimination, although, at higher temperatures, HIV‐1O RT showed a reduced ability to extend mispaired template‐primers.
FATE‐HD: a spatially and temporally explicit integrated model for predicting vegetation structure and diversity at regional scale
Authors: Isabelle Boulangeat , Damien Georges , Wilfried Thuiller
Published: November 2013

During the last decade, despite strenuous efforts to develop new models and compare different approaches, few conclusions have been drawn on their ability to provide robust biodiversity projections in an environmental change context. The recurring suggestions are that models should explicitly (i) include spatiotemporal dynamics; (ii) consider multiple species in interactions and (iii) account for the processes shaping biodiversity distribution. This article presents a biodiversity model (FATE‐HD) that meets this challenge at regional scale by combining phenomenological and process‐based approaches and using well‐defined plant functional groups. FATE‐HD has been tested and validated in a French National Park, demonstrating its ability to simulate vegetation dynamics, structure and diversity in response to disturbances and climate change. The analysis demonstrated the importance of considering biotic interactions, spatio‐temporal dynamics and disturbances in addition to abiotic drivers to simulate vegetation dynamics. The distribution of pioneer trees was particularly improved, as were all undergrowth functional groups.
Devolution, state restructuring and policy divergence in the UK
Authors: MacKinnon Danny
Published: November 2013

Devolution has become a key ‘global trend’ over recent decades as many states have decentralised power to sub‐state governments. The UK resisted this trend until the late 1990s when devolution was enacted by the then Labour Government, taking a highly asymmetrical form in which different territories have been granted different powers and institutional arrangements. Devolution allows the devolved governments to develop policies that are tailored to the needs of their areas, encouraging policy divergence, although this is countered by pressures to ensure that devolved approaches do not contradict those of the central state, promoting convergence. This review paper aims to assess the unfolding dynamics of devolution and policy divergence in the UK, spanning different policy areas such as economic development, health and social policy. The paper emphasises that devolution has altered the institutional landscape of public policy in the UK, generating some high‐profile examples of policy divergence, whilst also providing evidence of policy convergence. In addition, the passage of time underlines the nature of UK devolution as an unfolding process. Its underlying asymmetries have become more pronounced as the tendency towards greater autonomy for Scotland and Wales clashes with a highly centralised mode of policymaking in Westminster, the consequences of which have spilt over into the devolved territories in the context of the post‐2007 economic crisis through public expenditure cuts.
SEAWAT‐Based Simulation of Axisymmetric Heat Transport
Authors: Vandenbohede Alexander , Louwyck Andy , Vlamynck Nele
Published: November 2013

Simulation of heat transport has its applications in geothermal exploitation of aquifers and the analysis of temperature dependent chemical reactions. Under homogeneous conditions and in the absence of a regional hydraulic gradient, groundwater flow and heat transport from or to a well exhibit radial symmetry, and governing equations are reduced by one dimension (1D) which increases computational efficiency importantly. Solute transport codes can simulate heat transport and input parameters may be modified such that the Cartesian geometry can handle radial flow. In this article, SEAWAT is evaluated as simulator for heat transport under radial flow conditions. The 1971, 1D analytical solution of Gelhar and Collins is used to compare axisymmetric transport with retardation (i.e., as a result of thermal equilibrium between fluid and solid) and a large diffusion (conduction). It is shown that an axisymmetric simulation compares well with a fully three dimensional (3D) simulation of an aquifer thermal energy storage systems. The influence of grid discretization, solver parameters, and advection solution is illustrated. Because of the high diffusion to simulate conduction, convergence criterion for heat transport must be set much smaller (10−10) than for solute transport (10−6). Grid discretization should be considered carefully, in particular the subdivision of the screen interval. On the other hand, different methods to calculate the pumping or injection rate distribution over different nodes of a multilayer well lead to small differences only.
Epidermal growth factor receptor (EGFR), HER2 and insulin‐like growth factor‐1 receptor (IGF‐1R) status in ovarian adult granulosa cell tumours
Authors: Higgins Patricia A , Brady Aidan , Dobbs Stephen P , Salto‐Tellez Manuel , Maxwell Perry , McCluggage W Glenn
Published: November 2013

Aims

Adult granulosa cell tumours (AGCTs) are uncommon ovarian sex cord–stromal tumours which recur following surgical removal in up to 50% of patients. Treatment options for recurrent and advanced stage AGCTs are limited, with poor response to chemotherapy and radiotherapy. We aimed to assess epidermal growth factor receptor (EGFR), HER2 and insulin‐like growth factor‐1 receptor (IGF‐1R) status in AGCTs with a view to investigating whether or not these receptors might be potential therapeutic targets in these neoplasms.

Methods and results

Immunohistochemical staining for EGFR, HER2 and IGF‐1R was undertaken in 31 AGCTs. Tumour DNA was also analysed for mutations in the tyrosine kinase domain of EGFR (exons 18–21) by Cobas mutation RT–PCR. Twenty‐three of 31 (74%) AGCTs showed some degree of EGFR expression, generally with cytoplasmic or mixed membranous and cytoplasmic staining of variable intensity. Eleven of 27 (41%) cases exhibited strong membranous and cytoplasmic expression of IGF‐1R. HER2 expression was not seen. No mutations were found in exons 18–21 of the EGFR gene in hot‐spots of therapeutic relevance.

Conclusions

This study raises the possibility that anti‐EGFR and/or anti‐IGF‐1R therapies may be of potential benefit in ovarian AGCTs, and this requires further study. Lack of known mutations within the tyrosine kinase domain of EGFR suggests that EGFR‐related tyrosine kinase inhibitors may not be useful therapeutically.
Virus‐encoded ectopic CD74 enhances poxvirus vaccine efficacy
Authors: Walline Crystal C. , Deffit Sarah N. , Wang Nan , Guindon Lynette M. , Crotzer Victoria L. , Liu Jianyun , Hollister Kristin , Eisenlohr Laurence C. , Brutkiewicz Randy R. , Kaplan Mark H. , Blum Janice S.
Published: November 2013

Vaccinia virus (VV) has been used globally as a vaccine to eradicate smallpox. Widespread use of this viral vaccine has been tempered in recent years because of its immuno‐evasive properties, with restrictions prohibiting VV inoculation of individuals with immune deficiencies or atopic skin diseases. VV infection is known to perturb several pathways for immune recognition including MHC class II (MHCII) and CD1d‐restricted antigen presentation. MHCII and CD1d molecules associate with a conserved intracellular chaperone, CD74, also known as invariant chain. Upon VV infection, cellular CD74 levels are significantly reduced in antigen‐presenting cells, consistent with the observed destabilization of MHCII molecules. In the current study, the ability of sustained CD74 expression to overcome VV‐induced suppression of antigen presentation was investigated. Viral inhibition of MHCII antigen presentation could be partially ameliorated by ectopic expression of CD74 or by infection of cells with a recombinant VV encoding murine CD74 (mCD74‐VV). In contrast, virus‐induced disruptions in CD1d‐mediated antigen presentation persisted even with sustained CD74 expression. Mice immunized with the recombinant mCD74‐VV displayed greater protection during VV challenge and more robust anti‐VV antibody responses. Together, these observations suggest that recombinant VV vaccines encoding CD74 may be useful tools to improve CD4+ T‐cell responses to viral and tumour antigens.
Health‐promoting behaviour among women with abdominal obesity: a conceptual link to social support and perceived stress
Authors: Cho Jeong Hyun , Jae Sae Young , Choo IL Han , Choo Jina
Published: November 2013

Aim

To identify a conceptual link among health‐promoting behaviour, interpersonal support and perceived stress and to examine whether the link between interpersonal support and health‐promoting behaviour would be mediated by perceived stress among women with abdominal obesity.

Background

Abdominal obesity is a strong risk factor for cardiovascular disease in women and its reduction can be achieved by weight loss. Adopting health‐promoting behaviour may be critical for successful weight loss.

Design

A cross‐sectional, correlational study design.

Method

Study participants were 126 women with abdominal obesity, who comprised a baseline sample in the Community‐based, Heart and Weight Management Trial. The Data were collected between September 2010–November 2011. A multiple regression analysis and Sobel's test were performed.

Findings

Higher levels of interpersonal support and lower levels of perceived stress were significantly associated with higher levels of health‐promoting behaviour, after controlling for age, obesity‐related comorbidity, postmenopausal status and current smoking in the regression models. The association between interpersonal support and health‐promoting behaviour was significantly mediated by perceived stress in the Sobel's test; the magnitude of the association between interpersonal support and health‐promoting behaviour decreased when adding perceived stress to the predictor variables in the regression model.

Conclusion

Our findings indicate the practical significance of identifying the levels of interpersonal support and perceived stress among women seeking weight management interventions. Nurses need to develop effective strategies for enhancing social support and stress management skills in weight management interventions for facilitating health‐promoting behaviour.
Daytime Systolic Ambulatory Blood Pressure With a Two‐Step Switch From Candesartan to Olmesartan Monotherapy and the Fixed‐Dose Combination of Olmesartan/Amlodipine in Patients With Uncontrolled Essential Hypertension (SEVICONTROL‐2)
Authors: Bramlage Peter , Zemmrich Claudia , Gansz Andrea , Sturm Claus‐Dieter , Fimmers Rolf , Nadal Jennifer , Schmieder Roland E. , Schrader Joachim , Lüders Stephan
Published: November 2013

The objective of this study was to investigate the efficacy of the fixed‐dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single‐arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug‐related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.