bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mass Attenuation Coefficients, Electronic, Atomic, and Molecular Cross Sections, Effective Atomic Numbers, and Electron Densities for Compounds of Some Biomedically Important Elements at 59.5 keV
Authors: Akça Burcu , Erzeneoğlu Salih Z.
Published: November 2014

The mass attenuation coefficients for compounds of biomedically important some elements (Na, Mg, Al, Ca, and Fe) have been measured by using an extremely narrow collimated-beam transmission method in the energy 59.5 keV. Total electronic, atomic, and molecular cross sections, effective atomic numbers, and electron densities have been obtained by using these results. Gamma-rays of241Am passed through compounds have been detected by a high-resolution Si(Li) detector and by using energy dispersive X-ray fluorescence spectrometer (EDXRF). Obtained results have been compared with theoretically calculated values of WinXCom and FFAST. The relative difference between the experimental and theoretical values are −9.4% to +11.9% with WinXCom and −11.8% to +11.7% FFAST. Results have been presented and discussed in this paper.
A Novel Algorithm in the Management of Hypoglycemia in Newborns
Authors: Naveen Swapna , Rosy Chikati , Kandraju Hemasree , Sharma Deepak , Oleti Tejopratap , Murki Srinivas
Published: November 2014

Study Objective. To evaluate the safety of a new protocol in comparison to the standard protocol for managing hypoglycemia in neonates.Methods. Open label RCT-pilot study. Neonates admitted to NICU with hypoglycemia and requiring intravenous fluids were included. Fifty-seven eligible neonates were randomly allocated to either intervention group (starting fluids with 10% dextrose and increments of 1.5%) or standard protocol group (GIR of 6 mg/kg/min with increments of 2 mg/kg/min) till control of hypoglycemia. Primary outcome of the study was to know proportion of infants with subsequent hypoglycemia and hyperglycemia after enrolment.Results. The initial GIR (6 ± 0 mg/kg/min versus 4.8 ± 1.4 mg/kg/min,P< 0.001), the mean maximum GIR (6.7 ± 1.6 mg/kg/min versus 5.6 ± 2 mg/kg/min,P= 0.03), the maximum concentration of glucose infused (13.8 ± 2.9% versus 10.9 ± 1.9%,P< 0.001), and the total amount of glucose infused were significantly lower in the intervention group. The mean maximum blood sugar was significantly higher (129 ± 57 mg/dL versus 87 ± 30 mg/dL,P= 0.001) and there was a trend towards high proportion of infants with Hyperglycemia in the standard protocol group (n= 10, 39% versusn= 5, 16%,P= 0.07). The median difference between the highest and the lowest recorded sugar for any infant was significantly higher in the standard protocol group (median 93 mg/dL, IQR 52 to 147 mg/dL versus median 50 mg/dL, IQR 38 to 62.5 mg/dL,P= 0.03).Conclusion. A new and novel algorithm in the management of hypoglycemia in neonates is as safe as the standard protocol and requires further testing before routine implementation.
Validation of a Coding Algorithm to Identify Bladder Cancer and Distinguish Stage in an Electronic Medical Records Database
Authors: Mamtani Ronac , Haynes Kevin , Boursi Ben , Scott Frank I. , Goldberg David S. , Keefe Stephen M. , Vaughn David J. , Malkowicz S. Bruce , Lewis James D.
Published: November 2014

Studies on outcomes in bladder cancer rely on accurate methods to identify patients with bladder cancer and differentiate bladder cancer stage. Medical record and administrative databases are increasingly used to study cancer incidence, but few have distinguished cancer stage, and none have focused on bladder cancer. In this study, we used data from The UK Health Improvement Network (THIN) to identify patients with bladder cancer using at least one diagnostic code for bladder cancer, and distinguish muscle-invasive from non-invasive disease using a subsequent code for cystectomy. Algorithms were validated against a gold standard of physician-completed questionnaires, pathology reports, and consultant letters. Algorithm performance was evaluated by measuring positive predictive value (PPV) and corresponding 95% confidence interval (CI). Among all patients coded with bladder cancer (n = 194), PPV for any bladder cancer was 99.5% (95% CI, 97.2–99.9). PPV for incident bladder cancer was 93.8% (95% CI, 89.4–96.7). PPV for muscle-invasive bladder cancer was 70.1% (95% CI, 59.4–79.5) in patients with cystectomy (n = 95) and 83.9% (95% CI, 66.3–94.5) in those with cystectomy plus additional codes for metastases and death (n = 31). Using our codes for bladder cancer, the age- and sex-standardized incidence rate (SIR) of bladder cancer in THIN approximated that measured by cancer registries (SIR within 20%), suggesting that sensitivity was high as well. THIN is a valid and novel database for the study of bladder cancer. Our algorithm can be used to examine the epidemiology of muscle-invasive bladder cancer or outcomes following cystectomy for patients with muscle invasion. Cancer Epidemiol Biomarkers Prev; 24(1); 303–7. ©2014 AACR.
A Phase I Study of PF-04449913, an Oral Hedgehog Inhibitor, in Patients with Advanced Solid Tumors
Authors: Wagner Andrew J. , Messersmith Wells A. , Shaik M. Naveed , Li Sherry , Zheng Xianxian , McLachlan Karen R. , Cesari Rossano , Courtney Rachel , Levin Wendy J. , El-Khoueiry Anthony B.
Published: November 2014

Purpose: To estimate the maximum tolerated dose (MTD) of single-agent PF-04449913, and to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in patients with advanced tumors.

Experimental Design: A 3+3 design was used in this open-label, multicenter, phase I study and dose escalation/de-escalation applied until identification of the MTD. PF-04449913 was orally administered once daily in continuous 28-day treatment cycles. The starting dose was 80 mg.

Results: A total of 23 patients were enrolled; 19 were evaluable for first-cycle dose-limiting toxicity (DLT). The first-cycle DLT rate at the 640 mg dose level was 33.3%, and the MTD was estimated to be 320 mg once daily. The recommended phase II dose was not determined. PF-04449913 was generally well tolerated at doses of 80 to 320 mg once daily. The most common treatment-related adverse events (AE) were grade 1–2 dysgeusia, fatigue, decreased appetite, nausea, dizziness, dehydration, and diarrhea. Treatment-related grade 3 AEs only occurred in patients receiving PF-04449913 640 mg once daily. No treatment-related grade 4–5 AEs were reported. Pharmacokinetic analysis indicated a generally dose-proportional kinetics with biphasic elimination, supporting once-daily dosing. PF-04449913 modulated hedgehog signaling at the dose levels tested, as demonstrated by >80% downregulation of GLI1 expression in the skin of treated patients. Eight patients (34.8%) achieved stable disease; none had complete or partial response. Three patients with disease progression at enrollment had prolonged disease stabilization (≥6 months).

Conclusions: The results obtained in this study support further evaluation of PF-04449913 in patients with advanced solid tumors. Clin Cancer Res; 21(5); 1044–51. ©2014 AACR.
Plasma Metabolomic Profiles of Breast Cancer Patients after Short-term Limonene Intervention
Authors: Miller Jessica A. , Pappan Kirk , Thompson Patricia A. , Want Elizabeth J. , Siskos Alexandros P. , Keun Hector C. , Wulff Jacob , Hu Chengcheng , Lang Julie E. , Chow H.-H. Sherry
Published: November 2014

Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anticancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biologic activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/postintervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography coupled to a linear trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P < 0.01), and significant increases in bile acids (P ≤ 0.05) and multiple collagen breakdown products (P < 0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor tissues (P ≤ 0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Furthermore, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting. Cancer Prev Res; 8(1); 86–93. ©2014 AACR.
Severe Adverse Immunologic Reaction in a Patient with Glioblastoma Receiving Autologous Dendritic Cell Vaccines Combined with GM-CSF and Dose-Intensified Temozolomide
Authors: Mitchell Duane A. , Sayour Elias J. , Reap Elizabeth , Schmittling Robert , DeLeon Gabriel , Norberg Pamela , Desjardins Annick , Friedman Allan H. , Friedman Henry S. , Archer Gary , Sampson John H.
Published: November 2014

Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimulating immunologic responses are developed for clinical evaluation, the risk of inflammatory and autoimmune toxicities also may be exacerbated. In this report, we describe the induction of a severe (grade 3) immunologic reaction in a patient with newly diagnosed glioblastoma (GBM) receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF and administered coordinately with cycles of dose-intensified temozolomide. Shortly after the eighth administration of the admixed intradermal vaccine, the patient experienced dizziness, flushing, conjunctivitis, headache, and the outbreak of a disseminated macular/papular rash and bilateral indurated injection sites. Immunologic workup of patient reactivity revealed sensitization to the GM-CSF component of the vaccine and the production of high levels of anti–GM-CSF autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed continued vaccination without incident. Despite the known lymphodepletive and immunosuppressive effects of temozolomide, these observations demonstrate the capacity for the generation of severe immunologic reactivity in patients with GBM receiving DC-based therapy during adjuvant dose-intensified temozolomide. Cancer Immunol Res; 3(4); 320–5. ©2014 AACR.
Immunity to the Vacuolar ATPase Complex Accessory Unit ATP6S1 in Patients with Malignant Melanoma
Authors: Zhou Jun , Gupta Meghna , Wu Xinqi , Yoon Charles , Giobbie-Hurder Anita , Hodi F. Stephen
Published: November 2014

The augmentation of high-titer antibodies to ATP6S1 is associated with favorable clinical outcomes in patients who received vaccination with autologous, irradiated tumor cells engineered to secrete GM-CSF and allogeneic bone marrow transplantation. Cellular immune responses to ATP6S1 are unknown. To define its role as an immune target, examination of cellular responses to ATP6S1 and immunity related to current therapies such as checkpoint blockade is needed. We used an overlapping peptide library representing the full-length ATP6S1 protein to screen for cellular responses from the peripheral blood of patients with stage III and IV melanoma. Reactive peptide pools were used to determine the individual peptide activity and epitopes. Recombinant ATP6S1 protein was used in an ELISA to assess potential correlation with humoral immune responses and changes in immunity related to CTLA-4 blockade with ipilimumab in these patients. We observed a broad array of CD4+ and CD8+ cellular responses against ATP6S1, including the identification of several MHC class I and II ATP6S1 epitopes. The generation of specific CD4+ and cytotoxic T cells revealed potent functional capability elicited by ipilimumab treatment in patients with metastatic melanoma, which revealed potent functional capability, including cytokine production, proliferation responsiveness to melanoma cell lines, and tumor-cell killing. Furthermore, the augmented humoral immune responses to ATP6S1 as a function of ipilimumab treatment were associated with beneficial clinical outcomes. These results support the continued development of ATP6S1 as a biomarker and therapeutic target. Cancer Immunol Res; 3(1); 59–67. ©2014 AACR.
Retinal Ganglion Cell Distribution and Spatial Resolving Power in Deep-Sea Lanternfishes (Myctophidae)
Authors: de Busserolles Fanny , Marshall N. Justin , Collin Shaun P.
Published: November 2014

Topographic analyses of retinal ganglion cell density are very useful in providing information about the visual ecology of a species by identifying areas of acute vision within the visual field (i.e. areas of high cell density). In this study, we investigated the neural cell distribution in the ganglion cell layer of a range of lanternfish species belonging to 10 genera. Analyses were performed on wholemounted retinas using stereology. Topographic maps were constructed of the distribution of all neurons and both ganglion and amacrine cell populations in 5 different species from Nissl-stained retinas using cytological criteria. Amacrine cell distribution was also examined immunohistochemically in 2 of the 5 species using anti-parvalbumin antibody. The distributions of both the total neuron and the amacrine cell populations were aligned in all of the species examined, showing a general increase in cell density toward the retinal periphery. However, when the ganglion cell population was topographically isolated from the amacrine cell population, which comprised up to 80% of the total neurons within the ganglion cell layer, a different distribution was revealed. Topographic maps of the true ganglion cell distribution in 18 species of lanternfishes revealed well-defined specializations in different regions of the retina. Different species possessed distinct areas of high ganglion cell density with respect to both peak density and the location and/or shape of the specialized acute zone (i.e. elongated areae ventro-temporales, areae temporales and large areae centrales). The spatial resolving power was calculated to be relatively low (varying from 1.6 to 4.4 cycles per degree), indicating that myctophids may constitute one of the less visually acute groups of deep-sea teleosts. The diversity in retinal specializations and spatial resolving power within the family is assessed in terms of possible ecological functions and evolutionary history.
Clinically Isolated Neurosarcoidosis: A Recommended Diagnostic Path
Authors: Wegener Susanne , Linnebank Michael , Martin Roland , Valavanis Anton , Weller Michael
Published: November 2014

The involvement of the central nervous system in sarcoidosis can manifest with a variety of neurological symptoms, most of them nonspecific. We identified 13 patients with neurosarcoidosis diagnosed at our clinic. Six of 13 patients presented with clinically isolated neurosarcoidosis (CINS) without signs or symptoms of systemic disease. CINS patients were not different with respect to age, as well as imaging and spinal fluid findings, or disease course. However, we found spinal cord involvement in neurosarcoidosis patients much more common than previously described (in 8 out of 13 patients). Spinal cord affection was associated with older age at diagnosis and a less favorable response to therapy. Based on our findings, we propose a diagnostic path for neurosarcoidosis, including spinal magnetic resonance imaging (MRI) as a mandatory and early step during diagnostic workup. i 2014 S. Karger AG, Basel
Loss of MicroRNA-106b-25 Cluster Promotes Atrial Fibrillation by Enhancing Ryanodine Receptor Type-2 Expression and Calcium Release
Authors: Chiang David Y. , Kongchan Natee , Beavers David L. , Alsina Katherina M. , Voigt Niels , Neilson Joel R. , Jakob Heinz , Martin James F. , Dobrev Dobromir , Wehrens Xander H.T. , Li Na
Published: November 2014

Background—

Enhanced sarcoplasmic reticulum Ca
2+
-leak via ryanodine receptor type-2 (RyR2) contributes to the pathogenesis of atrial fibrillation (AF). Recent studies have shown that the level of RyR2 protein is elevated in atria of patients with paroxysmal AF, suggesting that microRNA-mediated post-transcriptional regulation of RyR2 might be an underlying mechanism. Bioinformatic analysis suggests that miR-106b and miR-93, members of the miR-106b-25 cluster, could bind to RyR2-3′-untranslated region and suppress its translation. Thus, we tested the hypothesis that loss of the miR-106b-25 cluster promotes AF via enhanced RyR2-mediated sarcoplasmic reticulum Ca
2+
-leak.

Methods and Results—

Quantitative real-time polymerase chain reaction showed that the levels of mature miR-106b, miR-93, and miR-25 were lower in atria of patients with paroxysmal AF when compared with patients in sinus rhythm. In vitro assay showed that miR-93 reduced RyR2-3′-untranslated region luciferase activity. Total RyR2 protein in atrial tissue of miR-106b-25
−/−
mice was increased by 42% when compared with wild-type littermates but still maintained a normal subcellular distribution. Ca
2+
-spark frequency and total sarcoplasmic reticulum Ca
2+
-leak were increased in atrial myocytes of miR-106b-25
−/−
mice. Telemetry ECG recordings revealed that miR-106b-25
−/−
mice exhibited more frequent atrial ectopy and were also more susceptible to pacing-induced AF than wild-type littermates. Increased sarcoplasmic reticulum Ca
2+
-release and AF susceptibility in miR-106b-25
−/−
mice were abolished by the RyR2 blocker K201.

Conclusions—

These results suggest that miR-106b-25 cluster–mediated post-transcriptional regulation of RyR2 is a potential molecular mechanism involved in paroxysmal AF pathogenesis. As such, the miR-106b-25 cluster could be a novel gene-therapy target in AF associated with enhanced RyR2 expression.
Cost‐Effectiveness of Supervised Exercise, Stenting, and Optimal Medical Care for Claudication: Results From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Trial
Authors: Reynolds Matthew R. , Apruzzese Patricia , Galper Benjamin Z. , Murphy Timothy P. , Hirsch Alan T. , Cutlip Donald E. , Mohler Emile R. , Regensteiner Judith G. , Cohen David J.
Published: November 2014

Background

Both supervised exercise (
SE
) and stenting (
ST
) improve functional status, symptoms, and quality of life compared with optimal medical care (
OMC
) in patients with claudication. The relative cost‐effectiveness of these strategies is not well defined.

Methods and Results

The Claudication: Exercise Versus Endoluminal Revascularization (
CLEVER
) study randomized patients with claudication due to aortoiliac stenosis to a 6‐month
SE
program, to
ST
, or to
OMC
. Participants who completed 6‐month follow‐up (n=98) were included in a health economic analysis through 18 months. Costs were assessed using resource‐based methods and hospital billing data. Quality‐adjusted life‐years were estimated using the
EQ
‐5D. Markov modeling based on the in‐trial results was used to explore the impact of assumptions about the longer term durability of observed differences in quality of life. Through 18 months, mean healthcare costs were $5178, $9804, and $14 590 per patient for
OMC
,
SE
, and
ST
, respectively. Measured quality‐adjusted life‐years through 18 months were 1.04, 1.16, and 1.20. In our base case analysis, which assumed that observed differences in quality of life would dissipate after 5 years, the incremental cost‐effectiveness ratios were $24 070 per quality‐adjusted life‐year gained for
SE
versus
OMC
, $41 376 for
ST
versus
OMC
, and $122 600 for
ST
versus
SE
. If the treatment effect of
ST
was assumed to be more durable than that of
SE
, the incremental cost‐effectiveness ratio for
ST
versus
SE
became more favorable.

Conclusions

Both
SE
and
ST
are economically attractive by
US
standards relative to
OMC
for the treatment of claudication in patients with aortoiliac disease.
ST
is more expensive than
SE
, with uncertain incremental benefit.

Clinical Trial Registration

URL:
www.clinicaltrials.gov
, Unique identifier: NCT00132743.
Pupillometry as a Glimpse into the Neurochemical Basis of Human Memory Encoding
Authors: Cohen Hoffing Russell , Seitz Aaron R.
Published: November 2014

Neurochemical systems are well studied in animal learning; however, ethical issues limit methodologies to explore these systems in humans. Pupillometry provides a glimpse into the brain's neurochemical systems, where pupil dynamics in monkeys have been linked with locus coeruleus (LC) activity, which releases norepinephrine (NE) throughout the brain. Here, we use pupil dynamics as a surrogate measure of neurochemical activity to explore the hypothesis that NE is involved in modulating memory encoding. We examine this using a task-irrelevant learning paradigm in which learning is boosted for stimuli temporally paired with task targets. We show that participants better recognize images that are paired with task targets than distractors and, in correspondence, that pupil size changes more for target-paired than distractor-paired images. To further investigate the hypothesis that NE nonspecifically guides learning for stimuli that are present with its release, a second procedure was used that employed an unexpected sound to activate the LC–NE system and induce pupil-size changes; results indicated a corresponding increase in memorization of images paired with the unexpected sounds. Together, these results suggest a relationship between the LC–NE system, pupil-size changes, and human memory encoding.
The Attentional Blink Impairs Detection and Delays Encoding of Visual Information: Evidence from Human Electrophysiology
Authors: Dell'Acqua Roberto , Dux Paul E. , Wyble Brad , Doro Mattia , Sessa Paola , Meconi Federica , Jolicœur Pierre
Published: November 2014

This article explores the time course of the functional interplay between detection and encoding stages of information processing in the brain and the role they play in conscious visual perception. We employed a multitarget rapid serial visual presentation (RSVP) approach and examined the electrophysiological P3 component elicited by a target terminating an RSVP sequence. Target-locked P3 activity was detected both at frontal and parietal recording sites and an independent component analysis confirmed the presence of two distinct P3 components. The posterior P3b varied with intertarget lag, with diminished amplitude and postponed latency at short relative to long lags—an electroencephalographic signature of the attentional blink (AB). Under analogous conditions, the anterior P3a was also reduced in amplitude but did not vary in latency. Collectively, the results provide an electrophysiological record of the interaction between frontal and posterior components linked to detection (P3a) and encoding (P3b) of visual information. Our findings suggest that, although the AB delays target encoding into working memory, it does not slow down detection of a target but instead reduces the efficacy of this process. A functional characterization of P3a in attentive tasks is discussed with reference to current models of the AB phenomenon.
Theta Oscillations Modulate Attentional Search Performance Periodically
Authors: Dugué Laura , Marque Philippe , VanRullen Rufin
Published: November 2014

Visual search—finding a target element among similar-looking distractors—is one of the prevailing experimental methods to study attention. Current theories of visual search postulate an early stage of feature extraction interacting with an attentional process that selects candidate targets for further analysis; in difficult search situations, this selection is iterated until the target is found. Although such theories predict an intrinsic periodicity in the neuronal substrates of attentional search, this prediction has not been extensively tested in human electrophysiology. Here, using EEG and TMS, we study attentional periodicities in visual search. EEG measurements indicated that successful and unsuccessful search trials were associated with different amounts of poststimulus oscillatory amplitude and phase-locking at ∼6 Hz and opposite prestimulus oscillatory phase at ∼6 Hz. A trial-by-trial comparison of pre- and poststimulus ∼6 Hz EEG phases revealed that the functional interplay between prestimulus brain states, poststimulus oscillations, and successful search performance was mediated by a partial phase reset of ongoing oscillations. Independently, TMS applied over occipital cortex at various intervals after search onset demonstrated a periodic pattern of interference at ∼6 Hz. The converging evidence from independent TMS and EEG measurements demonstrates that attentional search is modulated periodically by brain oscillations. This periodicity is naturally compatible with a sequential exploration by attention, although a parallel but rhythmically modulated attention spotlight cannot be entirely ruled out.
A revision of the genus Ora Clark, 1865 (Coleoptera: Scirtidae) in Argentina (part I)—descriptions of new species
Authors: LIBONATTI MARÍA LAURA
Published: November 2014

Three new species of the genus Ora Clark are described from Argentina: O. brevieminentia sp. n., O. megadepressa sp. n. and O. sigmoidea sp. n. All the species are characterized by a pair of frontoclypeal foveae, dorsal surface of mandible covered with setae, third labial palpomere arising from the inner margin of second palpomere, anterior pronotal angles distinctly projected anteriorly, a pair of glabrous areas on abdominal ventrites 2–5, ventrite 5 emarginate, with a pair of foveae in females, and tegmen with an apical digitiform lobe. Ora brevieminentia is similar externally to O. gamma Champion and O. platensis Brèthes, but it differs in having a more convex body, a smaller total length/elytral width ratio, coarser elytral punctation and a shorter lateral protuberance on the penis. Ora megadepressa is similar externally to O. depressa Fabricius, but differs in that the body is wider, the tegmen is laterally spiny with the lobe less narrowed basally, and the penis is straight with the base and the longer subapical process directed to the right-hand. Ora sigmoidea is similar in body color and shape to O. brevenotata Pic, and the aedeagus resembles that of O. texana Champion. However, the lobe of the tegmen is less protruding, the laminar dorsal piece of the penis is broadened, the apex is truncate, and the S-shaped ventral piece is distinctly curved.
The Molecular Basis of Hereditary Enamel Defects in Humans
Authors: Wright J.T. , Carrion I.A. , Morris C.
Published: November 2014

The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel.
Uncertainty at the heart of a ritual in Lebanon 2011
Authors: Aubin-Boltanski Emma
Published: November 2014

In Lebanon and Syria, a network of Christian female mystics has been forming since the early 1980s. Every year on Good Friday, all these women relive Christ’s sufferings more or less dramatically. Some, crippled with pain, tend to isolate themselves. In contrast, others show the wounds that appear on their bodies to crowds of devotees. This article will focus on the ritual of ‘crucifixion’ ( insilâb). Based on a description of Catherine Fahmi’s insilâb, the author will show that stigmatization is both a paradigm and a process: even if it inscribes itself in a long imitatio Christi tradition, which has been formalized and theorized over the centuries, the ritual also contributes to deeply transforming the Passion myth. Uncertainty – along with its subsequent questions, concerns, and hesitations – is key to this process.
La Vierge et la Santa Maria. Les sœurs MIC et la plasticité des religions chinoises à l’Hôpital Général chinois de Manille (1921-1939)
Authors: Laugrand Frédéric
Published: November 2014

Originally from Canada and sent to the Philippines in 1921, the Missionary Sisters of the Immaculate Conception (MIC) were entrusted with the administration of the Chinese General Hospital in Manila. This mission put them in contact with many immigrants and residents from China. This paper examines the multiple challenges that the sisters met in dealing with a dying population they were trying to convert in the face of well established Buddhist and Taoist beliefs and practices. The sisters fought against these practices, turning the hospital where they worked into a place of ontological confrontation. Distributing medals and images of the Virgin Mary, the sisters also contributed to the plasticity of the existing Chinese religious traditions, especially the devotion to Santa Maria. The dedication of the sisters to care and education as well as their tolerance allowed them to develop lasting and profitable relationships with their patients. The Christianization of the Chinese nevertheless remained incomplete, their centuries-old traditions persisting. In the anthropological study of missions, this case study shows that misunderstandings often remain at the heart of the conversion process.
Promises unfulfilled: American religious sisters and gender inequality in the post-Vatican II Catholic Church
Authors: Murphy Ryan P
Published: November 2014

In light of the Vatican’s recent doctrinal investigation of American Catholic nuns, this paper considers gender inequality in the Catholic Church immediately before, during and after the Second Vatican Council. Using Weber’s frameworks of authority construction and literature on corporate structures that reify inequality and gendered workplaces, the author argues that viewing the Church as a complex social organization allows for a fuller understanding of the ways in which its structures of power are constructed and reproduced. Ultimately, the author contends that religious sisters are stakeholders in a hierarchical organization that has prevented them from assuming leadership roles and from developing official Church teaching. Finally, he identifies several hegemonic forces that perpetuate gender barriers in the Catholic Church, specifically the obligatory wearing of the religious habit and the ban on women’s ordination.
Lower limb amputation in England: prevalence, regional variation and relationship with revascularisation, deprivation and risk factors. A retrospective review of hospital data
Authors: Ahmad Naseer , Thomas G Neil , Gill Paramjit , Chan Colin , Torella Francesco
Published: November 2014

Objective

We describe the prevalence of major lower limb amputation across England and its relationship with revascularisation, patient demography and disease risk factors.

Design

Retrospective cohort study.

Setting

England 1 April 2003 to 31 March 2009.

Participants

Patients aged 50–84 years.

Main outcome measures

Age standardised prevalence rates were calculated using Hospital Episode Statistics as the numerator with census data as the denominator. The outcome measure ‘amputation with revascularisation’ was created if an amputation could be linked with a revascularisation. Logistic regression determined the odds of having an amputation with a revascularisation across England. Regression was performed unadjusted and repeated after controlling for demographic (age, sex, social deprivation) and disease risk factors (diabetes, hypertension, coronary heart disease, cerebrovascular disease, smoking).

Results

There were 25,312 amputations and 136,215 revascularisations, and 7543 cases were linked. The prevalence rate per 100,000 (95% confidence intervals) for amputation was 26.3 (26.0–26.6) with rates significantly higher in Northern England (North: 31.7; 31.0–32.3, Midlands: 26.0; 25.3–26.7, South: 23.1; 22.6–23.5). The revascularisation rate was 141.6 (140.8–142.3) with significantly higher rates again in Northern England (North: 182.1; 180.5–183.7, Midlands: 121.3; 119.8–122.9, South 124.9; 123.9–125.8). The odds of having an amputation with a revascularisation remained significantly higher in the North (OR 1.22; 1.13–1.33) even after controlling demographic and disease risk factors.

Conclusions

There is a North–South divide in England for both major lower limb amputation and revascularisation. The higher odds of having an amputation with a revascularisation in the North were not fully explained by greater levels of deprivation or disease risk factors.
Under-reporting of conflicts of interest among trialists: a cross-sectional study
Authors: Rasmussen Kristine , Schroll Jeppe , Gøtzsche Peter C , Lundh Andreas
Published: November 2014

Objectives

To determine the prevalence of conflicts of interest (COIs) among Danish physicians who are authors of clinical drug trial reports and determine the extent of undisclosed COIs in trial publications.

Design

Cross-sectional study.

Setting

The 100 most recent drug trial reports with at least one Danish non-industry employed physician author published in a journal adhering to the International Committee of Medical Journal Editors' (ICMJE) manuscript guidelines. For each article, two observers independently extracted trial characteristics and the authors' COIs. Disclosed COIs were compared to what was registered on the Danish Health and Medicines Authority's public disclosure list.

Participants

Trial authors who are Danish physicians.

Main outcome measures

Number of disclosed and undisclosed COIs.

Results

One observer screened 928 articles and two observers assessed 120 articles for eligibility. The 100 included trials were published from February 2011 to May 2013 and included 318 Danish non-industry employed authors. Eighty-six of the 318 authors (27%) reported one or more COIs in the journal article. We found undisclosed COIs for 40 of 318 authors (13%) related to the trial sponsor or manufacturer of trial drugs. Seventy-nine of 318 authors (25%) had undisclosed COIs related to competing companies manufacturing drugs for the same indication and 136 (43%) had undisclosed COIs with any drug manufacturer.

Conclusions

Almost half of all authors had undisclosed COIs in clinical trials reported in journals adhering to the International Committee of Medical Journal Editors’ manuscript guidelines. Self-declared COIs cannot be trusted, but public registries may assist editors in ensuring that more COIs are being reported.
Mind the Gap
Authors: Smith-Doerr Laurel , Vardi Itai
Published: November 2014

Asymmetrical convergence is the increasing overlap between academic and industrial sectors, but with academia moving closer toward for-profit industrial norms than vice versa. Although this concept, developed by Kleinman and Vallas, is useful, processes of asymmetrical convergence in daily laboratory life are largely unexplored. Here, observations of three lab groups of chemical scientists in academic and industry contexts illustrate variation in interactions with ethics-related policies (as defined by the respondents). Findings show more tension for academic science with business-based practices, such as the move toward greater accountability, than for industrial science with academic practices. This asymmetry is evident in the process of purposive decoupling: for example, where academic scientists use humor to distance themselves from the performance of compliance in required reporting and top-down ethics training requirements. This distancing from meaningless requirements (formalism) contrasts with mentoring around practices of professional behavior that are thought to matter (engagement). Convergence is evident in how safety policies seem more engaging than other kinds of policies. Yet, power structures shape engagement. Academic engagement often means rule following, and flows vertically from professor’s authority to student apprenticeship. Industry engagement includes collaborative problem solving and flows along a more horizontal peer structure where informal power is less visible.
Dermal Toxicity Studies
Authors: Chandra Sundeep A. , Stokes Alan H. , Hailey Rick , Merrill Christine L. , Melich David H. , DeSmet Kristina , Furst Sylvia M. , Peterson Richard A. , Mellon-Kusibab Katherine , Adler Rick R.
Published: November 2014

The field of dermal toxicity continues to evolve in order to accurately predict dermal (and systemic) responses in humans to topically applied chemicals. Although the testing methods have undergone extensive refinements, idiosyncrasies and unexpected issues during the conduct of these studies are not unusual due to the plethora of new vehicles available for formulating test substances, changing regulatory requirements, and introducting new strain and/or species of laboratory animals as no single species or method seems to suffice for evaluating skin toxicity. The objective of this article is to illustrate some pragmatic issues that should be considered during the conduct as well as interpretation of dermal toxicity studies. Routine procedure-related issues such as hair clipping, tape stripping, and wrapping the animal’s torso to prevent oral ingestion can influence the interpretation. Excipients used in dermal toxicity studies may be nontoxic when used alone but complex dermal formulations can result in unexpected irritation and toxicity. In conclusion, interpretation and risk assessment of dermal toxicity studies should be done in a comprehensive manner, taking into account procedure-related impact on study results, unique species susceptibility, limitation of gross visual (naked eye) observation for evidence of toxicity, and normal anatomical variation.
Drug Development and Nonclinical to Clinical Translational Databases
Authors: Monticello Thomas M.
Published: November 2014

The International Consortium for Innovation and Quality (IQ) in Pharmaceutical Development is a science-focused organization of pharmaceutical and biotechnology companies. The mission of the Preclinical Safety Leadership Group (DruSafe) of the IQ is to advance science-based standards for nonclinical development of pharmaceutical products and to promote high-quality and effective nonclinical safety testing that can enable human risk assessment. DruSafe is creating an industry-wide database to determine the accuracy with which the interpretation of nonclinical safety assessments in animal models correctly predicts human risk in the early clinical development of biopharmaceuticals. This initiative aligns with the 2011 Food and Drug Administration strategic plan to advance regulatory science and modernize toxicology to enhance product safety. Although similar in concept to the initial industry-wide concordance data set conducted by International Life Sciences Institute’s Health and Environmental Sciences Institute (HESI/ILSI), the DruSafe database will proactively track concordance, include exposure data and large and small molecules, and will continue to expand with longer duration nonclinical and clinical study comparisons. The output from this work will help identify actual human and animal adverse event data to define both the reliability and the potential limitations of nonclinical data and testing paradigms in predicting human safety in phase 1 clinical trials.
Diagnostic Yield of MRI for Pediatric Hearing Loss: A Systematic Review
Authors: Kachniarz Bart , Chen Jenny X. , Gilani Sapideh , Shin Jennifer J.
Published: November 2014

Objective

To perform a systematic review to analyze the diagnostic yield of magnetic resonance imaging (MRI) for pediatric hearing loss, including comparison to computed tomography (CT) and subgroup evaluation according to impairment severity and specific diagnostic findings (cochlear anomalies, enlarged vestibular aqueduct, cochlear nerve abnormalities, and brain findings).

Data Sources

Pubmed, EMBASE, and the Cochrane library were assessed from their inception through December 2013. Manual searches were also performed, and topic experts were contacted.

Review Methods

Data from studies describing the use of MRI with or without comparison to CT in the diagnostic evaluation of pediatric patients with hearing loss were evaluated, according to a priori inclusion/exclusion criteria. Two independent evaluators corroborated the extracted data. Heterogeneity was evaluated according to the I2 statistic.

Results

There were 29 studies that evaluated 2434 patients with MRIs and 1451 patients with CTs that met inclusion/exclusion criteria. There was a wide range of diagnostic yield from MRI. Heterogeneity among studies was substantial but improved with subgroup analysis. Meta‐analysis of yield differences demonstrated that CT had a greater yield than MRI for enlarged vestibular aqueduct (yield difference 16.7% [95% CI, 9.1%‐24.4%]) and a borderline advantage for cochlear anomalies (4.7% [95% CI, 0.1%‐9.5%]). Studies were more likely to report brain findings with MRI.

Conclusions

These data may be utilized in concert with that from studies of risks of MRI and risk/yield of CT to inform the choice of diagnostic testing.
Lymphedema Outcomes in Patients with Head and Neck Cancer
Authors: Smith Brad G. , Hutcheson Katherine A. , Little Leila G. , Skoracki Roman J. , Rosenthal David I. , Lai Stephen Y. , Lewin Jan S.
Published: November 2014

Objective

We sought to describe the presentation of external head and neck lymphedema in patients treated for head and neck cancer and to examine their initial responses to complete decongestive therapy.

Study Design

Case series with chart review.

Setting

MD Anderson Cancer Center, Houston, Texas.

Subjects and Methods

The charts of patients who were evaluated for head and neck cancer at MD Anderson Cancer Center after treatment (January 2007–January 2013) were retrospectively reviewed. Response to complete decongestive therapy was evaluated per changes in lymphedema severity rating or surface tape measures. Predictors of therapy response were examined on the basis of regression models.

Results

The cases of 1202 patients were evaluated. Most patients (62%) had soft reversible pitting edema (MD Anderson Cancer Center stage 1b). Treatment response was evaluated for 733 patients; 439 (60%) improved after complete decongestive therapy. Treatment adherence independently predicted complete decongestive therapy response (P <. 001).

Conclusions

These data support the effectiveness of a head and neck cancer–specific regimen of lymphedema therapy for cancer patients with external head and neck lymphedema. Our findings suggest that head and neck lymphedema is distinct from lymphedema that affects other sites, thus requiring adaptations in traditional methods of management and measurement.
Direct comparison of visual and quantitative bone marrow FDG-PET/CT findings with bone marrow biopsy results in diffuse large B-cell lymphoma: does bone marrow FDG-PET/CT live up to its promise?
Authors: Adams Hugo JA , Kwee Thomas C , Fijnheer Rob , Dubois Stefan V , Nievelstein Rutger AJ , de Klerk John MH
Published: November 2014

Background

Detection of bone marrow involvement using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been proposed as a non-invasive alternative to standard blind bone marrow biopsy (BMB) of the posterior iliac crest in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, studies that directly compare FDG-PET/CT results with histopathology are currently lacking.

Purpose

To directly compare both visual and quantitative bone marrow FDG-PET/CT to BMB at the right posterior iliac crest in patients with newly diagnosed DLBCL.

Material and Methods

A total of 40 patients with newly diagnosed DLBCL, who had undergone FDG-PET/CT before BMB of the right posterior iliac crest, were retrospectively included. FDG-PET/CT images were visually assessed for bone marrow involvement in the right posterior iliac crest. 3D partial volume corrected mean standardized uptake value (cSUVmean), maximum standardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were measured in the right posterior iliac crest, using volume of interest analysis. BMB of the right posterior iliac crest was used as reference standard for bone marrow involvement.

Results

Sensitivity and specificity of visual FDG-PET/CT analysis for the detection of bone marrow involvement in the right posterior iliac crest were 14.3% (95% confidence interval [CI], 0.5–53.4%) and 100% (95% CI, 87.6–100%), respectively. cSUVmean, SUVmax, and SUVpeak of BMB-negative patients (1.4 ± 0.49, 2.2 ± 0.69, and 1.7 ± 0.59, respectively) considerably overlapped with those of BMB-positive patients (1.8 ± 0.53, 2.7 ± 0.71, and 2.2 ± 0.61, respectively).

Conclusion

In a local, head-to-head comparison with BMB, the diagnostic value of both visual and quantitative FDG-PET/CT for the detection of bone marrow involvement is low in patients with newly diagnosed DLBCL.