bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose site reactions and related findings after vaccine administration in safety studies
Authors: Baldrick Paul
Published: March 2016

Potential new human vaccines undergo toxicology testing to evaluate local reactogenicity and systemic toxicity. A review of 30 recently published and in‐house repeat dose toxicity studies with a variety of vaccines was performed. Species tested were generally rat or rabbit, usually by intramuscular (although occasionally subcutaneous) injection. Results showed no unexpected findings indicating vaccine toxicity, but classic signs of enhanced acute and/or chronic inflammation at the dose site compared with that seen in injected control animals, often accompanied by changes in draining lymph nodes and the spleen (lymphoid hyperplasia and/or increased weight). Other associated signs of a response to vaccine dosing were altered clinical pathology parameters (commonly raised blood neutrophil count and altered globulin level). No obvious difference in dose site or systemic reaction was seen across vaccine, species or the dose route used. A non‐dose recovery period of 2 to 4 weeks was sufficient to show evidence of reversibility of dose site effects. Injection site, lymphoid tissue and clinical pathological changes can be interpreted as related to an expected reaction after vaccine dosing, with generation of an immune response largely as a result of the presence of adjuvant, although direct vaccine antigen involvement was also occasionally demonstrated by the presence of a slightly increased inflammatory response seen over adjuvant treatment only. Overall, the need for toxicity testing of vaccines is in line with current regulatory guideline requirements and has proven to be a valuable part of the safety evaluation process prior to human use. Copyright © 2016 John Wiley & Sons, Ltd.
Performance evaluation of automated segmentation software on optical coherence tomography volume data
Authors: Tian Jing , Varga Boglarka , Tatrai Erika , Fanni Palya , Somfai Gabor Mark , Smiddy William E. , Debuc Delia Cabrera
Published: March 2016

Over the past two decades a significant number of OCT segmentation approaches have been proposed in the literature. Each methodology has been conceived for and/or evaluated using specific datasets that do not reflect the complexities of the majority of widely available retinal features observed in clinical settings. In addition, there does not exist an appropriate OCT dataset with ground truth that reflects the realities of everyday retinal features observed in clinical settings. While the need for unbiased performance evaluation of automated segmentation algorithms is obvious, the validation process of segmentation algorithms have been usually performed by comparing with manual labelings from each study and there has been a lack of common ground truth. Therefore, a performance comparison of different algorithms using the same ground truth has never been performed. This paper reviews research‐oriented tools for automated segmentation of the retinal tissue on OCT images. It also evaluates and compares the performance of these software tools with a common ground truth.

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Assessing the efficacy of coherent anti‐Stokes Raman scattering microscopy for the detection of infiltrating glioblastoma in fresh brain samples
Authors: Galli Roberta , Uckermann Ortrud , Temme Achim , Leipnitz Elke , Meinhardt Matthias , Koch Edmund , Schackert Gabriele , Steiner Gerald , Kirsch Matthias
Published: March 2016

Coherent anti‐Stokes Raman scattering (CARS) microscopy is an emerging technique for identification of brain tumors. However, tumor identification by CARS microscopy on bulk samples and in vivo has been so far verified retrospectively on histological sections, which only provide a gross reference for the interpretation of CARS images without matching at cellular level. Therefore, fluorescent labels were exploited for direct assessment of the interpretation of CARS images of solid and infiltrative tumors. Glioblastoma cells expressing green fluorescent protein (GFP) were used for induction of tumors in mice (n = 7). The neoplastic nature of cells imaged by CARS microscopy was unequivocally verified by addressing two‐photon fluorescence of GFP on fresh brain slices and in vivo. In fresh unfixed biopsies of human glioblastoma (n = 10), the fluorescence of 5‐aminolevulinic acid‐induced protoporphyrin IX was used for identification of tumorous tissue. Distinctive morphological features of glioblastoma cells, i.e. larger nuclei, evident nuclear membrane and nucleolus, were identified in the CARS images of both mouse and human brain tumors. This approach demonstrates that the chemical contrast provided by CARS allows the localization of infiltrating tumor cells in fresh tissue and that the cell morphology in CARS images is useful for tumor recognition.

Experimental glioblastoma expressing green fluorescent protein.

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Experimental glioblastoma expressing green fluorescent protein.
easySTORM: a robust, lower‐cost approach to localisation and TIRF microscopy
Authors: Kwakwa Kwasi , Savell Alexander , Davies Timothy , Munro Ian , Parrinello Simona , Purbhoo Marco A. , Dunsby Chris , Neil Mark A.A. , French Paul M.W.
Published: March 2016

TIRF and STORM microscopy are super‐resolving fluorescence imaging modalities for which current implementations on standard microscopes can present significant complexity and cost. We present a straightforward and low‐cost approach to implement STORM and TIRF taking advantage of multimode optical fibres and multimode diode lasers to provide the required excitation light. Combined with open source software and relatively simple protocols to prepare samples for STORM, including the use of Vectashield for non‐TIRF imaging, this approach enables TIRF and STORM imaging of cells labelled with appropriate dyes or expressing suitable fluorescent proteins to become widely accessible at low cost.

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What Proportion of Incident Radiographic Vertebral Fractures in Older Men Is Clinically Diagnosed and Vice Versa: A Prospective Study
Authors: Ensrud Kristine E , Blackwell Terri L , Fink Howard A , Zhang Jie , Cauley Jane A , Cawthon Peggy M , Black Dennis M , Bauer Douglas C , Curtis Jeffrey R , Orwoll Eric S , Barrett-Connor Elizabeth , Kado Deborah M , Marshall Lynn M , Shikany James M , Schousboe John T ,   for the Osteoporotic Fractures in Men (MrOS) Research Group
Published: March 2016

To determine the proportion of incident radiographic vertebral fractures (vfx) also diagnosed as incident clinical vfx in older men and vice-versa, we used data from 4398 community-dwelling men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study. Incident radiographic vfx were identified by comparing baseline and follow-up lateral thoracic and lumbar spine study films (average 4.6 years between films) using a semiquantitative (SQ) method and defined as a change in SQ reading of ≥1 at a given vertebral level from baseline to follow-up study radiograph. Participants were contacted triannually to ascertain incident clinical vfx; community spinal imaging studies were obtained and clinical vfx were confirmed when the study radiologist determined that the community imaging study showed a new deformity of higher grade than was present in the same vertebra on the baseline study radiograph. A total of 237 incident radiographic vfx were identified in 197 men, whereas 31 men experienced 37 confirmed incident clinical vfx. Of incident radiographic vfx, 13.5% were also clinically diagnosed as incident fractures, with clinical diagnoses made for 16.3% of the radiographic vfx with SQ grade change ≥2. Of incident clinical vfx, 86.5% were identified as incident radiographic vfx, most of them with SQ grade change ≥2. In summary, less than 15% of incident radiographic vfx were also clinically diagnosed, whereas the majority of incident clinical vfx were identified as severe radiographic vfx. These results in men supplement those previously published for women and suggest a complex relationship between clinical and radiographic vfx in older adults. Published 2016.† American Society for Bone and Mineral Research.
Impact of the U.S. Food and Drug Administration's Safety-Related Announcements on the Use of Bisphosphonates After Hip Fracture
Authors: Kim Seoyoung C , Kim Dae Hyun , Mogun Helen , Eddings Wesley , Polinski Jennifer M , Franklin Jessica M , Solomon Daniel H
Published: March 2016

The U.S. Food and Drug Administration (FDA) issued several announcements related to potential risk of bisphosphonates including osteonecrosis of the jaw (2005), atrial fibrillation (2007), and atypical femur fracture (2010). We aimed to evaluate the impact of three FDA drug safety announcements on the use of bisphosphonates in patients with hip fracture using claims data from a U.S. commercial health plan (2004-2013). We calculated the proportion of patients in each quarter who received a bisphosphonate or other osteoporosis medication in the 6 months following hospitalization for hip fracture. Segmented logistic regression models examined the time trends. Among 22,598 patients with hip fracture, use of bisphosphonate decreased from 15% in 2004 to 3% in the last quarter of 2013. Prior to the 2007 announcement, there was a 4% increase in the odds of bisphosphonate use every quarter (OR 1.04; 95% CI, 1.02 to 1.07). After the 2007 announcement, there was a 4% decrease in the odds of bisphosphonate use (OR 0.96; 95% CI, 0.93 to 0.99) every quarter. The announcement in 2007 was associated with a significant decline in the rate of change of bisphosphonate uses over time (p < 0.001), but no impact on other osteoporosis medication use (p = 0.2). After the 2010 announcement, the odds of bisphosphonate use continued to decrease by 4% (OR 0.96; 95% CI, 0.94 to 0.98) each quarter and the odds of other osteoporosis medication use remained stable over time (OR 0.99; 95% CI, 0.96 to 1.02). The FDA safety announcement related to atrial fibrillation in 2007 was significantly associated with a decrease in bisphosphonate use among patients with hip fracture. © 2016 American Society for Bone and Mineral Research.
Rare EN1 Variants and Pediatric Bone Mass
Authors: Mitchell Jonathan A , Chesi Alessandra , McCormack Shana E , Roy Sani M , Cousminer Diana L , Kalkwarf Heidi J , Lappe Joan M , Gilsanz Vicente , Oberfield Sharon E , Shepherd John A , Kelly Andrea , Zemel Babette S , Grant Struan FA
Published: March 2016

A recent whole-genome sequencing study in search of variation associated with adult areal bone mineral density (aBMD) identified rare variants near EN1, with markedly large effect sizes, and a common variant near SOX6. To understand the developmental effects of these loci, we sought to determine if they were associated with pediatric dual-energy X-ray absorptiometry–derived aBMD and bone mineral content (BMC) and if the associations were modified by sex. Our sample comprised 733 females and 685 males of European ancestry enrolled in the longitudinal Bone Mineral Density in Childhood Study (up to 7 annual study visits). Sex- and age-specific Z-scores, adjusted for height, were calculated for the total hip, femoral neck, spine, and distal radius. Total body less head (TBLH) BMC Z-scores were also calculated. The previously reported single nucleotide polymorphisms (SNPs) near EN1 and SOX6 were derived from our imputed data set. Linear mixed-effects models were used to test associations between each SNP and bone Z-scores, plus interactions with sex were explored. The rare T allele of lead EN1 SNP rs11692564 was associated with higher aBMD Z-score for total hip (beta = 0.62, p = 9.0 × 10−4) and femoral neck (beta = 0.53, p = 0.010). In sex-stratified analyses, this variant was associated with higher bone Z-scores in females only, with the associations being strongest for total hip (sex interaction p = 1.9 × 10−4; beta females = 0.86, p = 6.6 × 10−6) and femoral neck (sex interaction p = 0.016; beta females = 0.73, p = 0.001). The common G allele of SOX6 SNP rs11024028 was associated with higher aBMD Z-score for total hip (beta = 0.12, p = 0.009), femoral neck (beta = 0.13, p = 0.003), and TBLH-BMC (beta = 0.09, p = 0.007); furthermore, this association strengthened in males in the sex-stratified analyses. Our findings reveal that rare genetic variation near EN1 and common variation near SOX6 operates in childhood and has implications for the lifelong risk of osteoporosis and fracture. The sex differences observed need to be independently replicated. © 2016 American Society for Bone and Mineral Research.
Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation
Authors: Álvarez‐Santos Mayra , Carbajal Verónica , Tellez‐Jiménez Olivia , Martínez‐Cordero Erasmo , Ruiz Victor , Hernández‐Pando Rogelio , Lascurain Ricardo , Santibañez‐Salgado Alfredo , Bazan‐Perkins Blanca
Published: March 2016

The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE‐PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin‐linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr696 increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385–2396, 2016. © 2016 Wiley Periodicals, Inc.
Apigenin Reduces Survival of Choriocarcinoma Cells by Inducing Apoptosis via the PI3K/AKT and ERK1/2 MAPK Pathways
Authors: Lim Whasun , Park Sunwoo , Bazer Fuller W. , Song Gwonhwa
Published: March 2016

Apigenin is a flavonoid found in parsley, onions, oranges, tea, chamomile, wheat, and sprouts. It has a variety of biological properties including anti‐oxidant, anti‐mutagenic, anti‐carcinogenic, anti‐inflammatory, anti‐proliferative, and anti‐spasmodic effects. Based on epidemiological and case‐control studies, apigenin is regarded as a novel chemotherapeutic agent against various cancer types. However, little is known about the effects of apigenin on choriocarcinoma cells. Therefore, we investigated the anti‐cancer effects of apigenin on choriocarcinoma cells (JAR and JEG3) in the present study. Apigenin reduced viability and migratory properties, increased apoptosis, and suppressed mitochondrial membrane potential in both the JAR and JEG3 cells. In addition, apigenin predominantly decreased phosphorylation of AKT, P70RSK, and S6 whereas the phosphorylation of ERK1/2 and P90RSK was increased by apigenin treatment of JAR and JEG3 cells in a dose‐dependent manner. Moreover, treatment of JAR and JEG3 cells with both apigenin and pharmacological inhibitors of PI3K/AKT (LY294002) and ERK1/2 (U0126) revealed synergistic anti‐proliferative effects. Collectively, these results indicated that the apigenin is an invaluable chemopreventive agent that inhibits progression and metastasis of choriocarcinoma cells through regulation of PI3K/AKT and ERK1/2 MAPK signal transduction mechanism. J. Cell. Physiol. 231: 2690–2699, 2016. © 2016 Wiley Periodicals, Inc.
Extended‐Release Once‐Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate‐Release Tofacitinib and Impact of Food
Authors: Lamba Manisha , Wang Rong , Fletcher Tracey , Alvey Christine , Kushner Joseph , Stock Thomas C.
Published: March 2016

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended‐release (XR) formulation has been designed to provide a once‐daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice‐daily immediate‐release (IR) formulation. We conducted 2 randomized, open‐label, phase 1 studies in healthy volunteers. Study A characterized single‐dose and steady‐state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single‐dose and steady‐state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high‐fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half‐life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax) after single‐ and multiple‐dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. Cmax increased by 27% under the fed state. On repeat administration, negligible accumulation (<20%) of systemic exposures was observed for both formulations. Steady state was achieved within 48 hours of dosing with the XR formulation. Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies.
Anaerobic digestion of wastewater from the production of bleached chemical thermo‐mechanical pulp – higher methane production for hardwood than softwood
Authors: Larsson Madeleine , Truong Xu‐Bin , Björn Annika , Ejlertsson Jörgen , Svensson Bo H , Bastviken David , Karlsson Anna
Published: March 2016

BACKGROUND

Chemical thermo‐mechanical pulp (CTMP) mills holds a large biomethane potential in their wastewater. Their broadened market has involved increased bleaching and utilization of different raw materials. Therefore, the main aim of this study was to obtain and maintain a well‐functioning anaerobic digestion (AD) process, with a high methane yield and total organic carbon (TOC) reduction, when digesting CTMP wastewater, from different production protocols including shifts in raw material and bleaching. A lab‐scale upflow anaerobic sludge bed (UASB) reactor was used for the tests.

RESULTS

The variations in raw material (spruce, birch and aspen) and consequently in TOC‐loading (3.6–6.6 kg TOC m−3 and day−1) did not affect the UASB process negatively. Methane production values from 360 to 500 NmL g−1 TOC were obtained, with the highest yield for wastewater from the production of birch‐ followed by aspen‐ and spruce pulp. The acetic acid and filtered‐TOC (fTOC) reduction ranged from 90 to 95% and 61 to 73%, respectively.

CONCLUSIONS

A well‐functioning process maintained during shifts in raw material for pulp production which shows that AD is feasible for CTMP mills with a diversified product portfolio. Furthermore, the increased use of hardwood and bleaching will most likely increase their potential as a biomethane producer. © 2016 Society of Chemical Industry
(1, k)‐Coloring of Graphs with Girth at Least Five on a Surface
Authors: Choi Hojin , Choi Ilkyoo , Jeong Jisu , Suh Geewon
Published: March 2016

A graph is ‐colorable if its vertex set can be partitioned into r sets so that the maximum degree of the graph induced by is at most for each . For a given pair , the question of determining the minimum such that planar graphs with girth at least g are ‐colorable has attracted much interest. The finiteness of was known for all cases except when . Montassier and Ochem explicitly asked if d2(5, 1) is finite. We answer this question in the affirmative with ; namely, we prove that all planar graphs with girth at least five are (1, 10)‐colorable. Moreover, our proof extends to the statement that for any surface S of Euler genus γ, there exists a where graphs with girth at least five that are embeddable on S are (1, K)‐colorable. On the other hand, there is no finite k where planar graphs (and thus embeddable on any surface) with girth at least five are (0, k)‐colorable.
Equistarable Graphs and Counterexamples to Three Conjectures on Equistable Graphs
Authors: Milanič Martin , Trotignon Nicolas
Published: March 2016

Equistable graphs are graphs admitting positive weights on vertices such that a subset of vertices is a maximal stable set if and only if it is of total weight 1. Strongly equistable graphs are graphs such that for every and every nonempty subset T of vertices that is not a maximal stable set, there exist positive vertex weights assigning weight 1 to every maximal stable set such that the total weight of T does not equal c. General partition graphs are the intersection graphs of set systems over a finite ground set U such that every maximal stable set of the graph corresponds to a partition of U. General partition graphs are exactly the graphs every edge of which is contained in a strong clique. In 1994, Mahadev, Peled, and Sun proved that every strongly equistable graph is equistable, and conjectured that the converse holds as well. In 2009, Orlin proved that every general partition graph is equistable, and conjectured that the converse holds as well. Orlin's conjecture, if true, would imply the conjecture due to Mahadev, Peled, and Sun. An “intermediate” conjecture, posed by Miklavič and Milanič in 2011, states that every equistable graph has a strong clique. The above conjectures have been verified for several graph classes. We introduce the notion of equistarable graphs and based on it construct counterexamples to all three conjectures within the class of complements of line graphs of triangle‐free graphs. We also show that not all strongly equistable graphs are general partition.
Introducing the Hospitalist Morale Index: A new tool that may be relevant for improving provider retention
Authors: Chandra Shalini , Wright Scott M. , Ghazarian Sharon , Kargul George M. , Howell Eric E.
Published: March 2016

OBJECTIVE

To develop a valid instrument to assess morale and explore the relationship between morale and intent to leave employment due to unhappiness.

PATIENTS AND METHODS

An expert panel identified 46 drivers of hospitalist morale. In May 2009, responders of our single‐site pilot survey rated each driver in terms of current contentment and importance to their morale. With exploratory factor analysis, a 28‐item/7‐factor instrument emerged. In May 2011, the refined scale was distributed to 108 hospitalists from 2 academic and 3 community hospitals. Confirmatory factor analysis (CFA) was used for internal validation and refinement of the Hospitalist Morale Index. Importance ratings and contentment assessments were used to generate item scores, which were then combined to generate factor scores and personal morale scores. Results were used to validate the instrument and evaluate the relationship between hospitalist morale and intent to leave due to unhappiness.

RESULTS

The 2011 response rate was 86%. The final CFA resulted in a 5‐factor and 5–stand‐alone‐item model. Personal morale scores were normally distributed (mean = 2.79, standard deviation = 0.58). For every categorical increase on a global question that assessed overall morale, personal morale scores rose 0.23 points (P < 0.001). Each 1‐point increase in personal morale score was associated with an 85% decrease (odds ratio: 0.15, 95% confidence interval: 0.05‐0.41, P < 0.001) in the odds of intending to leave because of unhappiness.

CONCLUSION

The Hospitalist Morale Index is a validated instrument that evaluates hospitalist morale across multiple dimensions of morale. The Hospitalist Morale Index may help program leaders monitor morale and develop customized and effective retention strategies. Journal of Hospital Medicine 2016;11:425–431. © 2016 Society of Hospital Medicine
Predictors of patient satisfaction with inpatient hospital pain management across the United States: A national study
Authors: McFarland Daniel C. , Shen Megan Johnson , Holcombe Randall F.
Published: March 2016

Satisfactory pain management of hospitalized patients remains a national unmet need for the United States. Although prior research indicates that inpatient pain management may be improving nationally, not all populations of patients rate pain management as equally satisfactory. County‐level predictors, such as demographics and population density, and hospital‐level predictors (eg, hospital‐bed number), are understudied determinants of pain management patient satisfaction. We created a multivariate regression model of pain management patient satisfaction scores as indicated by Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey results based on county and hospital level predictors. Number of hospital beds (β = −0.16), percent foreign‐born (β = −0.16), and population density (β = −0.08) most strongly predicted unfavorable ratings, whereas African American (β = 0.23), white (β= 0.23), and younger population (β = 0.08) most strongly predicted favorable ratings. Greater attention should be placed on pain management in larger hospitals that serve foreign‐born patients in population‐dense areas. Journal of Hospital Medicine 2016;11:498–501. © 2016 Society of Hospital Medicine
Pilot study aiming to support sleep quality and duration during hospitalizations
Authors: Gathecha Evelyn , Rios Rebeca , Buenaver Luis F. , Landis Regina , Howell Eric , Wright Scott
Published: March 2016

BACKGROUND

Sleep is a vital part to healing and recovery, hence poor sleep during hospitalizations is highly undesirable. Few studies have assessed interventions to optimize sleep among hospitalized patients.

OBJECTIVE

To assess the effect of sleep‐promoting interventions on sleep quality and duration among hospitalized patients.

DESIGN

Quasi‐experimental prospective study.

SETTING

Academic medical center.

PARTICIPANTS

Adult patients on the general medicine ward.

INTERVENTION

Nurse‐delivered sleep‐promoting interventions augmented by sleep hygiene education and environmental control to minimize sleep disruption.

MEASUREMENTS

Objective and subjective measurement of sleep parameters using validated sleep questionnaires, daily sleep diary, and actigraphy monitor.

RESULTS

Of the 112 patients studied, the mean age was 58 years, 55% were female, the mean body mass index was 32, and 43% were in the intervention group. Linear mixed models tested mean differences in 7 sleep measures and group differences in slopes representing nightly changes in sleep outcomes over the course of hospitalization between intervention and control groups. Only total sleep time, computed from sleep diaries, demonstrated significant overall mean difference of 49.6 minutes (standard error [SE] = 21.1, P < 0.05). However, significant differences in average slopes of subjective ratings of sleep quality (0.46, SE = 0.18, P < 0.05), refreshing sleep (0.54, SE = 0.19, P < 0.05), and sleep interruptions (−1.6, SE = 0.6, P < 0.05) indicated improvements during hospitalization within intervention patients compared to controls.

CONCLUSION

This study demonstrated that there is an opportunity to identify patients not sleeping well in the hospital. Sleep‐promoting initiatives, both at the unit level as well as individualized offerings, may improve sleep during hospitalizations, particularly over the course of the hospitalization. Journal of Hospital Medicine 2016;11:467–472. © 2016 Society of Hospital Medicine
Comparative data on the differentiation and growth of bone ornamentation in gnathostomes (Chordata: Vertebrata)
Authors: de Buffrénil Vivian , Clarac François , Canoville Aurore , Laurin Michel
Published: March 2016

Bone ornamentation, in the form of rounded pits framed by a network of ridges, is a frequent feature among a great diversity of gnathostome taxa. However, the basic osteogenic processes controlling the differentiation and development of these reliefs remain controversial. The present study is a broad comparative survey of this question with the classical methods used in hard tissue histology and paleohistology. Distinct processes, unevenly distributed among taxa, are involved in the creation and growth of pits and ridges. The simplest one is mere differential growth between pit bottom (slow growth) and ridge top (faster growth). The involvement of several complex remodeling processes, with the local succession of resorption and reconstruction cycles, is frequent and occurs in all major gnathostome clades. Some broad, inclusive clades (e.g., Temnospondyli) display consistency in the mechanisms controlling ornamentation, whereas other clades (e.g., Actinopterygii) are characterized by the diversity of the mechanisms involved. If osteogenic mechanisms are taken into account, bone ornamentation should be considered as a character extremely prone to homoplasy. Maximum likelihood (ML) optimizations reveal that the plesiomorphic mechanism creating ornamentation is differential apposition rate over pits (slow growth) and ridges (faster growth). In some taxas e.g., temnospondyls vs lissamphibians or pseudosuchians, bone ornamentation is likely to be a homoplastic feature due to a convergence process driven by similar selective pressures. ML models of character evolution suggest that the presence of resorption in the development of ornamentation may be selectively advantageous, although support for this conclusion is only moderate. J. Morphol. 277:634–670, 2016. © 2016 Wiley Periodicals, Inc.
Reproductive system of females of the Magdalena river endemic stingray Potamotrygon magdalenae: Anatomical and functional aspects
Authors: del Mar Pedreros‐Sierra Tania , Arrieta‐Prieto Dagoberto M. , Mejía‐Falla Paola A.
Published: March 2016

We studied anatomical and functional aspects of the reproductive system of females of the Magdalena river stingray Potamotrygon magdalenae using microscopic and macroscopic analysis of each organ. Although the reproductive tract was fully functional on both side, the left organs possibly have a greater contribution to reproductive success, because left ovary and uterus were more developed and had higher number of oocytes and embryos, respectively, than the right ones. This species has histotrophic viviparity given by the presence of uterine trophonemata and by glandular character in pregnant and postpartum females. We suggest that the epigonal organ is involved in the degradation of components of atretic follicles and the embryos begin to develop surrounded by a gelatinous tertiary envelope produced by the oviducal gland. This latter organ is composed by three zones in mature females, club, papillary, and baffle zone, as described for other elasmobranchs. From the anatomical observations, a maturity scale comprising six sexual maturity stages (Immature I, Immature II, early mature, pregnant, post‐partum, and regenerating) was established for female P. magdalenae, and it can be useful as basis for reproductive studies of other potamotrygonid species. Finally, we propose a continuous reproductive cycle for P. magdalenae. J. Morphol. 277:680–697, 2016. © 2016 Wiley Periodicals, Inc.
Realistic aortic phantom to study hemodynamics using MRI and cardiac catheterization in normal and aortic coarctation conditions
Authors: Urbina Jesús , Sotelo Julio A. , Springmüller Daniel , Montalba Cristian , Letelier Karis , Tejos Cristián , Irarrázaval Pablo , Andia Marcelo E. , Razavi Reza , Valverde Israel , Uribe Sergio A.
Published: March 2016

Purpose

To design and characterize a magnetic resonance imaging (MRI)‐compatible aortic phantom simulating normal and aortic coarctation (AoCo) conditions and to compare its hemodynamics with healthy volunteers and AoCo patients.

Materials and Methods

The phantom is composed of an MRI‐compatible pump, control unit, aortic model, compliance chamber, nonreturn, and shutoff valves. The phantom without and with AoCo (13, 11, and 9 mm) was studied using 2D and 3D phase‐contrast data and with a catheterization unit to measure pressures. The phantom data were compared with the mean values of 10 healthy volunteers and two AoCo patients.

Results

Hemodynamic parameters in the normal phantom and healthy volunteers were: heart rate: 68/61 bpm, cardiac output: 3.5/4.5 L/min, peak flow and peak velocity (Vpeak) in the ascending aorta (AAo): 270/357 mL/s (significantly, P < 0.05) and 97/107 cm/s (not significantly, P = 0.16), and pressure in the AAo of the normal phantom of 131/58 mmHg. Hemodynamic parameters in the 13, 11, and 9 mm coarctation phantoms and Patients 1 and 2 were: heart rate: 75/75/75/97/78 bpm, cardiac output: 3.3/3.0/2.9/4.0/5.8 L/min, peak flow in the AAo: 245/265/215/244/376 mL/s, Vpeak in the AAo: 96/95/81/196/187 cm/s, Vpeak after the AoCo: 123/187/282/247/165 cm/s, pressure in the AAo: 124/56, 127/51, 133/50, 120/51 and 87/39 mmHg, and a trans‐coarctation systolic pressure gradient: 7, 10, 30, 20, and 11 mmHg.

Conclusion

We propose and characterize a normal and an AoCo phantom, whose hemodynamics, including velocity, flow, and pressure data are within the range of healthy volunteers and patients with AoCo. J. Magn. Reson. Imaging 2016;44:683–697.
In vivo detection of hyperacute neuronal compaction and recovery by MRI following electric trauma in rats
Authors: Tóth Arnold , Kátai Emese , Kálmán Endre , Bogner Péter , Schwarcz Attila , Dóczi Tamás , Sík Attila , Pál József
Published: March 2016

Purpose

To verify the following phenomenon in vivo using quantitative magnetic resonance imaging (MRI). Neuronal compression may occur following brain injuries in the cortex and hippocampus. As well being characterized by previous histological studies in rats, the majority of these neurons undergo hyperacute recovery rather than apoptotic death.

Materials and Methods

Twenty male Wistar rats were assigned into injured or sham‐injured groups (n = 10). The injured group underwent an electric trauma model to provoke compacted neuron formation. A T1 map was acquired prior to the injury and 10 T1 maps were acquired consecutively over a period of 2.5 hours after the injury, using a 3.0T scanner. Voxelwise statistical analyses were performed between timepoints. To enable comparison with the histological appearance of the compacted neurons, silver staining was performed on a sham‐injured rat and five injured rats, 10, 40, 90, 150, and 300 minutes after the injury.

Results

A significant (corrected P < 0.05) increase in average T1 from the preinjury (895.24 msec) to the first postinjury timepoint (T1 = 951.37 msec) was followed by a significant (corrected P < 0.05) decrease (return) up to the last postinjury timepoint (T1 = 913.16 msec) in the voxels of the cortex and hippocampus. No significant (corrected P < 0.05) change in T1 was found in the sham‐injured group.

Conclusion

The spatial and temporal linkages between the MRI T1 changes and the histological findings suggest that neuronal compaction and recovery is associated with T1 alterations. MRI therefore offers the possibility of in vivo investigations of neuronal compaction and recovery. J. MAGN. RESON. IMAGING 2016;44:814–822.
Oximetric angiosome imaging in diabetic feet
Authors: Zheng Jie , Muccigrosso David , Zhang Xiaodong , An Hongyu , Coggan Andrew R. , Adil Bashir , Hildebolt Charles F. , Vemuri Chandu , Geraghty Patrick , Hastings Mary K. , Mueller Michael J.
Published: March 2016

Purpose

To develop a noncontrast oximetric angiosome imaging approach to assess skeletal muscle oxygenation in diabetic feet.

Materials and Methods

In four healthy and five subjects with diabetes, the feasibility of foot oximetry was examined using a 3T clinical magnetic resonance imaging (MRI) scanner. The subjects' feet were scanned at rest and during a toe‐flexion isometric exercise. The oxygen extraction fraction of skeletal muscle was measured using a susceptibility‐based MRI method. Our newly developed MR foot oximetric angiosome model was compared with the traditional angiosome model in the assessment of the distribution of oxygen extraction fraction.

Results

Using the traditional angiosome during the toe‐flexion exercise, the oxygen extraction fraction in the medial foot of healthy subjects increased (4.9 ± 3%) and decreased (–2.7 ± 4.4%) in subjects with diabetes (difference = 7.6%; 95% confidence interval = –13.7 ± 1.4; P = 0.02). Using the oximetric angiosome, the percent difference in the areas of oxygen extraction fraction within the 0.7–1.0 range (expected oxygen extraction fraction during exercise) between rest and exercise was higher in healthy subjects (8 ± 4%) than in subjects with diabetes (4 ± 4%; P = 0.02).

Conclusion

This study demonstrates the feasibility of measuring skeletal muscle oxygen extraction fraction in the foot muscle during a toe‐flexion isometric exercise. Instead of assessing oxygen extraction fraction in a foot muscle region linked to a supplying artery (traditional angiosome), the foot oximetric angiosome model assesses oxygen extraction fraction by its different levels in all foot muscle regions and thus may be more appropriate for assessing local ischemia in ulcerated diabetic feet. J. Magn. Reson. Imaging 2016. J. MAGN. RESON. IMAGING 2016;44:940–946.
MR spectroscopy for in vivo assessment of the oncometabolite 2‐hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T
Authors: Bisdas Sotirios , Chadzynski Grzegorz L. , Braun Christian , Schittenhelm Jens , Skardelly Marco , Hagberg Gisela E. , Ethofer Thomas , Pohmann Rolf , Shajan G. , Engelmann Jörn , Tabatabai Ghazaleh , Ziemann Ulf , Ernemann Ulrike , Scheffler Klaus
Published: March 2016

Purpose

To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T.

Materials and Methods

Spectra were acquired with a 9.4T whole‐body scanner with the use of a custom‐built head coil (16 channel transmit and 31 channel receive). A modified stimulated echo acquisition mode (STEAM) sequence was used for localization. Eighteen patients with brain tumors of probable glial origin participated in this study. The study was performed in accordance with the guidelines of the local Ethics Committee.

Results

The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2‐hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish α‐ketoglutarate lost by conversion to 2HG. We also observed significantly reduced glutathione (GSH) levels (39%, P = 0.019), which could be similarly caused by depletion of dihydronicotinamide‐adenine dinucleotide phosphate (NADPH) during this conversion in IDH mutant gliomas.

Conclusion

We demonstrate that MRS at 9.4T provides a noninvasive measure of 2HG in vivo, which may be used for therapy planning and prognostication, and may provide insights into related pathophysiologic metabolic alterations associated with IDH mutations. J. MAGN. RESON. IMAGING 2016;44:823–833.
Utility of noncontrast‐enhanced time‐resolved four‐dimensional MR angiography with a vessel‐selective technique for intracranial arteriovenous malformations
Authors: Fujima Noriyuki , Osanai Toshiya , Shimizu Yukie , Yoshida Atsushi , Harada Taisuke , Nakayama Naoki , Kudo Kohsuke , Houkin Kiyohiro , Shirato Hiroki
Published: March 2016

Purpose

To evaluate the utility of a vessel‐selective four‐dimensional (4D) magnetic resonance angiography (MRA) technique for the evaluation of intracranial arteriovenous malformations (AVMs).

Materials and Methods

Twelve AVM patients were evaluated retrospectively. Time‐of‐flight (TOF) MRA, nonvessel‐selective 4D‐MRA (NS‐4D‐MRA), and vessel‐selective 4D‐MRA (VS‐4D‐MRA) were performed using a 3T MR unit in all patients, and used to identify feeding arteries and draining veins and measure nidus size. The diagnostic accuracy of the three techniques was compared using digital subtraction angiography (DSA). If a multifeeder was observed, the percentage of blood flow of each feeding artery to the entire nidus was evaluated and compared to the DSA findings using the “error value,” defined as the degree of overestimation of the blood flow. All imaging findings were assessed by two neuroradiologists.

Results

In both raters, the detectability of feeding arteries by VS‐4D‐MRA (12 and 11 patients) was significantly higher than those of TOF‐MRA (7 and 6 patients) and NS‐4D‐MRA (8 and 7 patients) (P < 0.016). The detectability of drainer veins by TOF‐MRA (10 and 10 patients) was significantly higher than that of VS‐4D‐MRA (7 and 6 patients). In the percentage of the blood flow of each feed artery to the entire nidus, the DSA findings (error value; 27.1 ± 5.7) indicated overestimations of the blood flow compared to the VS‐4D‐MRA (error value; 7.1 ± 3.9) (P < 0.001).

Conclusion

VS‐4D‐MRA was shown to be a useful technique for the evaluation of intracranial AVMs, especially for detecting feed arteries and estimating details of the nidus structure. J. MAGN. RESON. IMAGING 2016;44:834–845.
Contribution of each masticatory muscle to the bite force determined by MRI using a novel metal‐free bite force gauge and an index of total muscle activity
Authors: Takahashi Minoru , Yamaguchi Satoshi , Fujii Tsuyoshi , Watanabe Makoto , Hattori Yoshinori
Published: March 2016

Purpose

To develop a metal‐free bite force gauge that can monitor the bite force in a strong magnetic field and to analyze the correlations between bite‐force and total T2 shift of the mastication muscles.

Materials and Methods

The gauge used a micro‐pressure sensor made of optical fiber. Ten subjects performed a 60‐s isometric bite task at 40% of maximum clenching in various occlusal support conditions (intact dentition, right molar loss, or left molar loss). Spin‐echo images were taken with a 1.5 Tesla scanner before and immediately after the task to correlate the bite force with the mean voxel count, mean shift in transverse relaxation time (ΔT2), and total T2 shift of each masticatory muscle.

Results

Measurements of total T2 shift identified significant correlations between the bite force and activities of the superficial layer of the bilateral masseter muscle, regardless of the occlusion condition (intact dentition: left, P = 0.007 and right, P < 0.001; right molar loss: left, P = 0.02 and right, P = 0.021; and left molar loss: left, P = 0.022 and right, P = 0.049). In contrast, significant correlations were not detected between the bite force and mean ΔT2 (intact dentition: left, P = 0.102 and right, P = 0.053; right molar loss: left, P = 0.393 and right, P = 0.868; and left molar loss: left, P = 0.531 and right, P = 0.92).

Conclusion

Measurement of total T2 shift using a metal‐free bite force gauge is a more sensitive index of individual muscle activity than mean ΔT2 during a bite task. J. MAGN. RESON. IMAGING 2016;44:804–813.
Quiet diffusion‐weighted head scanning: Initial clinical evaluation in ischemic stroke patients at 1.5T
Authors: Rösch Julie , Ott Martin , Heismann Bjoern , Doerfler Arnd , Engelhorn Tobias , Sembritzki Klaus , Grodzki David M.
Published: March 2016

Purpose

To compare the quality and diagnostic value of routine single‐shot, echo‐planar imaging, diffusion‐weighted imaging (ss‐EPI‐DWI) to those of quiet readout segmented EPI‐DWI (q‐DWI) in magnetic resonance imaging (MRI) of acute stroke.

Materials and Methods

Twenty‐six patients with acute stroke underwent a 1.5T MRI including diffusion‐weighted ss‐EPI and q‐DWI. The two sequences were protocolled to have identical spatial resolution and spatial coverage. q‐DWI was tested with (regular q‐DWI) and without (fast q‐DWI) averaging in 13 patients each. The acoustic noise generated by each sequence was measured. Quantitative and qualitative assessments regarding signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR), lesion conspicuity, level of artifacts, overall image quality as well as diagnostic content were performed.

Results

SNR and CNR values of the q‐DWI scans were considerably higher than those of ss‐EPI DWI (P ≤ 0.0078). No statistical difference was found for lesion conspicuity (P ≥ 0.125). Statistical differences were found for level of artifacts (P ≥ 0.0078) and overall image quality (P ≥ 0.002). Both were evaluated better in the ss‐EPI DWI than in the regular and fast q‐DWI. Apart from one fast q‐DWI patient, radiologists voted the images to have the same diagnostic content, with upper 90% confidence limits of 0.238 for regular q‐DWI and 0.429 for fast q‐DWI.

Conclusion

If the acoustic burden is critical to the patient, q‐DWI is an equivalent quiet alternative to ss‐EPI DWI for use in stroke patients. J. Magn. Reson. Imaging 2016;44:1238–1243.
Soft computing‐based approach for optimal design of on‐chip comparator and folded‐cascode op‐amp using colliding bodies optimization
Authors: De Bishnu Prasad , Kar R. , Mandal D. , Ghoshal S. P.
Published: March 2016

This paper presents an efficient approach for the optimal designs of two analog circuits, namely complementary metal oxide semiconductor) two‐stage comparator with p‐channel metal oxide semiconductor input driver and n‐channel input and folded‐cascode operational amplifier using a recently proposed meta‐heuristic‐based optimization algorithm named as colliding bodies optimization (CBO). It is a multi‐agent algorithm that does not depend upon any internal control parameter, making the algorithm extremely simple. The main objective of this paper is to optimize the metal oxide semiconductor (MOS) transistors' sizes using CBO in order to reduce the areas occupied by the circuits and to get better performance parameters of the circuits. Simulation Program with Integrated Circuit Emphasis simulation has been carried out by using the optimal values of MOS transistors' sizes and other design parameters to validate that CBO‐based design is satisfying the desired specifications. Simulation results demonstrate that the design specifications are closely met and the required functionalities are achieved. The simulation results also confirm that the CBO‐based approach is superior to the other algorithms in terms of MOS area and performance parameters like gain, power dissipation, etc., for the examples considered. Copyright © 2016 John Wiley & Sons, Ltd.