bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative study of presurgical skin infiltration depth measurements of melanocytic lesions with OCT and high frequency ultrasound
Authors: Varkentin Arthur , Mazurenka Mikhail , Blumenröther Elias , Meinhardt‐Wollweber Merve , Rahlves Maik , Broekaert Sigrid M. C. , Schäd‐Trcka Susanne , Emmertinst Steffen , Morgner Uwe , Roth Bernhard
Published: December 2016

A reliable, fast, and non‐invasive determination of melanoma thickness in vivo is highly desirable for clinical dermatology as it may facilitate the identification of surgical melanoma margins, determine if a sentinel node biopsy should be performed or not, and reduce the number of surgical interventions for patients. In this work, optical coherence tomography (OCT) and high frequency ultrasound (HFUS) are evaluated for quantitative in vivo preoperative assessment of the skin infiltration depth of melanocytic tissue. Both methods allow non‐invasive imaging of skin at similar axial resolution. Comparison with the Breslow lesion thickness obtained from histopathology revealed that OCT is slightly more precise in terms of thickness determination while HFUS has better contrast. The latter does not require image post‐processing, as necessary for the OCT images. The findings of our pilot study suggest that non‐invasive OCT and HFUS are able to determine the infiltration depth of lesions like melanocytic nevi or melanomas preoperatively and in vivo with a precision comparable to invasive histopathology measurements on skin biopsies. In future, to further strengthen our findings a statistically significant study comprising a larger amount of data is required which will be conducted in an extended clinical study in the next step.

Comparison of optical coherence tomography and high frequency ultrasound B‐Scans and a H&E stained histology of a melanocytic nevus.

magnified image

Comparison of optical coherence tomography and high frequency ultrasound B‐Scans and a H&E stained histology of a melanocytic nevus.
Diagnostics of femoral head status in humans using laser spectroscopy – In vitro studies
Authors: Lin Huiying , Li Wansha , Zhang Hao , Chen Peng , Chen Delong , He Wei , Svanberg Sune , Svanberg Katarina
Published: December 2016

Osteonecrosis of the femoral head (ONFH), a recalcitrant and disabling disease, is caused by inadequate or fully disrupted blood supply to the affected segment of the subchondral bone. Theoretically, there will develop gas‐filled pores during the bone decay process due to lacking blood supply. Unfortunately, the relationship between the gas‐filled pores and ONFH is still unclear. Here, we have introduced diode laser absorption spectroscopy to detect oxygen and water vapor signals in the femoral heads from hip replacement in 19 patients. Five samples are affected by osteoarthritis (OA) and the others are related to ONFH. Oxygen and water vapor signals could be obtained, demonstrating the presence of gas‐filled pores in both the OA and ONFH groups while the measurement results showed no significant difference. A study of gas exchange was also performed on one excised bone sample to study how these gas pores communicate with the ambient air. The results suggested that the obtained oxygen signals inside the bone samples originate from the invasion of ambient air, which is not expected in vivo. In conclusion, the ability to detect the gas signal of laser absorption spectroscopy shows the potential for the medical application of assessing the human femoral head in vivo.

magnified image
Effect of Teriparatide or Risedronate in Elderly Patients With a Recent Pertrochanteric Hip Fracture: Final Results of a 78-Week Randomized Clinical Trial
Authors: Malouf-Sierra Jorge , Tarantino Umberto , García-Hernández Pedro A , Corradini Costantino , Overgaard Søren , Stepan Jan J , Borris Lars , Lespessailles Eric , Frihagen Frede , Papavasiliou Kyriakos , Petto Helmut , Aspenberg Per , Caeiro José Ramón , Marin Fernando
Published: December 2016

We present final results of a study comparing teriparatide 20 μg every day (QD) with risedronate 35 mg once per week (QW) started within 2 weeks after surgery for a pertrochanteric hip fracture. Patients with BMD T-score ≤ –2.0 and 25OHD ≥9.2 ng/mL were randomized to receive 26-week double-dummy treatment plus calcium and vitamin D, followed by 52-week open-label treatment with the same assigned active drug. Primary endpoint was change from baseline in lumbar spine (LS) BMD at 78 weeks. Secondary and exploratory endpoints were change in BMD at the proximal femur, function, hip pain (Charnley score and 100 mm Visual Analog Scale [VAS]), quality of life (Short Form-36), radiology outcomes, and safety. Data were analyzed with mixed models for repeated measures (MMRM) and logistic regression. Totally, 224 patients were randomized; 171 (teriparatide: 86) contributed to the efficacy analyses (mean ± SD age: 77 ± 7.7 years, 77% females). Mean baseline LS, femoral neck (FN), and total hip (TH) T-scores were –2.16, –2.63, and –2.51, respectively. At 78 weeks, BMD increased significantly more with teriparatide compared to risedronate at the LS (+11.08% versus +6.45%; p < 0.001) and FN (+1.96% versus –1.19%; p = 0.003), with no significant between-group difference in TH BMD. Timed up-and-go (TUG) test was significantly faster with teriparatide at 6, 12, 18, and 26 weeks (differences: –3.2 to –5.9 s; p = 0.045 for overall difference). Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks (adjusted difference: –11.3 mm, p = 0.033; –10.0 and –9.3 mm at 12 and 26 weeks, respectively; p = 0.079 for overall difference). Other secondary and exploratory outcomes were not different. Teriparatide group showed two new hip fractures versus seven with risedronate (p = 0.171) and more frequent hypercalcemia and hyperuricemia. In conclusion, 78-week treatment with teriparatide showed significantly greater increases in LS and FN BMD, less pain, and a faster TUG test versus risedronate. © 2016 American Society for Bone and Mineral Research.
Assessment of Sex Differences in Fracture Risk Among Patients With Anorexia Nervosa: A Population-Based Cohort Study Using The Health Improvement Network
Authors: Nagata Jason M , Golden Neville H , Leonard Mary B , Copelovitch Lawrence , Denburg Michelle R
Published: December 2016

Though previous studies have demonstrated an increased fracture risk in females with anorexia nervosa (AN), fracture risk in males is not well characterized. The objective of this study was to examine sex differences in fracture risk and site-specific fracture incidence in AN. We performed a population-based retrospective cohort study using The Health Improvement Network (THIN; a large database of anonymized electronic medical records collected at primary care clinics throughout the United Kingdom). The median calendar year for the start of the observation period was 2004–2005. We identified 9239 females and 556 males <60 years of age with AN, and 97,889 randomly selected sex-, age-, and practice-matched participants without eating disorders (92,329 females and 5560 males). Multivariable Cox regression was used to estimate the hazard ratio (HR) for incident fracture. Median age at start of observation was 29.8 years in females and 30.2 years in males. The HR for fracture associated with AN differed by sex and age (interaction p = 0.002). Females with AN had an increased fracture risk at all ages (HR, 1.59; 95% confidence interval [CI], 1.45 to 1.75). AN was associated with a higher risk of fracture among males >40 years of age (HR, 2.54; 95% CI, 1.32 to 4.90; p = 0.005) but not among males ≤40 years. Females with AN had a higher risk of fracture at nearly all anatomic sites. The greatest excess fracture risk was noted at the hip/femur (HR, 5.59; 95% CI, 3.44 to 9.09) and pelvis (HR, 4.54; 95% CI, 2.42 to 8.50) in females and at the vertebrae (HR, 7.25; 95% CI, 1.21 to 43.45) for males with AN. AN was associated with higher incident fracture risk in females across all age groups and in males >40 years old. Sites of highest fracture risk include the hip/femur and pelvis in females and vertebrae in males with AN. © 2016 American Society for Bone and Mineral Research.
Na+/H+ exchanger NHE1 and NHE2 have opposite effects on migration velocity in rat gastric surface cells
Authors: Paehler vor der Nolte Anja , Chodisetti Giriprakash , Yuan Zhenglin , Busch Florian , Riederer Brigitte , Luo Min , Yu Yan , Menon Manoj B. , Schneider Andreas , Stripecke Renata , Nikolovska Katerina , Yeruva Sunil , Seidler Ursula
Published: December 2016

Following superficial injury, neighbouring gastric epithelial cells close the wound by rapid cell migration, a process called epithelial restitution. Na+/H+ exchange (NHE) inhibitors interfere with restitution, but the role of the different NHE isoforms expressed in gastric pit cells has remained elusive. The role of the basolaterally expressed NHE1 (Slc9a1) and the presumably apically expressed NHE2 (Slc9a2) in epithelial restitution was investigated in the nontransformed rat gastric surface cell line RGM1. Migration velocity was assessed by loading the cells with the fluorescent dye DiR and following closure of an experimental wound over time. Since RGM1 cells expressed very low NHE2 mRNA and have low transport activity, NHE2 was introduced by lentiviral gene transfer. In medium with pH 7.4, RGM1 cells displayed slow wound healing even in the absence of growth factors and independently of NHE activity. Growth factors accelerated wound healing in a partly NHE1‐dependent fashion. Preincubation with acidic pH 7.1 stimulated restitution in a NHE1‐dependent fashion. When pH 7.1 was maintained during the restitution period, migratory speed was reduced to ∼10% of the speed at pH 7,4, and the residual restitution was further inhibited by NHE1 inhibition. Lentiviral NHE2 expression increased the steady‐state pHi and reduced the restitution velocity after low pH preincubation, which was reversible by pharmacological NHE2 inhibition. The results demonstrate that in RGM1 cells, migratory velocity is increased by NHE1 activation, while NHE2 activity inhibit this process. A differential activation of NHE1 and NHE2 may therefore, play a role in the initiation and completion of the epithelial restitution process.
Evidence for the hERG Liability of Antihistamines, Antipsychotics, and Anti‐Infective Agents: A Systematic Literature Review From the ARITMO Project
Authors: Hazell Lorna , Raschi Emanuel , De Ponti Fabrizio , Thomas Simon H. L. , Salvo Francesco , Ahlberg Helgee Ernst , Boyer Scott , Sturkenboom Miriam , Shakir Saad
Published: December 2016

A systematic review was performed to categorize the hERG (human ether‐a‐go‐go–related gene) liability of antihistamines, antipsychotics, and anti‐infectives and to compare it with current clinical risk of torsade de pointes (TdP). Eligible studies were hERG assays reporting half‐minimal inhibitory concentrations (IC50). A “hERG safety margin” was calculated from the IC50 divided by the peak human plasma concentration (free Cmax). A margin below 30 defined hERG liability. Each drug was assigned an “uncertainty score” based on volume, consistency, precision, and internal and external validity of evidence. The hERG liability was compared to existing knowledge on TdP risk (www.credibledrugs.org). Of 1828 studies, 82 were eligible, allowing calculation of safety margins for 61 drugs. Thirty‐one drugs (51%) had evidence of hERG liability including 6 with no previous mention of TdP risk (eg, desloratadine, lopinavir). Conversely, 16 drugs (26%) had no evidence of hERG liability including 6 with known, or at least conditional or possible, TdP risk (eg, chlorpromazine, sulpiride). The main sources of uncertainty were the validity of the experimental conditions used (antihistamines and antipsychotics) and nonuse of reference compounds (anti‐infectives). In summary, hERG liability was categorized for 3 widely used drug classes, incorporating a qualitative assessment of the strength of available evidence. Some concordance with TdP risk was observed, although several drugs had hERG liability without evidence of clinical risk and vice versa. This may be due to gaps in clinical evidence, limitations of hERG/Cmax data, or other patient/drug‐specific factors that contribute to real‐life TdP risk.
MTEP impedes the neuronal polarization and the activity of the Akt–NF‐κB pathway in rat hippocampal neurons
Authors: Zhang Xiaohua , Hu Ming , Zhang Lin , An Jing , Yan Wenhui , Zhang Zhichao , Liu Jianxin , Lu Haixia , Chen Xinlin , Liu Yong
Published: December 2016

Metabotropic glutamate receptor 5 (mGluR5) is extensively involved in neural survival, differentiation, dendritic morphology, synaptic plasticity, and neural circuit formation. However, little is known about its role in neuronal polarization and axon outgrowth. In this study, we applied the selective agonist (RS)‐2‐chloro‐5‐hydroxyphenylglycine sodium salt and antagonist 3‐[(2‐methyl‐4‐thaizolyl) ethynyl] pyridine (MTEP) of mGluR5 to the cultured hippocampal neurons to observe the neuronal polarization and axon outgrowth, and further explored the possible intracellular signal transduction pathway. The results demonstrated that MTEP administration significantly attenuates the proportion of polarized neurons and the length of the axon, indicated by SMI312 (an axon marker) and Tuj‐1 (a marker of all the neurites) double‐labeling immunofluorescence. Western blot analysis showed that MTEP administration also inhibited the activation of AKT and nuclear translocation of nuclear factor‐κB (NF‐κB) p65, and decreased the phosphorylation of p65 as well. Furthermore, Akt inhibitor LY294002 treatment resulted in neuronal polarization delay and axon outgrowth retardation, while suppressing the phosphorylation and nuclear translocation of p65. We concluded that mGluR5 could regulate neuronal polarity and axon outgrowth during the morphological differentiation of rat developing neurons, and the intracellular signaling pathway of Akt–NF‐κB might be involved in the action of mGluR5. © 2016 Wiley Periodicals, Inc.
Antibiotic prescribing practices in aged care facilities in regional NSW and the ACT
Authors: Pringle Samantha , Simpson Maree , Nielsen Sharon , Cooper Carl , Vanniasinkam Thiru
Published: December 2016

Background

Antibiotic resistance is a major global threat to mankind. Inappropriate antibiotic use has been identified as one of the greatest contributors to antibiotic resistance. There is currently a paucity of data on antibiotic use in aged care facilities, globally and in the Australian setting.

Aim

To investigate the current antibiotic prescribing practices and use in aged care facilities in the Riverina, New South Wales (NSW), and metropolitan Australian Capital Territory (ACT).

Method

Care managers of aged care facilities in the ACT and Riverina, as well as pharmacists who service aged care facilities in regional NSW and ACT, were asked to complete a questionnaire relating to antibiotic use in aged care facilities. Data obtained were subjected to statistical analysis.

Results

Most facilities in the ACT (85%) and NSW (90%) had some form of protocol in place for the prescribing and obtaining of antibiotics for residents. The most commonly prescribed antibiotic across participating facilities was cephalexin and the most common indication for antibiotic use was urinary tract infection. No statistically significant differences in antibiotic use and antibiotic prescribing practices were observed between metropolitan ACT and regional NSW aged care facilities. There was a statistically significant association between facilities with residents taking antibiotics for ongoing conditions and those that have experienced situations in the past 12 months in which the initially prescribed antibiotic did not work and another had to be used (p = 0.004944).

Conclusion

The data from this study can inform further studies that may be used to inform the development of antimicrobial stewardship initiatives in aged care facilities.
Prognostic value of biochemical variables for survival after surgery for metastatic bone disease of the extremities
Authors: Sørensen Michala Skovlund , Hovgaard Thea Bechman , Hindsø Klaus , Petersen Michael Mørk
Published: December 2016

BACKGROUND AND OBJECTIVE:Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables.

METHODS:In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C‐reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses.

RESULTS:Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 109/L, neutrophil 5.68 × 109/L, lymphocyte 1.37 × 109/L, C‐reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors.

CONCLUSIONS:We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex.
Brusatol overcomes chemoresistance through inhibition of protein translation
Authors: Harder Bryan , Tian Wang , La Clair James J. , Tan Aik‐Choon , Ooi Aikseng , Chapman Eli , Zhang Donna D.
Published: December 2016

The NRF2 pathway activates a cell survival response when cells are exposed to xenobiotics or are under oxidative stress. Therapeutic activation of NRF2 can also be used prior to insult as a means of disease prevention. However, prolonged expression of NRF2 has been shown to protect cancer cells by inducing the metabolism and efflux of chemotherapeutics, leading to both intrinsic and acquired chemoresistance to cancer drugs. This effect has been termed the “dark side” of NRF2. In an effort to combat this chemoresistance, our group discovered the first NRF2 inhibitor, the natural product brusatol, however the mechanism of inhibition was previously unknown. In this report, we show that brusatol's mode of action is not through direct inhibition of the NRF2 pathway, but through the inhibition of both cap‐dependent and cap‐independent protein translation, which has an impact on many short‐lived proteins, including NRF2. Therefore, there is still a need to develop a new generation of specific NRF2 inhibitors with limited toxicity and off‐target effects that could be used as adjuvant therapies to sensitize cancers with high expression of NRF2.
Clinical Determinants of Parkinson's Disease‐associated Pain Using the King's Parkinson's Disease Pain Scale
Authors: Rodríguez‐Violante Mayela , Alvarado‐Bolaños Alonso , Cervantes‐Arriaga Amin , Martinez‐Martin Pablo , Rizos Alexandra , Chaudhuri K. Ray
Published: December 2016

Background

Pain is a frequent feature in Parkinson's disease (PD). Current knowledge on pain and its associated factors in PD has been obtained using nondisease‐specific tools. Recently, the King's Parkinson's Disease Pain Scale (KPPS) was published as the first disease‐specific scale. The aim of this study was to assess PD‐associated pain and its main determinants using the KPPS.

Methods

A cross‐sectional study was carried out. Consecutive patients with PD were recruited from a movement disorders clinic. Clinical and demographical data were collected. The KPPS, the Movement Disorders Society Unified Parkinson's Disease Rating Scale, and the Non‐Motor Symptoms Scale were used to assess all participants.

Results

In total, 314 patients were included. Overall, 88.6% of the sample reported at least 1 type of pain. The mean ± standard KPPS score was 18.8 ± 19.5. Factors associated with higher KPSS scores were female sex (P < 0.001), levodopa treatment (P < 0.001), the presence of depressed mood (P < 0.001), wearing off (P = 0.003), and dyskinesia (P = 0.005). Participants who had postural instability and gait difficulty motor subtypes had higher KPPS scores compared with those who had other subtypes. Multivariate regression analysis showed that only sex, motor subtype, depressed mood, and Non‐Motor Symptoms Scale sleep/fatigue domain scores achieved statistical significance as determinants (all P < 0.01).

Conclusion

PD‐associated pain is a frequent symptom that tends to increase in both frequency and severity as disease progresses. Risk factors for increased burden include female gender, postural instability and gait difficulty motor subtypes, mood alterations, and sleep/fatigue disturbances.
Academic productivity of faculty associated with microsurgery fellowships
Authors: Ruan Qing Zhao , Ricci Joseph A. , Silvestre Jason , Ho Olivia A. , Lee Bernard T.
Published: December 2016

Background

The Hirsch index (h‐index) is widely recognized as a reliable measure of academic productivity. While previous studies have applied the h‐index to surgical disciplines, none have analyzed microsurgery faculty. This manuscript aims to examine the h‐index of microsurgery fellowship faculty to categorize its applicability to microsurgeons as a determinant of academic output.

Methods

Faculty demographics and institution characteristics were obtained from the American Society of Reconstructive Microsurgery (ASRM) and official program websites. Faculty h‐indices were calculated using the Scopus database (Elsevier, USA). Data was assessed using bivariate analysis and multiple linear regression models to determine the relationship between independent variables and total publications, career h‐index and 5‐year h‐index (h5‐index) of each faculty.

Results

A total of 139 faculties from 22 programs met inclusion criteria. The median faculty age was 44 (IQR 13) and 84.9% of faculty were male. Faculty size, number of years of fellowship existence, number of fellows, FACS memberships, number of free flaps annually, and academic appointment title were significantly associated with the total publications, h‐index, and h5‐index. Multivariable analysis based on the significant independent variables demonstrated that geographical region and faculty ranks were significantly associated with the h5‐index.

Conclusions

Variables associated with seniority (age, years of practice after fellowship, and academic appointment) were positively correlated with the h‐index. Given the increased use of bibliometrics in academic medicine, these results show that h‐index is a viable tool that can be used to assess research productivity among academic microsurgeons.
A safflower oil based high‐fat/high‐sucrose diet modulates the gut microbiota and liver phospholipid profiles associated with early glucose intolerance in the absence of tissue inflammation
Authors: Danneskiold‐Samsøe Niels Banhos , Andersen Daniel , Radulescu Ilinca Daria , Normann‐Hansen Ann , Brejnrod Asker , Kragh Marie , Madsen Tobias , Nielsen Christian , Josefsen Knud , Fretté Xavier , Fjære Even , Madsen Lise , Hellgren Lars I. , Brix Susanne , Kristiansen Karsten
Published: December 2016

Scope

Omega‐6 (n‐6) PUFA‐rich diets are generally considered obesogenic in rodents. Here, we examined how long‐term intake of a high‐fat/high‐sucrose (HF/HS) diet based on safflower oil affected metabolism, inflammation, and gut microbiota composition.

Methods and results

We fed male C57BL/6J mice a HF/HS diet based on safflower oil—rich in n‐6 PUFAs—or a low‐fat/low‐sucrose diet for 40 wk. Compared to the low‐fat/low‐sucrose diet, intake of the safflower‐based HF/HS diet only led to moderate weight gain, while glucose intolerance developed at week 5 prior to signs of inflammation, but concurrent with increased levels of linoleic acid and arachidonic acid in hepatic phospholipids. Intake of the HF/HS diet resulted in early changes in the gut microbiota, including an increased abundance of Blautia, while late changes coincided with altered inflammatory profiles and increased fasting plasma insulin. Analysis of immune cells in visceral fat and liver revealed no differences between diets before week 40, where the number of immune cells decreased in the liver of HF/HS‐fed mice.

Conclusion

We suggest that a diet‐dependent increase in the n‐6 to omega‐3 (n‐3) PUFA ratio in hepatic phospholipids together with gut microbiota changes contributed to early development of glucose intolerance without signs of inflammation.
Sesamol ameliorates diet‐induced obesity in C57BL/6J mice and suppresses adipogenesis in 3T3‐L1 cells via regulating mitochondria‐lipid metabolism
Authors: Liu Zhigang , Qiao Qinglian , Sun Yali , Chen Yuwei , Ren Bo , Liu Xuebo
Published: December 2016

Scope

The aim of the current study was to investigate the effect of sesamol, a natural powerful antioxidant and anti‐inflammatory phenol derivative of sesame oil, on adiposity and adiposity‐related metabolic disturbances in mice fed with western diet, and the potential underlying mechanisms focusing on the mitochondria‐lipid metabolism.

Methods and results

In the experimental model that consisted of 3‐month‐old C57BL/6J mice divided into three groups with/without sesamol in the drinking water including standard diet, high fat and high fructose diet (HFFD), and HFFD with sesamol. Results demonstrated that sesamol mitigated bodyweight gain, development of insulin resistance induced by HFFD. Sesamol was found partially normalized serum and hepatic lipid contents, as well as suppressed HFFD‐induced lipogenesis in liver via regulating mitochondria‐related triglyceride/cholesterol metabolism genes expressions. Importantly, sesamol decreased mass and adipocyte sizes of white adipose tissues and brown adipose tissues by improving mitochondria‐related genes expressions includingPgc1aandUcp1. Moreover, sesamol was also found to reduce differentiation and mitochondrial metabolic inhibitors (oligomycin and antimycin A) stimulated lipid accumulation in 3T3‐L1 adipocytes.

Conclusion

Taken together, this study provides compelling evidence that sesamol supplementation reduced adipocyte size and adipogenesis of diet‐induced obesity by regulating mitochondria lipid metabolism.
Creatine and creatine forms intended for sports nutrition
Authors: Andres Susanne , Ziegenhagen Rainer , Trefflich Iris , Pevny Sophie , Schultrich Katharina , Braun Hans , Schänzer Wilhelm , Hirsch‐Ernst Karen Ildico , Schäfer Bernd , Lampen Alfonso
Published: December 2016

Creatine is a popular ergogenic supplement in sports nutrition. Yet, supplementation of creatine occasionally caused adverse effects such as gastrointestinal complaints, muscle cramps and an increase in body weight. Creatine monohydrate has already been evaluated by different competent authorities and several have come to the conclusion that a daily intake of 3 g creatine per person is unlikely to pose safety concerns, focusing on healthy adults with exclusion of pregnant and breastfeeding women. Possible vulnerable subgroups were also discussed in relation to the safety of creatine.

The present review provides an up‐to‐date overview of the relevant information with special focus on human studies regarding the safety of creatine monohydrate and other marketed creatine forms, in particular creatine pyruvate, creatine citrate, creatine malate, creatine taurinate, creatine phosphate, creatine orotate, creatine ethyl ester, creatine pyroglutamate, creatine gluconate, and magnesium creatine chelate. Limited data are available with regard to the safety of the latter creatine forms. Considering an acceptable creatine intake of 3 g per day, most of the evaluated creatine forms are unlikely to pose safety concerns, however some safety concerns regarding a supplementary intake of creatine orotate, creatine phosphate, and magnesium creatine chelate are discussed here.
High dose‐per‐pulse electron beam dosimetry: Usability and dose‐rate independence of EBT3 Gafchromic films
Authors: Jaccard Maud , Petersson Kristoffer , Buchillier Thierry , Germond Jean‐François , Durán Maria Teresa , Vozenin Marie‐Catherine , Bourhis Jean , Bochud François O. , Bailat Claude
Published: December 2016

Purpose

The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose‐per‐pulse linear accelerator (linac), capable of delivering electron beams with a mean dose‐rate (Ḋm) ranging from 0.07 to 3000 Gy/s and a dose‐rate in pulse (Ḋp) of up to 8 × 106 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose‐rate dependence of their response.

Material and methods

Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋm dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Ḋm between 0.55 and 4.40 Gy/min, while Ḋp dependence was probed at the prototype machine for Ḋp ranging from 7 × 103 to 8 × 106 Gy/s. Ḋp dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo‐luminescent dosimeters (TLD) that have been reported as being dose‐rate independent up to such high dose‐rates.

Results

We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋm dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋp range attainable at the prototype linac confirming the absence of any dose‐rate dependence within the investigated range (7 × 103 to 8 × 106 Gy/s). This aspect was further corroborated by the linear relationship between the dose‐per‐pulse (Dp) measured by films and the charge per pulse (Cp) measured at the prototype linac exit.

Conclusion

Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose‐rate and energy independent.
Stereotactic radiosurgery planning of vestibular schwannomas: IsMRIat 3 Tesla geometrically accurate?
Authors: Schmidt M. A. , Wells E. J. , Davison K. , Riddell A. M. , Welsh L. , Saran F.
Published: December 2016

Purpose

MRIis a mandatory requirement to accurately plan Stereotactic Radiosurgery (SRS) for Vestibular Schwannomas. However,MRImay be distorted due not only to inhomogeneity of the static magnetic field and gradients but also due to susceptibility‐induced effects, which are more prominent at higher magnetic fields. We assess geometrical distortions around air spaces and considerMRIprotocol requirements forSRSplanning at 3 T.

Methods

Hardware‐related distortion and the effect of incorrect shimming were investigated with structured test objects. The magnetic field was mapped over the head on five volunteers to assess susceptibility‐related distortion in the naso‐oro‐pharyngeal cavities (NOPC) and around the internal ear canal (IAC).

Results

Hardware‐related geometric displacements were found to be less than 0.45 mm within the head volume, after distortion correction. Shimming errors can lead to displacements of up to 4 mm, but errors of this magnitude are unlikely to arise in practice. Susceptibility‐related field inhomogeneity was under 3.4 ppm, 2.8 ppm, and 2.7 ppm for the head,NOPCregion andIACregion, respectively. For theSRSplanning protocol (890 Hz/pixel, approximately 1 mm3isotropic), susceptibility‐related displacements were less than 0.5 mm (head), and 0.4 mm (IACandNOPC). Large displacements are possible inMRIexaminations undertaken with lower receiver bandwidth values, commonly used in clinicalMRI. Higher receiver bandwidth makes the protocol less vulnerable to sub‐optimal shimming. The shimming volume and theCT‐MRco‐registration must be considered jointly.

Conclusion

Geometric displacements can be kept under 1 mm in the vicinity of air spaces within the head at 3 T with appropriate setting of the receiver bandwidth, correct shimming and employing distortion correction.
A novel objective method for assessing high‐contrast spatial resolution in CT based on the Rayleigh criterion
Authors: Zhang Pu , Wan Guoqing , Li Fei , Li Xingdong , Liu Wenli , Wang Guangzhi
Published: December 2016

Purpose

In China, most quality assessments (QAs) of the high‐contrast resolution of medical computed tomography (CT) equipment is performed by subjective evaluation, which is simple but dependent on observer expertise. The purpose of this study was to compare the accuracy and degree of dispersion of evaluation results from observers with different expertise and to develop an objective, easily understandable new approach to minimize the error caused by the subjective nature of observer evaluation. The accuracy and reproducibility of this new approach was validated and compared using both subjective and objective evaluation methods.

Methods

This new objective evaluation method of high‐contrast resolution was based on measurements of CT phantom images. The intensity profile of the aluminum line pairs’ (LPs’) images was extracted and quantified following the Rayleigh criterion. The interpolation method was employed to improve the consistency of the middle profile lines of each LP group for application of the Rayleigh criterion. With the introduction of a normalized margin, the accuracy of the results increased to the decimal level. Five junior observers and three QA professionals evaluated the high‐contrast resolution of three different CT scanners using the subjective method, modulation transfer function (MTF) method, and the new objective method, and the results were compared statistically.

Results

The experimental standard deviations ranged from 0.4 LP/cm to 0.55 LP/cm for subjective visual inspection. The uncertainty of the expert group's results was much lower than that of the volunteer group. The experimental standard deviations of the MTF evaluation, according to both the standard deviation (SD) and point spread function (PSF) methods, were within the intervals of (0.04–0.06) LP/cm and (0.08–0.16) LP/cm, whereas that of the proposed objective evaluation method was approximately 0.02 LP/cm. The experimental data indicated that the results of the new objective evaluation were in accordance with those of the expert group's subjective evaluation and the MTF evaluation.

Conclusions

In this study, the subjective evaluation results from experienced observers showed relatively less uncertainty and more accuracy than those from inexperienced observers. Furthermore, a new objective evaluation approach that is easily understood, accurate, and reproducible was developed in this study. Results acquired using this new method were comparable with those of expert groups’ subjective evaluation and MTF evaluation. Specialized QA software that integrates the steps implemented in the new method is being developed to enhance the convenience of the approach and assist observers in obtaining accurate and replicable assessment results.
Use of pattern recognition for unaliasing simultaneously acquired slices in simultaneous multislice MR fingerprinting
Authors: Jiang Yun , Ma Dan , Bhat Himanshu , Ye Huihui , Cauley Stephen F. , Wald Lawrence L. , Setsompop Kawin , Griswold Mark A.
Published: December 2016

Purpose

The purpose of this study is to accelerate an MR fingerprinting (MRF) acquisition by using a simultaneous multislice method.

Methods

A multiband radiofrequency (RF) pulse was designed to excite two slices with different flip angles and phases. The signals of two slices were driven to be as orthogonal as possible. The mixed and undersampled MRF signal was matched to two dictionaries to retrieve T1 and T2 maps of each slice. Quantitative results from the proposed method were validated with the gold‐standard spin echo methods in a phantom. T1 and T2 maps of in vivo human brain from two simultaneously acquired slices were also compared to the results of fast imaging with steady‐state precession based MRF method (MRF‐FISP) with a single‐band RF excitation.

Results

The phantom results showed that the simultaneous multislice imaging MRF–FISP method quantified the relaxation properties accurately compared to the gold‐standard spin echo methods. T1 and T2 values of in vivo brain from the proposed method also matched the results from the normal MRF–FISP acquisition.

Conclusion

T1 and T2 values can be quantified at a multiband acceleration factor of two using our proposed acquisition even in a single‐channel receive coil. Further acceleration could be achieved by combining this method with parallel imaging or iterative reconstruction. Magn Reson Med 78:1870–1876, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Flow‐suppressed hyperpolarized 13C chemical shift imaging using velocity‐optimized bipolar gradient in mouse liver tumors at 9.4 T
Authors: Lee Hansol , Lee Joonsung , Joe Eunhae , Yang Seungwook , Song Jae Eun , Choi Young‐Suk , Wang Eunkyung , Joo Chan Gyu , Song Ho‐Taek , Kim Dong‐Hyun
Published: December 2016

Purpose

To optimize and investigate the influence of bipolar gradients for flow suppression in metabolic quantification of hyperpolarized 13C chemical shift imaging (CSI) of mouse liver at 9.4 T.

Methods

The trade‐off between the amount of flow suppression using bipolar gradients and
effect from static spins was simulated. A free induction decay CSI sequence with alternations between the flow‐suppressed and non–flow‐suppressed acquisitions for each repetition time was developed and was applied to liver tumor–bearing mice via injection of hyperpolarized [1‐13C] pyruvate.

Results

The in vivo results from flow suppression using the velocity‐optimized bipolar gradient were comparable with the simulation results. The vascular signal was adequately suppressed and signal loss in stationary tissue was minimized. Application of the velocity‐optimized bipolar gradient to tumor‐bearing mice showed reduction in the vessel‐derived pyruvate signal contamination, and the average lactate/pyruvate ratio increased by 0.095 (P < 0.05) in the tumor region after flow suppression.

Conclusion

Optimization of the bipolar gradient is essential because of the short 13C
and high signal in venous flow in the mouse liver. The proposed velocity‐optimized bipolar gradient can suppress the vascular signal, minimizing
‐related signal loss in stationary tissues at 9.4 T. Magn Reson Med 78:1674–1682, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
(S)Pinning down protein interactions by NMR
Authors: Teilum Kaare , Kunze Micha Ben Achim , Erlendsson Simon , Kragelund Birthe B.
Published: December 2016

Protein molecules are highly diverse communication platforms and their interaction repertoire stretches from atoms over small molecules such as sugars and lipids to macromolecules. An important route to understanding molecular communication is to quantitatively describe their interactions. These types of analyses determine the amounts and proportions of individual constituents that participate in a reaction as well as their rates of reactions and their thermodynamics. Although many different methods are available, there is currently no single method able to quantitatively capture and describe all types of protein reactions, which can span orders of magnitudes in affinities, reaction rates, and lifetimes of states. As the more versatile technique, solution NMR spectroscopy offers a remarkable catalogue of methods that can be successfully applied to the quantitative as well as qualitative descriptions of protein interactions. In this review we provide an easy‐access approach to NMR for the non‐NMR specialist and describe how and when solution state NMR spectroscopy is the method of choice for addressing protein ligand interaction. We describe very briefly the theoretical background and illustrate simple protein–ligand interactions as well as typical strategies for measuring binding constants using NMR spectroscopy. Finally, this review provides examples of caveats of the method as well as the options to improve the outcome of an NMR analysis of a protein interaction reaction.
No influence of CO2 on stable isotope analyses of soil waters with off‐axis integrated cavity output spectroscopy (OA‐ICOS)
Authors: Sprenger Matthias , Tetzlaff Doerthe , Soulsby Chris
Published: December 2016

Rationale

It was recently shown that the presence of CO2 affects the stable isotope (δ2H and δ18O values) analysis of water vapor via Wavelength‐Scanned Cavity Ring‐Down Spectroscopy. Here, we test how much CO2 is emitted from soil samples and if the CO2 in the headspace influences the isotope analysis with the direct equilibration method by Off‐Axis Integrated Cavity Output Spectroscopy (OA‐ICOS).

Methods

The headspace above different amounts of sparkling water was sampled, and its stable isotopic composition (δ2H and δ18O values) and CO2 concentration were measured by direct equilibration and by gas chromatography, respectively. In addition, the headspace above soil samples was analyzed in the same way. Furthermore, the gravimetric water content and the loss on ignition were measured for the soil samples.

Results

The experiment with the sparkling water showed that CO2 does not influence the stable isotope analysis by OA‐ICOS. CO2 was emitted from the soil samples and correlated with the isotopic fractionation signal, but no causal relationship between the two was determined. Instead, the fractionation signal in pore water isotopes can be explained by soil evaporation and the CO2 can be related to soil moisture and organic matter which both enhance microbial activity.

Conclusions

We found, despite the high CO2 emissions from soil samples, no need for a post‐correction of the pore water stable isotope analysis results, since there is no relation between CO2 concentrations and the stable isotope results of vapor samples obtained with OA‐ICOS. © 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.
Robust cooperative output regulation of heterogeneous Lur'e networks
Authors: Zhang Fan , Trentelman Harry L. , Scherpen Jacquelien M. A.
Published: December 2016

In this paper, we study robust cooperative output regulation problems for a directed network of Lur'e systems that consist of a nominal linear dynamics with an unknown static nonlinearity around it through negative feedback. We assume that the linear part of each agent is identical, but the nonlinearities are allowed to be different for distinct agents. In this sense, the network is heterogeneous. As is common in the context of Lur'e systems, the unknown nonlinearities are assumed to be sector bounded within one given sector. The interconnection graph among these agents is assumed to contain a directed spanning tree. Similar to classical output regulation problems, there is a virtual exosystem generating a reference signal in which all the agents are required to track cooperatively. Our designed distributed dynamic state/output feedback protocol makes a copy of the reference signal at each agent asymptotically, and then the robust cooperative output regulation problem becomes a robust tracking problem that can be handled by each agent via local information. It turns out that our cooperative protocols are fully distributed. Sufficient conditions on the existence of output synchronization protocols are given along with some discussions on these conditions. Finally, two simulation examples illustrate our design. Copyright © 2016 John Wiley & Sons, Ltd.
Director: A User Interface Designed for Robot Operation with Shared Autonomy
Authors: Marion Pat , Fallon Maurice , Deits Robin , Valenzuela Andrés , Pérez D'Arpino Claudia , Izatt Greg , Manuelli Lucas , Antone Matt , Dai Hongkai , Koolen Twan , Carter John , Kuindersma Scott , Tedrake Russ
Published: December 2016

Operating a high degree of freedom mobile manipulator, such as a humanoid, in a field scenario requires constant situational awareness, capable perception modules, and effective mechanisms for interactive motion planning and control. A well‐designed operator interface presents the operator with enough context to quickly carry out a mission and the flexibility to handle unforeseen operating scenarios robustly. By contrast, an unintuitive user interface can increase the risk of catastrophic operator error by overwhelming the user with unnecessary information. With these principles in mind, we present the philosophy and design decisions behindDirector—the open‐source user interface developed by Team MIT to pilot the Atlas robot in the DARPA Robotics Challenge (DRC). At the heart of Director is an integrated task execution system that specifies sequences of actions needed to achieve a substantive task, such as drilling a wall or climbing a staircase. These task sequences, developeda priori, make online queries to automated perception and planning algorithms with outputs that can be reviewed by the operator and executed by our whole‐body controller. Our use of Director at the DRC resulted in efficient high‐level task operation while being fully competitive with approaches focusing on teleoperation by highly trained operators. We discuss the primary interface elements that comprise Director, and we provide an analysis of its successful use at the DRC.
Application of a combined decision model based on optimal weights in incipient faults diagnosis for power transformer
Authors: Tingfang Yang , Haifeng Liu , Xiangjun Zeng , Wei Qiu , Wenbin Deng
Published: December 2016

A new method for the diagnosis of incipient transformer faults based on a combined decision model using IEC 60599 three‐ratio method, grey system theory (GS) algorithm, Dempster–Shafer evidence (DS) theory, and backpropagation (BP) neural network diagnosis method is proposed in this paper. The new method will eliminate the influence of any one individual diagnosis method due to insufficient information or diagnostic prejudices. In order to minimize the sum‐of‐squared errors of the proposed method, the optimal weights of every individual method which comprises the combined decision model are calculated based on their own diagnosis error ratios. Thus a combined decision model based on optimal weights (CDMOW) is formed. Then the optimal diagnosis result is obtained based on CDMOW. Results of diagnosis instances show that the use of CDMOW not only gives a much higher diagnostic accuracy rate but also more stability in fault diagnosis than any single method composing it. © 2016 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.