bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation analysis of the coherence-incoherence transition in a ring of nonlocally coupled logistic maps
Authors: Vadivasova Tatiana E. , Strelkova Galina I. , Bogomolov Sergey A. , Anishchenko Vadim S.
Published: September 2016

We present numerical results for a set of bifurcations occurring at the transition from complete chaotic synchronization to spatio-temporal chaos in a ring of nonlocally coupled chaotic logistic maps. The regularities are established for the evolution of cross-correlations of oscillations in the network elements at the bifurcations related to the coupling strength variation. We reveal the distinctive features of cross-correlations for phase and amplitude chimera states. It is also shown that the effect of time intermittency between the amplitude and phase chimeras can be realized in the considered ensemble.
Investigation of the phase stability of an X-band long pulse multibeam relativistic klystron amplifier
Authors: Liu Zhenbang , Huang Hua , Jin Xiao , Lei Lurong , Zhu Lei , Li Lele , Li Shifeng , Yan Wenkang , He Hu
Published: September 2016

To realize coherent high power microwave combining, an X-band long pulse multibeam relativistic klystron amplifier is designed, and the relative phase stability is investigated by three dimensions particle in cell simulation and high power microwave experiment. The simulation shows that the relative phase difference can be stabilized at gigawatt level radiation power. But the relative phase jitter increases in the experiment, then some measures are proposed to improve the stability of relative phase difference and avoid pulse shortening. A 0.98 GW radiation power with pulse duration of 160 ns is obtained in the experiment, the pulse shortening is avoided. The relative phase difference fluctuation between output microwave and input RF signal is less than ±25° in a single shot with duration of 100 ns. Then, the experiment of pulse repetition is carried out, and an output microwave with 0.98 GW radiation power at 25 Hz repetition rate is obtained. The power conversion efficiency is about 35% with pulse duration of 160 ns. The relative phase difference is less than ±30° at 25 Hz repetition rate in 100 ns.
Direct determination of defect density of states in organic bulk heterojunction solar cells
Authors: Verma Upkar K. , Tripathi Durgesh C. , Mohapatra Y. N.
Published: September 2016

The measurement of the occupied trap density of states (DOS) is important for optimization of organic bulk heterojunction solar cells. We demonstrate a direct method for obtaining it from the trap related peak in capacitance-voltage characteristics under different levels of illumination, and its correlation with the dark current density-voltage characteristics. We use the method to measure the parameters of DOS, occupied trap distribution, and its temperature dependence for poly(3-hexathiophene) (P3HT):phenyl-C61-butyric acid methyl ester (PCBM) based solar cells. The total occupied trap concentration is approximately 7 × 1015 cm−3 with a standard deviation for a truncated Gaussian distribution varying between 32 and 44 meV in the temperature range of 310–270 K within a total Gaussian DOS with a standard deviation of 92 meV.
Growth of hexagonal boron nitride on (111) Si for deep UV photonics and thermal neutron detection
Authors: Ahmed K. , Dahal R. , Weltz A. , Lu J.-Q. , Danon Y. , Bhat I. B.
Published: September 2016

Hexagonal boron nitride (hBN) growth was carried out on (111) Si substrates at a temperature of 1350 °C using a cold wall chemical vapor deposition system. The hBN phase of the deposited films was identified by the characteristic Raman peak at 1370 cm−1 with a full width at half maximum of 25 cm−1, corresponding to the in-plane stretch of B and N atoms. Chemical bonding states and composition of the hBN films were analyzed by X-ray photoelectron spectroscopy; the extracted B/N ratio was 1.03:1, which is 1:1 within the experimental error. The fabricated metal-hBN-metal devices demonstrate a strong deep UV (DUV) response. Further, the hBN growth on the vertical (111) surfaces of parallel trenches fabricated in (110) Si was explored to achieve a thermal neutron detector. These results demonstrate that hBN-based detectors represent a promising approach towards the development of DUV photodetectors and efficient solid-state thermal neutron detectors.
Inhomogeneous longitudinal distribution of Ni atoms on graphene induced by layer-number-dependent internal diffusion
Authors: Hasegawa M. , Tashima K. , Kotsugi M. , Ohkochi T. , Suemitsu M. , Fukidome H.
Published: September 2016

The intrinsic transport properties, such as carrier mobility and saturation velocity, of graphene are the highest among materials owing to its linear band dispersion and weak backscattering. However, the reported field-effect mobility of transistors using graphene as a channel is much lower than the intrinsic channel mobility. One of the reasons for this low mobility is the high contact resistance between graphene and metals used for the source and drain electrodes, which results from the interfacial roughness. Even Ni, which is a promising contact metal for many materials because of its high adhesion and lower contact resistance, does not meet the requirement as a contact metal for graphene. Noticing that the interfacial roughness between the a metal and graphene is strongly related to the onset of the contact resistance, we performed transmission electron microscopy and photoemission electron microscopy measurements to evaluate the microscopic lateral and longitudinal distributions of Ni atoms at the Ni/graphene interface formed on epitaxial graphene (EG) on 4H-SiC(0001). Our data revealed that the deposited Ni atoms diffused into the EG layers, but they did not reach the EG/SiC interface, and the diffusion was stronger on bilayered graphene than on monolayered graphene. We thus ascribe the layer-number-dependent internal diffusion of Ni atoms in EG as a cause of the microscopic interfacial roughness between graphene and the metal. Ensuring homogeneous distribution of the number of EG layers should be key to lowering the contact resistance.
High temperature exchange bias effect in melt-spun Mn55Bi45alloys
Authors: Song Yiming , Xiang Zhen , Wang Taolei , Niu Junchao , Xia Kada , Lu Wei , Zhang Hong , Cao Yongze , Yoshimura Satoru , Saito Hitoshi
Published: September 2016

In this paper, we report a high-temperature exchange bias (EB) effect in melt-spun Mn55Bi45 alloy ribbons. A remarkable spontaneous exchange bias (up to 1700 Oe) was achieved at temperature from 300 K to 550 K, which is far higher than what has so far been observed in other alloy systems. Such a phenomenon is attributed to the local antiferromagnetic cluster formed in the ferromagnetic matrix. The observation of high-temperature EB in the Mn55Bi45 alloy is of interest from the perspective of practical applications, and it is a good starting point for designing high-temperature spintronic devices.
Highly sensitive NO2 sensors by pulsed laser deposition on graphene
Authors: Kodu Margus , Berholts Artjom , Kahro Tauno , Avarmaa Tea , Kasikov Aarne , Niilisk Ahti , Alles Harry , Jaaniso Raivo
Published: September 2016

Graphene as a single-atomic-layer material is fully exposed to environmental factors and has therefore a great potential for the creation of sensitive gas sensors. However, in order to realize this potential for different polluting gases, graphene has to be functionalized—adsorption centers of different types and with high affinity to target gases have to be created at its surface. In the present work, the modification of graphene by small amounts of laser-ablated materials is introduced for this purpose as a versatile and precise tool. The approach has been demonstrated with two very different materials chosen for pulsed laser deposition (PLD)—a metal (Ag) and a dielectric oxide (ZrO2). It was shown that the gas response and its recovery rate can be significantly enhanced by choosing the PLD target material and deposition conditions. The response to NO2 gas in air was amplified up to 40 times in the case of PLD-modified graphene, in comparison with pristine graphene, and it reached 7%–8% at 40 ppb of NO2 and 20%–30% at 1 ppm of NO2. The PLD process was conducted in a background gas (5 × 10−2 mbar oxygen or nitrogen) and resulted in the atomic areal densities of the deposited materials of about 1015 cm−2. The ultimate level of NO2 detection in air, as extrapolated from the experimental data obtained at room temperature under mild ultraviolet excitation, was below 1 ppb.
A magnesium/amorphous silicon passivating contact for n-type crystalline silicon solar cells
Authors: Wan Yimao , Samundsett Chris , Yan Di , Allen Thomas , Peng Jun , Cui Jie , Zhang Xinyu , Bullock James , Cuevas Andres
Published: September 2016

Among the metals, magnesium has one of the lowest work functions, with a value of 3.7 eV. This makes it very suitable to form an electron-conductive cathode contact for silicon solar cells. We present here the experimental demonstration of an amorphous silicon/magnesium/aluminium (a-Si:H/Mg/Al) passivating contact for silicon solar cells. The conduction properties of a thermally evaporated Mg/Al contact structure on n-type crystalline silicon (c-Si) are investigated, achieving a low resistivity Ohmic contact to moderately doped n-type c-Si (∼5 × 1015 cm−3) of ∼0.31 Ω cm2 and ∼0.22 Ω cm2 for samples with and without an amorphous silicon passivating interlayer, respectively. Application of the passivating cathode to the whole rear surface of n-type front junction c-Si solar cells leads to a power conversion efficiency of 19% in a proof-of-concept device. The low thermal budget of the cathode formation, its dopant-less nature, and the simplicity of the device structure enabled by the Mg/Al contact open up possibilities in designing and fabricating low-cost silicon solar cells.
Sweet Poisons: Synthetic Strategies towards Tutin Glycosides
Authors: Nhu Duong , Larsen Lesley , Perry Nigel B. , Larsen David S. , Hawkins Bill C.
Published: September 2016

The polycyclic, polyoxygenated picrotoxane tutin was subjected to various glycosylation reaction conditions in an effort to synthesise β-linked tutin glycosides, recently found in toxic honeys. Cationic palladium-mediated glycosylation of tutin was successful; however, the α-linked tutin tetrabenzyl glucoside was obtained as the major product (5 : 1, α : β). Hydrogenolysis of the benzyl ether protecting groups resulted in concomitant tutin double-bond migration. Epoxide opening and rearrangement were observed upon acetylation of the tutin glucoside.
APMP key comparison for the measurement of air kerma for 60Co (APMP.RI(I)-K1.1)
Authors: Webb D V , Lee J -H , Budiantari C T , Laban J , Saito N , Srimanoroth S , Khaled N E
Published: September 2016

The results are reported for an APMP.R(I)-K1.1 comparison that extends the regional comparison of standards for air kerma APMP.R(I)-K1 to several laboratories unable to participate earlier. The comparison was conducted with the goal of supporting the relevant calibration and measurement capabilities (CMCs) planned for publication by the participant laboratories.

The comparison was conducted by the pilot laboratory, the Australian Radiation Protection and Nuclear Safety (ARPANSA), Australia, supported by the Institute of Nuclear Energy Research (INER), Taiwan, in a modified ring-shaped arrangement from September 2009 to November 2010, in parallel with an APMP.R(I)-K4 comparison being piloted by the INER. The laboratories that took part in the comparison were the ARPANSA, the Centre of Technology of Radiation Safety and Metrology (PTKMR-BATAN), Indonesia, the Division of Radiation and Medical Devices (DMSC), Thailand, the INER, the National Centre for Radiation Science (NCRS), New Zealand, the National Institute for Standards (NIS), Egypt and the National Metrology Institute of Japan (NMIJ/AIST), Japan. The two primary laboratories, ARPANSA and NMIJ, were chosen as the linking laboratories.

Three ionization chambers were used as transfer instruments to be calibrated in terms of air kerma in 60Co radiotherapy beams. The comparison result is based on the ratio between the air kerma calibration coefficients (NK
) determined by the participants and the mean of the results of the linking laboratories.

The mean comparison ratio was found to be within 0.5 % of the key comparison reference value KCRV. The largest deviation between any two comparison ratios for the three chambers in terms of air kerma was 2.0 %. An analysis of the participant uncertainty budgets enabled the calculation of degrees of equivalence (DoE) in terms of the deviations of the results and their associated uncertainties. As a result of this APMP comparison, the BIPM key comparison database (KCDB) should include three new entries since neither the PTKMR-BATAN nor the NCRS have yet been declared designated institutes and consequently their results cannot be entered.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Pink-eyed Dilution Protein Controls the Processing of Tyrosinase
Authors: Chen Kun , Manga Prashiela , Orlow Seth J.
Published: September 2016

The processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis, was investigated in melan-p1 melanocytes, which are null at the p locus. Endoglycosidase H digestion showed that a significant fraction of tyrosinase was retained in the endoplasmic reticulum. This retention could be rescued either by transfection of melan-p1 cells with an epitope-tagged wild-typep transcript or by treatment with either bafilomycin A1 or ammonium chloride. We found that the endoplasmic reticulum contains a significant amount of p protein, thus supporting a role for p within this compartment. Using immunofluoresence, we showed that most mature full-length tyrosinase in melan-p1 cells was located in the perinuclear area near the Golgi, in contrast to its punctate melanosomal pattern in wild-type melanocytes. Expression of p in melan-p1 cells restored tyrosinase to melanosomes. Triton X-114 phase separation revealed that an increased amount of tyrosinase was proteolyzed in melan-p1 cells compared with wild-type melanocytes. The proteolyzed tyrosinase was no longer membrane bound, but remained enzymatically active and a large proportion was secreted into the culture medium of melan-p1 cells. We conclude that p regulates posttranslational processing of tyrosinase, and hypopigmentation in melan-p1 cells is the result of altered tyrosinase processing and trafficking.
Discovery of keratin function and role in genetic diseases: the year that 1991 was
Authors: Coulombe Pierre A.
Published: September 2016

In 1991, a set of transgenic mouse studies took the fields of cell biology and dermatology by storm in providing the first credible evidence that keratin intermediate filaments play a unique and essential role in the structural and mechanical support in keratinocytes of the epidermis. Moreover, these studies intimated that mutations altering the primary structure and function of keratin filaments underlie genetic diseases typified by cellular fragility. This Retrospective on how these studies came to be is offered as a means to highlight the 25th anniversary of these discoveries.
Amyloid β-peptides interfere with mitochondrial preprotein import competence by a coaggregation process
Authors: Cenini Giovanna , Rüb Cornelia , Bruderek Michael , Voos Wolfgang
Published: September 2016

Aβ peptides play a central role in the etiology of Alzheimer disease (AD) by exerting cellular toxicity correlated with aggregate formation. Experimental evidence has shown intraneuronal accumulation of Aβ peptides and interference with mitochondrial functions. Nevertheless, the relevance of intracellular Aβ peptides in the pathophysiology of AD is controversial. Here we found that the two major species of Aβ peptides, in particular Aβ42, exhibited a strong inhibitory effect on the preprotein import reactions essential for mitochondrial biogenesis. However, Aβ peptides interacted only weakly with mitochondria and did not affect the inner membrane potential or the structure of the preprotein translocase complexes. Aβ peptides significantly decreased the import competence of mitochondrial precursor proteins via an extramitochondrial coaggregation mechanism. Coaggregation and import inhibition were significantly stronger for the longer peptide Aβ42, correlating with its importance in AD pathology. Our results demonstrate that direct interference of aggregation-prone Aβ peptides with mitochondrial protein biogenesis represents a crucial aspect of the pathobiochemical mechanisms contributing to cellular damage in AD.
Spinal Epidural Abscess in Adults: A 10-Year Clinical Experience at a Tertiary Care Academic Medical Center
Authors: Artenstein Andrew W. , Friderici Jennifer , Holers Adam , Lewis Deirdre , Fitzgerald Jan , Visintainer Paul
Published: September 2016

Background.  Delayed recognition of spinal epidural abscess (SEA) contributes to poor outcomes from this highly morbid and potentially lethal infection. We performed a case-control study in a regional, high-volume, tertiary care, academic medical center over the years 2005–2015 to assess the potential changing epidemiology, clinical and laboratory manifestations, and course of this disorder and to identify factors that might lead to early identification of SEA.

Methods.  Diagnostic billing codes consistent with SEA were used to identify inpatient admissions for abstraction. Subjects were categorized as cases or controls based on the results of spinal imaging studies. Characteristics were compared using Fisher's exact or Kruskal-Wallis tests. All P values were 2-sided with a critical threshold of <.05.

Results.  We identified 162 cases and 88 controls during the study period. The incidence of SEA increased from 2.5 to 8.0 per 10 000 admissions, a 3.3-fold change from 2005 to 2015 (P < .001 for the linear trend). Compared with controls, cases were significantly more likely to have experienced at least 1 previous healthcare visit or received antimicrobials within 30 days of admission; to have comorbidities of injection drug use, alcohol abuse, or obesity; and to manifest fever or rigors. Cases were also more likely to harbor coinfection at a noncontiguous site. When available, inflammatory markers were noted to be markedly elevated in cases. Focal neurologic deficits were seen with similar frequencies in both groups.

Conclusions.  Based on our analysis, it appears that selected factors noted at the time of clinical presentation may facilitate early recognition of SEA.
Design and descriptive data of the randomized Clubfoot Foot Abduction Brace Length of Treatment Study (FAB24)
Authors: Dobbs Matthew B. , Frick Steven L. , Mosca Vincent S. , Raney Ellen , VanBosse Harold J. , Lerman Joel A. , Talwalkar Vishwas R. , Steger-May Karen , Gurnett Christina A.
Published: September 2016

The aim of this study was to describe the design and baseline characteristics of participants enrolled in the prospective randomized-controlled Clubfoot Foot Abduction Brace Length of Treatment Study (FAB24). Foot abduction bracing is currently the standard of care for preventing clubfoot relapse. Current recommendations include full-time bracing for the first 3 months and then 8–12 h a day for 4 years; however, the optimal length of bracing is not known. The FAB24 trial is a clinical randomized study to determine the effectiveness of 2- versus 4-year foot abduction bracing. Participant enrollment for FAB24 was conducted at eight sites in North America and included enrollment and randomization of 139 participants with isolated clubfoot. This clinical trial will generate evidence-based data that will inform and improve patient care.
A Comparison of Usage and Outcomes Between Nurse Practitioner and Resident-Staffed Medical ICUs
Authors: Scherzer Rachel , Dennis Marie P. , Swan Beth Ann , Kavuru Mani S. , Oxman David A.
Published: September 2016

Objective:

To compare usage patterns and outcomes of a nurse practitioner–staffed medical ICU and a resident-staffed physician medical ICU.

Design:

Retrospective chart review of 1,157 medical ICU admissions from March 2012 to February 2013.

Setting:

Large urban academic university hospital.

Subjects:

One thousand one hundred fifty-seven consecutive medical ICU admissions including 221 nurse practitioner-staffed medical ICU admissions (19.1%) and 936 resident-staffed medical ICU admissions (80.9%).

Interventions:

None.

Measurements and Main Results:

Data obtained included age, gender, race, medical ICU admitting diagnosis, location at time of ICU transfer, code status at ICU admission, and severity of illness using both Acute Physiology and Chronic Health Evaluation II scores and a model for relative expected mortality. Primary outcomes compared included ICU mortality, in-hospital mortality, medical ICU length of stay, and post-ICU discharge hospital length of stay. Patients admitted to the nurse practitioner–staffed medical ICU were older (63 ± 16.5 vs 59.2 ± 16.9 yr for resident-staffed medical ICU; p = 0.019), more likely to be transferred from an inpatient unit (52.0% vs 40.0% for the resident-staffed medical ICU; p = 0.002), and had a higher severity of illness by relative expected mortality (21.3 % vs 17.2 % for the resident-staffed medical ICU; p = 0.001). There were no differences among primary outcomes except for medical ICU length of stay (nurse practitioner-resident-staffed 7.9 ± 7.5 d vs resident-staffed medical ICU 5.6 ± 6.5 d; p = 0.0001). Post-hospital discharge to nonhome location was also significantly higher in the nurse practitioner–ICU (31.7% in nurse practitioner–staffed medical ICU vs 23.9% in resident-staffed medical ICU; p = 0.24).

Conclusions:

We found no difference in mortality between an nurse practitioner–staffed medical ICU and a resident-staffed physician medical ICU. Our study adds further evidence that advanced practice providers can render safe and effective ICU care.
Heterogeneity of Specific CD4+ and CD8+ T Cells Stimulated by CMV pp65 and IE1 Antigens
Authors: Albiero Elena , Amati Eliana , Baumeister Elke , Einsele Hermann , Grigoleit Götz U. , Rodeghiero Francesco
Published: September 2016

Characterization of human cytomegalovirus-specific T cells (CMV-T) is of critical importance for their potential use in adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. Background frequencies of CMV-T in peripheral blood mononuclear cells (PBMCs) of CMV-seropositive healthy subjects are usually very low, hence the requirement for prolonged culture time and multiple stimulations to expand them. The evaluation of the end-culture specificity and composition has sometimes been neglected or difficult to assess in these settings. We explored the identity and the functionality of pp65-specific and IE1-specific T cells, enriched in short-term cultures from PBMCs. Antigen-specific T cells were further isolated by IFN-γ capture system and/or CD154 microbeads. Frequency of IE1-specific cytotoxic T cells in PBMCs secreting IFN-γ was higher compared with the pp65-specific one, whereas the latter cell types showed a higher median CD107a degranulation. Cell viability, rate of CMV-T increase, and multicytokine secretion profile after epitope-specific short-term cultures were heterogenous. T cells were mainly of late effector stages but they significantly dropped off upon CMV rechallenge with peptide pools. In parallel, CMV-T expansion was accompanied by a significant increase of cytotoxic naive/memory stem cells (CTLs), whereas the CD4+ counterpart significantly increased only upon stimulation with IE1. Outcome was variable and showed donor and epitope dependency. Differences in human leukocyte antigen and epitope dominance and variability in the relative number of CD3+ effector cells and IFN-γ/CD154 expression among healthy donors could reflect the observed individual CMV-specific cellular immunity. This heterogeneity raises points to be considered when approaching adoptive immunotherapy.
Pediatric Patients With Solid or Hematological Tumor Disease: Vancomycin Population Pharmacokinetics and Dosage Optimization
Authors: Guilhaumou Romain , Marsot Amélie , Dupouey Julien , Galambrun Claire , Boulamery Audrey , Coze Carole , Simon Nicolas , André Nicolas
Published: September 2016

Background:

In pediatric cancer patients, determination of optimal vancomycin dosage is essential because of high risk of inadequate concentrations and bacterial resistance. The aim of this study was to determine vancomycin pharmacokinetic parameters in this population and propose dosage optimization to achieve optimal concentration.

Methods:

We retrospectively reviewed the use of vancomycin in pediatric cancer patients with febrile neutropenia (hematological or solid tumor disease). Vancomycin was administered by continuous infusion, and dosages were adapted according to therapeutic drug monitoring results. Blood cultures were performed before the first dose of antibiotic. Vancomycin pharmacokinetic population parameters were determined using NONMEM software, and dosage simulations were performed according to the target concentration (20–25 mg/L).

Results:

One hundred twenty-one patients were included in this study, representing 301 vancomycin concentrations. Blood cultures were positive in 37.5% of patients, and observed pathogens were mainly Staphylococcus spp. (43.8% methicillin resistant). Volume of distribution (95% confidence interval) was 34.7 L (17.3–48.0), and total apparent clearance (CL) (95% confidence interval) was correlated to body weight, tumor disease, and cyclosporine coadministration: CL = θCL × (WT/70)0.75 L/h with θCL = 3.49 (3.02–3.96), 4.66 (3.98–5.31), and 4.97 (4.42–5.41) in patients managed for hematological malignancies with or without cyclosporine coadministration and for solid malignancies, respectively. Based on simulation results, vancomycin dosage (milligram per kilogram) should be adapted to each child on the basis of its body weight and cyclosporine coadministration.

Conclusions:

Our results highlight the requirement to adapt vancomycin dosage in cancer pediatric population. Simulations have allowed to describe new dosage schedules, and a chart was created for clinicians to adapt vancomycin dosage.
Cetuximab Pharmacokinetics Influences Overall Survival in Patients With Head and Neck Cancer
Authors: Pointreau Yoann , Azzopardi Nicolas , Ternant David , Calais Gilles , Paintaud Gilles
Published: September 2016

Background:

A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma (HNSCC).

Methods:

Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m2 followed by weekly infusions of 250 mg/m2. Twenty-one patients had locally advanced HNSCC, and 13 had metastatic/recurrent HNSCC. Cetuximab concentrations were measured by the enzyme-linked immunosorbent assay, and its pharmacokinetics was analyzed by a population approach. Survivals were analyzed with the log-rank test.

Results:

Cetuximab pharmacokinetics was best described using a 2-compartment model with both first-order and saturable (zero-order) eliminations. Estimated pharmacokinetic parameters (%CV) were central volume of distribution V1 = 3.18 L (6%), peripheral volume of distribution V2 = 5.4 L (42%), elimination clearance CL = 0.57 L/d (31%), distribution clearance Q = 0.64 L/d, and zero-order elimination rate k0 = 6.72 mg/d (29%). Both V1 and V2 increased with the body surface area. Adjunction of chemotherapy reduced CL and increased k0. OS was inversely related with cetuximab global clearance (P = 0.007) and was higher in patients with severe radiation dermatitis (P = 0.005).

Conclusions:

Cetuximab pharmacokinetics in patients with HNSCC can be described using a 2-compartment model combining linear and nonlinear mechanisms of elimination. OS is associated with both cetuximab global clearance and severe radiation dermatitis.
RETINAL MANIFESTATIONS OF SPINOCEREBELLAR ATAXIA TYPE 7 IN TWO CONSECUTIVE GENERATIONS
Authors: Yip Gary , Henao Martha , Huang Lynn L.
Published: September 2016

Purpose:

To report a diagnosis of spinocerebellar ataxia Type 7 (SCA-7) first diagnosed in the daughter followed by the father, with proven genetic testing and display of progressive anticipation of disease penetrance.

Methods:

A 5-year-old African American female admitted for failure to thrive underwent full ocular examination and fundus photography, with genetic confirmation of SCA-7. The father carried a previous diagnosis of possible solar retinopathy; however, with further genetic testing, he was also found to have SCA-7.

Results:

The patient was admitted for failure to thrive with suspicion of ataxia neurodegenerative disorder. Visual acuity was hand motion. Fundus examination showed retinal pigment epithelium pigmentary changes in the macula and peripheral retina. Further genetic workup revealed 96 CAG repeat expansion compared with a normal of <20 repeats. Ocular examination of patient's father displayed a milder form of retinopathy with genetic testing showing 47 CAG repeat expansion. Diagnosis of SCA-7 was made displaying genetic anticipation.

Conclusion:

Spinocerebellar ataxia Type 7 is a disease of expanded CAG repeats showing genetic anticipation. Patients display progressive cerebellar ataxia, dysarthria dysphagia, slow saccadic eye movements, and cone photoreceptor loss leading to progressive vision loss. CAG repeat length tends to expand with transmission resulting in dramatic symptoms in offspring sometimes resulting in diagnosis before parents' diagnosis. Awareness of this condition may help in earlier diagnosis and unnecessary testing resulting in more effective counseling for the patient and their family.
Robotic Resection of 3 Cm and Larger Thymomas is Associated with Low Perioperative Morbidity and Mortality
Authors: Wilshire Candice L. , Vallières Eric , Shultz Dale , Aye Ralph W. , Farivar Alexander S. , Louie Brian E.
Published: September 2016

Objective

The approach to thymoma resection has usually been determined by tumor size, although established guidelines do not exist. Minimally invasive approaches have been limited to tumors smaller than 5 cm, although 3 cm has been the suggested cutoff for performing an adequate oncologic procedure. No study has compared the perioperative outcomes of patients with 3 cm or larger tumors resected robotically versus sternotomy.

Methods

We reviewed patients who underwent resection of 3 cm or larger thymomas from 2004 to 2014. Patients were divided based on approach: robotic and open thymectomy/thymomectomy.

Results

Forty patients with tumors ranging from 3 to 13 cm were evaluated, 23 robotic and 17 open. Patient and tumor characteristics were similar. An R0 resection was primarily achieved: robotic, 91% (21/23); and open, 88% (15/17); P = 0.832. Adjuvant radiation rates were statistically equivalent: robotic, 17% (4/23) versus open, 41% (7/17); P = 0.191. Major postoperative complications were comparable: robotic, 4% (1/23) versus open, 29% (4/17); P = 0.184. Median chest tube duration was shorter for robotic (1 day) versus open (3 days); P = 0.001. The robotic approach had a shorter median intensive care unit stay compared to open (0 days vs 1day); P = 0.024. The median hospital stay was shorter for robotic (2 days) versus open (5 days); P < 0.001.

Conclusions

In 3 cm or larger thymomas, robotic thymectomy is feasible based on the ability to achieve a complete resection with similar adjuvant radiation therapy rates. Perioperatively, robotic thymectomy is associated with lower morbidity; and shorter chest tube duration, intensive care unit stay, and hospital stay compared to open. However, on-cologic outcomes are immature and require prolonged surveillance.
Behavioral Toxicity Revisited
Authors: Fava Giovanni A. , Cosci Fiammetta , Offidani Emanuela , Guidi Jenny
Published: September 2016

In 1968, DiMascio and Shader provided a conceptual framework for behavioral toxicity of psychotropic drugs (ie, the pharmacological actions of a drug that, within the dose range in which it has been found to possess clinical utility, may produce alterations in mood, perceptual, cognitive, and psychomotor functions that limit the capacity of the individual or constitute a hazard to one's well-being). A drug effect such as sedation or motor stimulation may be considered adverse for one patient and yet therapeutic and desired for another patient; within the same patient, it may be of value at one stage of one's illness and adverse at a later stage. The concept of behavioral toxicity encompasses adverse events that may be limited to the period of drug administration and/or persist long after their discontinuation. These latter phenomena can be subsumed under the rubric of iatrogenic comorbidity. Behavioral toxicity may ensue with any type of medical drug. Examples related to antidepressant drug use (onset of suicidality and aggression, switching from unipolar to bipolar course, withdrawal phenomena upon discontinuation, postwithdrawal persistent disorders) are discussed. Consideration of potential vulnerability to adverse events including behavioral toxicity should be placed in the context of the benefits that treatment may entail.
Yolk Sac Tumor in Extragonadal Pelvic Sites
Authors: Ravishankar Sanjita , Malpica Anais , Ramalingam Preetha , Euscher Elizabeth D.
Published: September 2016

We present the clinicopathologic features of 15 cases of extragonadal yolk sac tumor (EGYST) detected in female patients and reviewed at our institution from 1988 to 2016. We recorded: patient age, clinical presentation, tumor location, FIGO stage (where applicable), histologic patterns including presence/absence of Schiller-Duval bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. Patients’ ages ranged from 17 to 87 (median, 62) years and presentation included: abnormal uterine bleeding, 12; hematuria, 1; labial mass, 1; abdominal pain, 1. Primary sites were as follows: uterus (11), vagina (1), vulva (1), bladder (1), and peritoneum (1). Seven patients presented at FIGO stage III or IV. The following histologic patterns were observed: microcystic/reticular (7), glandular (8), solid (8), papillary (5), and hepatoid (1). An admixture of histologic patterns was present in 10 cases. Schiller-Duval bodies were seen in only 3 (23%) cases. Eight cases (46%), all uterine primaries, had associated somatic components, and 2 (15%) had a second germ cell component. In 13/14 (93%) cases, the yolk sac tumor component was either missed or misclassified as adenocarcinoma. Immunoperoxidase studies facilitated the diagnosis in all cases as follows: SALL4, 12/12; CDX2, 10/12; α fetoprotein, 7/14; glypican-3, 9/10; cytokeratin 20, 5/9 (rare cells); cytokeratin 7, 3/12 (nondiffuse); PAX8, 2/9 (variable expression). All patients received chemotherapy and all except 1 underwent surgical resection. Follow-up from 5 to 86 months was available for 13 patients: 5 died of disease, 6 are alive with disease, and 2 have no evidence of disease. EGYST arising in the female pelvis of peri/postmenopausal patients may be associated with a somatic component and represent either somatically derived YST or YST differentiation within a somatic carcinoma. EGYST in younger patients is likely a true germ cell neoplasm, and may respond to germ cell appropriate chemotherapy. The benefit of germ cell appropriate chemotherapy in somatically derived EGYST is less clear. Awareness that the presence of glandular or microcystic patterns may lead to under-recognition or misdiagnosis of EGYST in combination with immunomarkers for germ cell and yolk sac differentiation will facilitate the diagnosis.
EGFR Exon 20 Insertion/Duplication Mutations Characterize Fibrous Hamartoma of Infancy
Authors: Park Jason Y. , Cohen Cynthia , Lopez Dania , Ramos Erica , Wagenfuehr Jennifer , Rakheja Dinesh
Published: September 2016

Fibrous hamartoma of infancy (FHI) is a benign mesenchymal tumor histologically characterized by a mixture of intersecting fascicles of fibroblasts/myofibroblasts in collagenous stroma, nests of primitive oval or stellate cells in basophilic mucoid stroma, and mature adipose tissue. We hypothesized that FHI, because of histologic overlap with mesenchymal overgrowth tumors seen in CLOVES (Congenital Lipomatous Overgrowth with Vascular, Epidermal, Skeletal anomalies) and Proteus syndromes, may harbor mutations in signaling pathways associated with cellular proliferation. Formalin-fixed paraffin-embedded material from a discovery set of 4 cases of FHI was investigated by targeted next-generation sequencing of a panel of cancer-associated genes. The results were confirmed by targeted Sanger sequencing of EGFR exon 20. A validation set of 8 cases of FHI and 10 cases of other pediatric fatty tumors were investigated by targeted Sanger sequencing of EGFR exon 20. All 12 cases of FHI, and none of the 10 control tumors, showed EGFR exon 20 insertion/duplication mutations. This is the first report of molecular aberrations in FHI. The consistent occurrence of EGFR exon 20 insertion/duplication mutations in 100% of cases of FHI studied suggests that they must play a principal role in the pathogenesis of FHI, likely by conferring a potential for growth and local infiltration. Although surgical treatment will remain the mainstay of FHI treatment, tyrosine kinase inhibitors may have an adjunctive role in cases that are difficult to resect.
Intracranial Pressure Monitoring in Infants and Young Children With Traumatic Brain Injury
Authors: Dixon Rebecca R. , Nocera Maryalice , Zolotor Adam J. , Keenan Heather T.
Published: September 2016

Objective:

To examine the use of intracranial pressure monitors and treatment for elevated intracranial pressure in children 24 months old or younger with traumatic brain injury in North Carolina between April 2009 and March 2012 and compare this with a similar cohort recruited 2000–2001.

Design:

Prospective, observational cohort study.

Setting:

Twelve PICUs in North Carolina.

Patients:

All children 24 months old or younger with traumatic brain injury, admitted to an included PICU.

Interventions:

None.

Measurement and Main Results:

The use of intracranial pressure monitors and treatments for elevated intracranial pressure were evaluated in 238 children with traumatic brain injury. Intracranial pressure monitoring (risk ratio, 3.7; 95% CI, 1.5–9.3) and intracranial pressure therapies were more common in children with Glasgow Coma Scale less than or equal to 8 compared with Glasgow Coma Scale greater than 8. However, only 17% of children with Glasgow Coma Scale less than or equal to 8 received a monitoring device. Treatments for elevated intracranial pressure were more common in children with monitors; yet, some children without monitors received therapies traditionally used to lower intracranial pressure. Unadjusted predictors of monitoring were Glasgow Coma Scale less than or equal to 8, receipt of cardiopulmonary resuscitation, nonwhite race. Logistic regression showed no strong predictors of intracranial pressure monitor use. Compared with the 2000 cohort, children in the 2010 cohort with Glasgow Coma Scale less than or equal to 8 were less likely to receive monitoring (risk ratio, 0.5; 95% CI, 0.3–1.0), although the estimate was not precise, or intracranial pressure management therapies.

Conclusion:

Children in the 2010 cohort with a Glasgow Coma Scale less than or equal to 8 were less likely to receive an intracranial pressure monitor or hyperosmolar therapy than children in the 2000 cohort; however, about 10% of children without monitors received therapies to decrease intracranial pressure. This suggests treatment heterogeneity in children 24 months old or younger with traumatic brain injury and a need for better evidence to support treatment recommendations for this group of children.
Effectiveness of Autologous Fat Grafting in Adherent Scars: Results Obtained by a Comprehensive Scar Evaluation Protocol
Authors: Jaspers Mariëlle E. H. , Brouwer Katrien M. , van Trier Antoine J. M. , Groot Marloes L. , Middelkoop Esther , van Zuijlen Paul P. M.
Published: September 2016

Background:

Nowadays, patients normally survive severe traumas such as burn injuries and necrotizing fasciitis. Large skin defects can be closed but the scars remain. Scars may become adherent to underlying structures when the subcutical fat layer is damaged. Autologous fat grafting provides the possibility of reconstructing a functional sliding layer underneath the scar. Autologous fat grafting is becoming increasingly popular for scar treatment, although large studies using validated evaluation tools are lacking. The authors therefore objectified the effectiveness of single-treatment autologous fat grafting on scar pliability using validated scar measurement tools.

Methods:

Forty patients with adherent scars receiving single-treatment autologous fat grafting were measured preoperatively and at 3-month follow-up. The primary outcome parameter was scar pliability, measured using the Cutometer. Scar quality was also evaluated by the Patient and Observer Scar Assessment Scale and the DSM II ColorMeter. To prevent selection bias, measurements were performed following a standardized algorithm.

Results:

The Cutometer parameters elasticity and maximal extension improved 22.5 percent (p < 0.001) and 15.6 percent (p = 0.001), respectively. Total Patient and Observer Scar Assessment Scale scores improved from 3.6 to 2.9 on the observer scale, and from 5.1 to 3.8 on the patient scale (both p < 0.001). Color differences between the scar and normal skin remained unaltered.

Conclusions:

For the first time, the effect of autologous fat grafting on functional scar parameters was ascertained using a comprehensive scar evaluation protocol. The improved scar pliability supports the authors’ hypothesis that the function of the subcutis can be restored to a certain extent by single-treatment autologous fat grafting.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM
Authors: Hosek Sybil G. , Rudy Bret , Landovitz Raphael , Kapogiannis Bill , Siberry George , Rutledge Brandy , Liu Nancy , Brothers Jennifer , Mulligan Kathleen , Zimet Gregory , Lally Michelle , Mayer Kenneth H. , Anderson Peter , Kiser Jennifer , Rooney James F. , Wilson Craig M. ,   the Adolescent Trials Network (ATN) for HIV/AIDS Interventions
Published: September 2016

Background:

Young men who have sex with men (YMSM) are a key population for implementation of preexposure prophylaxis (PrEP) interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 US cities.

Methods:

Eligible participants were 18- to 22-year-old HIV-uninfected MSM who reported HIV transmission risk behavior in the previous 6 months. Participants were provided daily tenofovir disoproxil fumarate/emtricitabine (Truvada). Study visits occurred at baseline, monthly through week 12, and then quarterly through week 48. Dried blood spots were serially collected for the quantification of tenofovir diphosphate (TFV-DP).

Results:

Between March and September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age = 20.2; 54.5% black, 26.5% Latino). Diagnosis of sexually transmitted infections, including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with ≥4 pills per week. By week 48, 34% of participants had TFV-DP levels consistent with ≥4 pills per week, with a noticeable drop-off occurring at week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Condomless sex was reported by >80% of participants, and condomless anal sex with last partner was associated with higher TFV-DP levels.

Conclusions:

Acceptability of PrEP was high, and most participants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the United States may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.
Changes in Male Circumcision Prevalence and Risk Compensation in the Kisumu, Kenya Population, 2008–2013
Authors: Westercamp Matthew , Jaoko Walter , Mehta Supriya , Abuor Pauline , Siambe Perez , Bailey Robert C.
Published: September 2016

Background:

Three randomized controlled trials showed that voluntary medical male circumcision (VMMC) reduces the risk of female-to-male HIV transmission by approximately 60%. However, data from communities where VMMC programs have been implemented are needed to assess changes in circumcision prevalence and whether men and women compensate for perceived reductions in risk by increasing their HIV risk behaviors.

Methods:

Scale-up of free VMMC began in Kisumu, Kenya in 2008. Between 2009 and 2013, a sequence of 3 unlinked cross-sectional surveys were conducted. All individuals 15–49 years of age residing in randomly selected households were interviewed and offered HIV testing. Male circumcision status was confirmed by examination. Design-adjusted bivariate comparisons and multivariable analyses were used for statistical inference.

Results:

The prevalence of male circumcision increased from 32% (95% CI: 26% to 38%) in 2009 to 60% (95% CI: 56% to 63%) in 2013. The adjusted prevalence ratio of HIV and genital ulcer disease in circumcised compared with uncircumcised men was 0.48 (95% CI: 0.36 to 0.66) and 0.51 (95% CI: 0.37 to 0.69), respectively. There was no association between circumcision status and sexual behaviors, HIV knowledge, or indicators of risk perception.

Conclusions:

The conditions necessary for the VMMC program to have a significant public health impact are present in Kisumu, Kenya. Between 2009 and 2013, circumcision prevalence increased from 30% to 60%; HIV prevalence in circumcised men was half that of uncircumcised men, and there was no or minimal sexual risk compensation.