bluuebunny/crossref_metadata_2025 huggingface dataset:
Crumpled reduced graphene oxide–amine–titanium dioxide nanocomposites for simultaneous carbon dioxide adsorption and photoreduction
Authors: Nie Yao , Wang Wei-Ning , Jiang Yi , Fortner John , Biswas Pratim
Published: June 2016

Crumpled reduced graphene oxide–amine–titanium dioxide nanocomposites (CGOATI) for simultaneous CO2adsorption and photoreduction were synthesized by an one-step aerosol approach.
Reduction of ormaplatin and cis-diamminetetrachloroplatinum(iv) by ascorbic acid and dominant thiols in human plasma: kinetic and mechanistic analyses
Authors: Dong Jingran , Ren Yanli , Huo Shuying , Shen Shigang , Xu Jianzhong , Tian Hongwu , Shi Tiesheng
Published: June 2016

The reductions of Pt(iv) anticancer prodrugs [Pt(dach)Cl4] (ormaplatin/tetraplatin) and cis-[Pt(NH3)2Cl4] by several dominant reductants in human plasma have been characterized and analyzed kinetically and mechanistically.
Ullmann reaction through ecocatalysis: insights from bioresource and synthetic potential
Authors: Clavé Guillaume , Garel Claire , Poullain Cyril , Renard Brice-Loïc , Olszewski Tomasz K. , Lange Bastien , Shutcha Mylor , Faucon Michel-Pierre , Grison Claude
Published: June 2016

We report the elaboration of novel bio-sourced ecocatalysts for the Ullmann coupling reaction.
Mechanism and free energy profile of base-catalyzed Knoevenagel condensation reaction
Authors: Dalessandro Ellen V. , Collin Hugo P. , Valle Marcelo S. , Pliego Josefredo R.
Published: June 2016

A reliable theoretical calculation of the free energy profile of a base-catalyzed Knoevenagel reaction shows that hydroxide ion elimination step is rate determining.
Fabrication of anatase/rutile hierarchical nanospheres with enhanced n/p type gas sensing performance at room temperature
Authors: Shao Shaofeng , Wang Shimin , Jiang Fan , Wu Hongyan , Wu Tao , Lei Yating , Fei Jialei , Koehn Ralf
Published: June 2016

Porous Pt decorated anatase/rutile sensing nanospheres with high crystallinity and large surface area synthesized through psHT treatment present enhanced sensitivity and selectivity to VOCs vapor at room temperature.
Structure and function of histone methylation-binding proteins in plants
Authors: Liu Yanli , Min Jinrong
Published: June 2016

Post-translational modifications of histones play important roles in modulating many essential biological processes in both animals and plants. These covalent modifications, including methylation, acetylation, phosphorylation, ubiquitination, SUMOylation and so on, are laid out and erased by histone-modifying enzymes and read out by effector proteins. Recent studies have revealed that a number of developmental processes in plants are under the control of histone post-translational modifications, such as floral transition, seed germination, organogenesis and morphogenesis. Therefore, it is critical to identify those protein domains, which could specifically recognize these post-translational modifications to modulate chromatin structure and regulate gene expression. In the present review, we discuss the recent progress in understanding the structure and function of the histone methylation readers in plants, by focusing on Arabidopsis thaliana proteins.
Plasma model of discharge along a dielectric surface in N2/O2 mixtures
Authors: Sima Wenxia , Liu Chunxiang , Yang Ming , Shao Qianqiu , Xu Hang , Liu Sanwei
Published: June 2016

Surface discharge phenomena often occur across the insulator in power systems, damaging the electrical equipment, but the mechanism of the electron multiplication stage during surface discharge is not yet fully understood. As such, it is necessary to investigate the mechanism of discharge along a dielectric surface. In this paper, we develop a numerical fluid model, analyzing the dynamic characteristics of discharge including the electron density, electron temperature, surface charge density, and electric field. Our results show that the electron density peaks in the head of the streamer channel, at which time the electron temperature also reaches its maximum. A thin layer of plasma can be formed, filled with a mix of positive and negative charges, so the space normal electric field in the streamer channel can be positive or negative. In addition, the surface tangential electric field and electric potential are closely related, and the potential steadily increases because there is a steady tangential electric field in the streamer channel.
Note: Easy-to-maintain electron cyclotron resonance (ECR) plasma sputtering apparatus featuring hybrid waveguide and coaxial cables for microwave delivery
Authors: Akazawa Housei
Published: June 2016

The branched-waveguide electron cyclotron resonance plasma sputtering apparatus places quartz windows for transmitting microwaves into the plasma source not in the line of sight of the target. However, the quartz windows must be replaced after some time of operation. For maintenance, the loop waveguide branching from the T-junction must be dismounted and re-assembled accurately, which is a time-consuming job. We investigated substituting the waveguide branches with two sets of coaxial cables and waveguide/coaxial cable converters to simplify assembly as far as connection and disconnection go. The resulting hybrid system worked well for the purposes of plasma generation and film deposition.
Graphene-based Yagi-Uda antenna with reconfigurable radiation patterns
Authors: Wu Yongle , Qu Meijun , Jiao Lingxiao , Liu Yuanan , Ghassemlooy Zabih
Published: June 2016

This paper presents a radiation pattern reconfigurable Yagi-Uda antenna based on graphene operating at terahertz frequencies. The antenna can be reconfigured to change the main beam pattern into two or four different radiation directions. The proposed antenna consists of a driven dipole radiation conductor, parasitic strips and embedded graphene. The hybrid graphene-metal implementation enables the antenna to have dynamic surface conductivity, which can be tuned by changing the chemical potentials. Therefore, the main beam direction, the resonance frequency, and the front-to-back ratio of the proposed antenna can be controlled by tuning the chemical potentials of the graphene embedded in different positions. The proposed two-beam reconfigurable Yagi-Uda antenna can achieve excellent unidirectional symmetrical radiation pattern with the front-to-back ratio of 11.9 dB and the10-dB impedance bandwidth of 15%. The different radiation directivity of the two-beam reconfigurable antenna can be achieved by controlling the chemical potentials of the graphene embedded in the parasitic stubs. The achievable peak gain of the proposed two-beam reconfigurable antenna is about 7.8 dB. Furthermore, we propose a four-beam reconfigurable Yagi-Uda antenna, which has stable reflection-coefficient performance although four main beams in reconfigurable cases point to four totally different directions. The corresponding peak gain, front-to-back ratio, and 10-dB impedance bandwidth of the four-beam reconfigurable antenna are about 6.4 dB, 12 dB, and 10%, respectively. Therefore, this novel design method of reconfigurable antennas is extremely promising for beam-scanning in terahertz and mid-infrared plasmonic devices and systems.
“W-X-M” transformations in isomerization of B39− borospherenes
Authors: Gao Ting-Ting , Chen Qiang , Mu Yue-Wen , Lu Haigang , Li Si-Dian
Published: June 2016

The Stone-Wales transformation plays an important role in the isomerization of fullerenes and graphenic systems. The continuous conversions between neighboring six- and seven-membered rings in the borospherene (all-boron fullerene) B40 had been discovered (Martínez-Guajardo et al. Sci. Rep. 5, 11287 (2015)). In the first axially chiral borospherenes C3 B39− and C2 B39−, we identify three active boron atoms which are located at the center of three alternative sites involving five boron atoms denoted as “W”, “X”, and “M”, respectively. The concerted movements of these active boron atoms and their close neighbors between neighboring six- and seven-membered rings define the “W-X-M” transformation of borospherenes. Extensive first-principles molecular dynamics simulations and quadratic synchronous transit transition-state searches indicate that, via three transition states (TS1, TS2, and TS3) and two intermediate species (M1 and M2), the three-step “W-X-M” transformations convert the C3 B39− global minimum into its C2 isomer at room temperature (300 K) and vice versa. The maximum barriers are only 3.89 kcal/mol from C3 to C2 B39− and 2.1 kcal/mol from C2 to C3 B39−, rendering dynamic fluxionalities to these borospherenes. Therefore, the “W-X-M” transformation plays an important role in the borospherenes and borospherene-based nanostructures.
Growth and characterization of ultra-long ZnO nanocombs
Authors: Yang Shuming , Wang Yiming , Wang Liangjun , Zhang Guofeng , Vazinishayan Ali , Duongthipthewa Anchalee
Published: June 2016

ZnO nanocombs with 25 μm comb teeth were synthesized by chemical vapor deposition (CVD) method. Experiments were carried out to investigate the influence of carrier gas flow rate and temperature on ZnO comb teeth growth. The growth mechanism was demonstrated according to the morphology of prepared nanocombs under different growth parameters. The experimental results showed that the intensity of green emission significantly increased when the ZnO nanocombs became thinner and longer. It attributed to much more hanging bonds and oxygen vacancy on the surfaces of comb teeth.
Unconventional magnetization of Fe3O4 thin film grown on amorphous SiO2 substrate
Authors: Yin Jia-Xin , Liu Zhi-Guo , Wu Shang-Fei , Wang Wen-Hong , Kong Wan-Dong , Richard Pierre , Yan Lei , Ding Hong
Published: June 2016

High quality single crystal Fe3O4 thin films with (111) orientation had been prepared on amorphous SiO2 substrate by pulsed laser deposition. The magnetization properties of the films are found to be unconventional. The Verwey transition temperature derived from the magnetization jump is around 140K, which is higher than the bulk value and it can be slightly suppressed by out-plane magnetic field; the out-of-plane magnetization, which is unexpectedly higher than the in-plane value, is also significantly increased as compared with the bulk value. Our findings highlight the unusual magnetization of Fe3O4 thin film grown on the amorphous SiO2 substrate.
Backbone Phosphonamide-Functionalized Imidazol-2-ylidene Complexes
Authors: Majhi Paresh Kumar , Schnakenburg Gregor , Arduengo Anthony J. , Streubel Rainer
Published: June 2016

The synthesis of M(CO)5 complexes bearing 4-phosphonamide and 4,5-bis(phosphonamide)-imidazol-2-ylidene ligands (NHCP = phosphonamide-based N-heterocyclic carbene) is reported. Deprotonation of respective imidazolium hydrogensulfate salts with potassium tert-butoxide (KOtBu) in the presence of [M(CO)5(CH3CN)] afforded complexes with the formula [M(CO)5(NHCP)]. In a similar fashion, reaction of in situ generated NHCP with [Rh(cod)Cl]2 (cod = 1,5-cyclooctadiene) afforded a complex with the formula [Rh(cod)Cl(NHCP)]. Low-temperature deprotonation of the imidazolium NHCP·H2SO4 with potassium hexamethyldisilazide (KHMDS) in the presence of [AuCl(SMe2)] furnished the corresponding AuI NHC complex. All complexes were characterized by various spectroscopic and spectrometric methods. In addition, further structural confirmation is provided by key single-crystal X-ray structure determinations for three of the new complexes.
Hypersensitivity reactions to heparins
Authors: Gonzalez-Delgado Purificación , Fernandez Javier
Published: June 2016

Purpose of review

This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients.

Recent findings

Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.

Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.

Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives.

Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.
Large local reactions to insect envenomation
Authors: Carlson John , Golden David B.K.
Published: June 2016

Purpose of review

Insect stings often induce large local reactions (LLRs) that result in morbidity. These reactions do have an immunologic basis; however, patients presenting with LLRs should be managed differently than those with systemic allergic reactions, as described in this review.

Recent findings

Morbidity results from the inflammation itself along with the iatrogenic consequences of treatment. The prescription of antihistamine medications and the use of antibiotics are generally not indicated for patients with LLRs because of the risks/side-effects of these medications and the low probability of benefit. Some patients are also concerned over the possibility that a future sting will evolve into a life-threatening reaction. Although these reactions do involve IgE, patients are not at sufficient risk to warrant prescription of autoinjectable epinephrine. Venom-specific immunotherapy can be considered when LLRs are frequent and associated with significant impairment.

Clinicians can reduce morbidity from LLRs by reassuring the patients, avoiding medications that result in side-effects when they are not indicated, and referring to an allergist when there are additional concerns, such as frequent impairment.
Correct techniques for the use of bioabsorbable implants in orthopaedic trauma
Authors: Zamora Rodolfo , Jackson Adam , Seligson David
Published: June 2016

Since the mid 1980s, the materials and designs of bioabsorbable screws and rods have improved with better biocompatibility, absorbability, and biomechanics, thus reducing the rate of complications. This article describes the differences in the placement of bioabsorbable materials and conventional materials and how the differences affect applicability in orthopaedic procedures. Bioabsorbable screws and pins can be used for different types of fractures. However, when used it is important to consider the differences between bioabsorbable and conventional materials during the surgical technique. When using bioabsorbable materials, the following must be considered: the bone surface should be fully seen, even cannulated screws; the entire length of the pilot hole requires drilling or tapping; screws and rods are nonreversible; drilling of bioabsorbable materials is possible, if required; screws or rods, if long or prominent, can be cut or shaped to avoid skin complications; bioabsorbable implants cannot be seen on radiography (a drill bit or Kirschner wire must be used to assure that the final position of the screw or rod will be correct); and there are no self-adjustment properties when bioabsorbable screws or rods are inserted. Conventional materials and bioabsorbable materials require different insertion strategies. Recognizing these differences will help in the application of bioabsorbable implants and decrease the rate of complications.
Cutaneous lupus erythematosus: updates on pathogenesis and associations with systemic lupus
Authors: Stannard Jasmine N. , Kahlenberg J. Michelle
Published: June 2016

Purpose of review

Cutaneous lupus erythematosus (CLE) is a common manifestation among systemic lupus patients. There are no U.S. Food and Drug Administration approved therapies for CLE, and these lesions are frequently disfiguring and refractory to treatment. The present review will cover the recent inroads made into understanding the mechanisms behind CLE lesions and discuss promising therapeutic developments.

Recent findings

The definition of cutaneous lupus is being refined to facilitate diagnostic and research protocols. Research into the pathogenesis of CLE is accelerating, and discoveries are now identifying genetic and epigenetic changes which may predispose to particular disease manifestations. Furthermore, unique features of disease subtypes are being defined. Murine work supports a connection between cutaneous inflammation and systemic lupus disease activity. Importantly, human trials of type I interferon blockade hold promise for improving our treatment armamentarium for refractory CLE lesions.

Continued research to understand the mechanisms driving CLE will provide new methods for prevention and treatment of cutaneous lesions. These improvements may also have important effects on systemic disease activity, and thus, efforts to understand this link should be supported.
Outcomes of Isolated Varus Derotational Osteotomy in Children With Cerebral Palsy Hip Dysplasia and Predictors of Resubluxation
Authors: Chang Frank M. , May Allison , Faulk Leonard W. , Flynn Katherine , Miller Nancy H. , Rhodes Jason T. , Zhaoxing Pan , Novais Eduardo N.
Published: June 2016

Background:

The appropriate intervention for hip subluxation or dislocation in children affected by cerebral palsy (CP) remains controversial. The purpose of this retrospective study was to report radiographic and clinical outcomes following isolated femoral varus derotational osteotomy (VDRO) in children with CP hip dysplasia. Risk factors for resubluxation and avascular necrosis (AVN) were also examined.

Methods:

A cohort of 100 patients (199 hips) with CP treated with isolated VDRO between 2003 and 2009 was reviewed. All but 1 patient received bilateral surgery. Patients were followed for an average of 5.4 years (range, 1.03 to 10.20 y). Anteroposterior pelvic radiographs were used to assess migration percentage (MP), Shenton’s line, and presence of AVN. Resubluxation was defined as a postoperative break in Shenton’s line. Radiographic outcomes and risk analysis was performed in the 91 subjects (179 hips) with radiographic follow-up >1 year.

Results:

Significant improvement was observed in MP, and all hips had a reconstituted Shenton’s line following surgery. Over the course of follow-up, 16% of hips were noted to have a repeat break in Shenton’s line. Univariate risk analysis showed preoperative MP, Gross Motor Function Classification System (GMFCS) level, and age at surgery were risk factors for a recurrent line break. Preoperative MP and GMFCS level were found to be predictors of resubluxation in multivariate analysis. AVN was detected in 10 hips (5.7%). GMFCS level V patients were more at risk for resubluxation, but less at risk for AVN when compared with ambulatory (GMFCS I/II/II) patients and GMFCS level IV patients.

Conclusions:

Performing a VDRO without additional procedures provided a stable and concentrically reduced hip joint in this population of children with CP. Attention should be paid to initial ambulatory status during the postoperative period. Concomitant procedures such as pelvic osteotomy should be considered for patients of GMFCS level IV and V, as these patients were more at risk for recurrent subluxation.

Level of Evidence:

Level III—retrospective comparative study.
Radiation Exposure During Operative Fixation of Pediatric Supracondylar Humerus Fractures: Is Lead Shielding Necessary?
Authors: Martus Jeffrey E. , Hilmes Melissa A. , Grice Jared V. , Stutz Christopher M. , Schoenecker Jonathan G. , Lovejoy Steven A. , Mencio Gregory A.
Published: June 2016

Background:

Factors that impact radiation exposure during operative fixation of pediatric supracondylar humerus (SCH) fractures have been investigated; however, no studies have measured the equivalent dose at the patient’s radiosensitive organs. Our hypothesis was that intraoperative fluoroscopy exposes pediatric patients to a significant radiation load and lead shielding of radiosensitive organs is important. The goal of the study was to quantify the patient’s radiation exposure during the procedure by measuring the radiation load at the thyroid and gonads.

Methods:

A prospective quality improvement project of radiation exposure during percutaneous fixation of isolated SCH fractures was performed over a 4-week period. The c-arm image intensifier was used as the operating table and radiation dosimeters were positioned over the thyroid and gonadal lead shields. Fluoroscopy times were recorded, doses were calculated, and the dosimeters were analyzed. To assure that the prospective cohort was representative of a larger population of SCH fractures, demographics and fluoroscopy time of the prospective cohort were compared with a 12-month retrospective cohort in which dosimetry was not performed.

Results:

Prospective cohort—18 patients with type 2 (8) and type 3 (10) fractures were prospectively studied with intraoperative measurement of thyroid and gonadal radiation equivalent doses. Mean age was 4.9 years (1.9 to 9.5 y) and mean weight was 21.4 kg (13.1 to 33.5 kg). Mean fluoroscopy time was 65.0 seconds (25.3 to 168.4 s), and absorbed skin dose at the elbow was 0.47 mGy (0.18 to 1.21 mGy). The radiation dosimeters overlying the thyroid and gonads measured minimal radiation indicating equivalent doses of <0.01 mSv for all patients in the prospective cohort.

Retrospective cohort—163 patients with type 2 (60) and type 3 (103) fractures were retrospectively studied. The mean age was 5.5 years (0.02 to 13.7 y) and weight was 21.6 kg (2.0 to 71.9 kg). Mean fluoroscopy time was 74.1 seconds (10.2 to 288.9 s), and absorbed skin dose at the elbow was 0.53 mGy (0.07 to 2.07 mGy).

There were no statistically significant differences between the cohorts.

Conclusions:

The smaller prospective cohort had fluoroscopy times and radiation doses that were not statistically different from the larger retrospective cohort, suggesting that the dosimeter measurements are representative of intraoperative radiation exposure during fixation of pediatric SCH fractures. The equivalent dose to the thyroid and gonads was minimal and approximates daily background radiation. Shielding of radiosensitive organs is appropriate when practical to minimize cumulative lifetime radiation exposure, particularly in smaller patients and when longer fluoroscopy times are anticipated.

Level of Evidence:

Level 2.
Diverticular Abscess Managed With Long-term Definitive Nonoperative Intent Is Safe
Authors: Garfinkle Richard , Kugler Aaron , Pelsser Vincent , Vasilevsky Carol-Ann , Morin Nancy , Gordon Philip , Feldman Liane , Boutros Marylise
Published: June 2016

BACKGROUND:

Initial nonoperative management of diverticular abscess has become the standard of care; however, the need for elective resection after this index episode is unclear.

OBJECTIVE:

The purpose of this study was to assess the long-term outcomes of expectant management after initial nonoperative treatment of diverticular abscess.

DESIGN:

This was a retrospective chart review with prospective telephone follow-up of patients.

SETTINGS:

The study was conducted at a large tertiary academic colorectal surgery practice in Canada.

PATIENTS:

Adult patients with CT-documented acute sigmoid diverticulitis complicated by abscess managed nonoperatively from 2000 to 2013 were included.

INTERVENTIONS:

Long-term definitive nonoperative management of diverticular abscess.

MAIN OUTCOME MEASURES:

The primary outcome was emergency sigmoidectomy or death from recurrent diverticulitis. Secondary outcomes were recurrent diverticulitis and elective sigmoidectomy for diverticulitis.

RESULTS:

Of 135 patients with acute diverticulitis complicated by abscess, a total of 73 patients were managed with nonoperative intent and long-term expectant management. The median follow-up was 62 (Q1 to Q3: 28–98) months. After resolution of the index episode, 22 patients [30.1% (95% CI, 19.6%–40.6%)] experienced a recurrent episode of diverticulitis at a median of 23 (range, 9–40) months. Two patients [2.7% (95% CI, –1.0% to 6.4%)] had a recurrent episode with peritonitis that required sigmoidectomy with stoma at 6 and 64 months. Both patients underwent reversal after 4 and 8 months. Seven [9.6% (95% CI, 2.8%–16.4%)] patients experienced a complicated recurrence and underwent an elective sigmoidectomy [median time to colectomy, 33 (range, 16–56) months]. Thirteen patients [17.8% (95% CI, 9.0%–26.6%)] experienced an uncomplicated recurrence, all of whom were managed with continued nonoperative intent [median follow-up, 81 (range, 34–115) months]. No mortality occurred. On multivariate logistic regression, female gender (p = 0.048) and a previous episode of uncomplicated diverticulitis before the index diverticular abscess (p = 0.020) were associated with a recurrent episode.

LIMITATIONS:

This study was limited by its retrospective design and modest sample size.

CONCLUSIONS:

After initial successful nonoperative management of diverticulitis with abscess, expectant management with nonoperative intent is a safe long-term option with low rates of surgery, especially in the emergency setting. See Video, Supplemental Digital Content 1, on the nonoperative management of diverticular abscess at http://links.lww.com/DCR/A234.
The prevalence and co-occurrence of hematological complications at the time of diagnosis of chronic hepatitis C in Poland: a cross-sectional study
Authors: Pierucka Magdalena , Stalke Piotr , Zagożdżon Paweł , Smiatacz Tomasz , Zaucha Jan M.
Published: June 2016

Objectives

To evaluate the frequency, co-occurrence, and risk factors for hematological complications at the time of diagnosis of chronic hepatitis C (CHC).

Methods

This study included 1237 patients with CHC aged 18–88 years diagnosed in the years 1998–2010 in the Pomeranian region of Poland. Clinical data, cell blood count, liver biopsy, and biochemistry results were obtained retrospectively.

Results

Hematological complications were found in 31% of patients. The most frequent complication was thrombocytopenia (23.8%). The multivariate analysis showed a 5.1-fold increased risk (P<0.05) of at least one additional hematological complication in patients with thrombocytopenia. The greatest increase in risk (7.3) was related to leukopenia and cryoglobulinemia (2.3). The risk of leukopenia was correlated with the severity of thrombocytopenia. The risk of leukopenia and thrombocytopenia increased significantly from, respectively, stages 3 and 2 of liver fibrosis compared with patients without fibrosis.

Conclusion

In patients with CHC, decreases in cell blood count occur quite frequently. The most often is mild and solitary thrombocytopenia, but if severe, it may be accompanied by leukopenia, especially in women. The presence of thrombocytopenia and leukopenia in patients with CHC may indicate advanced liver fibrosis or its final stage: cirrhosis.
Advancement in management of epidermolysis bullosa
Authors: Cohn Heather I. , Teng Joyce M.C.
Published: June 2016

Purpose of review

Epidermolysis bullosa is a hereditary skin disorder characterized by skin fragility. However, the disease can manifest in many different organ systems, therefore children born with epidermolysis bullosa may have life long, complex medical needs. In this review, we will use a system-based approach to highlight important aspects of disease management and recent advancements in each of the areas. In addition, we will overview some of the cutting edge therapeutic developments in epidermolysis bullosa.

Recent findings

Recent advancements in supportive care of epidermolysis bullosa with focus on wound, pain, pruritus and nutrition status were discussed. Clinical surveillance and complication prevention are critical to improve clinical outcomes. Generalized epidermolysis bullosa is a systemic disease with increased morbidity and mortality; therefore, complex care using a multidisciplinary approach will provide the greatest benefits for patients. Current targeted treatments for epidermolysis bullosa aim at restoring the skin integrity using protein, cell, and gene therapies.

Improvement in care of epidermolysis bullosa in recent years results from keen clinical observation, novel molecular targeting, and the embracement of translational research.
Feeding Disorders in Children With Autism Spectrum Disorders Are Associated With Eosinophilic Esophagitis
Authors: Heifert Theresa A. , Susi Apryl , Hisle‐Gorman Elizabeth , Erdie‐Lalena Christine R. , Gorman Gregory , Min Steve B. , Nylund Cade M.
Published: June 2016

Objectives:

Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASDs) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE.

Methods:

A retrospective matched case‐cohort study was performed using the Military Health System database from October 2008 to September 2013. We performed a 1:5 case‐control match by age, sex, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined using diagnostic and procedure codes.

Results:

There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared with controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared with other atopic conditions, among both children with ASD (7.17, 95% confidence interval [CI] 4.87–10.5) and controls (11.5, 95% CI 7.57–17.5). Compared with controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39–1.88).

Conclusions:

Children with ASD are more likely to be diagnosed with EoE compared with controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE.
Development and Implementation of a Capstone Objective Structured Clinical Examination in Nurse Practitioner and Nurse-Midwifery Programs
Authors: Benbenek Mary , Dierich Mary , Wyman Jean , Avery Melissa , Juve Catherine , Miller Jane
Published: June 2016

Determining when advanced practice registered nurse students are safe and competent for beginning-level practice is challenging. This article describes the development and testing of a capstone objective structured clinical examination designed to evaluate the practice readiness of students enrolled in the family, adult-gerontology, women's health nurse practitioner, and nurse-midwifery tracks. Lessons learned from this process and how they were used to enhance the curricula are discussed.
Geo-climatic gradient shapes functional trait variations inSalix eriocephalaMichx
Authors: Shunmugam Arun S.K. , Soolanayakanahally Raju Y. , Guy Robert D.
Published: June 2016

Intraspecific variations in seasonal phenology and growth physiology reflect adaptation to local climate. To explore the patterns of local adaptation along latitudinal and longitudinal clines, we used thirty-four populations ofSalix eriocephalasourced from its natural ranges across Canada. The genotypes were examined for 6 phenology and 19 ecophysiology traits over two growing seasons under common garden condition. Photosynthetic assimilation rate (A) increased with increasein latitude when measured during free growth. In spite, the negative correlation between stomatal density and stomatal conductance (gs), higherAis facilitatedvialarger pore length among genotypes from short growing seasons. In addition, higherA, was positively associated with total leafnitrogen and leaf mass per unit area. No population level differences wereobserved for water use-efficiency (Δ13C), however nitrogen isotope discrimination (δ15N) displayed latitudinalclines. Growing season phenological traits considered in this study accounted highheritability (H2=0.65-0.94).Melampsorarust infestation also displayed a strong latitudinal cline with high-latitude genotypes being more susceptible. Overall, the results support the hypothesis that functional trait variations are largely explained by climate of origin and facilitate selection of parents with superior adaptive traits in the Canadian willow improvement program forbioenergy and environmental applications.
Characterizing the Non-Normal Distribution of Flow Cytometry Measurements from Transiently Expressed Constructs in Mammalian Cells
Authors: McLean Peter F. , Smolke Christina D. , Salit Marc
Published: June 2016

In mammalian cells, transient gene expression (TGE) is a rapid, minimal-investment alternative to single-copy integrations for testing of transgenic constructs. However, transient gene expression, as measured by flow cytometry with a fluorescent reporter, typically displays a broad, asymmetric distribution with a left-tail that is convolved with background signal. Common approaches for deriving a summary statistic for transiently expressed gene products impose a normal distribution on gated or ungated data. Summary statistics derived from these models are heavily biased by experimental conditions and instrument settings that are difficult to replicate and insufficient to accurately describe the underlying data. Here, we present a convolved gamma distribution as a superior model for TGE datasets. The 4-6 parameters of this model are sufficient to accurately describe the entire, ungated distribution of transiently transfected HEK cells expressing monomeric fluorescent proteins, that operates consistently across a range of transfection conditions and instrument settings. Based on these observations, a convolved gamma model of TGE distributions has the potential to significantly improve the accuracy and reproducibility of genetic device characterization in mammalian cells.
Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density
Authors: Walkup Ward G. , Mastro Tara , Schenker Leslie T. , Vielmetter Jost , Hu Rebecca , Iancu Ariella , Reghunathan Meera , Bannon B. Dylan , Mary B. Kennedy
Published: June 2016

SynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95,Discs-large,ZO-1) domains of PSD-95. We show that phosphorylation of synGAP by Ca2+/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. SynGAP is abundant enough in postsynaptic densities (PSDs) to occupy about one third of the PDZ domains of PSD-95. Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP’s ability to restrict binding of other proteins to the PDZ domains of PSD-95. We support this hypothesis by showing that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present at a higher ratio to PSD-95 in PSDs isolated from synGAP heterozygous mice.
Human germline mutation and the erratic evolutionary clock
Authors: Moorjani Priya , Gao Ziyue , Przeworski Molly
Published: June 2016

Our understanding of the chronology of human evolution relies on the “molecular clock” provided by the steady accumulation of substitutions on an evolutionary lineage. Recent analyses of human pedigrees have called this understanding into question, by revealing unexpectedly low germline mutation rates, which imply that substitutions accrue more slowly than previously believed. Translating mutation rates estimated from pedigrees into substitution rates is not as straightforward as it may seem, however. We dissect the steps involved, emphasizing that dating evolutionary events requires not “a mutation rate,” but a precise characterization of how mutations accumulate in development, in males and females—knowledge that remains elusive.
Improving construction sector resilience
Authors: Wilkinson Suzanne , Chang-Richards Alice Yan , Sapeciay Zulkfli , Costello Seosamh B.
Published: June 2016

Purpose

Improving the resilience of the construction sector helps countries recover quicker from crises and can assist with improving community resilience and recovery. This study aims to explore ways in which the construction sector might improve its resilience.

Design/methodology/approach

This paper examined past disasters and the role construction plays to understand what and how better construction resilience can be built, and the impact this will have on recovery and reconstruction.

Findings

The findings showed that after a crisis, the construction sector is called upon to manage building and infrastructure recovery and reconstruction. Construction organisations are needed by the community, as they provide physical resources, people, materials, logistics, management and technical expertise and rebuilding. To ensure that recovery and reconstruction programs are successfully implemented, it is necessary for the construction sector to be resilient. To achieve improved resilience in the construction industry, disaster resilience management needs to become mainstreamed into construction processes.

Research limitations/implications

Although larger organisations have some preparation to respond to crises, including having emergency or disaster plans, smaller companies struggle to achieve a reasonable level of resilience. It appears that senior management and key people in construction organisations are familiar with the procedures but that the majority of staff in organisations lack knowledge and skills.

Practical implications

Understanding the role the construction sector plays in disasters and providing directions for improving construction sector resilience will ultimately improve recovery and reconstruction outcomes.

Social Implications

This paper discusses how communities rely on services provided by construction organisations to enable them to recover from emergencies and crises. Pre-disaster construction company resilience impacts on the ability of construction companies to function post-disaster.

Originality/value

This paper focuses on a number of cases and shows where and how the construction sector has worked in disasters and provides a new analysis of the role the industry plays, and the various disaster stages where the industry has maximum impact.
Fitness costs of animal medication: antiparasitic plant chemicals reduce fitness of monarch butterfly hosts
Authors: Tao Leiling , Hoang Kevin M. , Hunter Mark D. , de Roode Jacobus C.
Published: June 2016

The emerging field of ecological immunology demonstrates that allocation by hosts to immune defence against parasites is constrained by the costs of those defences. However, the costs of non‐immunological defences, which are important alternatives to canonical immune systems, are less well characterized. Estimating such costs is essential for our understanding of the ecology and evolution of alternative host defence strategies.

Many animals have evolved medication behaviours, whereby they use antiparasitic compounds from their environment to protect themselves or their kin from parasitism. Documenting the costs of medication behaviours is complicated by natural variation in the medicinal components of diets and their covariance with other dietary components, such as macronutrients.

In the current study, we explore the costs of the usage of antiparasitic compounds in monarch butterflies (Danaus plexippus), using natural variation in concentrations of antiparasitic compounds among plants. Upon infection by their specialist protozoan parasite Ophryocystis elektroscirrha, monarch butterflies can selectively oviposit on milkweed with high foliar concentrations of cardenolides, secondary chemicals that reduce parasite growth. Here, we show that these antiparasitic cardenolides can also impose significant costs on both uninfected and infected butterflies.

Among eight milkweed species that vary substantially in their foliar cardenolide concentration and composition, we observed the opposing effects of cardenolides on monarch fitness traits. While high foliar cardenolide concentrations increased the tolerance of monarch butterflies to infection, they reduced the survival rate of caterpillars to adulthood. Additionally, although non‐polar cardenolide compounds decreased the spore load of infected butterflies, they also reduced the life span of uninfected butterflies, resulting in a hump‐shaped curve between cardenolide non‐polarity and the life span of infected butterflies.

Overall, our results suggest that the use of antiparasitic compounds carries substantial costs, which could constrain host investment in medication behaviours.
Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira® in healthy subjects
Authors: Hyland Elizabeth , Mant Tim , Vlachos Pantelis , Attkins Neil , Ullmann Martin , Roy Sanjeev , Wagner Volker
Published: June 2016

Aims

The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of the proposed adalimumab biosimilar MSB11022 (Merck) with Humira® (AbbVie), sourced from both the US (US reference product [US‐RP]) and Europe (European reference medicinal product [EU‐RMP]).

Methods

In this phase 1 double‐blind, parallel group trial (EMR200588‐001), 213 healthy volunteers were randomized 1 : 1 : 1 to receive a single dose (40 mg) of MSB11022, US‐RP or EU‐RMP in order to achieve 80% power assuming a 5% difference among groups and a 10% dropout rate. Following a preplanned blinded sample size re‐assessment after more than 50% of the originally planned subjects had been observed, the sample size was increased to 237 (79 per arm) to ensure 213 completers. Primary PK endpoints analyzed by non‐compartmental methods, were area under the curve (AUC) from time 0 extrapolated to infinity (AUC(0,∞)), maximum observed concentration (Cmax), and AUC from time 0 to the last quantifiable concentration (AUC(0,tlast)). PK equivalence was declared if the 90% CI for the test : reference ratio lay within the 80–125% equivalence margin. Bioequivalence was demonstrated if all three PK parameters met the PK equivalence criteria. Safety and tolerability were also evaluated.

Results

Mean serum concentration–time profiles for the three treatments were similar. MSB11022 demonstrated PK equivalence to US‐RP and EU‐RMP for all primary endpoints. The geometric means of AUC(0,∞), Cmax and AUC(0,tlast) following a single dose of MSB11022 were 2276.05 μg ml–1 h, 3.44 μg ml–1  and 1983.90 μg ml–1 h, respectively. Adverse events (AEs) were similar across all groups, with treatment‐emergent AEs (TEAEs) reported by 62.8%, 56.3% and 62.0% of subjects within the MSB11022, US‐RP and EU‐RMP groups, respectively. Most of the TEAEs were considered mild and unrelated to study drug. No deaths or severe AEs related to the study drug were reported.

Conclusions

Bioequivalence between MSB11022, US‐RP and EU‐RMP was demonstrated. Safety, tolerability and immunogenicity profiles were similar between subjects receiving MSB11022 and US‐RP or EU‐RMP. These data support the further clinical evaluation of MSB11022 as a proposed biosimilar of adalimumab.
Multifactorial Influences, Including Comorbidities, Contributing to Sleep Disturbance in Children with a Neurodevelopmental Disorder
Authors: Stores Gregory
Published: June 2016

The term neurodevelopmental disorder (NDD) implies an impairment of the growth and development of the CNS caused by genetic, metabolic, toxic, or traumatic factors. Childhood neuropsychiatric disorder is a subset of NDD. Sleep disturbance is reported in many children with NDD although the details of this association, including extent and types of sleep disturbance, etiology, and assessment and treatment issues, need to be clarified by further research. This review considers the nature of sleep disturbance in NDD. Emphasis is placed on sleep disorders (i.e., the specific conditions that cause sleep problems) of which many are now recognized in the International Classification of Sleep Disorders (ICSD‐3), and also intrinsic pathophysiological factors, physical and psychiatric comorbidities, and pharmacological and parental influences, which might contribute to the sleep disorders in children with NDD. The implications of this complexity for assessment and treatment in such children are then discussed. Appropriate treatment based on precise diagnosis of the causes of sleep disturbance is required to mitigate the harmful developmental effects of disordered sleep on children with NDD and their families.
Impact of age and sex on normal left heart structure and function
Authors: Hagström Linn , Henein Michael Y. , Karp Kjell , Waldenström Anders , Lindqvist Per
Published: June 2016

Background

Accurate age‐ and sex‐related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex‐related measurements of LV structural and functional measurements to serve such purpose.

Methods

We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions.

Results

Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40–0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end‐diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years.

Conclusion

Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females.