bluuebunny/crossref_metadata_2025 huggingface dataset:
Compensation of native donor doping in ScN: Carrier concentration control and p-type ScN
Authors: Saha Bivas , Garbrecht Magnus , Perez-Taborda Jaime A. , Fawey Mohammed H. , Koh Yee Rui , Shakouri Ali , Martin-Gonzalez Marisol , Hultman Lars , Sands Timothy D.
Published: June 2017

Scandium nitride (ScN) is an emerging indirect bandgap rocksalt semiconductor that has attracted significant attention in recent years for its potential applications in thermoelectric energy conversion devices, as a semiconducting component in epitaxial metal/semiconductor superlattices and as a substrate material for high quality GaN growth. Due to the presence of oxygen impurities and native defects such as nitrogen vacancies, sputter-deposited ScN thin-films are highly degenerate n-type semiconductors with carrier concentrations in the (1–6) × 1020 cm−3 range. In this letter, we show that magnesium nitride (MgxNy) acts as an efficient hole dopant in ScN and reduces the n-type carrier concentration, turning ScN into a p-type semiconductor at high doping levels. Employing a combination of high-resolution X-ray diffraction, transmission electron microscopy, and room temperature optical and temperature dependent electrical measurements, we demonstrate that p-type Sc1-xMgxN thin-film alloys (a) are substitutional solid solutions without MgxNy precipitation, phase segregation, or secondary phase formation within the studied compositional region, (b) exhibit a maximum hole-concentration of 2.2 × 1020 cm−3 and a hole mobility of 21 cm2/Vs, (c) do not show any defect states inside the direct gap of ScN, thus retaining their basic electronic structure, and (d) exhibit alloy scattering dominating hole conduction at high temperatures. These results demonstrate MgxNy doped p-type ScN and compare well with our previous reports on p-type ScN with manganese nitride (MnxNy) doping.
Single-crystal N-polar GaN p-n diodes by plasma-assisted molecular beam epitaxy
Authors: Cho YongJin , Hu Zongyang , Nomoto Kazuki , Xing Huili Grace , Jena Debdeep
Published: June 2017

N-polar GaN p-n diodes are realized on single-crystal N-polar GaN bulk wafers by plasma-assisted molecular beam epitaxy growth. The current-voltage characteristics show high-quality rectification and electroluminescence characteristics with a high on currents ∼10 kA/cm2, low off currents <10−5 A/cm2, on/off current ratio of >109, and interband photon emission. The measured electroluminescence spectrum is dominated by a strong near-band edge emission, while deep level luminescence is greatly suppressed. A very low dislocation density leads to a high reverse breakdown electric field of ∼2.2 MV/cm without fields plates—the highest reported for N-polar epitaxial structures. The low leakage current N-polar diodes open up several potential applications in polarization-engineered photonic and electronic devices.
Spin-pumping through a varying-thickness MgO interlayer in Fe/Pt system
Authors: Mihalceanu Laura , Keller Sascha , Greser Jochen , Karfaridis Dimitrios , Simeonidis Konstantinos , Vourlias George , Kehagias Thomas , Conca Andrés , Hillebrands Burkard , Papaioannou Evangelos Th.
Published: June 2017

The spin-pumping mechanism is probed through a tunnelling MgO interlayer in Fe/Pt bilayers. We show by ferromagnetic resonance technique and spin-pumping experiments that spin currents can tunnel through the MgO interlayer for thicknesses up to 2 nm and can produce significant voltages in the Pt layer. The electrical detection of spin-pumping furthermore reveals the critical role of rectification and shunting effects on the generated voltages. The non-zero spin current transport through a few monolayers of an insulating interlayer might initiate further studies on the role of very thin oxides in spin-pumping experiments.
High outcrossing rates and short-distance pollination in a species restricted to granitic inselbergs
Authors: Hmeljevski Karina Vanessa , Wolowski Marina , Forzza Rafaela Campostrini , Freitas Leandro
Published: June 2017

Plant populations that are spatially isolated may experience genetic isolation if gene flow via pollination or seed dispersal is limited. The high genetic differentiation among populations of Encholirium horridum L.B.Sm. indicates low gene flow for this species that occurs exclusively on granitic inselbergs in South-east Brazil. Here we describe reproductive and pollination attributes of this bromeliad assessing how they influence the current degree of genetic isolation among populations. The mating system, estimated using five microsatellites markers, indicated allogamy and low pollen pool structure. The breeding system assessed by hand-pollination treatments supported partial self-incompatibility combined with inbreeding depression. Flowers of E. horridum are bell-shaped with crepuscular/nocturnal anthesis, and high nectar production, suggesting chiropterophily. Its pollination system was actually generalist but bats and hummingbirds were more frequent than hawkmoths and crepuscular bees. The high local abundance and large floral display per individual plant contributed to short distance pattern of pollen movement by pollinators. At the intra-population level, this pollinator foraging pattern, with inbreeding depression, promotes low seed viability and individual variations on outcrossing rate. At the inter-population level, those features led to low gene flow. Overall, heterozygosity, maintained by self-incompatibility and inbreeding depression, and pollination by vertebrates described here for E. horridum are consistent with other attributes that are predicted for inselberg plants by the OCBIL theory, such as reduced dispersability and genetic isolation among populations. Those characteristics contribute to the isolation of E. horridum populations and heighten the importance of population-based conservation strategies for taxa that occur exclusively in those naturally fragmented inselbergs.
Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity
Authors: Snarr Brendan D. , Baker Perrin , Bamford Natalie C. , Sato Yukiko , Liu Hong , Lehoux Mélanie , Gravelat Fabrice N. , Ostapska Hanna , Baistrocchi Shane R. , Cerone Robert P. , Filler Elan E. , Parsek Matthew R. , Filler Scott G. , Howell P. Lynne , Sheppard Donald C.
Published: June 2017

Significance

The production of biofilms is an important strategy used by both bacteria and fungi to colonize surfaces and to enhance resistance to killing by immune cells and antimicrobial agents. We demonstrate that glycoside hydrolases derived from the opportunistic fungus
Aspergillus fumigatus
and Gram-negative bacterium
Pseudomonas aeruginosa
can be exploited to disrupt preformed fungal biofilms and reduce virulence. Additionally, these glycoside hydrolases can be used to potentiate antifungal drugs by increasing their hyphal penetration, to protect human cells from fungal-induced injury, and attenuate virulence of
A. fumigatus
in a mouse model of invasive aspergillosis. The findings of this study identify recombinant microbial glycoside hydrolases as promising therapeutics with the potential for antibiofilm activity against pathogens across different taxonomic kingdoms.
Hidden electrostatic basis of dynamic allostery in a PDZ domain
Authors: Kumawat Amit , Chakrabarty Suman
Published: June 2017

Significance

Allosteric regulation is a crucial component in biochemical pathways, where ligand binding to an allosteric site modulates the enzymatic activity at a distant functional site. There is rapid growth in interest toward rational design of allosteric drugs. PDZ domain proteins (frequently encountered in signaling protein complexes) are classic examples of allostery without significant structural changes (dynamic allostery), where ligand binding leads to modulation in distal side-chain motions. So far dynamic allostery has been attributed to purely entropic effects. In contrast, here we show that a significant internal redistribution and rewiring of electrostatic interactions provide the basis of dynamic allostery in PDZ domain protein. A dramatic population shift in the pairwise hydrogen-bonded interactions involving side chains leads to the allosteric response.
Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics
Authors: Marin-Gonzalez Alberto , Vilhena J. G. , Perez Ruben , Moreno-Herrero Fernando
Published: June 2017

Significance

The mechanical properties of nucleic acids regulate multiple biological processes ranging from complex chromosome packing to replication of a plasmid. Single-molecule experiments have reported puzzling differences between the mechanical properties of double-stranded DNA (dsDNA) and double-stranded RNA (dsRNA) subjected to force and torque. This study investigates these differences using constant-force, all-atom, microsecond-long molecular dynamics. We provide a physical mechanism that explains the nonintuitive opposite twist-stretch response of these molecules based on the change of the interstrand distance with the stretching force. Changes in interstrand distance are ultimately related to differences in the chemical structure of dsDNA and dsRNA molecules. The methodology and results shown here open the field to explore larger forces to test experimental measurements, and to challenge the predictions given by our simulations.
1T-TaS
2
as a quantum spin liquid
Authors: Law K. T. , Lee Patrick A.
Published: June 2017

Significance

In solids with an odd number of electrons per unit cell, band theory requires that they are metals, but strong interaction can turn them into insulators, called Mott insulators. In this case, the electrons form local moments that, in turn, form an antiferromagnetic ground state. In 1973, P. W. Anderson proposed that, in certain cases, quantum fluctuations may prevent magnetic order and result in a paramagnetic ground state called a quantum spin liquid. After many years of searching, a few examples have been discovered in the past several years. We point out that a well-studied material, TaS
2
, may be a spin liquid candidate. We propose further experiments that probe the exotic properties of this new state of matter.
An epistemology for practical knowledge
Authors: Campbell Lucy
Published: June 2017

Anscombe thought that practical knowledge – a person’s knowledge of what she is intentionally doing – displays formal differences to ordinary empirical, or ‘speculative’, knowledge. I suggest these differences rest on the fact that practical knowledge involves intention analogously to how speculative knowledge involves belief. But this claim conflicts with the standard conception of knowledge, according to which knowledge is an inherently belief-involving phenomenon. Building on John Hyman’s account of knowledge as the ability to use a fact as a reason, I develop an alternative, two-tier, epistemology which allows that knowledge might really come in a belief-involving and an intention-involving form.
Simultaneous determination of primary and secondary d- and l-amino acids by reversed-phase high-performance liquid chromatography using pre-column derivatization with two-step labelling method
Authors: Yokoyama Takehiko , Tokuda Masaharu , Amano Masafumi , Mikami Koji
Published: June 2017

This work describes a method for the simultaneous determination of primary d- and l-amino acids and secondary amino acids such as d- and l-proline. In order to remove interferences in the simultaneous determination of primary and secondary amines, the primary amines were derivatized with o-phthalaldehyde/N-acetyl-l-cysteine (OPA/NAC) and subsequently with 1-(9-fluorenyl)ethyl chloroformate (FLEC) for secondary amines, in a pre-column separation derivatization technique. These fluorescent diastereomers of the amino acids were obtained within 3 min at room temperature and determined simultaneously by changing wavelengths during analysis in a single eluting run in the high-performance liquid chromatography column. This method, referred to as the “two-step labelling method,” is effective for the simultaneous determination of d- and l-amino acids.
Correlating the synthesis protocol of aromatic polyimide film with the properties of polyamic acid precursor
Authors: Tan P C , Ooi B S , Ahmad A L , Low S C
Published: June 2017

Thousands of different copolyimide combinations render it technically impossible to have a single universal synthesis method to produce aromatic polyimide film. This study aimed to outline the selection of synthesis protocol, either through the casting of chemically imidized polyimide solution or thermal imidization of polyamic acid (PAA), to produce the polyimide film. The rheological behaviour, molecular weight, and solubility of five structurally different PAA were analysed and correlated to both imidization methods. In this work, a tough polyimide film was successfully synthesized by casting the chemically imidized polyimide derived from high viscosity (> 81 cP) and high molecular weight (≥ 1.35 x 106 g/mol) PAA. On the contrary, both low viscosity (< 13 cP) and high viscosity (> 81 cP) PAA demonstrated the possibility to produce polyimide film via thermal imidization route. The longer molecular chain of ODPA-6FpDA:DABA (3:2) polyimide produced from thermal imidization had restricted the passage of CO2 across the polyimide film when it was applied in the gas separation application. The outcome from this work serves as a guideline for the selection of suitable polyimide film synthesis protocol, which will minimize the time and chemical consumption in future exploration of new polyimide structure.
Effect of Low-Intensity Pulsed Ultrasound on Bone Healing at Osteotomy Sites After Open Wedge High Tibial Osteotomy
Authors: Goshima Kenichi , Sawaguchi Takeshi , Shigemoto Kenji , Iwai Sintaro , Nakanishi Akira , Ueoka Ken
Published: June 2017

Objective:

The purpose of this study was to evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on bone healing at osteotomy sites after open wedge high tibial osteotomy (OWHTO).

Materials and Methods:

Twenty-six patients underwent OWHTO without bone grafting. Thirty cases treated with LIPUS (group L) after surgery were compared with 13 cases without LIPUS treatment (group C). We divided the osteotomy gap into the lateral hinge and 4 zones on anteroposterior radiography, and the progression of gap filling was evaluated at 1, 3, and 6 months post-operatively in both groups.

Results:

In group L, the lateral hinge formed a union at 3 months postoperatively in 11 knees (84.6%). At 6 months, gap filling in 10 knees (76.9%) reached to zone 2. In group C, while the lateral hinge formed a union at 3 months postoperatively in all cases. At 6 months, gap filling in 6 knees (46.1%) reached to zone 2. The progression of gap filling were 8.5%, 18.9%, and 32.9% (at 1, 3, and 6 months after surgery, respectively) in group L, while the progress levels at the same time points were 7.7%, 16.6%, and 24.4% in group C. There were significant differences at 6 months after surgery between the 2 groups.

Discussion:

LIPUS accelerated bone healing at 6 months after OWHTO. It is important that the accuracy of LIPUS methods be further studied and improved.
Change in Calcaneal Bone Strength in Long-Term Care Residents Treated With Low-Intensity Pulsed Ultrasound
Authors: Okuizumi Hiroyasu , Koyano Kiyoshi , Kurosawa Kazuya , Kamide Naoto , Soyano Ayako
Published: June 2017

Objective:

We examined the effect of low-intensity pulsed ultrasound (LIPUS) on bone strength in osteoporotic elderly residents.

Materials and Methods:

This was a randomized controlled trial. Elderly residents with osteoporosis in a long–term care facility were treated with LIPUS (oscillation frequency 100 KHz) that involved treatment of the heel bone for 2 minutes a day. The selection of the treated heel was decided randomly with a personal computer. The heel bone mineral density before and after treatment was measured by calcaneal quantitative ultrasound (GE-1000 Express).

Results:

The study included 23 residents but 3 patients developed fractures and 1 withdrew from the study. Nineteen elder residents (average age 86.9 years) completed the study with ultrasonic quantitation before and after treatment. The average speed of sound (following SOS) of the treated and non-treated side was 1438.3 and 1437.4 m/s, respectively at baseline. After 3 months, the SOS was increased to 1450.8 and 1450.5 m/s, respectively, and after 8 months it increased to, 1452.8 and 1451.6 m/s. There were no significant changes between the treated and the non-treated side of the heel bone.

Discussion:

LIPUS had no effect on increasing bone density in the elderly residents when treatment duration was 2 minutes per day. We suggest that therapy for osteoporosis with LIPUS for the elderly should be studied in the future to reduce the number of prescribed oral agents.
Effect of Low-Intensity Pulsed Ultrasound (LIPUS) on Endochondral Ossification via the Wnt Signaling Pathway
Authors: Kumagai Ken , Yamaguchi Yasuteru , Miyatake Kazuma , Tanabe Hironori , Imai Sosuke , Saito Tomoyuki
Published: June 2017

Objective:

We have previously demonstrated that LIPUS stimulates endochondral ossification with decreased expression of sclerostin. The Wnt signaling pathway was examined in vitro to further address the effect of LIPUS on endochondral ossification.

Materials and Methods:

ATDC5 cells were plated at an initial density of 6 × 104 cells/well in a 6-multiwell plate and cultured in the presence of 5% FBS plus ITS. The bottom of the culture plate was treated every day with LIPUS for 20 minutes. The level of calcification and the expression of Wnt signaling were investigated.

Results:

The area of calcified nodules in the LIPUS-treated group was significantly greater than in the control group. The expression of Wnt was significantly elevated by LIPUS exposure. Markers associated with endochondral ossification were increased in the LIPUS-treated group. When sclerostin was added to the culture media, calcified nodule formation and the expression of Wnt were inhibited in both the LIPUS-treated group and the control group.

Discussion:

This study suggests that endochondral ossification was stimulated by LIPUS via the Wnt signaling pathway.
What Is the Relationship Between a Preclerkship Portfolio Review and Later Performance in Clerkships?
Authors: O’Brien Celia Laird , Thomas John X. , Green Marianne M.
Published: June 2017

Purpose

Medical educators struggle to find effective ways to assess essential competencies such as communication, professionalism, and teamwork. Portfolio-based assessment provides one method of addressing this problem by allowing faculty reviewers to judge performance, as based on a longitudinal record of student behavior. At the Feinberg School of Medicine, the portfolio system measures behavioral competence using multiple assessments collected over time. This study examines whether a preclerkship portfolio review is a valid method of identifying problematic student behavior affecting later performance in clerkships.

Method

The authors divided students into two groups based on a summative preclerkship portfolio review in 2014: students who had concerning behavior in one or more competencies and students progressing satisfactorily. They compared how students in these groups later performed on two clerkship outcomes as of October 2015: final grades in required clerkships, and performance on a clerkship clinical composite score. They used Mann–Whitney tests and multiple linear regression to examine the relationship between portfolio review results and clerkship outcomes. They used USMLE Step 1 to control for knowledge acquisition.

Results

Students with concerning behavior preclerkship received significantly lower clerkship grades than students progressing satisfactorily (P = .002). They also scored significantly lower on the clinical composite score (P < .001). Regression analysis indicated concerning behavior was associated with lower clinical composite scores, even after controlling for knowledge acquisition.

Conclusions

The results show a preclerkship portfolio review can identify behaviors that impact clerkship performance. A comprehensive portfolio system is a valid way to measure behavioral competencies.
Exploring Integration in Action: Competencies as Building Blocks of Expertise
Authors: Mylopoulos Maria , Borschel Debaroti (Tina) , O’Brien Tara , Martimianakis Sofia , Woods Nicole N.
Published: June 2017

Purpose

Competency frameworks such as the CanMEDS roles and the ACGME core competencies may lead to the implicit assumption that physicians can learn and practice individual competencies in isolation. In contrast, models of adaptive expertise suggest that the integration of competencies reflects the capabilities of an expert physician. Thus, educational programming aimed at teaching discrete roles or competencies might overlook expert physician capabilities that are central to patient care. To develop expertise, learning opportunities must reflect expert capabilities. To better understand the relationship between competency-based medical education and expert development, the authors sought to explore how integrated competencies are enacted during patient care by postgraduate medical trainees.

Method

Using a cognitive ethnographic approach, in 2014–2015 the authors conducted observations and—to refine and elaborate these observations—ad hoc informal interviews with 13 postgraduate trainee participants. Data collection resulted in 92 hours of observation, 26 patient case portraits, and a total of 220 pages of field notes for analysis. Through analysis, the authors identified and examined moments when postgraduate trainees appeared to be simultaneously enacting multiple competencies.

Results

The authors identified two key expert capabilities in moments of integrated competence: finding complexity and being patient-centered. They described two mechanisms for these forms of integration: valuing the patient’s narrative of their illness, and integrated understanding.

Conclusions

Understanding integrated competencies as the building blocks of expert capabilities, along with recognizing the importance of mechanisms that support integration, offers an opportunity to use existing competency-based frameworks to understand and teach adaptive expertise.
Enacting Pedagogy in Curricula: On the Vital Role of Governance in Medical Education
Authors: Casiro Oscar , Regehr Glenn
Published: June 2017

Managing curricula and curricular change involves both a complex set of decisions and effective enactment of those decisions. The means by which decisions are made, implemented, and monitored constitute the governance of a program. Thus, effective academic governance is critical to effective curriculum delivery. Medical educators and medical education researchers have been invested heavily in issues of educational content, pedagogy, and design. However, relatively little consideration has been paid to the governance processes that ensure fidelity of implementation and ongoing refinements that will bring curricular practices increasingly in line with the pedagogical intent. In this article, the authors reflect on the importance of governance in medical schools and argue that, in an age of rapid advances in knowledge and medical practices, educational renewal will be inhibited if discussions of content and pedagogy are not complemented by consideration of a governance framework capable of enabling change. They explore the unique properties of medical curricula that complicate academic governance, review the definition and properties of good governance, offer mechanisms to evaluate the extent to which governance is operating effectively within a medical program, and put forward a potential research agenda for increasing the collective understanding of effective governance in medical education.
Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four
Authors: Asztalos László , Szabó-Maák Zoltán , Gajdos András , Nemes Réka , Pongrácz Adrienn , Lengyel Szabolcs , Fülesdi Béla , Tassonyi Edömér
Published: June 2017

Background

Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block.

Methods

Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9).

Results

Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P < 0.0001 vs. 1.0 and 2.0 mg/kg), whereas neostigmine produced reversal in 11.3 ± 9.7 min in 77% of patients (P > 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group.

Conclusions

Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.
Mini-fluid Challenge of 100 ml of Crystalloid Predicts Fluid Responsiveness in the Operating Room
Authors: Biais Matthieu , de Courson Hugues , Lanchon Romain , Pereira Bruno , Bardonneau Guillaume , Griton Marion , Sesay Musa , Nouette-Gaulain Karine
Published: June 2017

Background

Mini-fluid challenge of 100 ml colloids is thought to predict the effects of larger amounts of fluid (500 ml) in intensive care units. This study sought to determine whether a low quantity of crystalloid (50 and 100 ml) could predict the effects of 250 ml crystalloid in mechanically ventilated patients in the operating room.

Methods

A total of 44 mechanically ventilated patients undergoing neurosurgery were included. Volume expansion (250 ml saline 0.9%) was given to maximize cardiac output during surgery. Stroke volume index (monitored using pulse contour analysis) and pulse pressure variations were recorded before and after 50 ml infusion (given for 1 min), after another 50 ml infusion (given for 1 min), and finally after 150 ml infusion (total = 250 ml). Changes in stroke volume index induced by 50, 100, and 250 ml were recorded. Positive fluid challenges were defined as an increase in stroke volume index of 10% or more from baseline after 250 ml.

Results

A total of 88 fluid challenges were performed (32% of positive fluid challenges). Changes in stroke volume index induced by 100 ml greater than 6% (gray zone between 4 and 7%, including 19% of patients) predicted fluid responsiveness with a sensitivity of 93% (95% CI, 77 to 99%) and a specificity of 85% (95% CI, 73 to 93%). The area under the receiver operating curve of changes in stroke volume index induced by 100 ml was 0.95 (95% CI, 0.90 to 0.99) and was higher than those of changes in stroke volume index induced by 50 ml (0.83 [95% CI, 0.75 to 0.92]; P = 0.01) and pulse pressure variations (0.65 [95% CI, 0.53 to 0.78]; P < 0.005).

Conclusions

Changes in stroke volume index induced by rapid infusion of 100 ml crystalloid predicted the effects of 250 ml crystalloid in patients ventilated mechanically in the operating room.
Metabolic abnormalities and oxidative stress in lupus
Authors: Lightfoot Yaima L. , Blanco Luz P. , Kaplan Mariana J.
Published: June 2017

Purpose of review

Upon antigen exposure, immune cells rely on cell-specific metabolic pathways to mount an efficient immune response. In autoimmunity, failure in critical metabolic checkpoints may lead to immune cell hyperactivation and tissue damage. Oxidative stress in autoimmune patients can also contribute to immune dysregulation and injury to the host. Recent insights into the immune cell metabolism signatures, specifically associated with systemic lupus erythematosus (SLE) and the consequences of heightened oxidative stress in patients, are discussed herein.

Recent findings

Glucose metabolism inhibitors, mechanistic target of rapamycin pathway modulators, and peroxisome proliferator-activated receptor gamma-activating compounds demonstrate therapeutic benefit in experimental models of lupus. Mitochondrial-derived reactive oxygen species (ROS) and molecular modifications induced by oxidative stress appear to be detrimental in lupus. Effective therapies tailored toward the reconfiguration of metabolic imbalances in lupus immune cells and the reduction of mitochondrial ROS production/availability are currently being tested.

A paucity of knowledge exists regarding the metabolic needs of a number of immune cells involved in the pathogenesis of SLE, including myeloid cells and B cells. Nonetheless, SLE-specific metabolic signatures have been identified and their specific targeting, along with mitochondrial ROS inhibitors/scavengers, could show therapeutic advantage in lupus patients.
Associations between postmenopausal endogenous sex hormones and C-reactive protein: a clearer picture with regional adiposity adjustment?
Authors: Conroy Shannon M. , Neilson Heather K. , O’Reilly Rachel , Woolcott Christy G. , Stanczyk Frank Z. , Courneya Kerry S. , Friedenreich Christine M.
Published: June 2017

Objective:

To better understand the pathogenesis of inflammatory-related diseases after menopause, we studied the adiposity-independent association between endogenous sex hormones and C-reactive protein (CRP), a biomarker of inflammation.

Methods:

We conducted a secondary, cross-sectional analysis of baseline data from the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2007), including 319 healthy, postmenopausal women not using hormone therapy. Multivariable linear regression models related serum CRP levels to estrogens, androgens, and sex hormone-binding globulin (SHBG), all on the natural logarithmic scale. Models were adjusted for age, lipids, medication, and former menopausal hormone therapy use, and also for adiposity (body mass index [BMI], per cent body fat [via whole-body dual x-ray absorptiometry], or intra-abdominal fat area [via computed tomography]).

Results:

Without adiposity adjustment, estrone, total estradiol, and free estradiol were significantly positively associated with CRP, whereas SHBG was significantly inversely associated with CRP. Of all adiposity measures, adjustment for BMI caused the greatest attenuation of CRP-estrogen associations; only free estradiol (β = 0.24, 95% confidence interval [CI] 0.06, 0.43) and SHBG (β = −0.37, 95% CI −0.60, −0.13) associations remained significant. Inverse associations between CRP-total testosterone became stronger with BMI adjustment (β = −0.20, 95% CI −0.40, −0.01). Differential associations across categories of BMI, former hormone therapy use, and years since menopause were suggestive, but not statistically significant (P
heterogeneity > 0.05).

Conclusions:

Prospective and systems epidemiological studies are needed to understand whether or not the cross-sectional associations we observed, independent of adiposity, between CRP-SHBG, CRP-total testosterone, and CRP-free estradiol, are causal.
PROGNOSTIC VALUE OF SUBRETINAL HYPERREFLECTIVE MATERIAL IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH BEVACIZUMAB
Authors: Pokroy Russell , Mimouni Michael , Barayev Edward , Segev Fani , Geffen Noa , Nemet Arie Y. , Segal Ori
Published: June 2017

Purpose:

To study the correlation between subretinal hyperreflective material (SHRM) seen on spectral domain optical coherence tomography at baseline and visual outcomes after intravitreal bevacizumab injection in neovascular age-related macular degeneration.

Methods:

Consecutive patient charts with treatment-naive center-involved neovascular age-related macular degeneration treated with 3 monthly intravitreal bevacizumab's, continued as needed, from 2011 to 2014 were reviewed. Baseline spectral domain optical coherence tomography SHRM parameters (height, width, area, reflectivity, border definition, and homogeneity) and established optical coherence tomography biomarkers of neovascular activity (intraretinal fluid, subretinal fluid, retinal volume, central retinal thickness, and pigment epithelial detachment presence) were collected. These baseline parameters were correlated with visual acuity at baseline, 3 and 12 months.

Results:

Seventy-three eyes of 73 patients, 47 (64.4%) having central SHRM at baseline, were studied. Mean age was 79.2 ± 8.9 years. Mean best-corrected visual acuity was 0.70 ± 0.57 logarithm of the minimum angle of resolution (20/100), 0.73 ± 0.55 (20/107), and 0.76 ± 0.63 (20/115) at baseline, 3 and 12 months, respectively. Baseline parameters with a significant predictive value of 12-month visual acuity by univariate analysis were presence of intraretinal fluid, presence of SHRM, highly reflective SHRM, well-defined SHRM borders, and thick SHRM. These parameters, with the exception of high reflectivity, were significant on multivariate regression analysis. The most predictive baseline parameter was well-defined SHRM borders.

Conclusion:

This study supports the use of SHRM as a prognostic biomarker when interpreting optical coherence tomography in neovascular age-related macular degeneration. Baseline parameters predicting poorer vision 1 year after intravitreal bevacizumab treatment were as follows: presence of central SHRM, well-defined SHRM borders, intraretinal fluid, and thicker SHRM.
Ocular Lesions in Congenital Toxoplasmosis in Santa Isabel do Ivaí, Paraná, Brazil
Authors: Sanders Ana Paula , dos Santos Tatiane , Felipe Cleusa Kimie Koike , Estevão Maria Lucia , Cícero Caroni , Evangelista Fernanda , Manrique Carlos Alexandre , Mizutani Angélica Sayuri , Falavigna-Guilherme Ana Lucia
Published: June 2017

We verified clinical and psychopedagogic aspects of congenital cases with ocular sequelae, 13 years after toxoplasmosis outbreak in Santa Isabel do Ivaí, and current seroprevalence of this zoonosis in pregnant women. Audiologic and ophthalmologic evaluations were performed in congenital cases, in addition to collection of clinical and psychopedagogic data. In pregnant women, current seroprevalence was observed. Among affected teenagers, 2 of 5 are behind in school grade, and 4 of 5 reported learning difficulties, requiring psychopedagogic monitoring, as well as ocular complaints. We observed predominance of small, scarred, dispersed, type II chorioretinal lesions (hypopigmented halo and hyperpigmented central area), and 1 case of ocular relapse. All patients presented normal audiologic assessment. Among 131 pregnant women, 62 (47.3%) were seronegative and 39 (29.8%) were IgG reactive. Only 1 reported acquiring infection during the outbreak. This is one of the few studies in Brazil showing the outcome of congenital toxoplasmosis, a decade after infection, in one of the world’s largest outbreaks.
Intussusception-related Hospitalizations Among Infants Before and After Private Market Licensure of Rotavirus Vaccines in Taiwan, 2001–2013
Authors: Yen Catherine , Shih Shu-Man , Tate Jacqueline E. , Wu Fang-Tzy , Huang Yhu-Chering , Parashar Umesh D. , Hsiung Chao A.
Published: June 2017

Introduction:

Rotavirus is a leading cause of acute gastroenteritis among Taiwanese children. Two globally licensed rotavirus vaccines recommended for inclusion in routine immunization programs that have been available for private market use in Taiwan since 2006 have been associated with a low risk of intussusception in postmarketing studies conducted in several countries. Our objective was to examine trends and characteristics of intussusception hospitalizations in Taiwan among children <12 months of age before and after rotavirus vaccine licensure to provide updated baseline and early postlicensure data.

Methods:

We extracted data on intussusception-related hospitalizations among children <12 months of age during 2001–2013 from the National Health Insurance Research Database. We examined patient demographics, clinical outcome and hospitalization trends, focusing on recommended ages for rotavirus vaccination (6–14, 15–24 and 25–34 weeks). We compared mean hospitalization rates for prevaccine licensure years 2001–2005 with those for postvaccine licensure years 2007–2013 using Poisson regression analysis.

Results:

During 2001–2013, 1998 intussusceptions hospitalizations were recorded. The mean age of hospitalization was 33 weeks. Almost all children recovered; 3 deaths occurred. The overall intussusception hospitalization rate was 75.1 per 100,000; seasonality was not evident. Hospitalization rates were greatest in children ≥25 weeks of age and occurred more frequently in boys. Prevaccine and postvaccine licensure trends in annual hospitalization rates did not significantly differ. However, mean hospitalization rates were lower during the postvaccine licensure period for children <12 months of age (rate ratio: 0.84, 95% confidence interval: 0.76–0.92) with the greatest decline among children 25–34 weeks of age (rate ratio: 0.66, 95% confidence interval: 0.55–0.78).

Conclusions:

Infant intussusception in Taiwan occurs at a rate within the range of other Asian countries is rare among children <3 months of age, has a male predominance and does not have a clear seasonality pattern. We did not observe a postlicensure increase in intussusception hospitalization rates in children 6–14 weeks of age.
Risk of embryopathies with use of antithyroidal medications
Authors: Andersen Stine L.
Published: June 2017

Purpose of review

Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications. The treatment of choice in pregnancy is antithyroidal medications (ATDs). The risk of embryopathies associated with the use of Methimazole (MMI) and Propylthiouracil (PTU) in early pregnancy is a matter of clinical attention and concern. This review describes current evidence and how scientific findings are reflected in current clinical guidelines.

Recent findings

Embryopathies after the use of ATDs were previously mainly described in case reports and considered rare. Recent large observational studies, including nonexposed control groups, have quantified an increased risk of embryopathies associated with use of ATDs during pregnancy. Findings suggest a risk of embryopathies with the use of both MMI and PTU, but the pattern of embryopathies differs, and embryopathies with the use of PTU appear less severe.

Current guidelines highlight the need for clinical attention on the use of ATDs in early pregnancy. Patients managed on ATDs for the treatment of hyperthyroidism should be counseled to report a pregnancy as early as possible. PTU is the recommended treatment in early pregnancy, but if the risk of relapse or worsening of hyperthyroidism is considered low, it is suggested that ATD treatment can be withdrawn followed by frequent monitoring of thyroid function.
RAS-positive thyroid nodules
Authors: Angell Trevor E.
Published: June 2017

Purpose of review

The current review focuses on the uncertainty regarding the management of rat sarcoma viral oncogene homolog RAS-positive thyroid nodules. The application of oncogene testing has been heralded for improving risk assessment for indeterminate cytology thyroid nodules and has grown in clinical use. RAS mutations are historically considered oncogenic. However, RAS mutation detection in thyroid nodules has proven problematic, as these mutations are found in benign and malignant lesions.

Recent findings

RAS-positive thyroid nodules frequently have indeterminate cytology and a finding of a positive RAS mutation identifies a significant number of benign lesions as well as thyroid cancers. Long-term follow-up of RAS-positive nodules with benign cytology shows an indolent course not consistent with eventual malignant transformation. Many RAS-positive nodules previously diagnosed as follicular variant of papillary thyroid carcinoma now will be reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features, indicating a more indolent nature of these RAS-positive lesions.

Recent findings have underscored that diagnosis of a RAS-positive thyroid nodule is not synonymous with thyroid malignancy. The ideal clinical and surgical management of these nodules remains challenging.
Is selenium supplementation in autoimmune thyroid diseases justified?
Authors: Winther Kristian H. , Bonnema Steen J. , Hegedüs Laszlo
Published: June 2017

Purpose of review

This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms.

Recent findings

Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves’ disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves’ orbitopathy.

The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves’ disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.
Degree heterogeneity and stability of ecological networks
Authors: Yan Gang , Martinez Neo D. , Liu Yang-Yu
Published: June 2017

A classic measure of ecological stability describes the tendency of a community to return to equilibrium after small perturbations. While many advances show how the network architecture of these communities severely constrains such tendencies, one of the most fundamental properties of network structure, i.e. degree heterogeneity—the variability of the number of links associated with each species, deserves further study. Here we show that the effects of degree heterogeneity on stability vary with different types of interspecific interactions. Degree heterogeneity consistently destabilizes ecological networks with both competitive and mutualistic interactions, while its effects on networks of predator–prey interactions such as food webs depend on prey contiguity, i.e. the extent to which the species consume an unbroken sequence of prey in community niche space. Increasing degree heterogeneity tends to stabilize food webs except those with the highest prey contiguity. These findings help explain why food webs are highly but not completely interval and, more broadly, deepen our understanding of the stability of complex ecological networks.
The morphological heterogeneity of cricket flow-sensing hairs conveys the complex flow signature of predator attacks
Authors: Steinmann Thomas , Casas Jérôme
Published: June 2017

Arthropod flow-sensing hair length ranges over more than an order of magnitude, from 0.1 to 5 mm. Previous studies repeatedly identified the longest hairs as the most sensitive, but recent studies identified the shortest hairs as the most responsive. We resolved this apparent conflict by proposing a new model, taking into account both the initial and long-term aspects of the flow pattern produced by a lunging predator. After the estimation of the mechanical parameters of hairs, we measured the flow produced by predator mimics and compared the predicted and observed values of hair displacements in this flow. Short and long hairs respond over different time scales during the course of an attack. By harbouring a canopy of hairs of different lengths, forming a continuum, the insect can fractionize these moments. Short hairs are more agile, but are less able to harvest energy from the air. This may result in longer hairs firing their neurons earlier, despite their slower deflection. The complex interplay between hair agility and sensitivity is also modulated by the predator distance and the attack speed, characteristics defining flow properties. We conclude that the morphological heterogeneity of the hair canopy mirrors the flow complexity of an entire attack, from launch to grasp.
Using Captain Scott's Discovery specimens to unlock the past: has Antarctic cyanobacterial diversity changed over the last 100 years?
Authors: Jungblut Anne D. , Hawes Ian
Published: June 2017

Evidence of climate-driven environmental change is increasing in Antarctica, and with it comes concern that this will propagate to impacts on biological communities. Recognition and prediction of change needs to incorporate the extent and timescales over which communities vary under extant conditions. However, few observations of Antarctic microbial communities, which dominate inland habitats, allow this. We therefore carried out the first molecular comparison of Cyanobacteria in historic herbarium microbial mats from freshwater ecosystems on Ross Island and the McMurdo Ice Shelf, collected by Captain R.F. Scott's ‘Discovery’ Expedition (1902–1903), with modern samples from those areas. Using 16S rRNA gene surveys, we found that modern and historic cyanobacteria assemblages showed some variation in community structure but were dominated by the same genotypes. Modern communities had a higher richness, including genotypes not found in historic samples, but they had the highest similarity to other cyanobacteria sequences from Antarctica. The results imply slow cyanobacterial 16S rRNA gene genotype turnover and considerable community stability within Antarctic microbial mats. We suggest that this relates to Antarctic freshwater 'organisms requiring a capacity to withstand diverse stresses, and that this could also provide a degree of resistance and resilience to future climatic-driven environmental change in Antarctica.