bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrading, production, and asset market performance
Authors: Gjerstad Steven D. , Porter David , Smith Vernon L. , Winn Abel
Published: November 2015

Significance

We conduct the first experimental study to our knowledge of production and trade in a stock-flow market for durable assets. When inexperienced consumers are allowed to resell assets they compete with producers and depress prices, disrupting production and causing inefficiency. Consumers with experience specializing as buyers compete less vigorously, which allows prices and production to converge to equilibrium.
Heterogeneous lamella structure unites ultrafine-grain strength with coarse-grain ductility
Authors: Wu Xiaolei , Yang Muxin , Yuan Fuping , Wu Guilin , Wei Yujie , Huang Xiaoxu , Zhu Yuntian
Published: November 2015

Significance

For centuries it has been a challenge to avoid strength–ductility trade-off, which is especially problematic for ultrastrong ultrafine-grained metals. Here we evade this trade-off dilemma by architecting a heterogeneous lamella structure, i.e., soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The heterogeneous deformation of this previously unidentified structure produces significant back-stress hardening in addition to conventional dislocation hardening, rendering it higher strain hardening than coarse-grained metals. The high back-stress hardening makes the material as strong as ultrafine-grained metals and as ductile as coarse-grained metals.
Direct measurements of the coordination of lever arm swing and the catalytic cycle in myosin V
Authors: Trivedi Darshan V. , Muretta Joseph M. , Swenson Anja M. , Davis Jonathon P. , Thomas David D. , Yengo Christopher M.
Published: November 2015

Significance

Myosins interact with actin filaments and convert the chemical energy from ATP hydrolysis into mechanical work. The swinging lever arm hypothesis describes the molecular mechanism of actomyosin-based force generation that is essential for cell motility, muscle contraction, and cell division. In this model the light chain-binding region of myosin undergoes a major conformational change, which drives force generation. However, the temporal kinetics of structural changes in the lever arm in relation to the product release steps of the catalytic cycle are not well established. By using a FRET-based strategy, we demonstrate the lever arm swing occurs in two steps, a rapid step prior to phosphate release and a slower step prior to ADP release.
Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA
Authors: Yin Ai-hua , Peng Chun-fang , Zhao Xin , Caughey Bennett A. , Yang Jie-xia , Liu Jian , Huang Wei-wei , Liu Chang , Luo Dong-hong , Liu Hai-liang , Chen Yang-yi , Wu Jing , Hou Rui , Zhang Mindy , Ai Michael , Zheng Lianghong , Xue Rachel Q. , Mai Ming-qin , Guo Fang-fang , Qi Yi-ming , Wang Dong-mei , Krawczyk Michal , Zhang Daniel , Wang Yu-nan , Huang Quan-fei , Karin Michael , Zhang Kang
Published: November 2015

Significance

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has allowed accurate prenatal diagnosis of aneuploidy without requirement of an invasive procedure; this approach has gained increasing clinical acceptance. In this manuscript, we evaluate whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying a high-risk fetus. We show that detection of fetal subchromosomal abnormalities is a viable extension of NIPT using SSP. Given the recent strong interest in NIPT using cell-free DNA, these results should be of broad interest and immediate clinical importance, even beyond the NIPT field, such as for detection of cell-free tumor DNA.
Mapping transient electric fields with picosecond electron bunches
Authors: Chen Long , Li Runze , Chen Jie , Zhu Pengfei , Liu Feng , Cao Jianming , Sheng Zhengming , Zhang Jie
Published: November 2015

Significance

Transient electric fields driven by intense lasers and particle beams play a key role in a number of applications from plasma-based particle accelerators to implosion dynamics of inertial fusion targets. Here, a method to map the 3D transient field structures with high resolutions both in time and space by use of picosecond electron bunches is presented. It is applied to measure the transient field evolution induced at a solid surface irradiated by a short pulse laser. This method can be applied to monitor field structures with much higher strength, which may find wide application in relevant research fields.
Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope
Authors: Tsai Shang-Yi A. , Chuang Jian-Ying , Tsai Meng-Shan , Wang Xiao-fei , Xi Zheng-Xiong , Hung Jan-Jong , Chang Wen-Chang , Bonci Antonello , Su Tsung-Ping
Published: November 2015

Significance

The endoplasmic reticulum (ER), although functioning as protein synthesis machinery in the cell, plays other important roles that have yet to be fully unveiled. We found here that the ER can directly send an envoy protein, the sigma-1 receptor (Sig-1R), to the nuclear envelope (NE), where the Sig-1R begins to recruit chromatin-remodeling molecules through the NE integral protein emerin to control gene transcription. Thus, the Sig-1R represents a molecule that shapes the functional connection between the NE and the DNA. We also demonstrate in this study that cocaine, a Sig-1R agonist, down-regulates the critical enzyme monoamine oxidase B that influences the cocaine-induced dopamine level in a dopamine transporter-independent manner via this never-before-described, to our knowledge, Sig-1R-linked genomic action of cocaine.
Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow
Authors: Dore Kim , Aow Jonathan , Malinow Roberto
Published: November 2015

Significance

NMDA receptors (R) are ion channels that participate in many important physiological and pathophysiological processes in the brain. Recent studies suggest that NMDARs can also act in a manner that does not require ion flow. One way this could occur is for agonist binding to the NMDAR to produce conformational movement of its cytoplasmic domain in the absence of ion flow. Here we use FRET imaging of genetically encoded fluorescent proteins linked to the cytoplasmic domain of NMDAR subunits to monitor directly agonist-driven movement within the cytoplasmic domain of NMDARs. This study demonstrates that transmembrane information transfer through the NMDAR is possible in the absence of ion flow through the receptor.
CLEC-2 in megakaryocytes is critical for maintenance of hematopoietic stem cells in the bone marrow
Authors: Nakamura-Ishizu Ayako , Takubo Keiyo , Kobayashi Hiroshi , Suzuki-Inoue Katsue , Suda Toshio
Published: November 2015

Hematopoietic stem cells (HSCs) depend on the bone marrow (BM) niche for their maintenance, proliferation, and differentiation. The BM niche is composed of nonhematopoietic and mature hematopoietic cells, including megakaryocytes (Mks). Thrombopoietin (Thpo) is a crucial cytokine produced by BM niche cells. However, the cellular source of Thpo, upon which HSCs primarily depend, is unclear. Moreover, no specific molecular pathway for the regulation of Thpo production in the BM has been identified. Here, we demonstrate that the membrane protein C-type lectin-like receptor-2 (CLEC-2) mediates the production of Thpo and other factors in Mks. Mice conditionally deleted for CLEC-2 in Mks (Clec2MkΔ/Δ) produced lower levels of Thpo in Mks. CLEC-2–deficient Mks showed down-regulation of CLEC-2–related signaling molecules Syk, Lcp2, and Plcg2. Knockdown of these molecules in cultured Mks decreased expression of Thpo. Clec2MkΔ/Δ mice exhibited reduced BM HSC quiescence and repopulation potential, along with extramedullary hematopoiesis. The low level of Thpo production may account for the decline in HSC potential in Clec2MkΔ/Δ mice, as administration of recombinant Thpo to Clec2MkΔ/Δ mice restored stem cell potential. Our study identifies CLEC-2 signaling as a novel molecular mechanism mediating the production of Thpo and other factors for the maintenance of HSCs.
DNAM-1 controls NK cell activation via an ITT-like motif
Authors: Zhang Zhanguang , Wu Ning , Lu Yan , Davidson Dominique , Colonna Marco , Veillette André
Published: November 2015

DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8+ T cells, and other immune cells. Upon recognition of its ligands, CD155 and CD112, DNAM-1 promotes NK cell–mediated elimination of transformed and virus-infected cells. It also has a key role in expansion and maintenance of virus-specific memory NK cells. Herein, the mechanism by which DNAM-1 controls NK cell–mediated cytotoxicity and cytokine production was elucidated. Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. Upon phosphorylation by Src kinases, this motif enabled binding of DNAM-1 to adaptor Grb2, leading to activation of enzymes Vav-1, phosphatidylinositol 3′ kinase, and phospholipase C-γ1. It also promoted activation of kinases Erk and Akt, and calcium fluxes. Although, as reported, DNAM-1 promoted adhesion, this function was signal-independent and insufficient to promote cytotoxicity. DNAM-1 signaling was also required to enhance cytotoxicity, by increasing actin polymerization and granule polarization. We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)–like motif coupling DNAM-1 to Grb2 and other downstream effectors.
A first-principles self-consistent model of plasma turbulence and kinetic neutral dynamics in the tokamak scrape-off layer
Authors: Wersal C. , Ricci P.
Published: November 2015

A first-principles self-consistent model that couples plasma and neutral physics suitable for the simulation of turbulent plasma behavior in the tokamak SOL is presented. While the plasma is modeled by the drift-reduced two fluid Braginskii equations, a kinetic model for the neutrals is developed, valid in short and in long mean free path scenarios. The model includes ionization, charge-exchange, recombination, and elastic collisional processes. The solution of the neutral kinetic equation is implemented within the GBS plasma turbulence code (Ricci et al 2012 Plasma Phys. Control. Fusion
54 124047) and it is performed by using the method of characteristics. The details of the numerical implementation are discussed. Finally, we show initial results of the first self-consistent simulations of plasma turbulence and neutral dynamics.
Weak and strong moments of ℓᵣ-norms of log-concave vectors
Authors: Latała Rafał , Strzelecka Marta
Published: November 2015

We show that for

p
≥
1

p\geq 1

and

r
≥
1

r\geq 1

the

p
p

-th moment of the

ℓ
r

\ell _r

-norm of a log-concave random vector is comparable to the sum of the first moment and the weak

p
p

-th moment up to a constant proportional to

r
r

. This extends the previous result of Paouris concerning Euclidean norms.
The link volume of 3-manifolds is not multiplicative under coverings
Authors: Remigio–Juárez Jair
Published: November 2015

We obtain an infinite family of

3
−

3-

manifolds

{

M

n

}

n
∈

N

\{{M}_n\}_{n\in \mathbb {N}}

and an infinite family of coverings

{

φ
n

:

M
~

n

→

M

n

}

n
∈

N

\{\varphi _n:\tilde {M}_n\to M_{n}\}_{n\in \mathbb {N}}

with covering degrees unbounded and satisfying that

LinkVol
⁡
[

M
~

]
=
LinkVol
⁡
[
M
]
.

\operatorname {LinkVol}[\tilde {M}]=\operatorname {LinkVol}[M].

This shows that link volume of 3-manifolds is not well behaved under covering maps, in particular, it is not multiplicative, and gives a negative answer to a question posed in a work of Rieck and Yamashita, namely, how good is the bound

LinkVol
⁡
[

M
~

]
≤
q
LinkVol
⁡
[
M
]

\operatorname {LinkVol}[\tilde {M}]\leq q \operatorname {LinkVol}[M]

, when

M
~

\tilde {M}

is a

q
q

-fold covering of

M
M

?
Fast, fully Bayesian spatiotemporal inference for fMRI data
Authors: Musgrove Donald R. , Hughes John , Eberly Lynn E.
Published: November 2015

We propose a spatial Bayesian variable selection method for detecting blood oxygenation level dependent activation in functional magnetic resonance imaging (fMRI) data. Typical fMRI experiments generate large datasets that exhibit complex spatial and temporal dependence. Fitting a full statistical model to such data can be so computationally burdensome that many practitioners resort to fitting oversimplified models, which can lead to lower quality inference. We develop a full statistical model that permits efficient computation. Our approach eases the computational burden in two ways. We partition the brain into 3D parcels, and fit our model to the parcels in parallel. Voxel-level activation within each parcel is modeled as regressions located on a lattice. Regressors represent the magnitude of change in blood oxygenation in response to a stimulus, while a latent indicator for each regressor represents whether the change is zero or non-zero. A sparse spatial generalized linear mixed model captures the spatial dependence among indicator variables within a parcel and for a given stimulus. The sparse SGLMM permits considerably more efficient computation than does the spatial model typically employed in fMRI. Through simulation we show that our parcellation scheme performs well in various realistic scenarios. Importantly, indicator variables on the boundary between parcels do not exhibit edge effects. We conclude by applying our methodology to data from a task-based fMRI experiment.
Using Cox cluster processes to model latent pulse location patterns in hormone concentration data
Authors: Carlson Nichole E. , Grunwald Gary K. , Johnson Timothy D.
Published: November 2015

Many hormones, including stress hormones, are intermittently secreted as pulses. The pulsatile location process, describing times when pulses occur, is a regulator of the entire stress system. Characterizing the pulse location process is particularly difficult because the pulse locations are latent; only hormone concentration at sampled times is observed. In addition, for stress hormones the process may change both over the day and relative to common external stimuli. This potentially results in clustering in pulse locations across subjects. Current approaches to characterizing the pulse location process do not capture subject-to-subject clustering in locations. Here we show how a Bayesian Cox cluster process may be adapted as a model of the pulse location process. We show that this novel model of pulse locations is capable of detecting circadian rhythms in pulse locations, clustering of pulse locations between subjects, and identifying exogenous controllers of pulse events. We integrate our pulse location process into a model of hormone concentration, the observed data. A spatial birth-and-death Markov chain Monte Carlo algorithm is used for estimation. We exhibit the strengths of this model on simulated data and adrenocorticotropic and cortisol data collected to study the stress axis in depressed and non-depressed women.
Modeling Long-term Vaccination Strategies With MenAfriVac in the African Meningitis Belt
Authors: Karachaliou Andromachi , Conlan Andrew J. K. , Preziosi Marie-Pierre , Trotter Caroline L.
Published: November 2015

Background.  The introduction of MenAfriVac in campaigns targeting people aged 1–29 years across the African meningitis belt has successfully reduced meningitis incidence and carriage due to Neisseria meningitidis group A (MenA). It is important to consider how best to sustain population protection in the long term.

Methods.  We created a mathematical model of MenA transmission and disease to investigate the potential impact of a range of immunization strategies. The model is age structured; includes classes of susceptible, carrier, ill, and immune people (who may be vaccinated or unvaccinated); and incorporates seasonal transmission and a stochastic forcing term that models between year variation in rates of transmission. Model parameters were primarily derived from African sources. The model can describe the typical annual incidence of meningitis in the prevaccine era, with irregular epidemics of varying size. Parameter and structural uncertainty were explored in sensitivity analyses.

Results.  Following MenAfriVac introduction at high uptake, the model predicts excellent short-term disease control. With no subsequent immunization, strong resurgences in disease incidence were predicted after approximately 15 years (assuming 10 years’ average vaccine protection). Routine immunization at 9 months of age resulted in lower average annual incidence than regular mass campaigns of 1- to 4-year-olds, provided coverage was above approximately 60%. The strategy with the lowest overall average annual incidence and longest time to resurgence was achieved using a combination strategy of introduction into the Expanded Programme on Immunization at 9 months, 5 years after the initial mass campaigns, with a catch-up targeting unvaccinated 1- to 4-year-olds.

Conclusions.  These results can be used to inform policy recommendations for long-term vaccination strategies with MenAfriVac.
Energetics of tent roosting in bats: the case of
Ectophylla alba
and
Uroderma bilobatum
(Chiroptera: Phyllostomidae).
Authors: Rodríguez-Herrera Bernal , Víquez-R Luis , Cordero-Schmidt Eugenia , Sandoval Jean M. , Rodríguez-Durán Armando
Published: November 2015

Roost selection in mammals is an important selective pressure, and many animals find shelter in previously existing structures. Furthermore, the microclimate of roosts is a crucial element for bat survival, and modified leaves are used for roosting (“tents”) by 22 species of bats. Our objective was to determine whether the inverted boat tents used by Ectophylla alba and pinnate tents used by Uroderma bilobatum provide energetic benefits. We measured the ambient temperature under modified and unmodified leaves (UMLs) of Heliconia imbricata and Cocos nucifera . We also measured temperature with (simulated bat presence) and without a heat source, and finally we measured bat energy expenditure at different temperatures. Our results show that when a heat source is present tents conserve heat better than a UML. The energy expenditure of E. alba and U. bilobatum increased up to 55% and 48%, respectively, with a decrease of temperature from 25°C to 20°C. We concluded that since the temperature at our study site drops below 25°C every night and remains that way until mid-morning, using a “tent” that maintains a temperature higher than ambient temperature, or close to 25°C degrees, provides an energetic advantage.

La selección del refugio en los mamíferos es una presión selectiva importante y muchos animales encuentran refugio en estructuras ya existentes. El microclima del refugio es un elemento crucial para la sobrevivencia de los murciélagos. Las hojas modificadas (tiendas) son utilizadas por 22 especies de murciélagos. Nuestro objetivo era determinar si la tienda de bote invertido utilizada por Ectophylla alba y tiendas pinnadas utilizadas por Uroderma bilobatum brindan un beneficio energético a los murciélagos. Se midió la temperatura bajo hojas modificadas y no modificadas de Heliconia imbricata y Cocos nucifera . Además se midió la temperatura con fuente (simulando la presencia de murciélagos) y sin fuente de calor, finalmente se midió el gasto energético de los murciélagos a diferentes temperaturas. Los resultados muestran que cuando hay una fuente de calor presente, la tienda conserva el calor mejor que una hoja no modificada. El gasto energético de E. alba y U. bilobatum puede incrementarse hasta 55% y 48%, respectivamente, cuando la temperatura decrece entre 25°C y 20°C. Concluimos que como la temperatura en este sitio de estudio baja de los 25°C cada noche y hasta media mañana, utilizar una tienda que mantiene la temperatura arriba o cerca de los 25°C, provee una ventaja energética.
Survival of fishers in the southern Sierra Nevada region of California
Authors: Sweitzer Richard A. , Thompson Craig M. , Green Rebecca E. , Barrett Reginald H. , Purcell Kathryn L.
Published: November 2015

Fishers in the western United States were recently proposed for listing under the U.S. Endangered Species Act because of concerns for loss of suitable habitat and evidence of a diversity of mortality risks that reduce survival. One of 2 remnant populations of fishers in California is in the southern Sierra Nevada region, where we studied them at 2 research sites in the Sierra National Forest. Our objectives were to evaluate whether survival was lower for male fishers and dispersal-aged individuals or if survival varied seasonally. We captured and monitored 232 radiocollared fishers from March 2007 to March 2014 and used model analyses to identify important predictors of survival. Fifty-two percent ( n = 120) of the radiocollared fishers died, and survival varied by sex and season, but not by age or between study sites. There was no evidence that dispersal-aged fishers experienced lower survival than older fishers. Annual survival trended lower for male (0.62 [95% CI 0.54–0.70]) compared to female fishers (0.72 [95% CI 0.67–0.78]), was lowest in the spring to mid-summer season (0.83 [95% CI 0.78–0.87]), and highest in late fall and winter (0.92 [95% CI 0.89–0.94]). Lower survival among male fishers appeared linked to males moving over large areas to locate mates, while lower survival for females was potentially related to high energetic cost of reproduction. It was possible but unknown if lower survival among all fishers in spring was linked to secondary exposure to toxicants dispersed around illicit marijuana grow sites. Six-month survival of juvenile fishers was 0.85 for females and 0.79 for males, but lower at 0.62 for females and 0.57 for males when adjusted for deaths before late September. Annual survival among adult female fishers was 20% lower than 0.90, a value that prior modeling suggested was required for population expansion in the overall southern Sierra Nevada. Survival data from our study imply a greater challenge for maintaining self-sustaining fisher populations in the southern Sierra Nevada region, and resource managers are working to mitigate several of the human-associated factors that limit population growth.
A sky-high view of the Third Pole: an interview with Tandong Yao and Weiming Fan
Authors: Qiu Jane
Published: November 2015

The Tibetan Plateau and surrounding mountain regions covers 5 million square kilometres—nearly half the China's landmass—with an average elevation of over 4000 metres. It's often regarded as the Third Pole because it has the largest stock of ice outside the Arctic and the Antarctic. Tibetan Plateau research is one of China's Strategic Pioneering Programmes that was launched in 2012 with a budget of 300 million yuan (US $47 million) over 5 years and is led by Chinese Academy of Sciences (CAS)’ Institute of Tibetan Plateau Research (ITP) in Beijing. In January 2014, CAS set up the Centre for Excellence in Tibetan Plateau Earth Sciences, headquartered in ITP, aiming at providing long-term support for this area of research and raising academic standards. NSR recently talked to glaciologist Tandong Yao and geologist Weiming Fan—ITP's director and deputy director, respectively—about why Tibetan Plateau research is important, what it is like to work there, how the region is faring in face of climate change and why international collaboration is important.
Rmg8, a New Gene for Resistance to Triticum Isolates of Pyricularia oryzae in Hexaploid Wheat
Authors: Anh Vu Lan , Anh Nguyen Tuan , Tagle Analiza Grubanzo , Vy Trinh Thi Phuong , Inoue Yoshihiro , Takumi Shigeo , Chuma Izumi , Tosa Yukio
Published: November 2015

Blast, caused by Pyricularia oryzae, is one of the major diseases of wheat in South America. We identified a new gene for resistance to Triticum isolates of P. oryzae in common wheat ‘S-615’, and designated it “resistance to Magnaporthe grisea 8” (Rmg8). Rmg8 was assigned to chromosome 2B through molecular mapping with simple-sequence repeat markers. To identify an avirulence gene corresponding to Rmg8, Triticum isolate Br48 (avirulent on S-615) was crossed with 200R29 (virulent on S-615), an F1 progeny derived from a cross between an Eleusine isolate (MZ5-1-6) and Br48. Segregation analysis of their progeny revealed that avirulence of Br48 on S-615 was conditioned by a single gene, which was designated AVR-Rmg8. AVR-Rmg8 was closely linked to AVR-Rmg7, which corresponded to Rmg7 located on chromosome 2A of tetraploid wheat.
Comparison of Continuous Noninvasive Blood Pressure Monitoring by TL-300 With Standard Invasive Blood Pressure Measurement in Patients Undergoing Elective Neurosurgery
Authors: Lin Wen-Qian , Wu Huang-Hui , Su Chang-Sheng , Yang Jian-Teng , Xiao Jin-Rong , Cai Yu-Ping , Wu Xiao-Zhi , Chen Guo-Zhong
Published: November 2015

Background:

Intraoperative blood pressure (BP) is one of the basic vital signs monitoring. Compared with standard invasive BP measurement, TL-300 allows for a continuous and beat-to-beat noninvasive intraoperative BP monitoring. The current retrospective study compared the accuracy and precision of this noninvasive technique for continuous BP monitoring with that of standard invasive BP measurement in patients undergoing elective neurosurgery.

Materials and Methods:

BP records of 23 patients undergoing elective neurosurgery, measured by both noninvasive TL-300 and invasive radial arterial catheter method, were retrospectively analyzed. Variability in BP data was analyzed by using linear regressions and Bland-Altman analysis.

Results:

Four thousand three hundred eighty-one pairs of BP measurements from a total of 23 patients were included. The coefficient of determination of systolic, diastolic, and mean BP were 0.908, 0.803, and 0.922, respectively. And their bias was found to be 1.3±5.87 mm Hg (95% limits of agreement: −10.2 to +12.8 mm Hg), 2.8±6.40 mm Hg (95% limits of agreement: −9.8 to +15.3 mm Hg), and 1.8±4.20 mm Hg (95% limits of agreement: −6.4 to +10.1 mm Hg), respectively.

Conclusions:

TL-300 system is a promising noninvasive alternative to the invasive arterial catheter method for intraoperative BP monitoring, with a high accuracy and precision. With the limitation of the current retrospective study, further prospective method comparison studies are needed.
Simultaneous Acquired Self-limited Hemophagocytic Lymphohistiocytosis and Kikuchi Necrotizing Lymphadenitis in a 16-Year-Old Teenage Girl
Authors: Sykes Joseph A. , Badizadegan Kamran , Gordon Paul , Sokol Dawn , Escoto Marcella , Ten Irina , Vyas Shayan , Torres Adalberto , Levine Ann-Marie
Published: November 2015

Objectives

The aim of this study was to increase education and awareness among pediatric practitioners of possibility of simultaneous hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease/Kikuchi disease occurring in the pediatric population and the diagnostic dilemma it can present. We describe a case presentation of acquired and self-limited simultaneous hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease in a 16-year-old in the United States who presented with fevers, night sweats, and joint pain, along with tiredness and decreased appetite along with pancytopenia and elevated lactate dehydrogenase. To the best of our knowledge, simultaneous hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto in the pediatric population has not been described in North America but remains fairly common in Asia. The literature on both diseases and their simultaneous occurrence is comprehensively reviewed.

Methods

This was a case report and review of the literature.

Results

The patient was diagnosed with both hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease based on bone marrow aspiration/biopsy and axillary node biopsy, respectively. Both illnesses resolved completely.

Conclusions

Benign causes of pancytopenia and elevated lactate dehydrogenase exist, but they may not be always straightforward diagnostically. Bone marrow aspiration and lymph node biopsy may be helpful in ascertaining the diagnosis. Hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease may represent a continuum of illness.
Antibiotic Prescribing Patterns Across the Continuum of Care for Children Hospitalized With Community-Acquired Pneumonia
Authors: Milner Tiffany L. , McCulloh Russell , Koster Michael , Biondi Eric , Hill Vanessa , Ralston Shawn
Published: November 2015

Objectives

The aim of this study was to describe the variation in antibiotic prescribing practices for uncomplicated community-acquired pneumonia across the continuum of care for hospitalized pediatric patients to better inform future efforts at standardizing antibiotic therapy throughout a single hospitalization.

Methods

This is a retrospective cohort study involving 4 hospitals caring for children aged 3 months to 18 years, hospitalized between January 1, 2011, and December 31, 2012, with diagnosis of uncomplicated pneumonia and without complex chronic medical conditions.

Data collected include antibiotics prescribed before hospitalization, at the emergency department (ED) encounter, during hospitalization, and at hospital discharge.

Results

Six hundred nine children met inclusion criteria, with a mean age of 5.3 years and median length of stay of 2 days. Emergency department providers prescribed narrow-spectrum therapy 27% of the time, whereas discharging providers prescribed narrow-spectrum therapy 56% of the time. Third- and fourth-generation cephalosporins were less often prescribed in the preadmission setting and at discharge but were more often prescribed in the ED and inpatient setting. There was an association between inpatient prescription of broad-spectrum antibiotics when a blood culture was obtained, when broad-spectrum antibiotics were prescribed in the ED, and with increasing length of stay.

Conclusion

Broad-spectrum antibiotic therapy for community-acquired pneumonia, especially third- and fourth-generation cephalosporins, often originates in the ED. When initiated in this setting, it is likely to be continued in the inpatient setting.
Electronic Health Record–Related Events in Medical Malpractice Claims
Authors: Graber Mark L. , Siegal Dana , Riah Heather , Johnston Doug , Kenyon Kathy
Published: November 2015

Background

There is widespread agreement that the full potential of health information technology (health IT) has not yet been realized and of particular concern are the examples of unintended consequences of health IT that detract from the safety of health care or from the use of health IT itself. The goal of this project was to obtain additional information on these health IT–related problems, using a mixed methods (qualitative and quantitative) analysis of electronic health record–related harm in cases submitted to a large database of malpractice suits and claims.

Methods

Cases submitted to the CRICO claims database and coded during 2012 and 2013 were analyzed. A total of 248 cases (<1%) involving health IT were identified and coded using a proprietary taxonomy that identifies user- and system-related sociotechnical factors. Ambulatory care accounted for most of the cases (146 cases). Cases were most typically filed as a result of an error involving medications (31%), diagnosis (28%), or a complication of treatment (31%). More than 80% of cases involved moderate or severe harm, although lethal cases were less likely in cases from ambulatory settings. Etiologic factors spanned all of the sociotechnical dimensions, and many recurring patterns of error were identified.

Conclusions

Adverse events associated with health IT vulnerabilities can cause extensive harm and are encountered across the continuum of health care settings and sociotechnical factors. The recurring patterns provide valuable lessons that both practicing clinicians and health IT developers could use to reduce the risk of harm in the future. The likelihood of harm seems to relate more to a patient's particular situation than to any one class of error.
Early metazoan life: divergence, environment and ecology
Authors: Erwin Douglas H.
Published: November 2015

Recent molecular clock studies date the origin of Metazoa to 750–800 million years ago (Ma), roughly coinciding with evidence from geochemical proxies that oxygen levels rose from less than 0.1% present atmospheric level (PAL) to perhaps 1–3% PAL O2. A younger origin of Metazoa would require greatly increased substitution rates across many clades and many genes; while not impossible, this is less parsimonious. Yet the first fossil evidence for metazoans (the Doushantuo embryos) about 600 Ma is followed by the Ediacaran fossils after 580 Ma, the earliest undisputed bilaterians at 555 Ma, and an increase in the size and morphologic complexity of bilaterians around 542 Ma. This temporal framework suggests a missing 150–200 Myr of early metazoan history that encompasses many apparent novelties in the early evolution of the nervous system. This span includes two major glaciations, and complex marine geochemical changes including major changes in redox and other environmental changes. One possible resolution is that animals of these still unknown Cryogenian and early Ediacaran ecosystems were relatively simple, with highly conserved developmental genes involved in cell-type specification and simple patterning. In this model, complex nervous systems are a convergent phenomenon in bilaterian clades which occurred close to the time that larger metazoans appeared in the fossil record.
Early animal evolution and the origins of nervous systems
Authors: Budd Graham E.
Published: November 2015

Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour.
Unlocking the early fossil record of the arthropod central nervous system
Authors: Edgecombe Gregory D. , Ma Xiaoya , Strausfeld Nicholas J.
Published: November 2015

Extant panarthropods (euarthropods, onychophorans and tardigrades) are hallmarked by stunning morphological and taxonomic diversity, but their central nervous systems (CNS) are relatively conserved. The timing of divergences of the ground pattern CNS organization of the major panarthropod clades has been poorly constrained because of a scarcity of data from their early fossil record. Although the CNS has been documented in three-dimensional detail in insects from Cenozoic ambers, it is widely assumed that these tissues are too prone to decay to withstand other styles of fossilization or geologically older preservation. However, Cambrian Burgess Shale-type compressions have emerged as sources of fossilized brains and nerve cords. CNS in these Cambrian fossils are preserved as carbon films or as iron oxides/hydroxides after pyrite in association with carbon. Experiments with carcasses compacted in fine-grained sediment depict preservation of neural tissue for a more prolonged temporal window than anticipated by decay experiments in other media. CNS and compound eye characters in exceptionally preserved Cambrian fossils predict divergences of the mandibulate and chelicerate ground patterns by Cambrian Stage 3 (
ca
518 Ma), a dating that is compatible with molecular estimates for these splits.
Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution
Authors: Hejnol Andreas , Lowe Christopher J.
Published: November 2015

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of ‘evo-devo’. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters—the partitioned brain of arthropods and the ventral centralized nerve cords of annelids—a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited.
Evolution of brain elaboration
Authors: Farris Sarah M.
Published: November 2015

Large, complex brains have evolved independently in several lineages of protostomes and deuterostomes. Sensory centres in the brain increase in size and complexity in proportion to the importance of a particular sensory modality, yet often share circuit architecture because of constraints in processing sensory inputs. The selective pressures driving enlargement of higher, integrative brain centres has been more difficult to determine, and may differ across taxa. The capacity for flexible, innovative behaviours, including learning and memory and other cognitive abilities, is commonly observed in animals with large higher brain centres. Other factors, such as social grouping and interaction, appear to be important in a more limited range of taxa, while the importance of spatial learning may be a common feature in insects with large higher brain centres. Despite differences in the exact behaviours under selection, evolutionary increases in brain size tend to derive from common modifications in development and generate common architectural features, even when comparing widely divergent groups such as vertebrates and insects. These similarities may in part be influenced by the deep homology of the brains of all Bilateria, in which shared patterns of developmental gene expression give rise to positionally, and perhaps functionally, homologous domains. Other shared modifications of development appear to be the result of homoplasy, such as the repeated, independent expansion of neuroblast numbers through changes in genes regulating cell division. The common features of large brains in so many groups of animals suggest that given their common ancestry, a limited set of mechanisms exist for increasing structural and functional diversity, resulting in many instances of homoplasy in bilaterian nervous systems.
Brain evolution by brain pathway duplication
Authors: Chakraborty Mukta , Jarvis Erich D.
Published: November 2015

Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits.
An option space for early neural evolution
Authors: Jékely Gáspár , Keijzer Fred , Godfrey-Smith Peter
Published: November 2015

The origin of nervous systems has traditionally been discussed within two conceptual frameworks. Input–output models stress the sensory-motor aspects of nervous systems, while internal coordination models emphasize the role of nervous systems in coordinating multicellular activity, especially muscle-based motility. Here we consider both frameworks and apply them to describe aspects of each of three main groups of phenomena that nervous systems control: behaviour, physiology and development. We argue that both frameworks and all three aspects of nervous system function need to be considered for a comprehensive discussion of nervous system origins. This broad mapping of the option space enables an overview of the many influences and constraints that may have played a role in the evolution of the first nervous systems.
Evolving cohesion metrics of a research network on rare diseases: a longitudinal study over 14 years
Authors: Benito Amat Carlos , Perruchas Francois
Published: November 2015

Research collaboration is necessary, rewarding, and beneficial. Cohesion between team members is related to their collective efficiency. To assess collaboration processes and their eventual outcomes, agencies need innovative methods - and social network approaches are emerging as a useful analytical tool. We identified the research output and citation data of a network of 61 research groups formally engaged in publishing rare disease research between 2000 and 2013. We drew the collaboration networks for each year and computed the global and local measures throughout the period, relating connectivity with the normalized impact. Although global network measures remained steady over the whole period, the local and subgroup metrics revealed a growing cohesion between the teams. Transitivity and density showed little or no variation throughout the period. In contrast the following points indicated an evolution towards greater network cohesion: the emergence of a giant component (which grew from just 30% to reach 85% of groups); the decreasing number of communities (following a tripling in the average number of members); the growing number of fully connected subgroups; and increasing average strength. Normalized citation measures, although ranking the member groups as above average impact for Spanish biomedical output, do not support correlation between collaboration and citation impact. The Spanish research network on rare diseases has evolved towards a growing cohesion - as revealed by local and subgroup metrics following social network analysis. This greater cohesion does not translate into a greater impact, as measured by the citation analysis of the papers.
Exploring phylogenomic relationships within Myriapoda: should high matrix occupancy be the goal?
Authors: Fernández Rosa , Edgecombe Gregory D. , Giribet Gonzalo
Published: November 2015

Myriapods are one of the dominant terrestrial arthropod groups including the diverse and familiar centipedes and millipedes. Although molecular evidence has shown that Myriapoda is monophyletic, its internal phylogeny remains contentious and understudied, especially when compared to those of Chelicerata and Hexapoda. Until now, efforts have focused on taxon sampling (e.g., by including a handful of genes in many species) or on maximizing matrix occupancy (e.g., by including hundreds or thousands of genes in just a few species), but a phylogeny maximizing sampling at both levels remains elusive. In this study, we analyzed forty Illumina transcriptomes representing three myriapod classes (Diplopoda, Chilopoda and Symphyla); twenty-five transcriptomes were newly sequenced to maximize representation at the ordinal level in Diplopoda and at the family level in Chilopoda. Eight supermatrices were constructed to explore the effect of several potential phylogenetic biases (e.g., rate of evolution, heterotachy) at three levels of mean gene occupancy per taxon (50%, 75% and 90%). Analyses based on maximum likelihood and Bayesian mixture models retrieved monophyly of each myriapod class, and resulted in two alternative phylogenetic positions for Symphyla, as sister group to Diplopoda + Chilopoda, or closer to Diplopoda, the latter hypothesis having been traditionally supported by morphology. Within centipedes, all orders were well supported, but two nodes remained in conflict in the different analyses despite dense taxon sampling at the family level, situating the order Scolopendromorpha as sister group to a morphologically-anomalous grouping of Lithobiomorpha + Geophilomorpha in a subset of analyses. Interestingly, this anomalous result was obtained for all analyses conducted with the most complete matrix (90% of occupancy), being at odds not only with the sparser but more gene-rich supermatrices (75% and 50% supermatrices) or with the matrices optimizing phylogenegic informativeness and the most conserved genes, but also with previous hypotheses based on morphology, development or other molecular data sets. We discuss the implications of these findings in the context of the ever more prevalent quest for completeness in phylogenomic studies. [Chilopoda; Diplopoda; Symphyla: gene tree; species tree; node calibration; missing data.]
Haplotag: software for haplotype-based genotyping-by-sequencing analysis
Authors: Tinker Nicholas A , Bekele Wubishet A , Hattori Jiro
Published: November 2015

Genotyping-by-sequencing (GBS) and related methods are based on high-throughput short-read sequencing of genomic complexity reductions followed by discovery of SNPs within sequence tags. This provides a powerful and economical approach to whole-genome genotyping, facilitating applications in genomics, diversity analysis, and molecular breeding. However, due to the complexity of analysing large data sets, applications of GBS may require substantial time, expertise and computational resources. Haplotag, the novel GBS software described here, is freely available and operates with minimal user-investment on widely-available computer platforms. Haplotag is unique in fulfilling the following set of criteria: (1) operates without a reference genome; (2) can be used in a polyploid species; (3) provides a discovery mode and a production mode; (4) discovers polymorphisms based on a model of tag-level haplotypes within sequenced tags; (5) reports SNPs as well as haplotype-based genotypes; (6) provides an intuitive visual “passport” for each inferred locus. Haplotag is optimized for use in a self-pollinating plant species.