bluuebunny/crossref_metadata_2025 huggingface dataset:
Language teaching and learning as a transdisciplinary endeavour
Authors: Liddicoat Anthony J.
Published: March 2019

Language teaching and learning is commonly considered as a research discipline that resides within the field of
‘applied linguistics’, at least in the way the field is conceptualized by English-speaking academia. However, if we consider
language teaching and learning as practice, this fit is not as neat as it at first might appear. Teaching, learning and using an
additional language is complex and multifaceted; it involves languages, cultures, learning, communication, identities, etc., which
in turn are situated academically within a host of disciplines. Research in language teaching and learning is therefore
transdisciplinary in the sense that multiple disciplines can provide different lenses through which to understand the same
phenomena and to build new understandings of the object of interest. Moreover, as a field in which languages and cultures are
inherently brought into contact, language teaching and learning is also at an intersection between disciplines that are
conceptualized and developed differently in different languages and academic traditions. For example, ‘language teaching’ as a
disciplinary area does not map well onto its French translation equivalent ‘didactique des langues’. These
interactions across academic traditions therefore represent an often-unacknowledged form of transdisciplinarity. This contribution
will examine how language teaching and learning can be informed by a transdisciplinary perspective in both these senses. In
particular, it will focus on the idea of language learning from an intercultural perspective to examine how multiple disciplines
and different disciplinary traditions contribute to shaping understanding of the field; it will also consider some of the
challenges of bringing multiple disciplines to bear on this understanding.
Extracellular vesicles derived from natural killer cells use multiple cytotoxic proteins and killing mechanisms to target cancer cells
Authors: Wu Chun‐Hua , Li Jingbo , Li Li , Sun Jianping , Fabbri Muller , Wayne Alan S. , Seeger Robert C. , Jong Ambrose Y.
Published: March 2019

Extracellular vesicles (EVs) are secreted membrane vesicles, which play complex physiological and pathological functions in intercellular communication. Recently, we isolated natural killer (NK) cell‐derived EVs (NK‐EVs) from ex vivo expansion of NK cell cultures. The isolated NK‐EVs contained cytotoxic proteins and several activated caspases, and they induced apoptosis in target cells. In this report, the protein levels of cytotoxic proteins from NK‐EV isolates were analysed by ELISA. The mean values of perforin (PFN, 550 ng/mL), granzyme A (GzmA, 185 ng/mL), granzyme B (GzmB, 23.4 ng/mL), granulysin (GNLY, 56 ng/mL), and FasL (2.5 ng/mL) were obtained from >60 isolations using dot plots. The correlation between cytotoxicity and cytotoxic protein levels was examined by linear regression. PFN, GzmA, GzmB, GNLY all had a positive, moderate correlation with cytotoxicity, suggesting that there is not a single cytotoxic protein dominantly involved in killing and that all of these proteins may contribute to cytotoxicity. To further explore the possible killing mechanisms, cells were treated with NK‐EVs, proteins extracted and lysates assessed by Western blotting. The levels of Gzm A substrates, SET and HMG2, were diminished in targeted cells, indicating that GzmA may induce a caspase‐independent death pathway. Also, cytochrome C was released from mitochondria, a central hallmark of caspase‐dependent death pathways. In addition, several ER‐associated proteins were altered, suggesting that NK‐EVs may induce ER stress resulting in cell death. Our results indicate that multiple killing mechanisms are activated by NK‐derived EVs, including caspase‐independent and ‐dependent cell death pathways, which can mediate cytotoxicity against cancer cells.

Abbreviations: NK: natural killer cells; aNK: activated NK cells; EV: extracellular vesicles; ER: endoplasmic reticulum; ALL: acute lymphoblastic leukaemia; FBS: foetal bovine serum. GzmA: granzyme A; GzmB: granzyme B; GNLY: granulysin; PFN: perforin
STUDIES OF THE Vi (γ2c) SUBGROUP OF γ-GLOBULIN
Authors: Yount William J. , Kunkel Henry G. , Litwin Stephen D.
Published: March 2019

The Journal of Experimental Medicine, Vol. 125, No. 1, January 1, 1967, page 180, Fig. 1.

Owing to a printing error Fig. 1 was oriented incorrectly on the page. The position of the above figure is correct, and it should replace the figure on page 180. The legend and text are correct as originally printed.
CRYSTALLINE PEPSIN
Authors: Northrop John H.
Published: March 2019

In Vol. 13, No. 6, July 20, 1930, page 743, line 24, for "Millon" read "Molisch."
Ano1 mediates pressure-sensitive contraction frequency changes in mouse lymphatic collecting vessels
Authors: Zawieja Scott D. , Castorena Jorge A. , Gui Peichun , Li Min , Bulley Simon A. , Jaggar Jonathan H. , Rock Jason R. , Davis Michael J.
Published: March 2019

Lymphatic collecting vessels exhibit spontaneous contractions with a pressure-dependent contraction frequency. The initiation of contraction has been proposed to be mediated by the activity of a Ca2+-activated Cl− channel (CaCC). Here, we show that the canonical CaCC Anoctamin 1 (Ano1, TMEM16a) plays an important role in lymphatic smooth muscle pacemaking. We find that isolated murine lymphatic muscle cells express Ano1, and demonstrate functional CaCC currents that can be inhibited by the Ano1 inhibitor benzbromarone. These currents are absent in lymphatic muscle cells from Cre transgenic mouse lines targeted for Ano1 genetic deletion in smooth muscle. We additionally show that loss of functional Ano1 in murine inguinal-axillary lymphatic vessels, whether through genetic manipulation or pharmacological inhibition, results in an impairment of the pressure–frequency relationship that is attributable to a hyperpolarized resting membrane potential and a significantly depressed diastolic depolarization rate preceding each action potential. These changes are accompanied by alterations in action potential shape and duration, and a reduced duration but increased amplitude of the action potential–induced global “Ca2+ flashes” that precede lymphatic contractions. These findings suggest that an excitatory Cl− current provided by Ano1 is critical for mediating the pressure-sensitive contractile response and is a major component of the murine lymphatic action potential.
Air moisture signals in a stable oxygen isotope chronology of dwarf shrubs from the central Tibetan Plateau
Authors: Wernicke Jakob , Stark Georg , Wang Lily , Grießinger Jussi , Bräuning Achim
Published: March 2019

Background and Aims

Annually resolved biological climate proxies beyond the altitudinal and latitudinal distribution limit of trees are rare. In such regions, several studies have demonstrated that annual growth rings of dwarf shrubs are suitable proxies for palaeoclimatic investigations. In High Asia, the pioneer work of Liang et al. (Liang E, Lu X, Ren P, Li X, Zhu L, Eckstein D, 2012. Annual increments of juniper dwarf shrubs above the tree line on the central Tibetan Plateau: a useful climatic proxy. Annals of Botany109: 721–728) confirmed the suitability of shrub growth-ring chronologies for palaeoclimatic research. This study presents the first sensitivity study of an annually resolved δ18O time series inferred from Wilson juniper (Juniperus pingii var. wilsonii) from the northern shoreline of lake Nam Co (Tibetan Plateau).

Methods

Based on five individual dwarf shrub discs, a statistically reliable δ18O chronology covering the period 1957–2009 was achieved (expressed population signal = 0.80). Spearman’s correlation analysis between the δ18O chronology and climate variables from different sources was applied. In a first step, the suitability of various climate data was evaluated.

Key Results

Examinations of climate–proxy relationships revealed significant negative correlations between the δ18O shrub chronology and summer season moisture variability of the previous and current year. In particular, relative humidity of the previous and current vegetation period significantly determined the proxy variability (ρ = −0.48, P < 0.01). Furthermore, the δ18O variability of the developed shrub chronology significantly coincided with a nearby tree-ring δ18O chronology of the same genus (r = 0.62, P < 0.01).

Conclusions

The δ18O shrub chronology reliably recorded humidity variations in the Nam Co region. The chronology was significantly correlated with a nearby moisture-sensitive tree-ring δ18O chronology, indicating a common climate signal in the two chronologies. This climate signal was likely determined by moisture variations of the Asian summer monsoon. Local climate effects were superimposed on the supra-regional climate signature of the monsoon circulation. Opposing δ18O values between the two chronologies were interpreted as plant-physiological differences during isotopic fractionation processes.
Maturational Changes in Human Dorsal and Ventral Visual Networks
Authors: Ciesielski Kristina T R , Stern Moriah E , Diamond Adele , Khan Sheraz , Busa Evelina A , Goldsmith Timothy E , van der Kouwe Andre , Fischl Bruce , Rosen Bruce R
Published: March 2019

Developmental neuroimaging studies report the emergence of increasingly diverse cognitive functions as closely entangled with a rise-fall modulation of cortical thickness (CTh), structural cortical and white-matter connectivity, and a time-course for the experience-dependent selective elimination of the overproduced synapses. We examine which of two visual processing networks, the dorsal (DVN; prefrontal, parietal nodes) or ventral (VVN; frontal-temporal, fusiform nodes) matures first, thus leading the neuro-cognitive developmental trajectory. Three age-dependent measures are reported: (i) the CTh at network nodes; (ii) the matrix of intra-network structural connectivity (edges); and (iii) the proficiency in network-related neuropsychological tests. Typically developing children (age ~6 years), adolescents (~11 years), and adults (~21 years) were tested using multiple-acquisition structural T1-weighted magnetic resonance imaging (MRI) and neuropsychology. MRI images reconstructed into a gray/white/pial matter boundary model were used for CTh evaluation. No significant group differences in CTh and in the matrix of edges were found for DVN (except for the left prefrontal), but a significantly thicker cortex in children for VVN with reduced prefrontal ventral-fusiform connectivity and with an abundance of connections in adolescents. The higher performance in children on tests related to DVN corroborates the age-dependent MRI structural connectivity findings. The current findings are consistent with an earlier maturational course of DVN.
Can we nudge farmers into saving water? Evidence from a randomised experiment
Authors: Chabé-Ferret Sylvain , Le Coent Philippe , Reynaud Arnaud , Subervie Julie , Lepercq Daniel
Published: March 2019

We test whether social comparison nudges can promote water-saving behaviour among farmers as a complement to traditional CAP measures. We conducted a randomised controlled trial among 200 farmers equipped with irrigation smart meters in South-West France. Treated farmers received weekly information on individual and group water consumption over four months. Our results rule out medium to large effect-sizes of the nudge. Moreover, they suggest that the nudge was effective at reducing the consumption of those who irrigate the most, although it appears to have reduced the proportion of those who do not consume water at all.
Wrist band photoplethysmography in detection of individual pulses in atrial fibrillation and algorithm-based detection of atrial fibrillation
Authors: Väliaho E -S , Kuoppa P , Lipponen J A , Martikainen T J , Jäntti H , Rissanen T T , Kolk I , Castrén M , Halonen J , Tarvainen M P , Hartikainen J E K
Published: March 2019

Aims

Atrial fibrillation (AF) is the most common tachyarrhythmia and a significant cause of cardioembolic strokes. Atrial fibrillation is often intermittent and asymptomatic making detection a major clinical challenge. We evaluated a photoplethysmography (PPG) wrist band in individual pulse detection in patients with AF and tested the reliability of two commonly used algorithms for AF detection.

Methods and results

A 5-min PPG was recorded from patients with AF or sinus rhythm (SR) with a wrist band and analysed with two AF detection algorithms; AFEvidence and COSEn. Simultaneously registered electrocardiogram served as the golden standard for rhythm analysis and was interpreted by two cardiologists. The study population consisted of 213 (106 AF, 107 SR) patients. The wrist band PPG achieved individual pulse detection with a sensitivity of 91.7 ± 11.2% and a positive predictive value (PPV) of 97.5 ± 4.6% for AF, with a sensitivity of 99.4 ± 1.5% [7.7% (95% confidence interval, 95% CI 5.5% to 9.9%); P < 0.001] and PPV of 98.1 ± 4.1% [0.6% (95% CI −0.6% to 1.7%); P = 0.350] for SR. The pulse detection sensitivity was lower 86.7 ± 13.9% with recent-onset AF (AF duration <48 h, n = 43, 40.6%) as compared to late AF (≥48 h, n = 63, 59.4%) with 95.1 ± 7.2% [−8.3% (95% CI −12.9% to −3.7%); P = 0.001]. For the detection of AF from the wrist band PPG, the sensitivities were 96.2%/95.3% and specificity 98.1% with two algorithms.

Conclusion

The wrist band PPG enabled accurate algorithm-based detection of AF with two AF detection algorithms and high individual pulse detection. Algorithms allowed accurate detection of AF from the PPG. A PPG wrist band provides an easy solution for AF screening.
Re-examining access points to the different levels of health care: a cross-sectional series in Austria
Authors: Hoffmann Kathryn , George Aaron , Jirovsky Elena , Dorner Thomas E
Published: March 2019

Background

There is high variation in service utilization behaviour, health equity and outcomes among countries based upon the organization of access to primary and secondary care levels. Austria is a country with universal health coverage and access without clear delineation between access to primary and secondary care. The aim of this study was to investigate development of access points to the Austrian system over time and subsequent utilization.

Methods

The databases used were the Austrian Health Interview Surveys 2006/2007 and 2014, including 15 747 and 15 771 persons, respectively. Descriptive analysis of health services utilization behaviour and demographic factors were conducted. Logistic regression models were applied. Furthermore, differences between the two periods are shown.

Result

Utilization of all services assessed was high in 2014 when compared to 2006/2007. Between these periods, a 6–7% increase in use of secondary care services was found. There was a 10.8% increase in access to specialist care services and 4.1% increase in hospital outpatient visits, each without prior General Practitioner (GP) visits. The largest increases were found in those groups that had previously demonstrated the lowest utilization behaviour of accessing specialist consultations and consultations without a prior GP visit.

Conclusion

Despite the lack of change to the health care system or access to care, there was an increase in utilization of secondary care services, with a lower percentage of patients seeking direct GP consultation. This is concerning for systems development, cost containment and quality of care, as it demonstrates a possible trend shifting away from primary care as initial access point.
Sucrose-inducible heterologous expression of phytase in high cell density cultivation of the thermotolerant methylotrophic yeast Ogataea thermomethanolica
Authors: Boonchoo Kriengsak , Puseenam Aekkachai , Kocharin Kanokarn , Tanapongpipat Sutipa , Roongsawang Niran
Published: March 2019

In this study, production of fungal phytase in thermotolerant methylotrophic yeast Ogataea thermomethanolica TBRC656 employing methanol-inducible OtAOX promoter and sucrose-inducible OtMal promoter was investigated in a high cell density fed-batch fermentation. Although a similar maximum cell concentration was obtained in both expression systems, the OtMal system gave ~2-fold higher phytase activity, specific yield, production yield, volumetric productivity and specific productivity rate compared with the OtAOX system. In addition to being more efficient, the OtMal system is more flexible because sucrose or sugarcane molasses can be utilized as less expensive carbon sources instead of glycerol in batch and fed-batch stages. Phytase yields from the OtMal system produced using sucrose or sugarcane molasses are comparable with those obtained with glycerol. We estimate the cost of phytase production by the OtMal system using sucrose or sugarcane molasses to be ~85% lower than the OtAOX system.
Phenotypic characterization and virulence-related properties of Escherichia albertii strains isolated from children with diarrhea in Brazil
Authors: Lima Mauricio P , Yamamoto Denise , Santos Ana Carolina de Mello , Ooka Tadasuke , Hernandes Rodrigo T , Vieira Mônica A M , Santos Fernanda Fernandes , Silva Rosa Maria , Hayashi Tetsuya , Gomes Tânia A T
Published: March 2019

Escherichia albertii are emerging enteropathogens, whose identification is difficult, as they share biochemical characteristics and some virulence-related genes with diarrheagenic Escherichia coli (DEC). Studies on phylogeny, phenotypic characteristics and potential virulence factors of human E. albertii strains are scarce. In this study, we identified by multiplex PCR five E. albertii among 106 strains isolated from diarrheic children in São Paulo, Brazil, which were previously classified as atypical enteropathogenic E. coli. All strains were investigated regarding their phylogeny, biochemical properties, virulence-related properties, antimicrobial resistance and presence of putative virulence-related genes. All strains belonged to different E. albertii lineages and adhered to and produced attaching and effacing lesions on HeLa cells. Three strains invaded Caco-2 cells, but did not persist intracellularly, and three formed biofilms on polystyrene surfaces. All strains were resistant to few antibiotics and only one carried a self-transmissible resistance plasmid. Finally, among 38 DEC and 18 extraintestinal pathogenic E. coli (ExPEC) virulence-related genes searched, six and three were detected, respectively, with paa and cdtB being found in all strains. Despite the limited number of strains, this study provided additional knowledge on human E. albertii virulence potential, showing that they share important virulence factors with DEC and ExPEC.
HPV vaccine, Twitter, and gay, bisexual and other men who have sex with men
Authors: Budenz Alexandra , Klassen Ann , Leader Amy , Fisher Kara , Yom-Tov Elad , Massey Philip
Published: March 2019

This study aimed to quantify human papillomavirus (HPV) vaccine Twitter messaging addressing gay, bisexual and other men who have sex with men (GB+MSM) and describes messaging by vaccine sentiment (attitudes towards vaccine) and characteristics (topic of messaging). Between August 2014 and July 2015, we collected 193 379 HPV-related tweets and classified them by vaccine sentiment and characteristics. We analysed a subsample of tweets containing the terms ‘gay’, ‘bisexual’ and ‘MSM’ (N = 2306), and analysed distributions of sentiment and characteristics using chi-square. HPV-related tweets containing GB+MSM terms occupied 1% of our sample. The subsample had a largely positive vaccine sentiment. However, a proportion of ‘gay’ and ‘bisexual’ tweets did not mention the vaccine, and a proportion of ‘gay’ and ‘MSM’ tweets had a negative sentiment. Topics varied by GB+MSM term—HPV risk messaging was prevalent in ‘bisexual’ (25%) tweets, and HPV transmission through sex/promiscuity messaging was prevalent in ‘gay’ (18%) tweets. Prevention/protection messaging was prevalent only in ‘MSM’ tweets (49%). Although HPV vaccine sentiment was positive in GB+MSM messaging, we identified deficits in the volume of GB+MSM messaging, a lack of focus on vaccination, and a proportion of negative tweets. While HPV vaccine promotion has historically focused on heterosexual HPV transmission, there are opportunities to shape vaccine uptake in GB+MSM through public health agenda setting using social media messaging that increases knowledge and minimizes HPV vaccine stigma. Social media-based HPV vaccine promotion should also address the identities of those at risk to bolster vaccine uptake and reduce the risk of HPV-attributable cancers.
Cancer Treatment-Related Infertility: A Critical Review of the Evidence
Authors: Poorvu Philip D , Frazier A Lindsay , Feraco Angela M , Manley Peter E , Ginsburg Elizabeth S , Laufer Marc R , LaCasce Ann S , Diller Lisa R , Partridge Ann H
Published: March 2019

Cancer treatments may compromise the fertility of children, adolescents, and young adults, and treatment-related infertility represents an important survivorship issue that should be addressed at diagnosis and in follow-up to ensure optimal decision-making, including consideration of pursuing fertility preservation. Risk of infertility varies substantially with patient and treatment factors. The ability to accurately assess fertility risk for many patients is hampered by limitations of the current literature, including heterogeneity in patient populations, treatments, and outcome measures. In this article, we review and synthesize the available data to estimate fertility risks from modern cancer treatments for both children and adult cancer survivors to enable clinicians to counsel patients about future fertility.
Selling Ghana Greener Pastures: Green Card Entrepreneurs, Visa Lottery, and Mobility
Authors: Goodman Carly Beth
Published: March 2019

Since 1994, people in Ghana have eagerly registered for the United States Diversity Visa lottery, an annual program that makes immigrant visas available to residents of countries that historically sent few immigrants to the United States. Although the green card lottery was not created to facilitate immigration from Africa, Ghanaians embraced the lottery enthusiastically. The program dovetailed with the growing popularity of international migration—framed as seeking “greener pastures”—since the country’s adoption of neoliberal economic reforms beginning in the 1980s. In particular, the lottery in Ghana was amplified by urban visa entrepreneurs whose self-interested efforts marketing the program drove demand for diversity visas and related migration services. Examining how and why visa entrepreneurs disseminated information about the lottery and found paying customers eager for assistance, this article historicizes how Ghanaians thought about citizenship, mobility, and their place in the world, illuminating how people navigated structural adjustment and neoliberal logic in Ghana in the 1990s and 2000s. The United States became a prime destination for contingent reasons related to transformations of Ghana’s economy and politics that made permanent emigration more desirable and spurred urban residents to set up and expand small-scale enterprises. In a context of heightened global migration restrictions in the 1990s and 2000s, the visa lottery, a migration program that operated as a game of chance, took root in Ghanaians’ imaginations.
Differences in educational attainment by country of origin: Evidence from Australia
Authors: Parasnis Jaai , Swan Jemma
Published: March 2019

This study investigates native–migrant differences in engagement in post-school education. Using a longitudinal survey of youth in Australia, we find that immigrants originating from non-English-speaking countries are significantly more likely to continue with further study between the ages of 18 and 23 years. On the other hand, there are no significant differences between immigrants from English-speaking countries and native youth. We find several important factors influencing study decisions, including parents and family background, academic ability, aspirations and age at migration; however, accounting for these factors does not fully explain the higher probability of pursuing higher education for immigrants from non-English-speaking countries. Exploring the country of origin effect, we find that immigrants from countries with low tertiary education levels are more likely to study in Australia, while differences in parental attitudes in their origin countries do not have a significant effect. The results show the importance of country of origin on the study decisions of youth, underlining the impact of migration settings on education of next generation.
A compact jet at the infrared heart of the prototypical low-luminosity AGN in NGC 1052
Authors: Fernández-Ontiveros J A , López-Gonzaga N , Prieto M A , Acosta-Pulido J A , Lopez-Rodriguez E , Asmus D , Tristram K R W
Published: March 2019

The feeble radiative efficiency characteristic of Low-Luminosity Active Galactic Nuclei (LLAGNs) is ascribed to a sub-Eddington accretion rate, typically at log (Lbol/Ledd) ≲ −3. At the finest angular resolutions that are attainable nowadays using mid-infrared (mid-IR) interferometry, the prototypical LLAGN in NGC 1052 remains unresolved down to $\lt \!5\, \rm {mas}$ ($0.5\, \rm {pc}$). This is in line with non-thermal emission from a compact jet, a scenario further supported by a number of evidences: the broken power-law shape of the continuum distribution in the radio-to-UV range; the ${\sim } 4{{\ \rm per\ cent}}$ degree of polarization measured in the nuclear mid-IR continuum, together with the mild optical extinction ($A_V \sim 1\, \rm {mag}$); and the ‘harder when brighter’ behaviour of the X-ray spectrum, indicative of self-Compton synchrotron radiation. A remarkable feature is the steepness of the IR-to-UV core continuum, characterized by a power-law index of ∼2.6, as compared to the canonical value of 0.7. Alternatively, to explain the interferometric data by thermal emission would require an exceptionally compact dust distribution when compared to those observed in nearby AGN, with $A_V \gtrsim 2.8\, \rm {mag}$ to account for the IR polarization. This is in contrast with several observational evidences against a high extinction along the line of sight, including the detection of the nucleus in the UV range and the well-defined shape of the power-law continuum. The case of NGC 1052 shows that compact jets can dominate the nuclear emission in LLAGN across the whole electromagnetic spectrum, a scenario that might be common among this class of active nuclei.
Multiwavelength spectroscopy of the black hole candidate MAXI J1813-095 during its discovery outburst
Authors: Armas Padilla M , Muñoz-Darias T , Sánchez-Sierras J , De Marco B , Jiménez-Ibarra F , Casares J , Corral-Santana J M , Torres M A P
Published: March 2019

MAXI J1813-095 is an X-ray transient discovered during an outburst in 2018. We report on X-ray and optical observations obtained during this event, which indicate that the source is a new low-mass X-ray binary. The outburst lasted ∼70 d and peaked at LX(0.5–10 keV) ∼ 7.6 × 1036 erg s−1, assuming a distance of 8 kpc. Swift/XRT follow-up covering the whole activity period shows that the X-ray emission was always dominated by a hard power-law component with a photon index in the range of 1.4–1.7. These values are consistent with MAXI J1813-095 being in the hard state, in agreement with the ∼30 per cent fractional root-mean-square amplitude of the fast variability (0.1–50 Hz) inferred from the only XMM–Newton observation available. The X-ray spectra are well described by a Comptonization emission component plus a soft, thermal component (kT ∼ 0.2 keV), which barely contributes to the total flux (≲8 per cent). The Comptonization y-parameter (∼1.5), together with the low temperature and small contribution of the soft component supports a black hole accretor. We also performed optical spectroscopy using the Very Large Telescope and Gran Telescopio Canarias telescopes during outburst and quiescence, respectively. In both cases, the spectrum lacks emission lines typical of X-ray binaries in outburst. Instead, we detect the Ca ii triplet and H α in absorption. The absence of velocity shifts between the two epochs, as well as the evolution of the H α equivalent width, strongly suggest that the optical emission is dominated by an interloper, likely a G–K star. This favours a distance ≳3 kpc for the X-ray transient.
Intraoperative High Impedance Levels During Placement of Deep Brain Stimulating Electrode
Authors: Lyons Mark K , Neal Matthew T , Patel Naresh P
Published: March 2019

BACKGROUND AND IMPORTANCE

Deep brain stimulation (DBS) is a well-established treatment for medically refractory Parkinson's disease (PD), essential tremor (ET), and dystonia. The field of DBS is expanding and techniques are under investigation for the treatment of several neurological disorders. A critical component of the success of these procedures depends significantly on the reliability and durability of devices implanted. Immediate feedback during surgery often gives the surgeon and patient a sense of confidence of long term success. When impedances are found to be elevated during the implantation of the DBS leads, appropriate trouble shooting measures are critical.

CLINICAL PRESENTATION

We present a 73-yr-old male undergoing awake subthalamic DBS with microelectrode recordings for severe PD. Once the optimal trajectory and depth were ascertained, the permanent DBS electrode was placed. High impedances were recorded. Troubleshooting procedures were performed and were all negative as to the cause of the values. Correct impedance levels of the DBS electrode was confirmed with extracranial testing, but continued high values were found again with intracranial positioning of the electrode. A postoperative computerized tomography (CT) scan confirmed intracranial air surrounding all of the contacts. The patient went on to outpatient programming with excellent clinical results.

CONCLUSION

The presence of pneumocephalus surrounding the DBS lead contacts at the target nucleus may have accounted for the intraoperative impedance findings. When all troubleshooting checks have not identified an explanation for the high impedances, intraoperative imaging may demonstrate pneumocephalus around the lead contacts, which should resolve and impedances return to normal values.
Non-relativistic and relativistic magnetic reconnection with the effects of optically thin synchrotron cooling
Authors: Takeshige Satoshi , Takahashi Hiroyuki R , Shibata Kazunari
Published: March 2019

We performed special relativistic resistive magnetohydrodynamic simulations of Petscheck-type magnetic reconnection including an optically thin synchrotron cooling. The magnetization parameter, σ0, which is the ratio of Poynting flux to mass flux in the upstream plasma, is taken to be 0.01 and 3. For the non-relativistic plasma (σ0 = 0.01), the radiative cooling subtracts thermal energy mainly in the upstream plasma and a plasma is strongly compressed at the slow shock. The cooling in the post-shock region and plasmoid also reduces the thermal energy and it forms a narrower outflow. The reconnection rate slightly increases as a result of the radiative cooling, since the plasma beta in the inflow region becomes small. The effect of decreasing thermal energy in the outflow region is more prominent for the relativistic plasma (σ0 = 3). In this case, the outflow temperature increases and the plasma internal energy becomes comparable to the plasma rest mass energy. The subtraction of this thermal energy by radiative cooling leads to a decrease in plasma inertia and the outflows are more accelerated than without radiative cooling. The reconnection rate is also enhanced by its Lorentz contraction effect. For both non-relativistic and relativistic simulations, it is concluded that the reconnection rate is determined by the plasma beta in the inflow region.
Psychosocial Factors in Painful Diabetic Neuropathy: A Systematic Review of Treatment Trials and Survey Studies
Authors: Kioskli Kitty , Scott Whitney , Winkley Kirsty , Kylakos Stavros , McCracken Lance M
Published: March 2019

Objective

Diabetes mellitus is associated with a number of complications that can adversely impact patients’ quality of life. A common and often painful complication is painful diabetic neuropathy. The aims of this study were to systematically review and summarize evidence from studies of psychological treatments and psychosocial factors related to painful diabetic neuropathy and assess the methodological quality of these studies.

Methods

Electronic databases, related reviews, and associated reference lists were searched. Summaries of participants’ data relating to the efficacy of psychological treatments and/or to associations between psychosocial factors and outcomes in painful diabetic neuropathy were extracted from the included studies. The methodological quality of included studies was assessed using two standardized quality assessment tools.

Results

From 2,921 potentially relevant titles identified, 27 studies were included in this systematic review. The evidence suggests that depression, anxiety, sleep, and quality of life are the most studied variables in relation to pain outcomes in painful diabetic neuropathy and are consistently associated with pain intensity. The magnitude of the associations ranged from small to large.

Conclusions

Research into psychosocial factors in painful diabetic neuropathy is unexpectedly limited. The available evidence is inconsistent and leaves a number of questions unanswered, particularly with respect to causal associations between variables. The evidence reviewed indicates that depression, anxiety, low quality of life, and poor sleep are associated with pain in painful diabetic neuropathy. The disproportionate lack of research into psychological treatments for painful diabetic neuropathy represents a significant opportunity for future research.
Neuromodulation of the Dorsal Root Ganglion for Chronic Postsurgical Pain
Authors: Antony Ajay B , Schultheis B Carsten , Jolly Suneil M , Bates Daniel , Hunter Corey W , Levy Robert M
Published: March 2019

Objective

The objective of this study is to review the available evidence for dorsal root ganglion (DRG) stimulation for the treatment of complex regional pain syndrome type II (CRPS II; peripheral causalgia) associated with chronic neuropathic postsurgical pain (NPP).

Design

Available literature was identified through a search of the US National Library of Medicine’s Medline database, PubMed.gov. References from published articles also were reviewed for relevant citations.

Results

The data published to date support the use of DRG stimulation to treat chronic NPP of the groin, knee, and foot. NPP following procedures such as thoracotomy, hernia surgery, and knee replacement surgery were identified as some of the conditions for which DRG stimulation is likely to be effective.

Conclusion

DRG stimulation is known to be an effective treatment for focal neuropathic pain. Currently, NPP of the foot, groin, and knee all appear to be the conditions with the most clinical experience, backed by a limited but growing body of evidence. However, prospective studies lag behind real-world clinical experience and are needed to confirm these findings.
The Evolution of Neuromodulation in the Treatment of Chronic Pain: Forward-Looking Perspectives
Authors: Fishman Michael A , Antony Ajay , Esposito Michael , Deer Timothy , Levy Robert
Published: March 2019

Background

The field of neuromodulation is continually evolving, with the past decade showing significant advancement in the therapeutic efficacy of neuromodulation procedures. The continued evolution of neuromodulation technology brings with it the promise of addressing the needs of both patients and physicians, as current technology improves and clinical applications expand.

Design

This review highlights the current state of the art of neuromodulation for treating chronic pain, describes key areas of development including stimulation patterns and neural targets, expanding indications and applications, feedback-controlled systems, noninvasive approaches, and biomarkers for neuromodulation and technology miniaturization.

Results and Conclusions

The field of neuromodulation is undergoing a renaissance of technology development with potential for profoundly improving the care of chronic pain patients. New and emerging targets like the dorsal root ganglion, as well as high-frequency and patterned stimulation methodologies such as burst stimulation, are paving the way for better clinical outcomes. As we look forward to the future, neural sensing, novel target-specific stimulation patterns, and approaches combining neuromodulation therapies are likely to significantly impact how neuromodulation is used. Moreover, select biomarkers may influence and guide the use of neuromodulation and help objectively demonstrate efficacy and outcomes.
Size-Dependent elastic response in functionally graded microbeams considering generalized first strain gradient elasticity
Authors: Sidhardh S , Ray M C
Published: March 2019

In this article, the size-dependent mechanical response of an isotropic functionally graded (FG) microbeam has been investigated. The size-effects over the elastic response have been modeled by the Mindlin–Toupin strain gradient theory, with the coefficients evaluated from the generalized first strain gradient theory of elasticity. In order to facilitate the derivation of the exact solutions to the governing differential equations of equilibrium, an exponentially graded FG beam is chosen. These exact solutions are derived for a simply supported beam subjected to a sinusoidally distributed mechanical load. Following this, an element-free Galerkin (EFG) model involving moving least squares interpolations across the domain is also developed here. The EFG model is validated with the exact solutions for the exponentially graded beam. Finally, the EFG model is extended to the more general case of a power law-graded beam. The mechanical responses for the power law-graded beams under various loading and boundary conditions are presented here. These results may serve as benchmark for further studies over size-effects in FG beams.
Autoantibodies to a novel Rpp38 (Th/To) derived B-cell epitope are specific for systemic sclerosis and associate with a distinct clinical phenotype
Authors: Koenig Martial , Bentow Chelsea , Satoh Minoru , Fritzler Marvin J , Senécal Jean-Luc , Mahler Michael
Published: March 2019

Objective

Detection of antinuclear antibodies and specific autoantibodies is important in the diagnosis and classification of SSc. Several proteins of the Th/To complex, including Rpp25, Rpp38 and hPop1 are the target of autoantibodies in SSc patients. However, very little is known about the epitope distribution of this autoantigen. Consequently, we screened Rpp25, Rpp38 and hPop1 for B cell epitopes and evaluated their clinical relevance.

Methods

Serum pools with (n = 2) and without (n = 1) anti-Th/To autoantibodies were generated and used for epitope discovery. Identified biomarker candidate sequences were then utilized to synthesize synthetic, biotinylated, soluble peptides. The peptides were tested to determine reactivity with sera from SSc cohorts (n = 202) and controls (n = 159) using a chemiluminescence immunoassay. Additionally, samples were also tested for antibodies to full-length recombinant Rpp25 antibodies by chemiluminescence immunoassay.

Results

Several immunodominant regions were found on the three proteins. The strongest reactivity was observed with an Rpp38 peptide (aa 229–243). Autoantibodies to the Rpp38 peptide were detected in 8/149 (5.4%) limited cutaneous SSc patients, but not in any of 159 controls (P = 0.003 by two-sided Fisher's exact probability test). Although reactivity to the novel antigenic peptide was correlated with the binding to Rpp25 (rho = 0.44; P < 0.0001), subsets of patient sera either reacted strongly with Rpp25 or with the novel Rpp38-derived peptide.

Conclusion

A novel Rpp38 epitope holds promise to increase the sensitivity in the detection of anti-Th/To autoantibodies, thus enhancing the serological diagnosis of SSc.
The TLR5 agonist flagellin modifies phenotypical and enhances functional activation of lung mucosal antigen presenting cells in neonatal mice
Authors: Sharma Pankaj , Levy Ofer , Dowling David J.
Published: March 2019

Intranasal mucosal vaccines are of interest in that they may induce protective mucosal immune responses. Activation of lung antigen presenting cells (APCs), a phenotyoically and functionally heterogeneous cell population located at distinct mucosal sites, may be key to the immunogenicity of such vaccines. Characterizing responsiveness of newborn lung APCs to adjuvants may inform design of efficacious intranasal vaccines for early life, when most infections occur. We characterized APCs from neonatal (<7 days of life) and adult (6-8 weeks of age) mice. Neonatal mice displayed a relatively high abundance of alveolar macrophages (AMs), with lower percentages of plasmacytoid dendritic cells (pDCs), CD103+ (cDC1) and CD11b+ (cDC2) DCs. Furthermore, neonatal CD103+ and CD11b+ DC subsets demonstrated an inverse expression of maturation markers as compared to adult mice. Upon stimulation of lung APC subsets with a panel of pattern recognition receptor (PRR), including TLR and STING, agonists, CD11c+ enriched cells from neonatal and adult mice lungs demonstrated distinct maturation profiles. The TLR5 ligand, flagellin, was most effective at activating neonatal lung APCs, inducing significantly higher expression of maturation markers on CD103+ (cDC1) and CD11b+ (cDC2) subsets. Intranasal administration of flagellin induced a distinct migration of CD103+ and CD11b+ DC subsets to the mediastinal lymph nodes (mLNs) of neonatal mice. Overall, these findings highlight age specific differences in the maturation and responsiveness of lung APC subsets to different PRR agonists. The unique efficacy of flagellin in enhancing lung APC activity suggests that it may serve as an effective adjuvant for early life mucosal vaccines.
The protein repertoire in early vertebrate embryogenesis
Authors: Peshkin Leonid , Lukyanov Alexander , Kalocsay Marian , Gage Robert Michael , Wang DongZhuo , Pells Troy J. , Karimi Kamran , Vize Peter D. , Wühr Martin , Kirschner Marc W.
Published: March 2019

We present an unprecedentedly comprehensive characterization of protein dynamics across early development inXenopus laevis, available immediately via a convenient Web portal. This resource allows interrogation of the protein expression data in conjunction with other data modalities such as genome wide mRNA expression. This study provides detailed data for absolute levels of ∼14K uniqueXenopusproteins representing homologues of ∼9K unique human genes – a rich resource for developmental biologists. The purpose of this manuscript is limited to presenting and releasing the data browser.

Highlights

Relative protein expression from stage IV oocyte, blastula, gastrula, neurula, and early organogenesis

Biological triplicates with confidence intervals on protein expression reflect certainty in dynamic patterns

Convenient time-series Web-browser integrated with the multi-media Xenbase portal

Gene-symbol search and multi-gene protein/mRNA juxtaposition capabilities
Alzheimer disease and Apolipoprotein E4: meningeal brain lymphatics point to new clues in pathogenesis
Authors: Mentis Alexios-Fotios A. , Chrousos George P.
Published: March 2019

The role of the lymphatic system in brain function and/or dysfunction has long been an enigma. However, recent reports that meningeal lymphatic vessels exist within the mouse and human brain, as well as evidence that mouse meningeal lymphatic vessels play a role in clearing the toxic amyloid-beta peptide connected with Alzheimer’s disease (AD), may herald novel diagnostic and therapeutic avenues. Here, we explore new evidence connecting the lymphatic system of the brain with AD. In particular, we focus on new findings showing that meningeal lymphatic vessels play a role in drainage of cerebrospinal fluid and egress of immune cells from the brain, and that disrupting this vessel system leads to accumulation of amyloid - beta peptide and cognitive dysfunction. We also discuss the hypothesis that apolipoprotein E isoform e4 (APO E4) ─ the leading genetic risk for developing AD ─ is involved in meningeal lymphatic vessel function. By reanalyzing previously published RNA-Seq data, we show that APO E4 knock-in microglia cells express lower levels of genes representing lymphatic markers (a phenomenon we call “attenuated lymphaticness”) and of genes in which functional missense mutations are linked to lymphedema. Accordingly, we propose the hypothesis that APO E4 is involved in the shrinkage of lymphatic vessels. This notion could lead, if verified by additional anatomic and mechanistic data, to the concept that APO E4-related AD (such as in late onset AD or trisomy 21-related AD) is related to lymphosclerosis coupled with lymphedema.
A failed top-down control from prefrontal cortex to amygdala in generalized anxiety disorder: evidence from resting-state fMRI with Granger causality analysis
Authors: Dong Mengshi , Xia Likun , Lu Min , Li Chao , Xu Ke , Zhang Lina
Published: March 2019

Objective

In generalized anxiety disorder (GAD), abnormal top-down control from prefrontal cortex (PFC) to amygdala is a widely accepted hypothesis through which “emotional dysregulation model” may be explained. However, whether and how the PFC directly exerted abnormal top-down control on amygdala remained largely unknown. We aim to investigate the amygdala-based effective connectivity by using Granger causality analysis (GCA).

Methods

Thirty-five drug-naive patients with GAD and thirty-six healthy controls (HC) underwent resting-state functional MR imaging. We used seed-based Granger causality analysis to examine the effective connectivity between the bilateral amygdala and the whole brain. The amygdala-based effective connectivity was compared between the two groups.

Results

In HC, the left middle frontal gyrus exerted inhibitory influence on the right amygdala, while in GAD group, this influence was disrupted (single voxel P < 0.001, Gaussian random field corrected with P < 0.01).

Conclusion

Our finding might provide new insight into the “insufficient top-down control” hypothesis in GAD.