bluuebunny/crossref_metadata_2025 huggingface dataset:
The critical period for brown adipocyte development: Genetic and environmental influences
Authors: Chabowska‐Kita Agnieszka , Kozak Leslie P.
Published: January 2016

Objective

The current review summarizes recent advances in the origin of brown adipocytes in rodents and humans.

Methods

This review describes recent insights into induction of the brown adipocyte phenotype (BAP) in white fat (WAT) revealed by murine studies during the early postnatal period and reversible temperature transitions. The origin of adipocytes and identity of progenitors as indicated by lineage tracing experiments are reviewed.

Results

We describe a genetic model for brown adipocyte development that involves the appearance of brown adipocytes in WAT at 21 days of age and a mechanism of post‐weaning involution relevant for acquisition of the BAP in fully functional WAT in mice. Under normal physiological conditions, the BAP is dormant with the potential to be stimulated by changes in the external environment. Current evidence for the acquisition of brown adipocytes by interconversion of mature adipocytes versus de novo recruitment of progenitors suggests that mechanisms for acquisition of the BAP in WAT in mice are depot‐specific and controlled by allelic variation.

Conclusions

Although the BAP is highly variable among mice, there is no information on genetic variability in the expression of brown adipocytes in humans. Thus, deeper understanding of genetic mechanisms underlying development of functional brown adipocytes is crucial.
Natural and synthetic vocalizations of brown rat pups, Rattus norvegicus, enhance attractiveness of bait boxes in laboratory and field experiments
Authors: Takács Stephen , Kowalski Pawel , Gries Gerhard
Published: January 2016

BACKGROUND

Rats are often neophobic and thus do not readily enter trap boxes which are mandated in rodent management to help reduce the risk of accidental poisoning or capture of non‐target animals. Working with brown rats, Rattus norvegicus, as a model species, our overall objective was to test whether sound cues from pups could be developed as a means to enhance captures of rats in trap boxes.

RESULTS

Recording vocalizations from three‐day‐old pups after removal from their natal nest with both sonic and ultrasonic microphones revealed frequency components in the sonic range (1.8–7.5 kHz) and ultrasonic range (18–24 kHz, 33–55 kHz, 60–96 kHz). In two‐choice laboratory bioassays, playback recordings of these vocalizations induced significant phonotactic and arrestment responses by juvenile, subadult and adult female and male rats. The effectiveness of engineered ‘synthetic’ rat pup sounds was dependent upon their frequency components, sound durations and the sound delivery system. Unlike other speakers, a piezoelectric transducer emitting sound bursts of 21 kHz with a 63‐KHz harmonic, and persisting for 20–300 ms, proved highly effective in attracting and arresting adult female rats. In a field experiment, a battery‐powered electronic device fitted with a piezoelectric transducer and driven by an algorithm that randomly generated sound cues resembling those recorded from rat pups and varying in fundamental frequency (19–23 kHz), duration (20–300 ms) and intermittent silence (300–5000 ms) significantly enhanced captures of rats in trap boxes baited with a food lure and soiled bedding material of adult female rats.

CONCLUSION

Our study provides proof of concept that rat‐specific sound cues or signals can be effectively reproduced and deployed as a means to enhance capture of wild rats. © 2016 Society of Chemical Industry
Larvicidal activity of natural and modified triterpenoids against Aedes aegypti (Diptera: Culicidae)
Authors: da Silva Gloria NS , Trindade Frances TT , dos Santos Francine , Gosmann Grace , e Silva Alexandre A , Gnoatto Simone CB
Published: January 2016

BACKGROUND

Insecticide resistance to commonly used substances demands new molecules for the chemical control of the dengue vector Aedes aegypti. Because natural product sources have been an alternative to obtain larvicidal compounds, the aim of this study was to evaluate the triterpenoids betulinic (BA) and ursolic (UA) acids and their semi‐synthetic derivatives against larval Ae. aegypti. BA, UA, ten derivatives modified at the C‐3 position and a positive control (diflubenzuron) were evaluated. Larvicidal assays were carried out with early fourth‐instar larvae, and mortality was observed between 48 and 96 h. Doses from 200 to 10 ppm were used to calculate lethal concentrations (LCs).

RESULTS

Natural compounds, i.e. UA and BA, had the lowest LCs (LC50 of 112 and 142 ppm respectively), except for the modified compound 2b (LC50 of 130 ppm). Larvicidal activity increased significantly from 48 to 96 h for all the compounds evaluated, ranging from 20 to 50% after 48 h and from 48 to 76% after 96 h. Some derivatives, e.g. 2a and 2d, had up to a three‐fold larvicidal activity increase from 48 to 96 h.

CONCLUSION

BA, UA and their derivatives showed larvicidal activity against Ae. aegypti larvae, increasing significantly from 48 to 96 h. The presence of a hydroxyl group is essential for larvicidal potential in these triterpenoids. © 2016 Society of Chemical Industry
On the need for increased rigour and care in the conduct and interpretation of network meta‐analyses in drug development
Authors: Carroll Kevin , Hemmings Robert
Published: January 2016

The rise over recent years in the use of network meta‐analyses (NMAs) in clinical research and health economic analysis is little short of meteoric driven, in part, by a desire from decision makers to extend inferences beyond direct comparisons in controlled clinical trials. But is the increased use and reliance of NMAs justified? Do such analyses provide a reliable basis for the relative effectiveness assessment of medicines and, in turn, for critical decisions relating to healthcare access and provisioning? And can such analyses also be used earlier, as part of the evidence base for licensure? Despite several important publications highlighting inherently unverifiable assumptions underpinning NMAs, these assumptions and associated potential for serious bias are often overlooked in the reporting and interpretation of NMAs. A more cautious, and better informed, approach to the use and interpretation of NMAs in clinical research is warranted given the assumptions that sit behind such analyses. Copyright © 2015 John Wiley & Sons, Ltd.
Analysis of hydrogen in materials with and without high hydrogen mobility
Authors: Stevie F. A.
Published: January 2016

Hydrogen is a very important element but analysis of hydrogen in solids can be difficult and is not available for many analytical techniques. This paper provides an overview of the capabilities of SIMS and NRA to measure hydrogen concentrations and distributions. Bulk analysis methods provide an overall result, but depth profiles are often needed. SIMS can produce useful and quantifiable depth profiles for hydrogen and the isotopes deuterium and tritium. Hydrogen analysis at the surface and imaging with good lateral resolution can also be achieved with SIMS. However, hydrogen can have high mobility in a variety of materials and this will affect SIMS analysis. For those cases, other surface analysis methods such as hydrogen forward scattering and nuclear reaction analysis are preferred. Hydrogen analysis examples in silicon and in niobium are used for materials without and with high hydrogen mobility respectively. Copyright © 2016 John Wiley & Sons, Ltd.
Study of surface corrosion on AA 2017‐T4 aluminum alloy by using electrochemical parameters
Authors: Abreu C. M. , Cabeza M. , Feijoo I.
Published: January 2016

In this study, we applied potentiodynamic polarization to the analysis of surface corrosion in a 2017‐T4 alloy during a stress corrosion cracking (SCC) test in 1 m NaCl solution. A constant load SCC test was chosen, classifying the applied load into three categories – no load, medium load, and high load – with the material's yield strength as a maximum load. Electrochemical measurements carried out during the SCC test allowed us, by plotting the current density versus the applied potential on a logarithmic scale, to determine the electrochemical characteristic parameters for each load category. These parameters, combined with both cross‐sectional and surface morphological analysis, were used to qualitatively characterize the corrosion of the aluminum alloy. All tests performed revealed two different attack behaviors, one characterized by shallow pits and the other by a deep, intergranular penetration. The presence of each behavior depends on the intensity of the applied load, which involves variations in the polarization curve and therefore modifies the electrochemical parameters. Copyright © 2016 John Wiley & Sons, Ltd.
A comparison of change point models with application to longitudinal lung function measurements in children with cystic fibrosis
Authors: Moss Angela , Juarez‐Colunga E. , Nathoo Farouk , Wagner Brandie , Sagel Scott
Published: January 2016

Cystic fibrosis (CF) is a hereditary lung disease characterized by loss of lung function over time. Lung function in CF is believed to decline at a higher rate during the adolescence period. It has been also hypothesized that there is a subgroup of individuals for whom lung disease remains relatively stable with only a slight decline over their lifetime. Using data from the University of Colorado CF Children's Registry, we investigate four change point models to model the decline of lung function in children and adolescents: (i) a two‐component mixture random change point model, (ii) a two‐component mixture‐fixed change point model, (iii) a random change point model, and (iv) a fixed change point model. The models are investigated through posterior predictive simulation at the individual and population levels, and a simulation study examining the effects of model misspecification. The data support the mixed random change point model as the preferred model, with roughly 30% of adolescents experiencing a steady decline of 0.5 %FEV1 per year and 70% experiencing an increase in decline of 4.4 %FEV1 per year beginning on average at 14.6 years of age. Copyright © 2016 John Wiley & Sons, Ltd.
Elastic and anelastic relaxations accompanying relaxor ferroelectric behaviour of Ba6GaNb9O30 tetragonal tungsten bronze from resonant ultrasound spectroscopy
Authors: Rotaru Andrei , Schiemer Jason A. , Carpenter Michael A.
Published: January 2016

Tetragonal tungsten bronze (TTB) structures offer some promise as lead-free ferroelectrics and have an advantage of great flexibility in terms of accessible composition ranges due to the number of crystallographic sites available for chemical substitution. The ferroic properties of interest are coupled with strain, which will be important in the context of stability, switching dynamics and thin film properties. Coupling of strain with the ferroelectric order parameter gives rise to changes in elastic properties, and these have been investigated for a ceramic sample of Ba6GaNb9O30 (BGNO) by resonant ultrasound spectroscopy. Room temperature values of the shear and bulk moduli for BGNO are rather higher than for TTBs with related composition which are orthorhombic at room temperature, consistent with suppression of the ferroelectric transition. Instead, a broad, rounded minimum in the shear modulus measured at ~1 MHz is accompanied by a broad rounded maximum in acoustic loss near 115 K and signifies relaxor freezing behaviour. Elastic softening with falling temperature from room temperature, ahead of the freezing interval, is attributed to the development of dynamical polar nanoregions (PNRs), whilst the nonlinear stiffening below ~115 K is consistent with a spectrum of relaxation times for freezing of the PNR microstructure.
Essential role of HDAC6 in the regulation of PD‐L1 in melanoma
Authors: Lienlaf M. , Perez-Villarroel P. , Knox T. , Pabon M. , Sahakian E. , Powers J. , Woan K.V. , Lee C. , Cheng F. , Deng S. , Smalley K.S.M. , Montecino M. , Kozikowski A. , Pinilla-Ibarz J. , Sarnaik A. , Seto E. , Weber J. , Sotomayor E.M. , Villagra A.
Published: January 2016

Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been demonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples and cell lines, down‐regulates the expression of PD‐L1, an important co‐stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD‐1 in T‐cells. Our data suggests that this novel mechanism of PD‐L1 regulation is mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Additionally, we observed that selective HDAC6 inhibitors impairs tumor growth and reduce the in vivo expression of several inhibitory check‐point molecules and other regulatory pathways involved in immunosurveillance. Most importantly, these results provide a key pre‐clinical rationale and justification to further study isotype selective HDAC6 inhibitors as potential immuno‐modulatory agents in cancer.
PHOSPHORUS DEFICIENCY IMPAIRS SHOOT REGROWTH OF SUGARCANE VARIETIES
Authors: ZAMBROSI FERNANDO C. BACHIEGA , RIBEIRO RAFAEL VASCONCELOS , MACHADO EDUARDO CARUSO , GARCIA JÚLIO CÉSAR
Published: January 2016

The shoot regrowth vigour of sugarcane varieties having contrasting phosphorus (P) efficiency was evaluated under varying soil P availability. The P-inefficient (IAC91–1099 and IACSP94–2101) and -efficient (IACSP94–2094 and IACSP95–5000) sugarcane varieties were grown under low (25 mg P kg−1 soil) or high (400 mg P kg−1 soil) P supply at planting. After 90 days (first cycle of growth), the shoots were harvested and regrowth was studied 70–75 days later by evaluating photosynthesis, leaf area formation, biomass production and P uptake. The shoot dry matter (DM) of sugarcane regrowth subjected to a low P supply was genotype-dependent, with the P-efficient varieties exhibiting greater values than the inefficient ones. This result was explained by the greater efficiency of IACSP94–2094 and IACSP95–5000 in acquiring P rather than P utilization efficiency for shoot biomass production. The root P stored during the first cycle of growth would represent only a minor fraction (< 20%) of the total P content in the shoots at the end of the regrowth period. Thus, we argue that the improved shoot P uptake of the P-efficient varieties was related to their ability to sustain P acquisition after harvesting rather than to the remobilization of root P reserves. Moreover, our data revealed that net CO2 assimilation per leaf area was not associated with differential performance among varieties under P deficiency, suggesting a more critical role of total leaf area in photosynthate supply for sugarcane regrowth. In conclusion, sugarcane regrowth is improved in P-efficient varieties under P deficiency conditions, a finding of practical relevance as such ability might benefit the productivity and the longevity of sugarcane ratoons in low P tropical soils.
Echoes of Universalist Testament Literature in Christian and Rabbinic Texts
Authors: Simkovich Malka Z.
Published: January 2016

The ancient text known as the Testament of Abraham is preserved in Coptic in the same codex as two other works, the Testament of Isaac and the Testament of Jacob. These testaments were probably written in the late first or early second centuries CE by Jewish writers, although the manuscript of the Coptic codex containing them is dated to 962. These books were considered part of the “testament” literary genre, which featured a biblical hero imparting his last words of religious wisdom to his family gathered at his bedside. Scholars agree that the stylistic and theological differences among these three testaments indicate that they were not written by the same author. Yet a close reading reveals that the Testament of Isaac is dependent on the Testament of Abraham, and that the Testament of Jacob is dependent on the two earlier texts. Moreover, the Testament of Abraham and the Testament of Isaac share similarities that distinguish them from the Testament of Jacob: unlike the Testament of Jacob, the Testament of Abraham and the Testament of Isaac reflect a universalist worldview that depicts a God concerned for all humankind, not only for his chosen people. This God reigns over all people, and themes specific to the Christian and Jewish faiths are virtually absent. Later Christian and Jewish literature concerning the theme of divine judgment exhibits elements that may reflect an awareness of a written or oral tradition that appears in the Testament of Abraham and the Testament of Isaac. The images of judgment and punishment, especially those in the Testament of Abraham, appear in the second-century Apocalypse of Peter and the fourth-century Vision of Paul, which is also known as the Apocalypse of Paul. Likewise, midrashic traditions regarding Abraham and Moses are reminiscent of traditions found in these testaments, particularly the Testament of Abraham. The possibility that early Christian apocalyptic texts were aware of these testaments is grounded in the fact that scholars give these texts a common place of origin, Egypt. The provenance of the midrashic texts is more difficult to identify, but because they share literary elements and theological concerns with the Testament of Abraham and the Testament of Isaac, I suggest that the authors of these midrashic traditions had access to written or oral traditions prominent in these testaments. This paper will examine early Christian apocalyptic and early Jewish midrashic texts that modify some of the traditions prominent in these testaments in order to accommodate their nonuniversalist rabbinic or early Christian worldviews.
Parents Just Don't Understand: Ambiguity in Stories about the Childhood of Jesus
Authors: Frilingos Christopher A.
Published: January 2016

The childhood and teenage years, which we think of as crucial to the formation of the adult personality, go all but unnoticed in the canonical accounts of the life of Jesus. Only the Gospel of Luke includes a story about a twelve-year-old Jesus debating with religious experts in the Jerusalem temple and arguing with his parents. Synopses and commentaries sometimes refer to the episode as the “Finding of Jesus in the Temple” (Luke 2:41–52 NRSV), because it begins when his parents lose track of him. Mary and Joseph, having taken Jesus with them on a pilgrimage to Jerusalem for Passover, begin to make the journey back home to Nazareth. Jesus remains in Jerusalem, without his parents’ permission: “but his parents did not know it” (καὶ οὐκ ἔγνωσαν οἱ γονες [Luke 2:43]). Mary and Joseph search for and find their son “after three days” (2:46), safe and sound, in the great temple of Jerusalem. The boy sits among the elders, asking questions and amazing all with his “understanding” (σύνεσις [2:47]). “Child, why have you done this to us?” Mary reproaches Jesus, “See, your father and I have been worried [ὀδυνώμενοι] looking for you!” (2:48). “Why were you looking for me?” Jesus replies, “Did you not know [οὐκ ᾔδειτε] that I must concern myself with the things of my father?” (2:49). The back and forth confuses the parents: “But they did not understand what he said to them” (καὶ αὐτοὶ οὐ συνκαν τὸ ῥμα ὃ ἐλάλησεν αὐτος [Luke 2:50]).
Cain as the Scion of Satan: The Evolution of a Gnostic Myth in theZohar
Authors: Yisraeli Oded
Published: January 2016

The relationship between kabbalistic thought and ancient gnostic ideas has been debated by numerous scholars. Early on, Gershom Scholem argued that the rise of kabbalah represents the “reappearance, in the heart of Judaism, of thegnostic tradition.” In his wake, Isaiah Tishby has posited that the concept of thesĕfirot“emerge[d] and develop[ed] from a historico-literary contact with the remnants of Gnosticism, which were preserved over a period of many generations in certain Jewish circles, until they found their way to the early Kabbalists.” Joseph Dan, on the other hand, maintains that “historical connections” must not be confused with “phenomenological similarities.” There is no evidence for the existence of the former, in his opinion; all that may be claimed is a typological correspondence between gnostic ideas and medieval Jewish kabbalistic mysticism. Moshe Idel likewise claims that some early Jewish motifs penetrated gnostic texts at the same time they continued to flourish within Jewish circles until they finally found form in medieval kabbalah. Yehuda Liebes has adopted a corresponding view, although he makes fruitful exegetical use of the relationship and parallels between various gnostic and Jewish sources. The issue thus remains firmly on the academic agenda.
Known Knowns and Known Unknowns: Epiphanius of Salamis and the Limits of Heresiology
Authors: Berzon Todd S.
Published: January 2016

In this essay, I explore the conceptual and discursive ruminations of Epiphanius of Salamis as he struggles in hisPanarionto survey and manage the ever-expanding heretical world. Instead of reading this heresiological treatise as an attestation of theological, ecclesiastical, and intellectual authority established through totalizing discourse, I approach it as an expression of ancient ethnographic writing and the ethnographic disposition, an authorial orientation toward the world that describes, regulates, and classifies peoples with both macroscopic and microscopic knowledge. Ethnography in the ancient world was a process of writing the world's people into texts, describing and classifying specific cultures and customs through the lens of the ethnographer's own culturally situated perspective. Frequently, the ethnographer used his text to elaborate his assumptions about the origins of human diversity. Customs and habits were explained as the products of larger macroscopic forces such as astrology, genealogy, climatology, universal history, and myth. In the process of translating the world into texts, ethnographic inquiry forced authors to confront their capacity to comprehend the world around them and ultimately to come to terms with the full scope of human diversity. I argue that reading thePanarionas a manifestation of Christian ethnography usefully foregrounds an intractable tension between knowledge (known knowns) and self-conscious ignorance (known unknowns) about the depths of human heterogeneity: ethnography is as much an illustration of incomprehension as it is a repository of erudition, mastery, and discovery.
“Ravishing Odors of Paradise”: Jesuits, Olfaction, and Seventeenth-Century North America
Authors: KETTLER ANDREW
Published: January 2016

In seventeenth-century North America, efforts at cultural accommodation through similarities in olfactory inclusive spiritual sensoriums helped to create cross-cultural concordance between Jesuit Fathers and Native Americans in New France, the St. Lawrence Valley, and the Pays d'en Haut. Jesuits engaged Native Americans towards Catholic conversion by using scentful tactics and sensory rhetoric. Jesuits increased their own respect for the olfactory during their North American encounters due to a siege mentality born of the Counter-Reformation and from a forcefully influential Native American respect for multisensory forms of environmental and spiritual literacy which included a heightened reverence for odors.
The Beard, Masculinity, and Otherness in the Contemporary American Novel
Authors: FERRY PETER
Published: January 2016

This article identifies the humble beard as a device used in twenty-first-century American literature to examine the contemporary condition of American masculinity. Drawing on readings from key writers of post-9/11 fiction, such as John Updike, Moshin Hamid, and Don DeLillo, the article calls for the need to move on from the reductive rendering of the beard as an irrefutable representation of Otherness to see the beard as a device used to explore the construction of masculinities in relation to key issues such as racialization, sexuality and the queering of the Other, and nationhood in the globalized and globalizing arena of the United States. Reading Amy Waldman's nuanced engagement with the beard in The Submission (2011) alongside key works on hegemonic masculinity, whiteness, and globalized masculinities, the article underlines the power of the beard in the contradictions and complexities of a changing American masculinity now performed beyond the physical borders of “the nation” on the global stage.
Horner syndrome in glandular fever: a case report
Authors: West E V , Sheerin F , Bates J E H M
Published: January 2016

Objective:

This study aimed to present and discuss the case of a patient with known glandular fever who presented with Horner syndrome.

Case report:

A 35-year-old patient with known glandular fever developed acute unilateral Horner syndrome, a previously undescribed complication of this common illness. Magnetic resonance imaging and magnetic resonance angiography showed that enlarged intra-carotid sheath lymphoid tissue was likely to be the underlying cause of sympathetic nerve disruption. The case is described, the anatomy of the sympathetic chain is discussed and possible alternative pathophysiological mechanisms are reviewed.

Conclusion:

This is the first report in the worldwide literature of Horner syndrome arising as a result of compression from enlarged lymph nodes in glandular fever.
Association of demographic, lifestyle factors and serum biomarkers with hypertension in elderly Chinese people
Authors: HONG XIUQIN , WONGTONGKAM NUALNONG , WARD PAUL RUSSELL , XIAIO SHUIYUAN , WANG SHULING , PENG QIAN , ZUO QI , ZENG DAN , WANG JIA , WANG CHENXU
Published: January 2016

Hypertension is a major cause of premature death in China. Understanding risk factors including behavioural and predisposing factors may help to prevent development of hypertension and control the extent of premature mortality. In this case-control design conducted in Hunan province, 416 hypertensive subjects were matched with an equal number of normotensive persons from nearly 9,000 volunteers. A self-report questionnaire was employed to collect demographic and lifestyle information, and fasting serum biomarkers related to lipid profile, renal function, glucose level and uric acid were assessed. When age and sex were stratified, serum biomarkers such as blood urea nitrogen and triglycerides showed a significant difference for hypertension, while lifestyle behaviours including university degree, alcohol use, Body Mass Index and psychological stress (job and married life) were also associated with hypertension. After adjusting for covariate confounding factors, only elevated triglyceride levels were strongly linked to high blood pressure, odds ratio = 1.55, 95 per cent confidence level = 1.16–2.06. To control high blood pressure, hypertriglyceridemia should be included in hypertension treatment and followed up to assess the substantial risk of cardiovascular diseases.
Laser-induced diamond-like carbon film under different electric field directions
Authors: Shenjiang Wu , Dangjuan Li , Junhong Su
Published: January 2016

Ti electrodes were directly deposited at different positions on diamond-like carbon (DLC) films to form horizontal and longitudinal electric fields on their surfaces. TheID/IGratio increased with thesp3content in the membrane when the DLC film was laser-irradiated and the electric field intensity was 0 V/cm. The bias electric field intensity increased from 0 to 1000 V/cm, and the corresponding laser-induced damage threshold (LIDT) increased. The three-dimensional damage morphology of the DLC film with two different electrode structures was observed when the electric field intensity was 220 V/cm. Two types of electrode structures were observed in the Raman spectra under an electric field intensity of 110 V/cm and laser energy densities of 0 and 1.56 J/cm2. Results showed that the horizontal bias field had a more obvious influence than the longitudinal electric field on the decrease of thesp3–sp2hybridization, preventing the formation ofsp2clusters, thereby slowing down the graphitization process of DLC. Applying the bias field to the DLC film could slow down the DLC film graphitization process and improve the LIDT of the DLC film.
Regression approaches in the test-negative study design for assessment of influenza vaccine effectiveness
Authors: BOND H. S. , SULLIVAN S. G. , COWLING B. J.
Published: January 2016

Influenza vaccination is the most practical means available for preventing influenza virus infection and is widely used in many countries. Because vaccine components and circulating strains frequently change, it is important to continually monitor vaccine effectiveness (VE). The test-negative design is frequently used to estimate VE. In this design, patients meeting the same clinical case definition are recruited and tested for influenza; those who test positive are the cases and those who test negative form the comparison group. When determining VE in these studies, the typical approach has been to use logistic regression, adjusting for potential confounders. Because vaccine coverage and influenza incidence change throughout the season, time is included among these confounders. While most studies use unconditional logistic regression, adjusting for time, an alternative approach is to use conditional logistic regression, matching on time. Here, we used simulation data to examine the potential for both regression approaches to permit accurate and robust estimates of VE. In situations where vaccine coverage changed during the influenza season, the conditional model and unconditional models adjusting for categorical week and using a spline function for week provided more accurate estimates. We illustrated the two approaches on data from a test-negative study of influenza VE against hospitalization in children in Hong Kong which resulted in the conditional logistic regression model providing the best fit to the data.
Building Household and Community through Active Assemblages: A Late Formative Patio Group at Khonkho Wankane, Bolivia
Authors: Marsh Erik J.
Published: January 2016

A community is an active assemblage of human and non-human elements bound together by interactions. Archaeologies of communities shed light on sets of overlapping and geographically emplaced assemblages of individuals, practices, spaces, buildings, objects, animals and landscapes. This article presents an archaeology of communities based a remarkably well preserved Late Formative (ad 1–500) patio group at Khonkho Wankane, Bolivia. Excavation data provide a high-resolution chronology and document two varieties of assemblages: (1) those that played a greater role in biologically and socially reproducing the community, such as daily food and tool production; and (2) those that played a greater role in its transformation, such as gatherings, work parties and construction projects. In the patio group, intimate meetings took place in small, private spaces where incense was burned. Larger gatherings took place in an outdoor space where painted Kalasasaya small jars and bowls were active elements in interactions between residents and visitors. These events most likely involved work parties that contributed to the physical and social construction of the community. Assemblages at multiple scales built a diverse Late Formative community, which played a principal role in regional interaction networks. Within a few generations of residents leaving their homes in Khonkho, local and regional interactions generated the emergence of a state at Tiwanaku.
Mass-gathering Events: The Role of Advanced Nurse Practitioners in Reducing Referrals to Local Health Care Agencies
Authors: Kemp Anthony E.
Published: January 2016

Introduction

The introduction of advanced practitioner roles has challenged the traditional boundaries of health care. While studies have been undertaken to understand the role of physicians in respect of mass-gathering medicine, the role of advanced nurse practitioners (ANPs) has not been investigated.

Problem

Does the presence of an ANP reduce the referral rates of patients presenting for medical care at mass-gathering events to external health care resources?

Methods

A prospective observational study was undertaken to determine whether the presence of an ANP would reduce the patient referral rate to external health care services by first aiders and paramedics working within an event medical team. Patients identified as requiring referral were reviewed by an ANP as part of the on-site medical provision for four mass-gathering events in the south of England. Additionally, information was gathered identifying which patients would have been transported to hospital by ambulance compared to those actually transported following ANP review. Statistical analysis was undertaken for three key measures (referrals to all local health resources, referrals to hospital-based acute services, and transfers to hospital by ambulance).

Results

A rounded total of 842,000 people attended four mass-gathering events held over 14 days. Of these, 652 presented for medical care, many self-referring.

Using a one-tailed Fisher’s Exact Test and Phi analysis, this study demonstrated statistically significant reductions in the overall referral of patients to all external health care resources (P<.001; φ=0.44), to the emergency department (ED; P<.001; φ=0.43), and a reduction in ambulance transport (P<.001; φ=0.42). Effect size analysis demonstrated a medium-sized effect evident for all of the above, which was also demonstrated in economic terms.

The event medical team would have referred 105 (16.3%) of the 652 patient presentations to external health care services; 47 (7.2%) would have been transported by ambulance. In comparison, the ANP referred 23 patients (3.5%) with 11 (1.7%) being transported by ambulance. It also was noted that the first aiders and paramedics could be more selective in their referral habits that were focused primarily on the ED.

Conclusions

Appropriately trained and experienced ANPs working within event medical teams have a positive impact on referral rates from mass-gathering events.

KempAE. Mass-gathering events: the role of advanced nurse practitioners in reducing referrals to local health care agencies. Prehosp Disaster Med. 2016;31(1):58–63.
ASSESSING WELFARE IMPACTS OF SOME DEBT-CONSOLIDATION EPISODES IN THE EUROPEAN UNION
Authors: Viegas Miguel , Ribeiro Ana Paula
Published: January 2016

This paper aims at characterizing the debt-consolidation processes put forward by some European countries in order to assess welfare and, in particular, the inequality effects involved. For this purpose, we built a general equilibrium heterogeneous-agent model capable of exploring the relationship between fiscal policy variables and the endogenous cross-section distribution of income and wealth. Using a utilitarian welfare criterion, results show that different strategies yield different outcomes. Despite the positive welfare gains observed, transition costs affect all episodes and are determinant in sorting among the welfare-enhancing strategies. Our results confirm the superiority of adjustments partially based on the reduction of unproductive expenditures over those based on tax raises or on the reduction of social transfer. Welfare is further enhanced when consolidation strategies involve an equilibrated mix between expenditure and transfer cuts and tax increases, because debt consolidation processes mostly or exclusively based on social transfers cuts have a strong negative effect on welfare inequality. Moreover, shock volatility and persistency (also shaping inequality) help explain different results across countries: under high income inequality, consolidation processes are expected to yield smaller inequality effects on welfare, whereas a worse consumption–leisure trade-off may arise.
INEQUALITY AND INTERNATIONAL TRADE: THE ROLE OF SKILL-BIASED TECHNOLOGY AND SEARCH FRICTIONS
Authors: Ritter Moritz
Published: January 2016

I embed a competitive search model of the labor market into a small open economy model with heterogeneous firms and workers. Search frictions generate equilibrium unemployment and income inequality between identical workers, in addition to income differences between skill groups. A quantitative evaluation of the U.S. trade experience suggests that the effect of the increase in goods trade since 1980 may have contributed to the increase in the college premium, but not to the increase in residual inequality.
The “good death”: An integrative literature review
Authors: Cottrell Laura , Duggleby Wendy
Published: January 2016

Objective:

The “good death” is a dynamic concept and has evolved over time to become a “revivalist” good death: a planned, peaceful, and dignified death, at home, surrounded by family members. As the “good death” continues to evolve, the key questions are: How do cultural perceptions of death and dying change? What are the forces that shape Western attitudes and beliefs around death and dying? And how does the “good death” discourse frame the dying experience in contemporary society? The purpose of this manuscript is to describe the underlying discourse in the literature on the “good death” in Western societies.

Method:

An integrative literature review of data from experimental and nonexperimental sources in PubMed, CINAHL, PsychINFO, and SocINDEX of 39 articles from 1992 to 2014.

Results:

Four main themes emerged from reviewing 39 articles on the “good death”: (1) the “good death” as control, (2) the wrong “good death,” (3) the threatened “good death,” and (4) the denial of dying.

Significance of Results:

Evolving in response to prominent social attitudes and values, the contemporary “good death” is a powerful, constraining discourse that limits spontaneity and encourages one way to die. Social, political, and demographic changes now threaten the stability of the “good death”; dying is framed as an increasingly negative or even unnecessary process, thus marginalizing the positive aspects of dying and rendering dying absent, invisible.
Lymphome
Authors: Lohri Andreas
Published: January 2016

Zusammenfassung. Maligne Lymphome unterteilen sich zwar in über 60 Entitäten, das grosszellige B-Zell-Lymphom, das follikuläre Lymphom, der Hodgkin und das Mantelzell-Lymphom machen aber mehr als die Hälfte aller Lymphome aus. Im revidierten Ann Arbor staging system gelten die Suffixe «A» und «B» nur noch für den Hodgkin. «E» erscheint nur noch bei Stadien I und II. Eine Knochenmarksuntersuchung wird beim Hodgkin nicht mehr verlangt, beim DLBCL (Diffuse large B cell lymphoma) nur, falls das PET keinen Knochenmark-Befall zeigt. Der PET-Untersuchung, speziell dem Interim-PET, kommt eine entscheidende Bedeutung zu. PET-gesteuerte Therapien führen zu weniger Toxizität. Gezielt wirkende Medikamente mit eindrücklicher Wirksamkeit wurden neu zugelassen. Deren Kosten sind hoch. Eine strahlen- und chemotherapiefreie Behandlung maligner Lymphome wird in Zukunft möglich sein.
Human pancreatic beta-like cells converted from fibroblasts
Authors: Zhu Saiyong , Russ Holger A. , Wang Xiaojing , Zhang Mingliang , Ma Tianhua , Xu Tao , Tang Shibing , Hebrok Matthias , Ding Sheng
Published: January 2016

Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes.
A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages
Authors: Kimmerling Robert J. , Lee Szeto Gregory , Li Jennifer W. , Genshaft Alex S. , Kazer Samuel W. , Payer Kristofor R. , de Riba Borrajo Jacob , Blainey Paul C. , Irvine Darrell J. , Shalek Alex K. , Manalis Scott R.
Published: January 2016

We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line lineages. Here we report that both cell types have greater intra- than inter-lineage transcriptional similarity. For CD8+ T-cells, genes with functional annotation relating to lymphocyte differentiation and function—including Granzyme B—are enriched among the genes that demonstrate greater intra-lineage expression level similarity. Analysis of gene expression covariance with matched measurements of time since division reveals cell type-specific transcriptional signatures that correspond with cell cycle progression. We believe that the ability to directly measure the effects of lineage and cell cycle-dependent transcriptional profiles of single cells will be broadly useful to fields where heterogeneous populations of cells display distinct clonal trajectories, including immunology, cancer, and developmental biology.
Transition state theory demonstrated at the micron scale with out-of-equilibrium transport in a confined environment
Authors: Vestergaard Christian L. , Mikkelsen Morten Bo , Reisner Walter , Kristensen Anders , Flyvbjerg Henrik
Published: January 2016

Transition state theory (TST) provides a simple interpretation of many thermally activated processes. It applies successfully on timescales and length scales that differ several orders of magnitude: to chemical reactions, breaking of chemical bonds, unfolding of proteins and RNA structures and polymers crossing entropic barriers. Here we apply TST to out-of-equilibrium transport through confined environments: the thermally activated translocation of single DNA molecules over an entropic barrier helped by an external force field. Reaction pathways are effectively one dimensional and so long that they are observable in a microscope. Reaction rates are so slow that transitions are recorded on video. We find sharp transition states that are independent of the applied force, similar to chemical bond rupture, as well as transition states that change location on the reaction pathway with the strength of the applied force. The states of equilibrium and transition are separated by micrometres as compared with angstroms/nanometres for chemical bonds.
Tripartite degrons confer diversity and specificity on regulated protein degradation in the ubiquitin-proteasome system
Authors: Guharoy Mainak , Bhowmick Pallab , Sallam Mohamed , Tompa Peter
Published: January 2016

Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system. Here we systematically analyse known degrons and propose a tripartite model comprising the following: (1) a primary degron (peptide motif) that specifies substrate recognition by cognate E3 ubiquitin ligases, (2) secondary site(s) comprising a single or multiple neighbouring ubiquitinated lysine(s) and (3) a structurally disordered segment that initiates substrate unfolding at the 26S proteasome. Primary degron sequences are conserved among orthologues and occur in structurally disordered regions that undergo E3-induced folding-on-binding. Posttranslational modifications can switch primary degrons into E3-binding-competent states, thereby integrating degradation with signalling pathways. Degradation-linked lysines tend to be located within disordered segments that also initiate substrate degradation by effective proteasomal engagement. Many characterized mutations and alternative isoforms with abrogated degron components are implicated in disease. These effects result from increased protein stability and interactome rewiring. The distributed nature of degrons ensures regulation, specificity and combinatorial control of degradation.
Large-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics
Authors: Malmström Erik , Kilsgård Ola , Hauri Simon , Smeds Emanuel , Herwald Heiko , Malmström Lars , Malmström Johan
Published: January 2016

The plasma proteome is highly dynamic and variable, composed of proteins derived from surrounding tissues and cells. To investigate the complex processes that control the composition of the plasma proteome, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in murine plasma. The strategy relies on the construction of a comprehensive protein tissue atlas from cells and highly vascularized organs using shotgun mass spectrometry. The protein tissue atlas was transformed to a spectral library for highly reproducible quantification of tissue-specific proteins directly in plasma using SWATH-like data-independent mass spectrometry analysis. We show that the method can determine drastic changes of tissue-specific protein profiles in blood plasma from mouse animal models with sepsis. The strategy can be extended to several other species advancing our understanding of the complex processes that contribute to the plasma proteome dynamics.
Reconciling diverse mammalian pigmentation patterns with a fundamental mathematical model
Authors: Mort Richard L. , Ross Robert J. H. , Hainey Kirsten J. , Harrison Olivia J. , Keighren Margaret A. , Landini Gabriel , Baker Ruth E. , Painter Kevin J. , Jackson Ian J. , Yates Christian A.
Published: January 2016

Bands of colour extending laterally from the dorsal to ventral trunk are a common feature of mouse chimeras. These stripes were originally taken as evidence of the directed dorsoventral migration of melanoblasts (the embryonic precursors of melanocytes) as they colonize the developing skin. Depigmented ‘belly spots’ in mice with mutations in the receptor tyrosine kinase Kit are thought to represent a failure of this colonization, either due to impaired migration or proliferation. Tracing of single melanoblast clones, however, has revealed a diffuse distribution with high levels of axial mixing—hard to reconcile with directed migration. Here we construct an agent-based stochastic model calibrated by experimental measurements to investigate the formation of diffuse clones, chimeric stripes and belly spots. Our observations indicate that melanoblast colonization likely proceeds through a process of undirected migration, proliferation and tissue expansion, and that reduced proliferation is the cause of the belly spots in Kit mutants.