bluuebunny/crossref_metadata_2025 huggingface dataset:
A theory of atmospheric oxygen
Authors: Laakso T. A. , Schrag D. P.
Published: April 2017

Geological records of atmospheric oxygen suggest that pO2 was less than 0.001% of present atmospheric levels (PAL) during the Archean, increasing abruptly to a Proterozoic value between 0.1% and 10% PAL, and rising quickly to modern levels in the Phanerozoic. Using a simple model of the biogeochemical cycles of carbon, oxygen, sulfur, hydrogen, iron, and phosphorous, we demonstrate that there are three stable states for atmospheric oxygen, roughly corresponding to levels observed in the geological record. These stable states arise from a series of specific positive and negative feedbacks, requiring a large geochemical perturbation to the redox state to transition from one to another. In particular, we show that a very low oxygen level in the Archean (i.e., 10−7 PAL) is consistent with the presence of oxygenic photosynthesis and a robust organic carbon cycle. We show that the Snowball Earth glaciations, which immediately precede both transitions, provide an appropriate transient increase in atmospheric oxygen to drive the atmosphere either from its Archean state to its Proterozoic state, or from its Proterozoic state to its Phanerozoic state. This hypothesis provides a mechanistic explanation for the apparent synchronicity of the Proterozoic Snowball Earth events with both the Great Oxidation Event, and the Neoproterozoic oxidation.
Demand for biomass to meet renewable energy targets in the United States: implications for land use
Authors: Oliver Anthony , Khanna Madhu
Published: April 2017

Renewable energy policies in the electricity and transportation sectors in the United States are expected to create demand for biomass and food crops (corn) that could divert land from food crop production. We develop a dynamic, open‐economy, price‐endogenous multi‐market model of the US agricultural, electricity and transportation sectors to endogenously determine the quantity and mix of bioenergy likely to be required to meet the state Renewable Portfolio Standards (RPSs) and the federal Renewable Fuel Standard (RFS) if implemented independently or jointly (RFS & RPS) over the 2007–2030 period and their implications for the extent and spatial pattern of diversion of land from other uses for biomass feedstock production. We find that the demand for biomass ranges from 100 million metric tons (MMT) under the RPS alone to 310 MMT under the RFS & RPS; 70% of the biomass in the latter case can be met by crop and forest residues, while the rest can be met by devoting 3% of cropland to energy crop production with 80% of this being marginal land. Our findings show significant potential to meet current renewable energy goals by expanding high‐yielding energy crop production on marginal land and using residues without conflicting with food crop production.
Randomized prospective study showing the non‐inferiority of tenofovir to entecavir in treatment‐naïve chronic hepatitis B patients
Authors: Koike Kazuhiko , Suyama Kazuaki , Ito Hiroshi , Itoh Hiroshi , Sugiura Wataru
Published: April 2017

Aim

The study aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) and entecavir hydrate (ETV) in nucleos(t)ide analog (NA)‐naïve Japanese chronic hepatitis B (CHB) patients.

Methods

This multicenter, randomized, double‐blinded study assessing the efficacy and safety of TDF 300 mg and ETV 0.5 mg in NA‐naïve CHB subjects was carried out from November 2011 to November 2014, and funded by GlaxoSmithKline. The subjects were assigned to the TDF arm or ETV arm in a 2:1 ratio. The primary efficacy endpoint was the non‐inferiority of TDF to ETV at week 24.

Results

A total of 166 subjects (TDF arm, 110; ETV arm, 56) were enrolled. The change (mean ± SE) in serum hepatitis B virus (HBV)‐DNA levels from baseline to week 24 was −4.63 ± 0.044 and −4.50 ± 0.063 log10 copies/mL in the TDF and ETV arms, respectively, indicating the non‐inferiority of TDF to ETV (P < 0.0001). The proportion of subjects with undetectable HBV‐DNA increased from 54 to 77% and 39 to 66% in the TDF and ETV arms with continuation of the treatment from week 24 to 48, respectively. Reduction in hepatitis B surface antigen level was greater in subjects with hepatitis B envelope antigen (+) and high alanine aminotransferase levels (≥80 IU/L). Prevalence of drug‐related adverse events at week 48 was 20% and 18% in the TDF and ETV arms, respectively.

Conclusions

The study is the first to report that TDF has non‐inferiority to ETV in treatment effectiveness (lowering of serum HBV‐DNA level) at week 24. ClinicalTrials.gov trial registration nos. NCT01480284 and GSK LOC115409.
Drugs and early modernity
Authors: Breen Benjamin
Published: April 2017

For centuries, medicinal and recreational drugs have evoked both utopian visions and darker themes: slavish obsession, physical dependency, altered mental states, and the feedback loop of labor and consumption. This article surveys recent work on the history of drugs from the 15th through 19th centuries, arguing that these works collectively demonstrate the importance of drugs and the drug trade in how we think about larger topics such as imperialism, globalization, modernization of commercial and political regimes, and the relationship between the individual and the marketplace. The search for new drugs—and, with them, new varieties of mental and physical experience—was not just a preoccupation of many early modern individuals. It was, arguably, a defining feature of early modernity itself.
Locating histories of bush‐based recreation in Australia
Authors: Harper Melissa
Published: April 2017

This article traces the historiography of bush‐based recreation in Australia. It shows how, until the 1990s, histories of bushwalking, camping, and rock climbing tended to be located within histories of national parks, places and regions, tourism, and environmentalism. The meanings attached to recreation were a secondary focus in much of this work. Stand‐alone histories of recreation have gradually emerged in the last 2 decades. These histories argue that bush‐based recreation has often played a significant role in individual lives, shaping identity, and subjectivities. More broadly, recreation has also influenced how settler Australians have engaged with the natural environment, working as a form of place making and a mode of belonging.
Utility of GATA3 in the differential diagnosis of pheochromocytoma
Authors: Perrino Carmen M , Ho Alex , Dall Christopher P , Zynger Debra L
Published: April 2017

Aims

GATA3 is a relatively new immunohistochemical marker which shows consistent nuclear expression in a variety of tumours, including breast and urothelial carcinoma. The staining pattern of GATA3 in adrenal lesions is not well established. We aim to describe the expression of GATA3 in adrenal tumours and determine if there is differential staining between pheochromocytoma and adrenal cortical carcinoma.

Methods and results

A retrospective search was performed to identify 74 adrenal lesions which were tested immunohistochemically for GATA3 expression. GATA3 was negative in 90% of adrenal cortical carcinoma. In contrast, pheochromocytomas were frequently positive (71%), including benign pheochromocytoma, pheochromocytoma with features concerning for malignancy, malignant (metastatic) pheochromocytoma and composite pheochromocytoma with ganglioneuroma. Metastatic lung adenocarcinoma in the adrenal gland had occasional (36%) expression, while metastatic clear cell renal cell carcinoma in the adrenal gland did not express GATA3.

Conclusion

As the most common pitfall in diagnosing adrenal cortical carcinoma is mistaking it for pheochromocytoma or vice versa, GATA3 may be useful in narrowing the differential diagnosis as a part of a panel of immunohistochemical markers. However, occasional GATA3 expression in the most common source of metastases within the adrenal gland, metastatic pulmonary adenocarcinoma, may confound the diagnosis due to the overlapping expression with pheochromocytoma and other carcinomas.
Effects of washing and membrane removal pretreatments on the antioxidant properties of grass carp (Ctenopharyngodon idella) protein hydrolysates produced by in vitro digestion
Authors: Zhang Xiaowei , Jiang Qixing , Xu Yanshun , Xia Wenshui
Published: April 2017

The effects of washing and membrane removal pretreatments on the antioxidant properties of grass carp protein hydrolysates prepared through in vitro digestion were investigated. Furthermore, antioxidant hydrolysate was fractionated using ultrafiltration membranes (10, 5, 3 and 1 kDa). Oxygen radical antioxidant capacity (ORAC), DPPH and ABTS‐scavenging activity in a gastrointestinal digest produced from pretreated minced grass carp was increased 1.74‐fold, 1.08‐fold and 1.72‐fold, respectively, compared to untreated minced carp. Compared to the alkaline protease hydrolysate, ORAC, ferric reducing antioxidant power, ABTS‐ and DPPH‐scavenging activity in a gastrointestinal digest prepared from pretreated minced carp were reduced by 11.5%, 60.9%, 16.3% and 78.4%, respectively. The ultrafiltration fraction (<1 kDa) displayed the highest antioxidant activity. The size of molecular weight and the amount of hydrophobic and aromatic residues in hydrolysates played an important role in antioxidant activity. Low‐molecular‐weight fish hydrolysates could serve as a potential source of functional ingredients for promoting health.
Polymorphisms in the promoter region of iNOS predispose to rheumatoid arthritis in south Indian Tamils
Authors: Negi V. S. , Mariaselvam C. M. , Misra D. P. , Muralidharan N. , Fortier C. , Charron D. , Krishnamoorthy R. , Tamouza R.
Published: April 2017

Nitric oxide synthase (NOS) catalyses the production of nitric oxide (NO) from L‐Arginine, which participates in diverse biological processes including inflammation and apoptosis. Macrophages, chondrocytes, osteoblasts and osteoclasts express inducible NOS (iNOS) at the site of synovial inflammation. NO produced at the inflamed joint may contribute to peri‐articular bone loss, mediate apoptosis and regulate Th1/Th2 balance in rheumatoid arthritis (RA). Variations in the promoter region of NOS gene regulate the nitric oxide synthase expression and iNOS (NOS2) polymorphisms have been associated with susceptibility to autoimmune disorders. Hence, this study was conducted to identify the possible contributions of NOS2 ‐1659G/A, ‐1026C/A, ‐277A/G promoter polymorphisms towards development of RA in South Indian Tamils. A total of 242 (219 females, 23 males) patients with RA (mean age 41.2 ± 10.9 years, disease duration 8.5 ± 4.3 years) and 279 age‐ and sex‐matched healthy individuals of South Indian Tamil ethnicity were genotyped for NOS2 ‐1659C/T, ‐1026G/T and ‐277A/G promoter polymorphisms by TaqMan chemistry. Nature of disease (erosive or nonerosive), the presence of extra‐articular manifestations, seropositivity for rheumatoid factor and anticyclic citrullinated peptide, serum C‐reactive protein (CRP) level and response to therapy were assessed for all patients. The three single nucleotide polymorphisms (SNPs) were in Hardy–Weinberg equilibrium. The frequency of GG genotype and G allele of NOS2‐277 was higher in patients (pc = 5.7 × 10−9, OR = 6.09, 95% CI = 3.09–12.8 and pc = 4 × 10−13, OR = 2.37, 95% CI = 2.06–3.62, respectively) compared to controls. Similarly, the frequency of NOS2‐1026 (rs2779249) GT genotype and the T allele was higher in patients with RA (pc = .01, OR = 1.61, 95% CI = 1.09–2.36, and pc = .04, OR = 1.40, 95% CI = 1.02–1.91, respectively). However, no significant difference in frequency of NOS2‐1659C/T polymorphism was observed between patients and controls. None of the studied SNPs were associated with erosive disease, seropositivity or extra‐articular manifestations. The ‐277A/G and ‐1026 G/T promoter polymorphisms in iNOS may confer susceptibility to RA in South Indian Tamils.
Emotional labour in mental health nursing: An integrative systematic review
Authors: Edward Karen‐leigh , Hercelinskyj Gylo , Giandinoto Jo‐Ann
Published: April 2017

Emotional labour is the effort consumed by suppressing one's own emotions to care for others effectively while also caring for oneself. Mental health nurses are required to engage in effective therapeutic interactions in emotionally‐intense situations. The aim of the present integrative systematic review was to investigate the emotional labour of mental health work and how this manifested, the impacts, and the ways to mitigate these impacts. In June 2016, using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology, a systematic search of the bibliographic databases was undertaken to identify relevant literature. Screening, data extraction, and synthesis were performed by three reviewers. The inclusion criteria included any original research that investigated the emotional work of mental health nurses. We identified a total of 20 papers to be included in this review. Thematic synthesis of the findings revealed three emergent themes: emotional labour and caring, emotional exhaustion, and self‐protection (expressed as emotional intelligence). Emotional labour, emotional exhaustion, and emotional intelligence were considered to be intrinsically linked, where they were both the influencing factor for burnout and a contributor to attrition. The results highlighted that emotional labour could inspire the development and personal growth of emotional intelligence in mental health nurses. In light of these findings, recommendations for clinical practice were considered; they included supportive work environments, involving nurses in shared decision‐making, and the provision of ongoing professional development opportunities that facilitate the development of emotional intelligence and resilience.
The Murky Tale of Flint's Deceptive Water Data
Authors: Langkjær-Bain Robert
Published: April 2017

When children in Flint, Michigan showed signs of lead poisoning, residents rightly suspected their tap water was to blame. Authorities denied the fact for months, but the official water test data was misleading – so citizens fought back with statistics of their own. By Robert Langkjær-Bain
The charge state of titanium ions in Pd‐doped Ti:CMAS glass and glass‐ceramics
Authors: Golovchak Roman , Davis Mark J. , Vullo Paula , Astashkin Andrei , Nichols Laura , Ingram Adam , Jain Himanshu
Published: April 2017

We have investigated the role of charge state of Ti in the electronic properties and structure of electrically conductive CMAS‐TiO2‐Pd glass and glass‐ceramics by X‐ray photoelectron spectroscopy, electron paramagnetic resonance, positron annihilation lifetime spectroscopy, and fluorescence spectroscopy. These studies suggest the concentration of Ti3+ ions was, at most, ~0.1 wt% in glass‐ceramics devitrified in the reducing atmosphere of forming gas; no other glass or glass‐ceramic samples exhibited measurable levels of Ti3+. The observed fluorescence at liquid nitrogen temperature in parent glasses and glass‐ceramics obtained in air is explained by UV‐induced charge‐transfer processes involving Ti4+ ions and oxygen surroundings. The X‐ray photoelectron spectroscopy data are correlated with rutile, anorthite, diopside, and titanite crystalline phases identified in Pd‐free and Pd‐doped Ti:CMAS glass‐ceramics earlier.
Phase equilibria study and thermodynamic description of the BaO‐CaO‐Al2O3 system
Authors: Zhang Rui , Mao Huahai , Taskinen Pekka
Published: April 2017

A combined experimental investigation and thermodynamic assessment was performed for the BaO‐CaO‐Al2O3 system. By using a high‐temperature equilibration/quenching technique and scanning electron microscopy, electron probe microanalysis, and X‐ray powder diffraction analysis, the phase equilibria at 1500°C and phase stability of BaCa2Al8O15 phase were determined. An extensive literature survey was conducted for the experimental and thermodynamic modeling data of the BaO‐CaO‐Al2O3 system. According to the literature data and the present measurements, a thermodynamic assessment was made in order to obtain a set of self‐consistent thermodynamic parameters to describe the BaO‐CaO‐Al2O3 system. Based on the thermodynamic parameters acquired in this work, isothermal sections at 1100°C, 1250°C, 1400°C, 1475°C, and 1500°C and the BaO·Al2O3‐CaO·Al2O3 and BaO·6Al2O3‐CaO·6Al2O3 joints were calculated and compared with the available experimental data.
Magneto‐optical effects of Ge‐Ga‐Sb(In)‐S chalcogenide glasses with diamagnetic responses
Authors: Chen Gang , Xu Yantao , Guo Haitao , Cui Xiaoxia , Wang Pengfei , Lu Min , Xiao Xusheng , Guo Quan , Peng Bo
Published: April 2017

The Faraday effects of Ge‐Ga‐Sb(In)‐S serial chalcogenide glasses were investigated at the wavelengths of 635, 808, 980, and 1319 nm, respectively. The compositional dependences were analyzed and associated influencing factors including the absorption edge, the concentration of Sb3+/In3+ ions, and the wavelength dispersion of refraction index were discussed. 80GeS2·20Sb2S3 composition glass was found to have the largest Verdet constant (V=0.253, 0.219, 0.149, and 0.065 min·G−1·cm−1 for wavelengths 635, 808, 980, and 1319 nm, respectively) in these glasses, which is larger than that of commercial diamagnetic glasses (Schott, SF 6, V=0.069 min·G−1·cm−1@633 nm, for example). Sb3+ ions with high polarizability possessing s2‐sp electron jumps involving 1S0→1P1, 3P0,1,2 transitions are responsible for large Verdet constant, and Becquerel rule is proved to be an effective guidance for estimating the Verdet constant and further optimizing the compositions in chalcogenide glasses.
Processing and characterization of TiB2‐TiNiFeCrCoAl high‐entropy alloy composite
Authors: Fu Zhezhen , Koc Rasit
Published: April 2017

A series of TiB2‐TiNiFeCrCoAl high‐entropy alloy (HEA) composites with HEA contents of 5, 10, and 20 wt.% were fabricated to a relative density of above 95% without applied external pressure at 1550°C in flowing argon. Research indicates (i) the formation of liquid HEA is promoted with the assistance of an optimized ball mill process, which facilitates the sintering through a liquid phase sintering mechanism, and (ii) HEA can react with the oxide impurities in TiB2 and can consequently enhance the densification. Continual observations on microstructures and properties indicate that the sintered composites have a submicronmeter grain size of 0.90±0.11, 0.79±0.09, and 0.74±0.07 μm; a high hardness of 23.3±0.9, 21.6±1.0, and 17.5±1.2 GPa; and a high indentation fracture toughness of 8.7±0.4, 11.1±0.6, and 12.8±0.6 MPa·m1/2, respectively, for samples with 5, 10, and 20 wt.% HEA. The addition of HEA to TiB2 can significantly enhance the densification, results in fine microstructures, and improve the mechanical performance.
Fabrication and oxidation behavior of Al4SiC4 powders
Authors: Chen JunHong , Zhang ZhiHao , Mi WenJun , Wang EnHui , Li Bin , Chou Kuo‐Chih , Hou XinMei
Published: April 2017

Al4SiC4 powders with high purity were synthesized by heating the powder mixture of aluminum (Al), silicon (Si), and carbon (C) at 1800°C in argon. The microstructure is characterized as platelike single grain. Both the nonisothermal and isothermal oxidation behavior of Al4SiC4 was investigated at 800°C‐1500°C in air by means of thermogravimetry method. It is demonstrated that Al4SiC4 powder possesses good oxidation resistance up to 1200°C and is almost completely oxidized at 1400°C. At 800°C‐1100°C, the oxide scales consist of an Al2O3 outer layer and a transition layer. Al4SiC4 remains the main phase. At 1200°C, some spallation resulting from the increment of Al2O3 and the mismatch of thermal expansion coefficient between different product layers can be observed. Above 1300°C, the oxide layer is composed of two part, i.e., large‐scale Al2O3 crystals (outer layer) and mullite with less amount of SiO2 (inner layer). The oxidation behavior changes due to the different oxide products. For the reaction kinetics, a new kind of real physical picture model is adopted and obtains a good agreement with the experimental data. The apparent activation energy is calculated to be 176.9 kJ/mol (800°C‐1100°C) and 267.1 kJ/mol (1300°C‐1400°C).
The effect of Fe2+ state in electrical property variations of Sn‐doped hematite powders
Authors: Song Sehwan , Kim Jiwoong , Lee Dooyong , Lee Jisung , Min Taewon , Chae Jong‐Ah , Bae Jong‐Seong , Lee Jaekwang , Lee Jeong‐Soo , Park Sungkyun
Published: April 2017

The structural, electrical, and chemical properties of Sn‐doped Fe2O3 powders were investigated. Various quantities of Sn‐doped Fe2O3 powders were synthesized using solid‐state reactions. Rietveld analysis for the powders that were doped below 2% revealed a phase‐pure Sn‐doped Fe2O3 structure (i.e., identical to Fe2O3 structure). Alternatively, the analysis for the powders that were doped more than 3% exhibited secondary phase. The unit cell volume and electrical conductivity of the phase‐pure samples increased with an increase in the doping concentration. X‐ray photoelectron spectroscopy measurements showed an increased Fe2+ state with the increase in Sn doping concentration. Therefore, the improved electrical conductivity and unit cell volume with the increase in doping concentration of the phase‐pure powders might be related to the increased Fe2+ state.
Service user engagement: A co‐created interview schedule exploring mental health recovery in young adults
Authors: McCauley Claire‐Odile , McKenna Hugh , Keeney Sinead , McLaughlin Derek
Published: April 2017

Aim

The aim of this study was to co‐create of an interview schedule exploring mental health recovery in collaboration with young adult service users.

Background

Service user involvement in research has been increasingly recognized as providing a vital authentic insight into mental health recovery. Engagement and collaboration with service users have facilitated the exploration of inaccessible or under‐investigated aspects of the lived experience of mental health recovery, not only directing the trajectory of research, but making it relevant to their own contextual experience.

Design

A qualitative content analysis framework was employed in the co‐creation of a semi‐structured interview schedule through an engagement process with service users.

Methods

Two separate engagement groups took place at the premises of the service user organizations, between January ‐ February 2014. Miles and Huberman's analysis framework was chosen for this phase as it enabled the visual presentation of factors, concepts or variables and the established relationship between them.

Results

The lived experience of mental ill health in young adulthood and how this was understood by others was a particularly relevant theme for participants. Further themes were identified between the impact of painful experiences at this developmental life stage leading to a deeper understanding of others through finding meaning in their own mental health recovery journey.

Conclusion

Our findings identified that suffering painful experiences is an integral aspect in the process of mental health recovery. This understanding has particular relevance to mental health nursing practice, ensuring the care delivered is cognizant of the suffering or painful experiences that young adults are encountering.
Altered breeding biology of the European blackbird under artificial light at night
Authors: Russ Anja , Lučeničová Terézia , Klenke Reinhard
Published: April 2017

Artificial light at night (LAN) has become a stressor of global extent. Previous work has highlighted the high potential of LAN to interfere with annual and diel rhythms of seasonal organisms as well as to affect interactions at the community level. However, our understanding how LAN induced alterations of activity and breeding cycles affect the reproductive outcome and fitness of the birds is still limited. Here, we focus on the effects of night time illumination on the breeding biology of urban European blackbirds Turdus merula. Our results indicate that blackbirds prefer illuminated nest sites and advance their date of clutch initiation by 6 d per 1 lux of night time illumination. Furthermore, daily nest survival rates increased with increasing LAN although this effect was most pronounced for the transition from dark to slightly illuminated sites. We suggest that blackbirds breeding under low artificial night light conditions benefit from the LAN‐avoidance of their major predators (nocturnal) whereas predominant predators of blackbirds nesting in the city centre are diurnal and are, thus, not affected by LAN. Hence, it seems likely that both direct effects of LAN on the timing of reproduction as well as indirect effects on interspecific interactions might contribute to the observed changes in the breeding biology of European blackbirds. This study emphasizes the diverse ecological effects of the night time illumination which are – in its complexity – still poorly understood.
Characterising demographic contributions to observed population change in a declining migrant bird
Authors: Border Jennifer A. , Henderson Ian G. , Ash Dominic , Hartley Ian R.
Published: April 2017

Populations of Afro‐Palearctic migrant birds have shown severe declines in recent decades. To identify the causes of these declines, accurate measures of both demographic rates (seasonal productivity, apparent survival, immigration) and environmental parameters will allow conservation and research actions to be targeted effectively. We used detailed observations of marked breeding birds from a ‘stronghold’ population of whinchats Saxicola rubetra in England (stable against the declining European trend) to reveal both on‐site and external mechanisms that contribute to population change. From field data, a population model was developed based on demographic rates from 2011 to 2014. Observed population trends were compared to the predicted population trends to assess model‐accuracy and the influence of outside factors, such as immigration. The sensitivity of the projected population growth rate to relative change in each demographic rate was also explored. Against expectations of high productivity, we identified low seasonal breeding success due to nocturnal predation and low apparent first‐year survival, which led to a projected population growth rate (λ) of 0.818, indicating a declining trend. However, this trend was not reflected in the census counts, suggesting that high immigration was probably responsible for buffering against this decline. Elasticity analysis indicated λ was most sensitive to changes in adult survival but with covariance between demographic rates accounted for, most temporal variation in λ was due to variation in productivity. Our study demonstrates that high quality breeding habitat can buffer against population decline but high immigration and low productivity will expose even such stronghold populations to potential decline or abandonment if either factor is unsustainable. First‐year survival also appeared low, however this result is potentially confounded by high natal dispersal. First‐year survival and/or dispersal remains a significant knowledge gap that potentially undermines local solutions aimed at counteracting low productivity.
The CDS market reaction to restatement announcements
Authors: Du Lijing
Published: April 2017

I investigate the credit market's reaction to restatement announcements through changes in credit default swap (CDS) spreads. I document an overall positive association between CDS returns and restatement announcements. Specifically, I find that more positive CDS returns are associated with restatements (1) involving fraud and (2) affecting more accounts. Moreover, these reactions are sensitive to the underlying entities’ credit ratings and the market‐wide investor sentiment. Next, I compare CDS and stock market reactions and find that more negative stock returns are associated with restatements (1) involving fraud and (2) decreasing reported income.
Autophagy controls the pathogenicity of OPA1 mutations in dominant optic atrophy
Authors: Kane Mariame Selma , Alban Jennifer , Desquiret‐Dumas Valérie , Gueguen Naïg , Ishak Layal , Ferre Marc , Amati‐Bonneau Patrizia , Procaccio Vincent , Bonneau Dominique , Lenaers Guy , Reynier Pascal , Chevrollier Arnaud
Published: April 2017

Optic Atrophy 1 (OPA1) gene mutations cause diseases ranging from isolated dominant optic atrophy (DOA) to various multisystemic disorders. OPA1, a large GTPase belonging to the dynamin family, is involved in mitochondrial network dynamics. The majority of OPA1 mutations encodes truncated forms of the protein and causes DOA through haploinsufficiency, whereas missense OPA1 mutations are predicted to cause disease through deleterious dominant‐negative mechanisms. We used 3D imaging and biochemical analysis to explore autophagy and mitophagy in fibroblasts from seven patients harbouring OPA1 mutations. We report new genotype–phenotype correlations between various types of OPA1 mutation and mitophagy. Fibroblasts bearing dominant‐negative OPA1 mutations showed increased autophagy and mitophagy in response to uncoupled oxidative phosphorylation. In contrast, OPA1 haploinsufficiency was correlated with a substantial reduction in mitochondrial turnover and autophagy, unless subjected to experimental mitochondrial injury. Our results indicate distinct alterations of mitochondrial physiology and turnover in cells with OPA1 mutations, suggesting that the level and profile of OPA1 may regulate the rate of mitophagy.
Therapeutic effects of hydrogen on chronic graft‐versus‐host disease
Authors: Qian Liren , Liu Xiaopeng , Shen Jianliang , Zhao Defeng , Yin Wenjie
Published: April 2017

The incidence of chronic graft‐versus‐host disease (cGVHD) is rising recent years, which has been the leading cause of non‐transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti‐inflammatory, antioxidant, anti‐fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC‐incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen‐rich saline increased survival rate of cGVHD mice. Administration of hydrogen‐rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values.
Post‐traumatic stress disorder and beyond: an overview of rodent stress models
Authors: Schöner Johanna , Heinz Andreas , Endres Matthias , Gertz Karen , Kronenberg Golo
Published: April 2017

Post‐traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of ‘learned helplessness’ in canines. Rodent stress models make use of physiological or psychological stressors such as foot shock, underwater trauma, social defeat, early life stress or predator‐based stress. Apart from the brief exposure to an acute stressor, chronic stress models combining a succession of different stressors for a period of several weeks have also been developed. Chronic stress models in rats and mice may elicit characteristic PTSD‐like symptoms alongside, more broadly, depressive‐like behaviours. In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research—such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions—are discussed.
Ventilation strategy has a major influence on remote ischaemic preconditioning in mice
Authors: Davidson Sean M. , He Zhenhe , Dyson Alex , Bromage Daniel I. , Yellon Derek M.
Published: April 2017

Whether oxygen should be administered acutely during ST‐segment elevation myocardial infarction is debated. Despite this controversy, the possible influence of supplementary oxygen on animal models of ischaemia–reperfusion injury or cardioprotection is rarely considered. We used an in vivo mouse model of ischaemia and reperfusion to investigate the effect of ventilation with room air versus 100% oxygen. The coronary artery of anaesthetized mice was occluded for 40 min. followed by 2‐hrs reperfusion. Infarct size was measured by tetrazolium staining and expressed as a percentage of area at risk, determined using Evan's blue. Unexpectedly, infarct size in mice ventilated with 100% oxygen was significantly smaller than in those ventilated with room air (33 ± 5% versus 46 ± 3%; n = 6; P < 0.01). We tested a standard protocol of 3 × 5 min. cycles of remote ischaemic preconditioning (RIPC) and found this was unable to protect mice ventilated with 100% oxygen. RIPC protocols using 2.5‐ or 10‐min. occlusion were similarly ineffective in mice ventilated with oxygen. Similar disparate results were obtained with direct cardiac ischaemic preconditioning. In contrast, pharmacological protection using bradykinin administered at reperfusion was effective even in mice ventilated with 100% oxygen, reducing infarct size from 33 ± 5% to 21 ± 3% (n = 4–6; P < 0.01). Laser speckle contrast imaging of blood flow and direct pO2 measurements were made in the hindlimb, but these measurements did not correlate with protection. In conclusion, ventilation protocol can have a major influence on infarct size and ischaemic preconditioning protocols in mice.
Hypoxic preconditioning‐induced autophagy enhances survival of engrafted endothelial progenitor cells in ischaemic limb
Authors: Zhou Pei , Tan Yu‐zhen , Wang Hai‐jie , Wang Guo‐dong
Published: April 2017

Recent clinical studies have suggested that endothelial progenitor cells (EPCs) transplantation provides a modest benefit for treatment of the ischaemic diseases such as limb ischaemia. However, cell‐based therapies have been limited by poor survival of the engrafted cells. This investigation was designed to establish optimal hypoxia preconditioning and evaluate effects of hypoxic preconditioning‐induced autophagy on survival of the engrafted EPCs. Autophagy of CD34+VEGFR‐2+ EPCs isolated from rat bone marrow increased after treatment with 1% O2. The number of the apoptotic cells in the hypoxic cells increased significantly after autophagy was inhibited with 3‐methyladenine. According to balance of autophagy and apoptosis, treatment with 1% O2 for 2 hrs was determined as optimal preconditioning for EPC transplantation. To examine survival of the hypoxic cells, the cells were implanted into the ischaemic pouch of the abdominal wall in rats. The number of the survived cells was greater in the hypoxic group. After the cells loaded with fibrin were transplanted with intramuscular injection, blood perfusion, arteriogenesis and angiogenesis in the ischaemic hindlimb were analysed with laser Doppler‐based perfusion measurement, angiogram and the density of the microvessels in histological sections, respectively. Repair of the ischaemic tissue was improved significantly in the hypoxic preconditioning group. Loading the cells with fibrin has cytoprotective effect on survival of the engrafted cells. These results suggest that activation of autophagy with hypoxic preconditioning is an optimizing strategy for EPC therapy of limb ischaemia.
Evolution of virulence under intensive farming: salmon lice increase skin lesions and reduce host growth in salmon farms
Authors: Ugelvik M. S. , Skorping A. , Moberg O. , Mennerat A.
Published: April 2017

Parasites rely on resources from a host and are selected to achieve an optimal combination of transmission and virulence. Human‐induced changes in parasite ecology, such as intensive farming of hosts, might not only favour increased parasite abundances, but also alter the selection acting on parasites and lead to life‐history evolution. The trade‐off between transmission and virulence could be affected by intensive farming practices such as high host density and the use of antiparasitic drugs, which might lead to increased virulence in some host–parasite systems. To test this, we therefore infected Atlantic salmon (Salmo salar) smolts with salmon lice (Lepeophtheirus salmonis) sampled either from wild or farmed hosts in a laboratory experiment. We compared growth and skin damage (i.e. proxies for virulence) of hosts infected with either wild or farmed lice and found that, compared to lice sampled from wild hosts in unfarmed areas, those originating from farmed fish were more harmful; they inflicted more skin damage to their hosts and reduced relative host weight gain to a greater extent. We advocate that more evolutionary studies should be carried out using farmed animals as study species, given the current increase in intensive food production practices that might be compared to a global experiment in parasite evolution.
Extent of diagnostic agreement among medical referrals
Authors: Van Such Monica , Lohr Robert , Beckman Thomas , Naessens James M.
Published: April 2017

Rationale, aims and objectives

Diagnostic uncertainty is often encountered in a medical practice. Patients with ambiguous, uncertain, and undiagnosed problems are frequently referred for second opinions. Comparing referral diagnoses to final diagnoses provides an opportunity to determine how frequently final diagnoses vary and changes the direction of medical care.

Methods

A retrospective study was done at a single academic medical center using a sample of 286 patients referred by physician assistants, nurse practitioners, and physicians from primary care practices from January 1, 2009 to December 31, 2010. Patients' referral and final diagnoses were compared and classified into 1 of 3 categories: referral diagnosis and final diagnosis the same, referral diagnosis better defined/refined, and referral diagnosis distinctly different from final diagnosis. Episode costs for the respective categories were calculated for the referral visit and services that occurred at our facility within the first 30 days.

Results

In 12% (36/286) of cases, referral diagnoses were the same as final diagnoses. Final diagnoses were better defined/refined in 66% (188/286) of cases; but in 21% of cases (62/286), final diagnoses were distinctly different than referral diagnoses. Total costs for cases in category 3 (different final diagnoses) were significantly higher than costs for cases in category 1 (P = .0001) and category 2 (P = <.0001).

Conclusion

Referrals to advanced specialty care for undifferentiated problems are an essential component of patient care. Without adequate resources to handle undifferentiated diagnoses, a potential unintended consequence is misdiagnoses resulting in treatment delays and complications leading to more costly treatments.
A nationwide, cross‐sectional survey on unusual sleep postures and sleep‐disordered breathing‐related symptoms in people with Down syndrome
Authors: Kuroda H. , Sawatari H. , Ando S. , Ohkusa T. , Rahmawati A. , Ono J. , Nishizaka M. , Hashiguchi N. , Matsuoka F. , Chishaki A.
Published: April 2017

Background

People with Down syndrome (DS) often have sleep‐disordered breathing (SDB). Unusual sleep postures, such as leaning forward and sitting, are observed in people with DS. This study aimed to clarify the prevalence of unusual sleep postures and their relationships with SDB‐related symptoms (SDB‐RSs), such as snoring, witnessed apnoea, nocturnal awakening and excessive daytime sleepiness.

Methods

A questionnaire, including demographic characteristics and the presence of unusual sleep postures, as well as SDB‐RSs, was completed by 1149 parents of people with DS from Japan.

Results

Unusual sleep postures were recorded in 483 (42.0%) people with DS. These participants were significantly younger and had a history of low muscle tone more frequently than people without unusual sleep postures. In all ages, the leaning forward posture was more frequent than sitting. People with DS with unusual sleep postures suffered from SDB‐RSs. Those who slept in the sitting posture had more frequent SDB‐RSs than did those who slept with the leaning forward posture. Snoring, witnessed apnoea and nocturnal awakening were observed in 73.6, 27.2 and 58.2% of participants, respectively. Snoring increased with aging. Witnessed apnoea was more common in males and in those with hypothyroidism than in females and in those without hypothyroidism.

Conclusions

Our study shows that there is a close relationship between unusual sleep postures and SDB‐RSs. We recommend that all people with DS with unusual sleep postures should be checked for the presence of SDB.
Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata)
Authors: Miyabe‐Nishiwaki Takako , Hirata Akihiro , Kaneko Akihisa , Ishigami Akiyo , Miyamoto Yoko , Yamanaka Atsushi , Owaki Keishi , Sakai Hiroki , Yanai Tokuma , Suzuki Juri
Published: April 2017

Background

A 23‐year‐old male Japanese macaque (Macaca fuscata) showed left ptosis, which progressed to exophthalmos.

Methods

The macaque underwent a clinical examination, CT and MRI, and was euthanized. Necropsy and histopathological examination were performed after euthanasia.

Results

The CT revealed and MRI confirmed an intracranial mass at the skull base with orbital extension. At necropsy, there were a large hepatic mass and an intracranial mass compressing the left temporal lobe of the brain. Histopathological and immunohistological examinations revealed that the masses were hepatocellular carcinoma (HCC) and a metastatic lesion. In both the primary and metastatic lesions, neoplastic hepatocytes were arranged mainly in a trabecular pattern. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3 and CAM5.2) and hepatocyte paraffin 1 and negative for cytokeratin 7 and 20 and vimentin.

Conclusion

To our knowledge, this is the first case report of HCC with intracranial metastasis in a macaque.
ECONOMIC TRANSITION AND LABOUR MARKET DYNAMICS IN CHINA: AN INTERPRETATIVE SURVEY OF THE ‘TURNING POINT’ DEBATE
Authors: Athukorala Prema‐chandra , Wei Zheng
Published: April 2017

Has the Chinese economy approached the ‘Lewisian turning point’ that marks the ending of the initial phase of industrial transformation fuelled by surplus labour? In this paper we undertake an interpretative survey of the literature on this issue, in the context of China's labour market conditions prior to the reforms and structural change of the past three decades. The available evidence is mixed, and our assessment makes a strong case for probing institutional constraints to labour mobility from an economy‐wide perspective, going beyond the confines of the rural economy.
Understanding cell cycle and cell death regulation provides novel weapons against human diseases
Authors: Wiman K. G. , Zhivotovsky B.
Published: April 2017

Cell division, cell differentiation and cell death are the three principal physiological processes that regulate tissue homoeostasis in multicellular organisms. The growth and survival of cells as well as the integrity of the genome are regulated by a complex network of pathways, in which cell cycle checkpoints, DNA repair and programmed cell death have critical roles. Disruption of genomic integrity and impaired regulation of cell death may both lead to uncontrolled cell growth. Compromised cell death can also favour genomic instability. It is becoming increasingly clear that dysregulation of cell cycle and cell death processes plays an important role in the development of major disorders such as cancer, cardiovascular disease, infection, inflammation and neurodegenerative diseases. Research achievements in these fields have led to the development of novel approaches for treatment of various conditions associated with abnormalities in the regulation of cell cycle progression or cell death. A better understanding of how cellular life‐and‐death processes are regulated is essential for this development. To highlight these important advances, the Third Nobel Conference entitled ‘The Cell Cycle and Cell Death in Disease’ was organized at Karolinska Institutet in 2016. In this review we will summarize current understanding of cell cycle progression and cell death and discuss some of the recent advances in therapeutic applications in pathological conditions such as cancer, neurological disorders and inflammation.
Neonatal hypotonia
Authors: Law‐ye Bruno , Adamsbaum Catherine
Published: April 2017

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Cardiac Troponin I and Amino‐Terminal Pro B‐Type Natriuretic Peptide in Dogs With Stable Chronic Kidney Disease
Authors: Pelander L. , Häggström J. , Ley C.J. , Ljungvall I.
Published: April 2017

Background

Increased concentrations of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and cardiac troponin I (cTnI) in dogs with azotemia have been documented. Knowledge of mechanisms behind increased concentrations of cardiac biomarkers in dogs with azotemia is warranted for correct interpretation of test results.

Objectives

The aim of the article was to investigate possible associations between plasma concentrations of cTnI and NT‐proBNP, respectively, and patient characteristics, glomerular filtration rate (GFR), a plasma volume factor (PVF) derived from scintigraphic examination (PVf), systolic blood pressure (SBP), selected hematologic and biochemical variables, and echocardiographic measurements in dogs with stable chronic kidney disease (CKD) and in healthy dogs.

Animals

Fifty student‐, staff‐, and client‐owned dogs were included. Twenty‐three of the dogs were healthy and 27 were diagnosed with CKD.

Methods

In this cross‐sectional observational study, dogs with a previous diagnosis of CKD and healthy control dogs were included. At inclusion, all dogs were characterized by physical examination, repeated blood pressure measurements, complete urinalysis, hematology and biochemistry panel, echocardiography, abdominal ultrasound examination of the entire urinary tract, and scintigraphic examination for measurement of GFR.

Results

Plasma volume factor and PCV were independently associated with NT‐proBNP ( = 0.42; P < .0001). Age, body weight (BW), and SBP were independently associated with cTnI ( = 0.50; P < .0001).

Conclusions and Clinical Importance

Neither NT‐proBNP nor cTnI concentrations were independently associated with measured GFR. Thus, findings were not suggestive of passive accumulation of either marker, suggesting that increased circulating concentrations of cTnI and NT‐proBNP can be interpreted similarly in dogs with stable CKD as in dogs without CKD.