bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative study of bundle size effect on thermal conductivity of single-walled carbon nanotubes
Authors: Feng Ya , Inoue Taiki , An Hua , Xiang Rong , Chiashi Shohei , Maruyama Shigeo
Published: May 2018

Compared with isolated single-walled carbon nanotubes (SWNTs), thermal conductivity is greatly impeded in SWNT bundles; however, the measurement of the bundle size effect is difficult. In this study, the number of SWNTs in a bundle was determined based on the transferred horizontally aligned SWNTs on a suspended micro-thermometer to quantitatively study the effect of the bundle size on thermal conductivity. Increasing the bundle size significantly degraded the thermal conductivity. For isolated SWNTs, thermal conductivity was approximately 5000 ± 1000 W m–1 K–1 at room temperature, three times larger than that of the four-SWNT bundle. The logarithmical deterioration of thermal conductivity resulting from the increased bundle size can be attributed to the increased scattering rate with neighboring SWNTs based on the kinetic theory.
Interferometrically enhanced sub-terahertz picosecond imaging utilizing a miniature collapsing-field-domain source
Authors: Vainshtein Sergey N. , Duan Guoyong , Mikhnev Valeri A. , Zemlyakov Valery E. , Egorkin Vladimir I. , Kalyuzhnyy Nikolay A. , Maleev Nikolai A. , Näpänkangas Juha , Sequeiros Roberto Blanco , Kostamovaara Juha T.
Published: May 2018

Progress in terahertz spectroscopy and imaging is mostly associated with femtosecond laser-driven systems, while solid-state sources, mainly sub-millimetre integrated circuits, are still in an early development phase. As simple and cost-efficient an emitter as a Gunn oscillator could cause a breakthrough in the field, provided its frequency limitations could be overcome. Proposed here is an application of the recently discovered collapsing field domains effect that permits sub-THz oscillations in sub-micron semiconductor layers thanks to nanometer-scale powerfully ionizing domains arising due to negative differential mobility in extreme fields. This shifts the frequency limit by an order of magnitude relative to the conventional Gunn effect. Our first miniature picosecond pulsed sources cover the 100–200 GHz band and promise milliwatts up to ∼500 GHz. Thanks to the method of interferometrically enhanced time-domain imaging proposed here and the low single-shot jitter of ∼1 ps, our simple imaging system provides sufficient time-domain imaging contrast for fresh-tissue terahertz histology.
The tunable optical magneto-electric effect in patterned manganese oxide superlattices
Authors: Pei H. Y. , Zhang Y. J. , Guo S. J. , Ren L. X. , Yan H. , Chen C. L. , Jin K. X. , Luo B. C.
Published: May 2018

The optical magneto-electric (OME) effect has been widely investigated in magnetic materials, but obtaining the large and tunable OME effect is an ongoing challenge. We here design a tri-color superlattice composed of manganese oxides, Pr0.9Ca0.1MnO3, La0.9Sr0.1MnO3, and La0.9Sb0.1MnO3, where the space-inversion and time-reversal symmetries are broken. With the aid of the grating structure, the OME effect for near-infrared light in tri-color superlattices is investigated systematically through the Bragg diffraction method. The relative change of diffracted light intensity of the order n = ±1 has a strong dependence on the magnetization and polarization of the tri-color superlattice, whether the superlattice is irradiated in reflection or transmission geometries. Otherwise, the relative change of diffracted light intensity increases with the increase in the superlattice period and with the decrease in the grating period. The maximum relative change of diffracted light intensity in tri-color superlattices with the grating structure patterned is as large as 8.27%. These results pave the way for designing next-generation OME devices based on manganese oxides.
Controller design and stability analysis of grid connected DC microgrid
Authors: Chauhan Rajeev Kumar , Chauhan Kalpana , Guerrero Josep M.
Published: May 2018

DC microgrids are desired to provide the electricity for the remote areas which are far from the main grid. The microgrid gets popularity because DC power sources such as photovoltaics (PVs), battery banks, and fuel cells can be interconnected without AC/DC converters. The stochastic nature of PV power and variation in the demand are responsible for voltage fluctuations in the DC microgrids. The voltage stability is a most important issue in the case of DC microgrids. The challenging thing is to maintain the microgrid voltage up to a reference value for the variable load. This paper focuses on designing a controller to obtain the voltage stability of the microgrid. Two controllers [PI and fuzzy logic PI (FL-PI)] are designed for the voltage stability analysis of the DC microgrid. Real-time simulation results show that upon appropriate choice of controller parameters, the DC microgrid voltage can be kept constant regardless of the wide range of voltage variations of the source and the load. The simulation results show the comparison of two controllers. The FL-PI controller shows much better performance than the conventional PI controller for the DC grid voltage control. With the inclusion of the proposed controllers, controlled voltage will be obtained, whatever may be the load and its variation.
Modeling and impacts of the latent heat of phase change and specific heat for phase change materials
Authors: Scoggin J. , Khan R. S. , Silva H. , Gokirmak A.
Published: May 2018

We model the latent heats of crystallization and fusion in phase change materials with a unified latent heat of phase change, ensuring energy conservation by coupling the heat of phase change with amorphous and crystalline specific heats. We demonstrate the model with 2-D finite element simulations of Ge2Sb2Te5 and find that the heat of phase change increases local temperature up to 180 K in 300 nm × 300 nm structures during crystallization, significantly impacting grain distributions. We also show in electrothermal simulations of 45 nm confined and 10 nm mushroom cells that the higher amorphous specific heat predicted by this model increases nucleation probability at the end of reset operations. These nuclei can decrease set time, leading to variability, as demonstrated for the mushroom cell.
Significant mobility improvement of amorphous In-Ga-Zn-O thin-film transistors annealed in a low temperature wet ambient environment
Authors: Jallorina Michael Paul A. , Bermundo Juan Paolo S. , Fujii Mami N. , Ishikawa Yasuaki , Uraoka Yukiharu
Published: May 2018

Transparent amorphous oxide semiconducting materials such as amorphous InGaZnO used in thin film transistors (TFTs) are typically annealed at temperatures higher than 250 °C to remove any defects present and improve the electrical characteristics of the device. Previous research has shown that low cost and low temperature methods improve the electrical characteristics of the TFT. With the aid of surface and bulk characterization techniques in comparison to the device characteristics, this work aims to elucidate further on the improvement mechanisms of wet and dry annealing ambients that affect the electrical characteristics of the device. Secondary Ion Mass Spectrometry results show that despite outward diffusion of –H and –OH species, humid annealing ambients counteract outward diffusion of these species, leading to defect sites which can be passivated by the wet ambient. X-ray Photoelectron Spectroscopy results show that for devices annealed for only 30 min in a wet annealing environment, the concentration of metal-oxide bonds increased by as much as 21.8% and defects such as oxygen vacancies were reduced by as much as 18.2% compared to an unannealed device. Our work shows that due to the oxidizing power of water vapor, defects are reduced, and overall electrical characteristics are improved as evidenced with the 150 °C wet O2, 30 min annealed sample which exhibited the highest mobility of 5.00 cm2/V s, compared to 2.36 cm2/V s for a sample that was annealed at 150 °C in a dry ambient atmospheric environment for 2 h.
Invasive predators represent the greatest extinction threat to the endangered northern bettong (Bettongia tropica)
Authors: Whitehead Tegan , Vernes Karl , Goosem Miriam , Abell Sandra E.
Published: May 2018

Context Identification of key threats to endangered species is vital for devising effective management strategies, but may be hindered when relevant data is limited. A population viability approach may overcome this problem. Aims We aimed to determine the population viability of endangered northern bettongs (Bettongia tropica) in north-eastern Australia. We also assessed the key threats to the population resilience and how the population viability responds to increases in mortality rates and changes in fire and drought frequency. Methods Using population viability analysis (PVA) we modelled survival probability of B. tropica populations under likely scenarios, including: (1) increased predation; (2) changes in drought and fire frequency predicted with anthropogenic climate change; and (3) synergistic effects of predation, fire and drought. Key results Population viability models suggest that populations are highly vulnerable to increases in predation by feral cats (Felis catus), and potentially red fox (Vulpes vulpes) should they colonise the area, as juvenile mortality is the main age class driving population viability. If B. tropica become more vulnerable to predators during post-fire vegetation recovery, more frequent fires could exacerbate effects of low-level cat predation. In contrast, it was predicted that populations would be resilient to the greater frequency of droughts expected as a result of climate change, with high probabilities of extinctions only predicted under the unprecedented and unlikely scenario of four drought years in 10. However, since drought and fire are interlinked, the impacts of predation could be more severe with climate change should predation and fire interact to increase B. tropica mortality risk. Conclusion Like other Potoroids, B. tropica appear highly vulnerable to predation by introduced mammalian predators such as feral cats. Implications Managers need information allowing them to recognise scenarios when populations are most vulnerable to potential threats, such as drought, fire and predation. PVA modelling can assess scenarios and allow pro-active management based on predicted responses rather than requiring collection of extensive field data before management actions. Our analysis suggests that assessing and controlling predator populations and thereby minimising predation, particularly of juveniles, should assist in maintaining stability of populations of the northern bettong.
Urine specific gravity as an indicator of dehydration in Olympic combat sport athletes; considerations for research and practice
Authors: Zubac Damir , Reale Reid , Karnincic Hrvoje , Sivric Anamaria , Jelaska Igor
Published: May 2018

Urine specific gravity (USG) is the most commonly reported biochemical marker used in research and applied settings to detect fluid deficits in athletes, including those participating in combat sports. Despite the popularity of its use, there has been a growing debate regarding the diagnostic accuracy and the applicability of USG in characterizing whole‐body fluid status and fluctuations. Moreover, recent investigations report universally high prevalence of hypohydration (∼90%) via USG assessment in combat sport athletes, often in spite of stable body‐mass. Given the widespread use in both research and practice, and its use in a regulatory sense as a ‘hydration test’ in combat sports as a means to detect dehydration at the time of weigh‐in; understanding the limitations and applicability of USG assessment is of paramount importance. Inconsistencies in findings of USG readings, possibly as a consequence of diverse methodological research approaches and/or overlooked confounding factors, preclude a conclusive position stand within current combat sports research and practice. Thus the primary aim of this paper is to critically review the literature regarding USG assessment of hydration status in combat sports research and practice. When taken on balance, the existing literature suggests: the use of laboratory derived benchmarks in applied settings, inconsistent sampling methodologies, the incomplete picture of how various confounding factors affect end‐point readings, and the still poorly understood potential of renal adaptation to dehydration in combat athletes; make the utility of hydration assessment via USG measurement quite problematic, particularly when diet and training is not controlled.
Xpo7 is a broad-spectrum exportin and a nuclear import receptor
Authors: Aksu Metin , Pleiner Tino , Karaca Samir , Kappert Christin , Dehne Heinz-Jürgen , Seibel Katharina , Urlaub Henning , Bohnsack Markus T. , Görlich Dirk
Published: May 2018

Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future.
Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness
Authors: Puzantian Houry , Akers Scott R , Oldland Garrett , Javaid Khuzaima , Miller Rachana , Ge Yueya , Ansari Bilal , Lee Jonathan , Suri Arpita , Hasmath Zeba , Townsend Raymond , Chirinos Julio A
Published: May 2018

BACKGROUND

Large artery stiffening is increased in advanced chronic kidney disease (CKD) but likely develops progressively in earlier stages of CKD. Active matrix Gla-protein (MGP) is a potent vitamin K–dependent inhibitor of vascular calcification. A recent animal model demonstrated intrinsic abnormalities in vitamin K metabolism even in early CKD, but whether early human CKD is associated with vascular vitamin K deficiency is unknown.

METHODS

We enrolled 137 adults without HF with varying degrees of renal function: normal estimated glomerular filtration rate (eGFR; >90 ml/min; n = 59), mildly reduced eGFR (stage 2 CKD: eGFR = 60–89 ml/min; n = 53) or at least moderately reduced eGFR (stage 3–5 CKD; eGFR < 60 ml/min; n = 25). Carotid-femoral pulse wave velocity (CF-PWV) was measured with carotid and femoral tonometry. Dephospho-uncarboxylated matrix gla-protein (dp-ucMGP) was measured with enzyme-linked immunosorbent assay (ELISA) (VitaK; Maastricht University; The Netherlands).

RESULT

Dp-ucMGP levels were progressively increased with decreasing renal function (eGFR ≥ 90: 247 pmol/l; eGFR 60–89: 488 pmol/l; eGFR < 60: 953 pmol/l; P < 0.0001). These differences persisted after adjustment for multiple potential confounders (eGFR ≥ 90: 314 pmol/l; eGFR 60–89: 414 pmol/l; eGFR < 60: 770 pmol/l; P < 0.0001). In a multivariable model adjusted for various confounders, dp-ucMGP was a significant independent predictor of CF-PWV (β = 0.21; P = 0.019). In formal mediation analyses, dp-ucMGP mediated a significant relationship between eGFR and higher CF-PWV (β = −0.16; P = 0.005), whereas no significant dp-ucMGP–independent relationship was present (β = −0.02; P = 0.80).

CONCLUSIONS

CKD is associated with increased (inactive) dp-ucMGP, a vitamin K–dependent inhibitor of vascular calcification, which correlates with large artery stiffness. Further studies are needed to assess whether vitamin K2 supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffening in CKD.
Fingolimod phosphate inhibits astrocyte inflammatory activity in mucolipidosis IV
Authors: Weinstock Laura D , Furness Amanda M , Herron Shawn S , Smith Sierra S , Sankar Sitara B , DeRosa Samantha G , Gao Dadi , Mepyans Molly E , Scotto Rosato Anna , Medina Diego L , Vardi Ayelet , Ferreira Natalia S , Cho Soo Min , Futerman Anthony H , Slaugenhaupt Susan A , Wood Levi B , Grishchuk Yulia
Published: May 2018

Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinical and neuropathologic signs in humans. Using this model, we previously observed robust activation of microglia and astrocytes in early symptomatic stages of disease. Here we investigate the consequence of mucolipin-1 loss on astrocyte inflammatory activation in vivo and in vitro and apply a pharmacologic approach to restore Mcoln1−/− astrocyte homeostasis using a clinically approved immunomodulator, fingolimod. We found that Mcoln1−/− mice over-express numerous pro-inflammatory cytokines, some of which were also over-expressed in astrocyte cultures. Changes in the cytokine profile in Mcoln1−/− astrocytes are concomitant with changes in phospho-protein signaling, including activation of PI3K/Akt and MAPK pathways. Fingolimod promotes cytokine homeostasis, down-regulates signaling within the PI3K/Akt and MAPK pathways and restores the lysosomal compartment in Mcoln1−/− astrocytes. These data suggest that fingolimod is a promising candidate for preclinical evaluation in our MLIV mouse model, which, in case of success, can be rapidly translated into clinical trial.
Endophenotypes
Authors: Glahn David C. , Almasy Laura , Blangero John
Published: May 2018

Endophenotypes are traits that, while genetically related to an illness, are not used for diagnoses (e.g., a symptom). It is unlikely that specific genes directly code for any of our current psychiatric diagnoses. Rather, genes influence neurobiological processes that either increase or decrease risk for mental illness. One use of an endophenotype is to help characterize a genetic locus or gene previously identified as conferring risk for a particular illness. In this context, endophenotypes help to bridge the gap between a behavioral syndrome and molecular genetic variation. Alternately, endophenotypes can be used for novel locus or gene discovery, particularly when used in multivariate analyses. In this chapter, we define endophenotypes and describe different ways they have been applied to aid our understanding of the genetic architecture of psychiatric disorders.
Epigenomic Exploration of the Human Brain
Authors: Halene Tobias B. , Hasler Gregor , Mitchell Amanda , Akbarian Schahram
Published: May 2018

The exploration of the epigenome has become a flourishing area in the neurosciences. Scientists increasingly appreciate that even the position of genetic material within the nucleus is purposeful, and its spatial orientation conveys information with critical influence on transcription, genome integrity, and stability. Together, epigenetic and three-dimensional genome data hold promise to reveal how DNA variants and mutations come into play in brain disease. Powerful new technologies can now map transcriptome, DNA-methylome, and other epigenetic regulators on the level of single brain cells. Many of these findings are limited to preclinical studies. Nevertheless, the advent of chromatin-modifying drugs in cancer therapy and the discovery that approved medications such as valproic acid and lithium have a chromatin-modifying effect have spurred hopes for improved biological therapies. Here we summarize current concepts and emerging insights into epigenetic regulation, with a focus on human brain and the neurobiology and pharmacology of psychiatric disorders.
Epigenetics in Psychiatry
Authors: Subramanian Subha , Potash James B.
Published: May 2018

Epigenetic modifications such as DNA methylation (DNAm), histone acetylation and methylation, and those directed by small RNAs, are widely studied in psychiatry and may play a role in the etiology and pathophysiology of psychiatric disorders. This chapter provides a brief overview of the mechanisms regulating these epigenetic marks and the challenges in obtaining biologically meaningful epigenetic data, given the inaccessibility of the living human brain. Significant results to date from studies on the epigenetics of psychiatric disorders are presented, including the impact of stress on DNAm in psychiatric risk genes such as FKBP5, and the impact of drugs of abuse and of psychiatric medications on histone modifications. Future directions are discussed, including the study of newly discovered aspects of DNAm: 5-hydroxymethylcytosine and non-CpG methylation. Ongoing work aims to uncover neurobiological mechanisms of illness and to find epigenetic biomarkers in peripheral tissues that inform diagnosis, prognosis, and therapeutic response.
Animal Models
Authors: Kato Tadafumi
Published: May 2018

Animal models of mental disorders are important for the development of new treatment and biomarkers. Animal models should satisfy three validity criteria. The choice of species used for animal models depends on the purposes of the study. There are several established models of chromosomal abnormalities for autism and schizophrenia. Stress-induced animal models of depression are controversial. There have been no established models for bipolar disorder, but the authors recently proposed a genetic animal model showing recurrent spontaneous depression-like episodes. Optogenetic manipulation of neural circuit is also used for modeling of mental disorders. Progress in psychiatric genetics will lead to the generation of valid animal models of psychiatric disorders.
Chronic Shoulder Pain
Authors: Yang Sarah T. , Malik Tariq M.
Published: May 2018

Chronic shoulder pain has multiple etiologies, including tendon tears (rotator cuff or biceps tendon), subacromial impingement (leading to subacromial bursitis or tendinitis), osteoarthritis, and shoulder joint instability. The condition is often associated with limited mobility; therefore, most interventions aim at preserving range of motion. Among the various treatment modalities, physical therapy is an effective first intervention. Corticosteroid injections do not necessarily help all chronic shoulder pain but may allow effective physical therapy for functional improvement. Multimodal analgesics and modulating agents (anti-inflammatories, antiepileptics, etc.) can also be used as part of a conservative regimen. Surgery is recommended when conservative therapy fails.
National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program
Authors: Taylor Joseph J. , Ostroff Robert
Published: May 2018

This chapter will summarize what is considered to be the first randomized controlled trial to directly compare psychotherapeutic and psychopharmacological interventions for unipolar nonpsychotic depression. More specifically, the authors were interested in the degree to which cognitive behavioral therapy, interpersonal therapy, imipramine and a placebo condition ameliorated symptoms of depression in patients from outpatient psychiatric clinics at three academic medical centers in the United States. The chapter will discuss the design and implementation of the study before focusing on the results and their implications. The last section of the chapter will list similar studies and present a hypothetical clinical case that requires the reader to apply basic concepts learned from the study.
Outcomes
Authors: Scott David L.
Published: May 2018

Outcomes evaluate the impact of disease. In rheumatology they span measures of disease activity, end-organ damage, and quality of life. Some outcomes are categorical, such as the presence or absence of remission. Other outcomes involve extended numeric scales such as joint counts, radiographic scores, and quality of life measures. Outcomes can be measured in the short term—weeks and months—or over years and decades. Short-term outcomes, though readily related to treatment, may have less relevance for patients. Clinical trials focus on short-term outcomes whereas observational studies explore longer-term outcomes. The matrix of rheumatic disease outcomes is exemplified by rheumatoid arthritis. Its outcomes span disease activity assessments like joint counts, damage assessed by erosive scores, quality of life evaluated by disease-specific measures like the Health Assessment Questionnaire (HAQ) or generic measures like the Short Form 36 (SF-36), overall assessments like remission, and end result such as joint replacement or death. Outcome measures capture the impact of treating rheumatic diseases. They are influenced by disease severity and effective treatment. They also reflect many confounding factors. These include demographic factors like age, gender, and ethnicity and also deprivation, as poverty worsens outcomes. Comorbidities affect outcomes and patients with multiple comorbid conditions have worse quality of life with poorer outcomes. Patient self-assessment has grown in importance; it is simple and understandable. However, self-assessment can vary over time and does not always reflect assessors’ perspectives. Caution is needed comparing outcomes across units; the various confounding factors and measurement complexities make such comparative analyses challenging.
Autoimmune serology
Authors: Hamann Philip , McHugh Neil
Published: May 2018

Autoimmune serology has become central in the characterization of many rheumatic conditions and in many cases the presence of an autoantibody (e.g. anti-citrullinated peptide, rheumatoid factor, ANCA, ANA, ENA, anti-phospholipid antibody), may form part of the diagnostic criteria. Increasingly, as pathogenic mechanisms are derived, the role of these autoantibodies is becoming better understood. This chapter covers the key techniques (immunoflourescence, immunodiffusion, ELISA, immunoblotting, immunoprecipitation) used in autoantibody detection as well as the clinico-pathological significance of a positive result.
Lyme borreliosis
Authors: Krause Andreas , Fingerle Volker
Published: May 2018

Lyme borreliosis (LB) is a multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi. The most frequent clinical manifestations include erythema migrans, meningoplyneuritis, and arthritis. Diagnosis of LB is made on clinical grounds and usually supported by a positive serology. Early diagnosis and treatment almost always leads to a rapid healing of the disease. However, in late manifestations gradual remission of symptoms may take several weeks to months. In rare cases, the pathogen can persist for many years or induce a persisting immunopathological response that may cause acrodermatitis chronica atrophicans, chronic neuroborreliosis of the central nervous system, or antibiotic resistant Lyme arthritis. However, even these chronic manifestations usually slowly regress after thorough antibiotic and symptomatic therapy, although in part with irreversible organ defects.
Psoriatic arthritis
Authors: Coates Laura C. , Helliwell Philip S.
Published: May 2018

Psoriasis is a chronic skin condition affecting about 3% of Europeans and North Americans. About 15% of people afflicted with psoriasis will develop psoriatic arthritis—cutaneous risk factors for this are psoriasis of the nails, scalp, and flexures. Since most cases of arthritis develop in people with psoriasis, new screening tools, both clinical and imaging, are available. Some genetic factors may also explain susceptibility and severity. Historically, five clinical subgroups have been described but these may be simplified to axial and peripheral involvement, the latter dividing into oligo- and polyarticular patterns. The importance of these clinical subdivisions is still under debate and research but it is clear that there is marked heterogeneity in all manifestations of this disease. In recent times the importance of extra-articular features has gained prominence such that the metabolic syndrome and cardiovascular morbidity are now seen as important features of ’psoriatic disease’. The diverse changes seen in bone on imaging reflect both the underlying pathogenic mechanisms and the ways in which the disease progresses. Recent work with animal models and immunohistochemistry has further advanced our understanding of these features. In the biologic era renewed interest in psoriatic arthritis has stimulated research into outcome assessment and permitted clearer understanding of how these new drugs work on the different aspects of the disease. In addition, improved recognition of the impact of the disease on the person has stimulated the development of new patient-reported outcome tools.
Paediatric polymyositis and dermatomyositis
Authors: Pilkington Clarissa , McCann Liza
Published: May 2018

Juvenile polymyositis and dermatomyositis are inflammatory myopathies that affect muscle. Dermatomyositis also affects skin, and can have many extramuscular manifestations. Inflammatory myopathies are uncommon in childhood, with dermatomyositis occurring more than polymyositis. For this reason, published research has concentrated on juvenile dermatomyositis. The spectrum of disease severity ranges from mild cases that can recover completely without treatment, to multisystem inflammation that can be fatal. Treatments have improved over the decades, reducing mortality from 30% before the era of steroids, to less than 1% in the present day. Juvenile cases of dermatomyositis differ from those seen in adulthood, without tendency for associated malignancy, and a far greater incidence of calcinosis. Calcinosis can be deposited as small calcinotic lumps or as sheets of calcinosis. It is very difficult to treat and causes extensive morbidity, and depending on where the calcinosis is deposited, it can cause severe disability or even death.
Over the last decade, international collaborative work has concentrated on developing disease activity and assessment tools for both adult and juvenile forms of myositis. This will enable more subjective study of these rare diseases in multinational cohort studies, and enable clinical trials to investigate drug treatments. This work led to the first international double-blind placebo controlled trial of treatment in both adults and children with dermatomyositis (using rituximab as the drug). Further international collaboration has led to the development of core outcome variables, a definition of disease flare, and ongoing work on classification criteria.
Calcium pyrophosphate crystal deposition (CPPD)
Authors: Roddy Edward , Doherty Michael
Published: May 2018

Calcium pyrophosphate crystal deposition (CPPD) in articular cartilage is a common age-related phenomenon. Recent important advances in our understanding of the pathophysiology of pyrophosphate metabolism include the identification of a mutation within the ANK gene which associates with familial CPPD, and elucidation of the interleukin-1β‎‎ (IL-1β‎‎)-dependent mechanisms by which crystals invoke an inflammatory response. Risk factors for CPPD include age, prior joint damage and osteoarthritis, genetic factors, and occasionally metabolic diseases (hyperparathyroidism, haemochromatosis, hypomagnesaemia, and hypophosphatasia). CPPD is commonly asymptomatic or may present as osteoarthritis with CPPD, acute calcium pyrophosphate (CPP) crystal arthritis, or chronic CPP crystal inflammatory arthritis. Although radiographic chondrocalcinosis is often taken to be synonymous with CPPD, other calcium crystals can also have this appearance and definitive diagnosis requires identification of CPP crystals by compensated polarized light microscopy of aspirated synovial fluid. Recently, the ultrasonographic appearances of CPPD have been described. Treatment of CPPD is targeted to the clinical presentation. Acute CPP crystal arthritis is treated by aspiration and injection of glucocorticosteroid, local ice packs, non-steroidal anti-inflammatory drugs (NSAIDS), low-dose colchicine, oral or parenteral glucocorticosteroids, or adrenocorticotrophic hormone (ACTH). Treatment of osteoarthritis with CPPD is very similar to the treatment of osteoarthritis alone. There is no specific therapy for chronic CPP crystal inflammatory arthritis: options include NSAID, low-dose colchicine, low-dose glucocorticosteroid, methotrexate, and hydroxychloroquine. Recommendations for the management of CPPD are derived from a small evidence base and largely based on clinical experience and extrapolation from gout. Further research into diagnosis and management including novel treatment strategies such as IL-1β‎‎ blockade is much needed.
Haemoglobinopathies
Authors: Rees David
Published: May 2018

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.
Establishing the spectral turnover of blazar PKS 2155−304 as an outcome of radiative losses
Authors: Jagan Sitha K , Sahayanathan S , Misra R , Ravikumar C D , Jeena K
Published: May 2018

The broad-band optical/UV and X-ray spectra of blazars have been often modelled as synchrotron component arising from a broken power-law distribution of electrons. A broken power-law distribution is expected, since the high-energy electrons undergo radiative losses effectively. The change in the energy index should then be ≈1 and corresponds to a spectral index difference of 0.5. However, one of the long outstanding problems has been that the observed index change is significantly different. On the other hand, recent high-quality observations of blazars suggest that their local spectra may not be a power law, instead have a slight curvature and often represented by a log-parabola model. Using XMM–Newtonobservations spanning over 12 yr for the BL Lac PKS 2155−304, we show that the optical/UV and X-ray spectra can be well represented by a broken log-parabola model. Further, we show that such a spectrum can indicate the energy dependence of the electron escape time-scale from the main acceleration zone. This novel approach, besides addressing the observed difference in the photon spectral indices, also tries to explain the spectral turn over in far-UV/soft X-rays as a result of the radiative losses.
The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells
Authors: Abshire Elizabeth T , Chasseur Jennifer , Bohn Jennifer A , Del Rizzo Paul A , Freddolino Lydia , Goldstrohm Aaron C , Trievel Raymond C
Published: May 2018

The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. However, the mechanisms by which NOCT regulates these processes remain to be determined. Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain. The active site of NOCT is highly conserved with other exoribonucleases, and when directed to a transcript in cells, NOCT can reduce translation and abundance of that mRNA in a manner dependent on key active site residues. In contrast to the related deadenylase CNOT6L, purified recombinant NOCT lacks in vitro ribonuclease activity, suggesting that unidentified factors are necessary for enzymatic activity. We also find the ability of NOCT to repress reporter mRNAs in cells depends upon the 3′ end of the mRNA, as reporters terminating with a 3′ MALAT1 structure cannot be repressed by NOCT. Together, these data demonstrate that NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression, suggesting a molecular mechanism for its regulatory role in lipid metabolism and bone development.
Design of a clinical risk calculator for major clinical outcomes in patients with atherosclerotic renovascular disease
Authors: Vassallo Diana , Foley Robert N , Kalra Philip A
Published: May 2018

Background

Risk stratification in atherosclerotic renovascular disease (ARVD) can influence treatment decisions and facilitate patient selection for revascularization. In this study, we aim to use variables with the best predictive value to design a risk calculator that can assist clinicians with risk stratification and outcome prediction.

Methods

Patients with a radiological diagnosis of ARVD referred to our tertiary renal centre were recruited into this prospective cohort study between 1986 and 2014. Primary clinical endpoints included: death, progression to end-stage kidney disease and cardiovascular events (CVE). A stepwise regression model was used to select variables with the most significant hazard ratio for each clinical endpoint. The risk calculator was designed using Hypertext Markup Language. Survival and CVE-free survival were estimated at 1, 5 and 10 years.

Results

In total, 872 patients were recruited into the Salford ARVD study with a median follow-up period of 54.9 months (interquartile range 20.2–96.0). Only models predicting death and CVE showed good performance (C-index >0.80). Survival probabilities obtained from the risk calculator show that most patients with ARVD have reduced long-term survival. Revascularization improved outcomes in patients with higher baseline estimated glomerular filtration rate and lower proteinuria but not in those with co-existing comorbidities and higher levels of baseline proteinuria.

Conclusions

Although this risk calculator requires further independent validation in other ARVD cohorts, this study shows that a small number of easily obtained variables can help predict clinical outcomes and encourage a patient-specific therapeutic approach.
Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients
Authors: Hsaiky Lama M , Salinitri Francine D , Wong Judy , Jennings Sin-Ling T , Desai Neha H , Lobkovich Alison M , Cha Raymond
Published: May 2018

Background

Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis.

Methods

This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay.

Results

Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h–∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported.

Conclusions

Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.
Osteoid Osteoma: Radiologic Diagnosis and Treatment
Authors: Rassi Jonathan , Lampl Brooke , Wajid Haq , Ilaslan Hakan , Park Ellen
Published: May 2018

Osteoid osteoma is a benign, monostotic bone tumor accounting for 11% of all benign bone tumors and 3% of all primary bone tumors.1
,
2 Osteoid osteoma is up to three times more prevalent in males than in females, most commonly between the ages of 10 and 30 years.1
,
2
Supplemental Carbon Dioxide Stabilizes the Upper Airway in Volunteers Anesthetized with Propofol
Authors: Ruscic Katarina Jennifer , Bøgh Stokholm Janne , Patlak Johann , Deng Hao , Simons Jeroen Cedric Peter , Houle Timothy , Peters Jürgen , Eikermann Matthias
Published: May 2018

Background

Propofol impairs upper airway dilator muscle tone and increases upper airway collapsibility. Preclinical studies show that carbon dioxide decreases propofol-mediated respiratory depression. We studied whether elevation of end-tidal carbon dioxide (Petco
2) via carbon dioxide insufflation reverses the airway collapsibility (primary hypothesis) and impaired genioglossus muscle electromyogram that accompany propofol anesthesia.

Methods

We present a prespecified, secondary analysis of previously published experiments in 12 volunteers breathing via a high-flow respiratory circuit used to control upper airway pressure under propofol anesthesia at two levels, with the deep level titrated to suppression of motor response. Ventilation, mask pressure, negative pharyngeal pressure, upper airway closing pressure, genioglossus electromyogram, bispectral index, and change in end-expiratory lung volume were measured as a function of elevation of Petco
2 above baseline and depth of propofol anesthesia.

Results

Petco
2 augmentation dose-dependently lowered upper airway closing pressure with a decrease of 3.1 cm H2O (95% CI, 2.2 to 3.9; P < 0.001) under deep anesthesia, indicating improved upper airway stability. In parallel, the phasic genioglossus electromyogram increased by 28% (23 to 34; P < 0.001). We found that genioglossus electromyogram activity was a significant modifier of the effect of Petco
2 elevation on closing pressure (P = 0.005 for interaction term).

Conclusions

Upper airway collapsibility induced by propofol anesthesia can be reversed in a dose-dependent manner by insufflation of supplemental carbon dioxide. This effect is at least partly mediated by increased genioglossus muscle activity.
Surgical Alteration of Genital Hiatus Size and Anatomic Failure After Vaginal Vault Suspension
Authors: Vaughan Monique H. , Siddiqui Nazema Y. , Newcomb Laura K. , Weidner Alison C. , Kawasaki Amie , Visco Anthony G. , Bradley Megan S.
Published: May 2018

OBJECTIVE:

To compare anatomic outcomes after native tissue vaginal vault suspension among women categorized by their preoperative and 6-week postoperative genital hiatus size.

METHODS:

We performed a retrospective cohort study in women who underwent native tissue vaginal vault suspension between 2005 and 2015. We defined a wide genital hiatus as 4 cm or greater and a normal genital hiatus as less than 4 cm. We compared three groups: 1) women with a wide genital hiatus preoperatively and 6 weeks postoperatively (persistently wide group), 2) women with a wide genital hiatus preoperatively but normal genital hiatus 6 weeks postoperatively (improved group), and 3) women with a normal genital hiatus preoperatively and 6 weeks postoperatively (stably normal group). Our primary outcome was composite anatomic failure at medium term, defined as either recurrent prolapse beyond the hymen or retreatment for prolapse with surgery or a pessary. Data were analyzed with appropriate bivariate analysis and logistic regression.

RESULTS:

Our study population consisted of 260 women, with 39 of 260 (15.0%) in the persistently wide group, 157 of 260 (60.4%) improved, and 64 of 260 (24.6%) stably normal. Composite anatomic failure was significantly more likely in the persistently wide cohort as compared with the other groups (persistently wide 51.3%, improved 16.6%, stably normal 6.3%, overall P<.01, significant for all pairwise comparisons). These results were consistent when examining the anterior, apical, and posterior compartments individually. In a logistic regression analysis, the persistently wide group was associated with a 4.4-fold increased odds of composite failure (adjusted odds ratio [OR] 4.41, 95% CI 1.99–9.76, P<.01) compared with the improved group and a 15.8-fold increased odds compared with the stably normal group (adjusted OR 15.79, 95% CI 4.66–53.57, P<.01).

CONCLUSION:

Women with a preoperative genital hiatus 4 cm or greater that is not surgically normalized after native tissue vaginal vault suspension are at significantly increased odds of anatomic failure in all compartments.