bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging the Gap between Evidence and Practice for Adults with Medically Refractory Temporal Lobe Epilepsy: Is a Change in Funding Policy Needed to Stimulate a Shift in Practice?
Authors: Mansouri Alireza , Aldakkan Abdulrahman , Kosicka Magda J. , Tarride Jean-Eric , Valiante Taufik A.
Published: December 2015

Objective. Surgery for medically refractory epilepsy (MRE) in adults has been shown to be effective but underutilized. Comprehensive health economic evaluations of surgery compared with continued medical management are limited. Policy changes may be necessary to influence practice shift. Methods. A critical review of the literature on health economic analyses for adults with MRE was conducted. The MEDLINE, EMBASE, CENTRAL, CRD, and EconLit databases were searched using relevant subject headings and keywords pertaining to adults, epilepsy, and health economic evaluations. The screening was conducted independently and in duplicate. Results. Four studies were identified (1 Canadian, 2 American, and 1 French). Two were cost-utility analyses and 2 were cost-effectiveness evaluations. Only one was conducted after the effectiveness of surgery was established through a randomized trial. All suggested surgery to be favorable in the medium to long term (7-8 years and beyond). The reduction of medication use was the major cost-saving parameter in favor of surgery. Conclusions. Although updated evaluations that are more generalizable across settings are necessary, surgery appears to be a favorable option from a health economic perspective. Given the limited success of knowledge translation endeavours, funder-level policy changes such as quality-based purchasing may be necessary to induce a shift in practice.
Geometric Collocation Method on SO(3) with Application to Optimal Attitude Control of a 3D Rotating Rigid Body
Authors: Xiang Xiaojia , Wu Lizhen , Shen Lincheng , Li Jie
Published: December 2015

The collocation method is extended to the special orthogonal group SO(3) with application to optimal attitude control (OAC) of a rigid body. A left-invariant rigid-body attitude dynamical model on SO(3) is established. For the left invariance of the attitude configuration equation in body-fixed frame, a geometrically exact numerical method on SO(3), referred to as the geometric collocation method, is proposed by deriving the equivalent Lie algebra equation inso(3)of the left-invariant configuration equation. When compared with the general Gauss pseudo-spectral method, the explicit RKMK, and Lie group variational integrator having the same order and stepsize in numerical tests for evolving a free-floating rigid-body attitude dynamics, the proposed method is higher in accuracy, time performance, and structural conservativeness. In addition, the numerical method is applied to solve a constrained OAC problem on SO(3). The optimal control problem is transcribed into a nonlinear programming problem, in which the equivalent Lie algebra equation is being considered as the defect constraints instead of the configuration equation. The transcription method is coordinate-free and does not need chart switching or special handling of singularities. More importantly, with the numerical advantage of the geometric collocation method, the proposed OAC method may generate satisfying convergence rate.
Fuyuan Decoction Enhances SOX9 and COL2A1 Expression and Smad2/3 Phosphorylation in IL-1β-Activated Chondrocytes
Authors: Zhang Yudi , Li Rongheng , Zhong Yu , Zhang Sihan , Zhou Lingyun , Shang Shike
Published: December 2015

Fuyuan Decoction (FYD), a herbal formula in China, has been widely used for osteoarthritis (OA) treatment. Herein, we determined the effects of FYD on the expression of transcription factor SOX9 and its target gene collagen type II, alpha 1 (COL2A1) as well as the activation of Smad2/3 in interleukin- (IL-) 1β-stimulated SW1353 chondrosarcoma cells. Serum-derived FYD (FYD-CS) was prepared to treat SW1353 cells with or without SB431542, a TGF-β1 receptor inhibitor. Cell cycle progression was tested by flow cytometry. The expression of SOX9 and COL2A1 and the activation of Smad2/3 (p-Smad2/3) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or western blot. The results showed that, after treatment, FYD-CS, while inducing S-phase cell cycle arrest, enhanced cell proliferation and protected the cells against IL-1β- and/or SB431542-induced cell growth inhibition. Furthermore, FYD-CS reversed the decreased expression of COL2A1 and SOX9 induced by IL-1βand SB431542 and blocked the decreased phosphorylation of Smad2/3 induced by IL-1βalone or in combination with SB431542. Our results suggest that FYD promotes COL2A1 and SOX9 expression as well as Smad2/3 activation in IL-1β-induced chondrocytes, thus benefiting cell survival.
Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor
Authors: Ide Hiroki , Miyamoto Hiroshi
Published: December 2015

There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.
Structural Analysis of Polyhedral Oligomeric Silsesquioxane Coated SiC Nanoparticles and Their Applications in Thermoset Polymers
Authors: Reza-E-Rabby Md. , Jeelani Shaik , Rangari Vijaya K.
Published: December 2015

The SiC nanoparticles (NPs) were sonochemically coated with OctaIsobutyl (OI) polyhedral oligomeric silsesquioxane (POSS) to create a compatible interface between particle and thermoset polymer. X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD) techniques were used to analyze the structure of OI‐POSS coated SiC nanoparticles. These results revealed the formation of a covalent bonding between SiC and OI‐POSS. The transmission electron microscopy (TEM) analysis of OI‐POSS coated SiC nanoparticles has also shown the indication of attachment between these two nanoparticles. The OI‐POSS coated SiC nanoparticles were further reinforced into a thermoset resin system in order to evaluate mechanical and thermal properties of nanocomposites. The flexural strength, modulus, and glass transition temperature were found to be enhanced while SiC and OI‐POSS coated SiC were infused into epoxy system compared to those properties of neat epoxy resin.
Quantification of Outdoor Mobility by Use of Accelerometer-Measured Physical Behaviour
Authors: Taraldsen Kristin , Granat Malcolm H. , Helbostad Jorunn L.
Published: December 2015

Hip fractures in older persons are associated with both low levels of daily physical activity and loss of outdoor mobility. The aim was to investigate if accelerometer-based measures of physical behaviour can be used to determine if people undertake outdoor walking and to provide reference values for physical behaviour outcomes related to outdoor mobility. Older persons (n=245), ≥70 years, one year after hip fracture, participated. Six objective measures of physical behaviour collected by an activity monitor were compared with self-reported outdoor mobility assessed with the Nottingham Extended ADL scale. All measures of time and length in upright periods were significantly lower in participants who reported not walking outdoors (p<0.001). A set of cut-off points for the different physical behaviour variables was generated. Maximum length of upright events discriminated best between groups, with 31 minutes as a threshold to determine if a person is more likely to report that they walk outdoors (sensitivity: 0.805, specificity: 0.704, and AUC: 0.871) or 41 minutes or more to determine if a person is more likely to report outdoor walking on their own (AUC: 0.891). Physical behaviour variables from activity monitoring can provide information about patterns of physical behaviour related to outdoor activity performance.
A Multipurpose Key Agreement Scheme in Ubiquitous Computing Environments
Authors: Chang Chin-Chen , Lin Iuon-Chang , Wu Chia-Chi
Published: December 2015

Due to the rapid advancement of cryptographic techniques, the smart card has recently become a popular device because it is capable of storing and computing essential information with such properties as tamper resistance. However, many service providers must satisfy the user’s desire to be able to access services anytime and anywhere with the smart card computing devices. Therefore, multipurpose smart cards have become very popular identification tokens. In 2011, Wang et al. proposed an authentication and key agreement scheme for smart card use. Even so, two drawbacks still exist; that is, (1) the security requirement of mutual authentication has not been satisfied and (2) the authentication scheme cannot be used for multipurpose smart cards. In this paper, we propose an efficient and secure multipurpose, authenticated, key agreement scheme in which the user is required to register only once and can be authenticated without any registration center. Furthermore, the proposed scheme can be used in ubiquitous environments because of its low computation and communication overhead.
On the Second-Order Shape Derivative of the Kohn-Vogelius Objective Functional Using the Velocity Method
Authors: Bacani Jerico B. , Rabago Julius Fergy T.
Published: December 2015

The exterior Bernoulli free boundary problem was studied via shape optimization technique. The problem was reformulated into the minimization of the so-called Kohn-Vogelius objective functional, where two state variables involved satisfy two boundary value problems, separately. The paper focused on solving the second-order shape derivative of the objective functional using the velocity method with nonautonomous velocity fields. This work confirms the classical results of Delfour and Zolésio in relating shape derivatives of functionals using velocity method and perturbation of identity technique.
Maintenance of Self‐Renewal and Pluripotency in J1 Mouse Embryonic Stem Cells through Regulating Transcription Factor and MicroRNA Expression Induced by PD0325901
Authors: Ai Zhiying , Shao Jingjing , Shi Xinglong , Yu Mengying , Wu Yongyan , Du Juan , Zhang Yong , Guo Zekun
Published: December 2015

Embryonic stem cells (ESCs) have the ability to grow indefinitely and retain their pluripotency in culture, and this self‐renewal capacity is governed by several crucial molecular pathways controlled by specific regulatory genes and epigenetic modifications. It is reported that multiple epigenetic regulators, such as miRNA and pluripotency factors, can be tightly integrated into molecular pathways and cooperate to maintain self‐renewal of ESCs. However, mouse ESCs in serum‐containing medium seem to be heterogeneous due to the self‐activating differentiation signal of MEK/ERK. Thus, to seek for the crucial miRNA and key regulatory genes that establish ESC properties in MEK/ERK pathway, we performed microarray analysis and small RNA deep‐sequencing of J1 mESCs treated with or without PD0325901 (PD), a well‐known inhibitor of MEK/ERK signal pathway, followed by verification of western blot analysis and quantitative real‐time PCR verification; we found that PD regulated the transcript expressions related to self‐renewal and differentiation and antagonized the action of retinoic acid‐ (RA‐) induced differentiation. Moreover, PD can significantly modulate the expressions of multiple miRNAs that have crucial functions in ESC development. Overall, our results demonstrate that PD could enhance ESC self‐renewal capacity both by key regulatory genes and ES cell‐specific miRNA, which in turn influences ESC self‐renewal and cellular differentiation.
The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats
Authors: Kim Junhwan , Perales Villarroel José Paul , Zhang Wei , Yin Tai , Shinozaki Koichiro , Hong Angela , Lampe Joshua W. , Becker Lance B.
Published: December 2015

Cardiac arrest induces whole‐body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague‐Dawley rats are subjected to asphyxia‐induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time‐dependent decrease in state‐3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state‐3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state‐3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.
Assessment of Insulin Resistance in Subjects with Normal Glucose Tolerance, Hyperinsulinemia with Normal Blood Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed Type 2 Diabetes (Prediabetes Insulin Resistance Research)
Authors: Yang Guang , Li Chunlin , Gong Yanping , Fang Fusheng , Tian Hui , Li Jian , Cheng Xiaoling
Published: December 2015

Aim.To evaluate the differences in insulin resistance (IR) among subjects with normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM).Methods.5 NGT, 25 HINS, 25 IGT, and 25 T2DM subjects participated in this research. The hyperinsulinemic-euglycemic clamp technique (HECT) was performed in all of them to evaluate IR levels. The relative factors influencing IR were evaluated. The simple insulin sensitivity indices were calculated, and the correlation between each index and the M value was analyzed.Results.TheMvalues of NGT, HINS, IGT, and T2DM groups were 11.88 ± 2.93 mg·kg−1·min−1, 6.23 ± 1.73 mg·kg−1·min−1, 6.37 ± 2.12 mg·kg−1·min−1, and 6.19 ± 1.89 mg·kg−1·min−1, respectively.Mvalues in HINS, IGT, and T2DM groups were lower than those in the NGT group (P=0.005); however, the differences among the HINS, IGT, and T2DM groups were not statistically significant (P=0.835). The independent factors influencing theMvalue were waistline and fasting insulin level (FINS). The simple insulin sensitivity indices, especially Matsuda and Gutt index, were significantly associated with theMvalue (P<0.01).Conclusion.IR existed in the HINS, IGT, and T2DM groups, and IR levels were consistent in the three groups. The independent factors influencing IR were waistline and FINS.
Genetic Risk and the Development of Autoimmune Liver Disease
Authors: Karlsen Tom H. , Chung Brian K.
Published: December 2015

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) have collectively been recognized as autoimmune liver diseases. They have all been subjected to genome-wide association studies (GWAS) and several dozens susceptibility loci have been determined. The predominant feature of the genetic findings is that of a strong association with the human leukocyte antigen (HLA) and numerous weak associations scattered throughout the remainder of the genome. The non-HLA associations show some degree of overlap, not only between PBC, PSC and AIH, but also with other autoimmune and immune-mediated diseases. Mathematical modelling shows that the main fraction of autoimmune disease risk (including that of autoimmune liver diseases) is not explained by GWAS, proposing a major role of environmental factors. The HLA associations and autoantibodies observed in these conditions may hold clues as to the nature of such factors, which are exceedingly difficult to map by means of epidemiological study designs. The present review article explores the potential relationship between genetic risk as determined by GWAS and environmental risk in autoimmune liver diseases, and proposes a model for relevant thinking on the susceptibility genes in PBC, PSC and AIH.
Diagnostic Criteria for Autoimmune Hepatitis: Scores and More
Authors: Lohse Ansgar W.
Published: December 2015

The diagnosis of autoimmune hepatitis is a clinical diagnosis that combines the patient's history, clinical examination, laboratory and serological markers and the results of a liver biopsy. As the clinical spectrum of autoimmune hepatitis is very wide, making the diagnosis can sometimes be difficult, especially in non-expert hands. Diagnostic scores can help in making the diagnosis, and the simplified diagnostic score of the International Autoimmune Hepatitis Group has a sensitivity and specificity of around 90% in the different populations that have been studied. Therefore, it can be very helpful in everyday use, but nonetheless for some patients the score is not good enough. Limitations are patients with very acute presentations as well as atypical cases. In such cases, a trial of monotherapy with steroids and quick tapering of the steroids is recommended. If the disease responds well to treatment, but recurs after tapering the steroids, the diagnosis of autoimmune hepatitis is confirmed. In addition to its clinical use, diagnostic scores can also be helpful in defining the unified criteria in order to make scientific studies comparable.
Role of Histopathology in Autoimmune Hepatitis
Authors: Tiniakos Dina G. , Brain John G. , Bury Yvonne A.
Published: December 2015

The diagnosis of autoimmune hepatitis (AIH) is based on a combination of biochemical, immunological and histological features and exclusion of other causes of liver disease. Typical histological features include a chronic hepatitis pattern of injury with portal inflammation and interface activity, predominance of plasma cells in the portal infiltrate, emperipolesis, and hepatocellular rosette formation. Centrilobular injury with prominent hepatocellular necrosis and mononuclear inflammation is now recognised in the histological spectrum of AIH and may represent an early stage of the disease. Liver histology plays a major role in clinical diagnostic scoring systems and is important to confirm or support the clinical diagnosis of AIH. This review focuses on the role of histopathology in AIH and highlights the contribution of histological interpretation to the diagnosis of AIH, differential diagnosis from other entities, recognition of concurrent liver disease, and identification of the so-called overlap or variant syndromes, and addresses the importance of liver biopsy in the management and prognosis of patients with AIH.
AIH: Which Alternative for Difficult-to-Treat Patients?
Authors: Sebode Marcial , Schramm Christoph
Published: December 2015

Background: Oftentimes we are expected to make difficult decision when patients with autoimmune hepatitis (AIH) present themselves before us. Among these cases, advanced liver cirrhosis, fulminant AIH with hepatic failure or pregnancy with highly active AIH will pose challenges on their own. In patients where standard treatment has failed, the risk of disease progression including liver transplantation has to be weighed against the risk of drug-related side effects, including infectious complications. Key Messages: Standard treatment of AIH includes the use of drugs like corticosteroids and usually azathioprine. However, up to 15% of patients will require second-line treatment. There are no prospective studies evaluating second- or third-line treatment regimens in AIH. In our opinion, it is essential to differentiate between those patients who are intolerant and those who do not respond sufficiently to standard treatment. For patients intolerant to prednisolone due to steroid-induced side effects, budesonide may be a feasible alternative, unless liver cirrhosis forbids its use. Our experience indicates that 6-mercaptopurine may be given as an alternative to azathioprine, especially in cases of gastrointestinal side effects, with good tolerance and response rates of up to 70%. As a more expensive alternative, mycophenolat mofetil (MMF) has been shown to effectively suppress disease activity in a majority of patients intolerant to azathioprine. Of note, MMF is contraindicated in pregnancy. In patients with insufficient response to azathioprine, the dose should be increased up to 2.5 mg/kg of body weight, and measurement of azathioprine metabolites (6TGN and MMP) may aid the optimal dosage. Several other immunosuppressive treatment strategies have been tested and published in small case series. These include the calcineurin inhibitors cyclosporine A and tacrolimus, mTOR inhibitors, anti-tumor necrosis factor α treatment with infliximab, rituximab as well as cyclophosphamide. Conclusions: It is difficult to tell whether 1 strategy is superior to another in the case of difficult-to-treat AIH patients. Intolerance should be differentiated from insufficient response to standard treatment. The choice of second- and third-line treatment will depend on the comorbidities, patient's choice after informed consent and also local expertise.
Aspects of the Pathophysiology of Primary Biliary Cirrhosis
Authors: Corrigan Margaret , Hirschfield Gideon M.
Published: December 2015

Primary biliary cirrhosis is a classical autoimmune liver disease and is present in around 1 in 1,000 women over the age of 40. It has a number of diagnostic characteristics consistent with autoimmune liver injury, in particular, the high specificity of circulating anti-mitochondrial antibodies. Histologically, the disease is reflected as a granulomatous lymphocytic cholangitis that consequently leads to small bile duct loss and cholestasis. Progressive disease is characterised by the development of a biliary cirrhosis, with end-stage features of liver disease ultimately impacting patient outcomes. Studies support a combination of environmental and genetic risk factors that coalesce to lead to loss of immunological tolerance and persistent biliary inflammation. Significant advances have occurred recently in understanding the genetic risk factors for disease, as well as utilising human and murine studies to characterise the nature of the biliary injury and cholestatic response.
Surrogate Endpoints for Optimal Therapeutic Response to UDCA in Primary Biliary Cholangitis
Authors: van Buuren Henk R. , Lammers Willem J. , Harms Maren H. , Hansen Bettina E.
Published: December 2015

Background: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), as it can delay histological progression, improve long-term outcome and is extremely safe and well tolerated. However, UDCA is not always sufficient and the prognosis of patients inadequately responding to treatment is worse compared with the general population. Reliable identification of so-called non-responders is of key importance, not only for selecting patients who could benefit from additional, second-line therapy, but also for identifying those individuals who are at low risk of developing end-stage disease and in whom UDCA mono-therapy can be safely continued. Several laboratory surrogate endpoints for the long-term response to UDCA have been proposed, including the Barcelona, Paris, Toronto and Rotterdam criteria. All these criteria have limitations and the superiority of one over the other has not been firmly established. Key Messages: Recently the Global PBC Study Group developed a new prognostic tool by studying a large, representative and multinational cohort of 4,119 UDCA-treated patients. In a random sample of 2,488 cases, a risk score - the GLOBE score - was developed, predictive of transplantation-free survival. This risk score comprises age, and bilirubin, albumin, alkaline phosphatase and platelet count obtained after 1 year therapy, and has a performance (C statistic 0.81, 95% CI 0.79-0.83) that is markedly better than that of previously proposed response criteria. Comparable performance was found in an independent validation cohort of 1,631 cases (C statistic 0.82, 95% CI 0.79-0.84). A web app will allow the easy use of the score in clinical practice.
IgG4-Associated Cholangitis - A Mimic of PSC
Authors: Beuers Ulrich , Hubers Lowiek M. , Doorenspleet Marieke , Maillette de Buy Wenniger Lucas , Klarenbeek Paul L. , Boonstra Kirsten , Ponsioen Cyriel , Rauws Erik , de Vries Niek
Published: December 2015

IgG4-associated cholangitis (IAC) is an inflammatory disorder of the biliary tract representing a major manifestation of IgG4-related disease (IgG4-RD) often with elevation of serum IgG4 levels, infiltration of IgG4+ plasma cells in the affected tissue and good response to immunosuppressive treatment. Its first description may go back to 150 years ago. The clinical presentation of IAC is often misleading, mimicking other biliary diseases such as primary sclerosing cholangitis (PSC) or cholangiocarcinoma. The HISORt criteria - histopathological, imaging, and serological features (sIgG4), other organ manifestations of IgG4-RD and response to treatment - are the standard for the diagnosis of IAC. In this overview of a recent lecture, we summarize our original findings on IgG4-RD that (i) dominant IgG4+ B-cell clones identified by advanced next generation sequencing (NGS) are highly specific for IgG4-RD (meanwhile confirmed by others), are a highly accurate diagnostic marker to distinguish IgG4-RD from PSC and biliary/pancreatic malignancies and may be crucial in unravelling the pathophysiology of IgG4-RD; (ii) sIgG4/sIgG1 >0.24 have additional diagnostic value in comparison to sIgG4 in differentiating IAC from PSC; (iii) blood IgG4 mRNA is a highly accurate diagnostic marker comparable to NGS and may become an easily available and affordable diagnostic standard for distinguishing IgG4-RD from PSC and biliary/pancreatic malignancies; and (iv) ‘blue collar work' with long-term exposure to solvents, paints, oil products or industrial gases may be a risk factor for development of IgG4-RD. These findings may contribute to the understanding of the pathophysiology and to the early diagnosis and adequate treatment of IgG4-RD.
The Quality of Pain Treatment in Community-Dwelling Persons with Dementia
Authors: Li Jiwen , Snow A. Lynn , Wilson Nancy , Stanley Melinda A. , Morgan Robert O. , Sansgiry Shubhada , Kunik Mark E.
Published: December 2015

Background/Aims: Despite pervasive and debilitating pain among elders, it is underassessed and undertreated; and cognitive impairment can add challenges. We assessed the quality of pain care for community-dwelling elderly patients with dementia. Methods: We phone interviewed 203 Veterans Affairs primary care outpatients with dementia and pain and reviewed medical records to score 15 quality indicators of pain assessment and management. Results: Pain assessment was documented for 98%, and a standard pain scale was used for 94%. Modified pain scales were rarely used. Though 70% self-reported pain of ‘quite bad' or worse, charts documented no pain in 64%. When pain was identified, treatment was offered to 80%; but only 59% had a follow-up assessment within 6 months. Nonpharmacological interventions were underused. Conclusion: Community-dwelling elders with dementia are underdiagnosed and undertreated for pain.
LL-37 Triggers Formation of Streptococcus pyogenes Extracellular Vesicle-Like Structures with Immune Stimulatory Properties
Authors: Uhlmann Julia , Rohde Manfred , Siemens Nikolai , Kreikemeyer Bernd , Bergman Peter , Johansson Linda , Norrby-Teglund Anna
Published: December 2015

Reports have shown that the antimicrobial peptide LL-37 is abundantly expressed but has limited bactericidal effect in Streptococcus pyogenes infections. At sub-inhibitory concentrations, LL-37 has been reported to alter virulence gene expression. Here, we explored the interaction of S. pyogenes strains with LL-37, focusing on bacterial growth, cell surface alterations and pro-inflammatory responses. Bioscreen turbidity measurements of strain 5448 cultured in the presence or absence of LL-37 confirmed the poor antimicrobial effect, and revealed a significant increase in turbidity of bacterial cultures exposed to sub-inhibitory concentrations of LL-37. However, this was not linked to increased bacterial counts. Electron microscopy of LL-37-exposed bacteria revealed the presence of vesicle-like structures on the bacterial surface. The vesicles stained positive for LL-37 and were released from the bacterial surface. Concentrated supernatants enriched in these structures had a broader protein content, including several virulence factors, compared to supernatants from untreated bacteria. The supernatants from LL-37-exposed bacteria were pro-inflammatory and elicited resistin and myeloperoxidase release from neutrophils. This is the first report on S. pyogenes extracellular vesicle-like structures formed at the bacterial surface in response to LL-37. The associated increased pro-inflammatory activity further implicates LL-37 as a potential factor involved in S. pyogenes pathogenesis.
Molecular Pathology of Cryptorchidism-Induced Infertility
Authors: Docampo Maria José , Hadziselimovic Faruk
Published: December 2015

Cryptorchidism is the most common cause of non-obstructive azoospermia in man. In contrast to the general belief that temperature-dependent effects on the undescended gonad damage cryptorchid testes before sexual maturation is complete, molecular pathology strongly supports the theory that impaired mini-puberty is responsible for azoospermia and infertility in cryptorchidism. Molecular biological observations favor LH deficiency, with EGR4 as a master regulatory gene in Leydig cell dysgenesis, as the reason for impaired mini-puberty, and recent evidence supports the idea that infertility in cryptorchidism is a consequence of alterations in the Piwi pathway.
Germline Prolactin Receptor Mutation Is Not a Major Cause of Sporadic Prolactinoma in Humans
Authors: Bernard Valérie , Bouilly Justine , Beau Isabelle , Broutin Isabelle , Chanson Philippe , Young Jacques , Binart Nadine
Published: December 2015

Background/Aims: No genetic anomalies specifically predisposing humans to prolactinomas have so far been identified. The prolactin receptor (PRLR) is a good candidate, however, as Prlr knockout mice develop prolactinomas, and a case of familial hyperprolactinemia has been linked to PRLR mutation. The main objective of this study was to detect germline PRLR mutations in patients with sporadic prolactinomas unrelated to AIP or MEN1 mutation. Methods: We sequenced all PRLR exons and intron-exon junctions on genomic DNA from 88 patients with a median age of 24 years. Results: We identified 4 PRLR variations (p.Ile76Val, p.Ile146Leu, p.Glu108Lys and p.Glu554Gln) in 16 patients. One patient had the rare variant p.Glu554Gln in the heterozygous state. Another patient had the extremely rare p.Glu108Lys variant described here for the first time. The other 2 variants (p.Ile76Val and p.Ile146Leu) are relatively common in the general population. All these 4 variants have been functionally tested in vitro and have no effect on PRLR expression, localization and signaling after prolactin stimulation. Conclusion: Inactivating germline variations of PRLR are not associated with sporadic prolactinoma in this series. Nevertheless, somatic disruption of PRLR has not been excluded in this subset of pituitary tumors.
Siberia: Myths and Realities
Authors: Pereira N.G.O.
Published: December 2015

Janet Hartley’s Siberia: A History of The People is simultaneously a survey of the history of Siberia and its peoples from the 16th century to the present and a corrective to popular preconceptions. She succeeds on both counts for the most part, but more so for the first objective. Some of her conclusions with regard to the political history in particular are subject to closer scrutiny and possible objection. Nevertheless, the book is an important contribution to Siberian scholarship in English.
Recalling Russia’s Eighteenth Century: Imaginative Literature as Mnemonic Praxis
Authors: Zitser Ernest A.
Published: December 2015

This review article deals with Luba Golburt’s award-winning monograph on the literary treatment of Russia’s eighteenth century. After situating Golburt’s book within the context of recent publications on eighteenth-century Russian studies, the reviewer offers a summary of the pros and cons of the author’s methodological approach. The reviewer argues that The First Epoch constitutes a landmark contribution to both the ongoing reevaluation of early modern Russian history and to the scholarly study of the confluence between literary and mnemonic praxis.
Audiovisual Integration of Time-to-Contact Information for Approaching Objects
Authors: DeLucia Patricia R. , Preddy Doug , Oberfeld Daniel
Published: December 2015

Previous studies of time-to-collision (TTC) judgments of approaching objects focused on effectiveness of visual TTC information in the optical expansion pattern (e.g., visual tau, disparity). Fewer studies examined effectiveness of auditory TTC information in the pattern of increasing intensity (auditory tau), or measured integration of auditory and visual TTC information. Here, participants judged TTC of an approaching object presented in the visual or auditory modality, or both concurrently. TTC information provided by the modalities was jittered slightly against each other, so that auditory and visual TTC were not perfectly correlated. A psychophysical reverse correlation approach was used to estimate the influence of auditory and visual cues on TTC estimates. TTC estimates were shorter in the auditory than the visual condition. On average, TTC judgments in the audiovisual condition were not significantly different from judgments in the visual condition. However, multiple regression analyses showed that TTC estimates were based on both auditory and visual information. Although heuristic cues (final sound pressure level, final optical size) and more reliable information (relative rate of change in acoustic intensity, optical expansion) contributed to auditory and visual judgments, the effect of heuristics was greater in the auditory condition. Although auditory and visual information influenced judgments, concurrent presentation of both did not result in lower response variability compared to presentation of either one alone; there was no multimodal advantage. The relative weightings of heuristics and more reliable information differed between auditory and visual TTC judgments, and when both were available, visual information was weighted more heavily.
Sensitivity of Real-Data Simulations of the 3 May 1999 Oklahoma City Tornadic Supercell and Associated Tornadoes to Multimoment Microphysics. Part II: Analysis of Buoyancy and Dynamic Pressure Forces in Simulated Tornado-Like Vortices
Authors: Dawson Daniel T. , Xue Ming , Shapiro Alan , Milbrandt Jason A. , Schenkman Alexander D.
Published: December 2015

Vortex stretching by intense upward accelerations is a critical process for tornadogenesis and maintenance. Two high-resolution (250-m grid spacing) real-data simulations of the 3 May 1999 Oklahoma City, Oklahoma, supercell and associated tornadoes, using single- and triple-moment microphysics parameterization schemes, respectively, are examined. Microphysical, thermodynamic, and dynamic impacts on the vertical accelerations near and within simulated tornado-like vortices (TLVs) are analyzed. Systematic differences in behavior of the TLVS between the two experiments are found; the TLV in the triple-moment simulation is substantially more intense and longer lived than in the single-moment case. The triple-moment scheme in this case produces less rain and hail mass in the low levels and drop size distributions of rain shifted toward larger drops, relative to the single-moment scheme, leading to less latent cooling and warmer outflow. Trajectory analyses reveal that more parcels entering the TLV in the triple-moment simulation have a history of dynamically induced descent, whereas buoyantly driven descent is more prevalent in the single-moment experiment. It is found that the intensity and longevity of the TLV are tied to weaker negative or neutral thermal buoyancy in the air flowing into the TLV in the triple-moment case, consistent with previous observational and modeling studies. Finally, the contribution to buoyancy from pressure perturbations is found to be of prime importance within the TLV, where strong negative pressure perturbations lead to substantial positive buoyancy. This contribution compensates for the slight negative thermal buoyancy and negative dynamic pressure gradient acceleration in the triple-moment case.
Sensitivity Study on the Influence of Cloud Microphysical Parameters on Mixed-Phase Cloud Thermodynamic Phase Partitioning in CAM5
Authors: Tan Ivy , Storelvmo Trude
Published: December 2015

The influence of six CAM5.1 cloud microphysical parameters on the variance of phase partitioning in mixed-phase clouds is determined by application of a variance-based sensitivity analysis. The sensitivity analysis is based on a generalized linear model that assumes a polynomial relationship between the six parameters and the two-way interactions between them. The parameters, bounded such that they yield realistic cloud phase values, were selected by adopting a quasi–Monte Carlo sampling approach. The sensitivity analysis is applied globally, and to 20°-latitude-wide bands, and over the Southern Ocean at various mixed-phase cloud isotherms and reveals that the Wegener–Bergeron–Findeisen (WBF) time scale for the growth of ice crystals single-handedly accounts for the vast majority of the variance in cloud phase partitioning in mixed-phase clouds, while its interaction with the WBF time scale for the growth of snowflakes plays a secondary role. The fraction of dust aerosols active as ice nuclei in latitude bands, and the parameter related to the ice crystal fall speed and their interactions with the WBF time scale for ice are also significant. All other investigated parameters and their interactions with each other are negligible (<3%). Further analysis comparing three of the quasi–Monte Carlo–sampled simulations with spaceborne lidar observations by CALIOP suggests that the WBF process in CAM5.1 is currently parameterized such that it occurs too rapidly due to failure to account for subgrid-scale variability of liquid and ice partitioning in mixed-phase clouds.
Unforced Surface Air Temperature Variability and Its Contrasting Relationship with the Anomalous TOA Energy Flux at Local and Global Spatial Scales*
Authors: Brown Patrick T. , Li Wenhong , Jiang Jonathan H. , Su Hui
Published: December 2015

Unforced global mean surface air temperature () is stable in the long term primarily because warm anomalies are associated with enhanced outgoing longwave radiation () to space and thus a negative net radiative energy flux (, positive downward) at the top of the atmosphere (TOA). However, it is shown here that, with the exception of high latitudinal and specific continental regions, warm unforced surface air temperature anomalies at the local spatial scale [T(θ, ϕ), where (θ, ϕ) = (latitude, longitude)] tend to be associated with anomalously positive N(θ, ϕ). It is revealed that this occurs mainly because warm T(θ, ϕ) anomalies are accompanied by anomalously low surface albedo near sea ice margins and over high altitudes, low cloud albedo over much of the middle and low latitudes, and a large water vapor greenhouse effect over the deep Indo-Pacific.

It is shown here that the negative versus relationship arises because warm anomalies are associated with large divergence of atmospheric energy transport over the tropical Pacific [where the N(θ, ϕ) versus T(θ, ϕ) relationship tends to be positive] and convergence of atmospheric energy transport at high latitudes [where the N(θ, ϕ) versus T(θ, ϕ) relationship tends to be negative]. Additionally, the characteristic surface temperature pattern contains anomalously cool regions where a positive local N(θ, ϕ) versus T(θ, ϕ) relationship helps induce negative . Finally, large-scale atmospheric circulation changes play a critical role in the production of the negative versus relationship as they drive cloud reduction and atmospheric drying over large portions of the tropics and subtropics, which allows for greatly enhanced .
Climate Mechanism for Stronger Typhoons in a Warmer World*
Authors: Kang Nam-Young , Elsner James B.
Published: December 2015

Violent typhoons continue to have catastrophic impacts on economies and welfare, but how they are responding to global warming has yet to be fully understood. Here, an empirical framework is used to explain physically why observations support a tight connection between increasing ocean warmth and the increasing intensity of supertyphoons in the western North Pacific. It is shown that the energy needed for deep convection is on the rise with greater heat and moisture in the lower tropical troposphere but that this energy remains untapped when air pressure is high. Accordingly, tropical cyclone formation is becoming less common, but those that do form are likely to reach extreme intensities from the discharge of stored energy. These thermodynamic changes to the environment most significantly influence the upper portion of extreme typhoon intensities, indicating that supertyphoons are likely to be stronger at the expense of overall tropical cyclone occurrences in the western North Pacific.
Urban ‘Failures’: Municipal Governance, Planning and Power in Colonial Delhi, 1863–1910
Authors: Kishore Raghav
Published: December 2015

This article highlights the relationship between the ‘failures’ of municipal governance and the reproduction of its power in the colonial city. It examines the everyday operations of the Delhi Municipality between 1863 and 1910 and shows how the ‘failure’ to promote urban renewal actually provided ‘opportunities’ for the municipality’s own longevity. After the Rebellion of 1857, the Delhi Municipality was invested with a wide variety of powers to check sanitary offences and regulate building construction in Delhi. This article discusses how this very growth and centralisation of powers created severe challenges for the functions of the municipality. The growing complexity of its operations, recommendations of experts, costs of ambitious projects and resistance from city dwellers, it is suggested, constantly subverted municipal intentions. Yet, in bringing to light the ‘failure’ of municipal policies, this article will argue that failure was profoundly productive. Municipal ‘failure’ was always accompanied by the growth in its bureaucratic capabilities and regulatory powers.
Book Review: Rama Sundari Mantena, The Origins of Modern Historiography in India: Antiquarianism and Philology
Authors: Pandey Rakesh
Published: December 2015

Rama Sundari Mantena, The Origins of Modern Historiography in India: Antiquarianism and Philology, 1780–1880, New York: Palgrave Macmillan, 2012, pp. 261.
Book Review: Sekhar Bandyopadhyay, Decolonization in South Asia: Meanings of Freedom in Post-Independence West Bengal
Authors: Farooqui Amar
Published: December 2015

Sekhar Bandyopadhyay, Decolonization in South Asia: Meanings of Freedom in Post-Independence West Bengal, 1947–52, Abingdon: Routledge, 2009, pp. 246
Sustained corticosteroid- induced mania and psychosis despite cessation
Authors: Gable Mary , Depry Dwayne
Published: December 2015

Objective

Corticosteroids generally result in short-lasting neuropsychiatric symptoms following cessation, but the following case highlights an unusually long-lasting course of symptoms in a patient following near immediate cessation of medication, despite medication management and electroconvulsive therapy. The case presentation will be followed by a discussion of the presentation, treatment, and management of steroid-induced neuropsychiatric symptoms.

Methods

The patient was followed from symptom onset to resolution.

Results

The patient’s symptom course was unusually long and required a long course of multimodal therapy.

Conclusions

Corticosteroids are commonly used medications both in a wide variety of medical settings, and despite this, their neuropsychiatric effects are poorly understood. The affective and behavioral symptoms, in particular mania and psychosis, can be unpredictable and challenging to treat as in our patient, who developed a long-lasting psychotic episode on high-dose steroids despite discontinuation and treatment of nearly six months. This was despite having tolerated steroids multiple times in the past.
‘It felt like it was night all the time’: listening to the experiences of birth mothers whose children have been taken into care or adopted
Authors: Memarnia Nina , Nolte Lizette , Norris Clare , Harborne Alex
Published: December 2015

The child care literature consistently reports a lack of support for birth mothers following their child being taken into care or adopted. This is despite consistent evidence of the long-term consequences of the removal of children on their mental health. The aim of this study is to explore the effects of separation, the subsequent sense of identity and the experience of contact and support throughout the process. Semi-structured interviews were conducted with seven mothers recruited from birth mother support groups and the transcripts analysed using Interpretative Phenomenological Analysis (IPA). Four themes emerged: ‘no one in my corner’; disconnecting from emotion; renegotiating identity; and the children are gone but still here. The findings contribute to our understanding of the experiences of birth mothers whose children are removed from their care and are discussed within a range of psychological theories.
Potential and Prospects of Strengthening Transport Connectivity for Regional Economic Integration in Southern Asia
Authors: Kumar Nagesh
Published: December 2015

Despite geographical contiguity, Southern Asia remains among the least integrated sub-regions in the world. In the context of changed global context in the aftermath of the global financial crisis requiring the engines of growth to be rebalanced in favour of regional sources, inability to exploit the potential of regional economic integration and regional value chains can seriously limit the growth prospects of the sub-region. ESCAP analysis shows that while potential of intra-regional trade remains substantial, its exploitation is prevented by costs of trading within the sub-region which are often higher than trading with distant regions like the EU and North America, effectively denying the benefits of geographical proximity and contiguity to intra-regional trade. This situation is because of poorly developed surface transport networks and facilitation at the borders for mutual trade in the sub-region. This article reviews the key constraints on surface transport in the sub-region and makes a case for extended transport corridors that can maximize the network externalities while using the existing infrastructure optimally and benefiting the landlocked countries of the sub-region. It then highlights the relevance of two extended transport corridors—one a container train corridor and another a highway corridor proposed by UNESCAP—that can not only facilitate but have the potential to make the sub-region a hub of Asia–Europe trade. It is concluded with a few remarks on the way forward for a vision of transport connectivity in South Asia.