bluuebunny/crossref_metadata_2025 huggingface dataset:
Two in one or one in two? Pushing off from Jung with Wolfgang Giegerich
Authors: Saban Mark
Published: October 2015

This paper responds to a recent paper by Wolfgang Giegerich entitled ‘Two Jungs: apropos a paper by Mark Saban’. Giegerich disputes my assertion that the ‘rigorous notion’ at the heart of his psychology ‘finds no source in Jung's psychology, implicit or explicit’. In order to do this he posits the existence of two Jungs, an exoteric Jung and an esoteric Jung. The implications of Giegerich's binary scission of Jung are explored in this paper, and show that the tendency to exalt one Jung while disparaging the other betrays a comprehensive blindness toward the contradictory complexity of Jung's psychology as a whole. It is suggested that this blindness is the consequence of Giegerich's systematic prioritization of a neo‐Hegelian agenda that is in profound conflict with the telos of Jung's psychology.
Reflections on the Jungian nature of psychology as the discipline of interiority: a response to Saban's ‘Misunderstandings’
Authors: Hoedl John
Published: October 2015

Psychology as the discipline of interiority is the name of the psychology that has developed from Wolfgang Giegerich's work in the field of analytical psychology. This article offers a counterview to that of Mark Saban's claim that Giegerich's psychology is ‘irrelevant’ to Jungians today and is based on a fundamental misunderstanding of the nature of Jungian psychology. It will be shown that, in fact, it is a fundamental misunderstanding of Giegerich's work that has led Saban to form erroneous conclusions. Links between Jung's and Giegerich's conceptions of the ‘objective psyche’ will be highlighted, along with other examples of how, contrary to Saban's conclusions, psychology as the discipline of interiority has obvious connections to, and grounding in, Jungian psychology.
The effect of primary midwife‐led care on women's experience of childbirth: results from the COSMOS randomised controlled trial
Authors: McLachlan HL , Forster DA , Davey M‐A , Farrell T , Flood M , Shafiei T , Waldenström U
Published: October 2015

Objective

To determine the effect of primary midwife‐led care (‘caseload midwifery’) on women's experiences of childbirth.

Design

Randomised controlled trial.

Setting

Tertiary care women's hospital in Melbourne, Australia.

Population

A total of 2314 low‐risk pregnant women.

Methods

Women randomised to caseload care received antenatal, intrapartum and postpartum care from a primary midwife, with some care provided by a ‘back‐up’ midwife. Women in standard care received midwifery‐led care with varying levels of continuity, junior obstetric care or community‐based medical care.

Main outcome measures

The primary outcome of the study was caesarean section. This paper presents a secondary outcome, women's experience of childbirth. Women's views and experiences were sought using seven‐point rating scales via postal questionnaires 2 months after the birth.

Results

A total of 2314 women were randomised between September 2007 and June 2010; 1156 to caseload and 1158 to standard care. Response rates to the follow‐up questionnaire were 88 and 74%, respectively. Women in the caseload group were more positive about their overall birth experience than women in the standard care group (adjusted odds ratio 1.50, 95% CI 1.22–1.84). They also felt more in control during labour, were more proud of themselves, less anxious, and more likely to have a positive experience of pain.

Conclusions

Compared with standard maternity care, caseload midwifery may improve women's experiences of childbirth.

Tweetable abstract

Primary midwife‐led care (‘caseload midwifery’) improves women's experiences of childbirth.
Democracy prevention: The international collaboration of authoritarian regimes
Authors: von Soest Christian
Published: October 2015

Current scholarship increasingly argues that international factors and, more specifically, authoritarian collaboration fundamentally affect the persistence of authoritarian rule. In order to generate a better understanding of the nature and effects of these international dimensions of authoritarianism, this article provides a conceptual framework for various aspects of authoritarian collaboration to prevent democracy, particularly the relationship between authoritarian regime types and their international democracy‐prevention policies. It differentiates between authoritarian diffusion, learning, collaboration and support, as well as between deliberate efforts to avert democracy and efforts not explicitly geared towards strengthening autocracy. The article further distinguishes between crisis events and normal conditions where authoritarian rulers' hold on power is not in danger. It is argued that authoritarian powers' motivations to provide support to fellow autocrats are self‐serving rather than driven by an ideological commitment to creating an ‘authoritarian international’: authoritarian rulers first and foremost strive to maximise their own survival chances by selectively supporting acquiescent authoritarian regimes, maintaining geostrategic control and fostering their developmental goals.
Hidden insurance in a moral‐hazard economy
Authors: Bertola Giuseppe , Koeniger Winfried
Published: October 2015

We analyze the general equilibrium of an economy in which a competitive industry produces nonexclusive insurance services. The equilibrium is inefficient because insurance contracts cannot control moral hazard, and welfare can be improved by policies that reduce insurance by increasing its price above marginal cost. We discuss how insurance production costs that exceed expected claim payments interact with moral hazard in determining the equilibrium's inefficiency, and show that these costs can make insurance premia so actuarially unfair as to validate the standard first‐order conditions we exploit in our analysis.
Sequential procurement auctions and their effect on investment decisions
Authors: Cisternas Gonzalo , Figueroa Nicolás
Published: October 2015

We characterize the optimal mechanism and investment level in an environment where (i) two projects of independent costs are purchased sequentially, (ii) the buyer can commit to a two‐period mechanism, and (iii) the winner of the first project can invest in a cost‐reducing technology between auctions. We show that, in an attempt to induce more competition in the first period, the optimal mechanism gives an advantage to the first‐period winner in the second auction. As a result of this advantage, the first‐period winner invests more than the socially efficient level. Optimal advantages, therefore, create two different channels for cost minimization in buyer‐supplier relationships.
Anembryonic Gestation in Wild South American Sea Lion, Otaria flavescens
Authors: Grandi M. F. , Crespo E. A. , Dans S. L.
Published: October 2015

We present the first record and description of an anembryonic gestation in a wild South America sea lion, Otaria flavescens (Carnivora, Pinniped). This is the first report of an anembryonic gestation in a wild marine mammal species. This description furthers the knowledge of general aspects of the reproduction of an otariid species, which presents the particularities of delayed implantation and polygynic breeding system, and adds information on a reproductive abnormality in marine mammals.
Alterations in ductus venosus velocity indices in relation to umbilical venous pulsations and perinatal outcome
Authors: Dahlbäck Charlotte , Myren Ola Øra , Gudmundsson Saemundur
Published: October 2015

Introduction

Abnormal blood velocity in the ductus venosus is more frequently detected than pulsations in the umbilical vein, but both are considered to be indicators of fetal compromise. The aim of this study was to investigate blood flow patterns in the ductus venosus and the association between individual blood velocity ratios and pulsations in the umbilical vein and perinatal outcome.

Material and methods

Retrospective cohort study on Doppler ultrasound examination of ductus venosus and umbilical venous blood velocity in 358 high‐risk pregnancies. Ductus venosus blood velocity pattern was analyzed for pulsatility index and the following velocity ratios: S/ES, S/a and ES/a (where S is systole, ES is end‐systole, and a is atrial contraction). Ductus venosus ratio z‐scores were calculated and related to pulsations in the umbilical vein and adverse perinatal outcome.

Results

Systolic ratios in the ductus venosus were less frequently abnormal than ratios taking into account diastolic velocities, particularly at full‐term. High S/ES, ES/a ratios and pulsatility index (z‐score >2), were all related to presence of pulsations in the umbilical vein. Umbilical venous pulsations were the best indicator of adverse perinatal outcome.

Conclusions

Changes in ductus venosus blood flow during systole occur more rarely than diastolic changes, and alterations in end‐diastolic blood velocity in the ductus venosus might give false‐positive indications of worsening fetal condition. Umbilical venous pulsations seem to better predict adverse outcome of pregnancy than do indices in the ductus venosus.
Semiparametric Methods to Contrast Gap Time Survival Functions: Application to Repeat Kidney Transplantation
Authors: Shu Xu , Schaubel Douglas E.
Published: October 2015

Times between successive events (i.e., gap times) are of great importance in survival analysis. Although many methods exist for estimating covariate effects on gap times, very few existing methods allow for comparisons between gap times themselves. Motivated by the comparison of primary and repeat transplantation, our interest is specifically in contrasting the gap time survival functions and their integration (restricted mean gap time). Two major challenges in gap time analysis are non-identifiability of the marginal distributions and the existence of dependent censoring (for all but the first gap time). We use Cox regression to estimate the (conditional) survival distributions of each gap time (given the previous gap times). Combining fitted survival functions based on those models, along with multiple imputation applied to censored gap times, we then contrast the first and second gap times with respect to average survival and restricted mean lifetime. Large-sample properties are derived, with simulation studies carried out to evaluate finite-sample performance. We apply the proposed methods to kidney transplant data obtained from a national organ transplant registry. Mean 10-year graft survival of the primary transplant is significantly greater than that of the repeat transplant, by 3.9 months (), a result that may lack clinical importance.
Surface air plasma-induced cell death and cytokine release of human keratinocytes in the context of psoriasis
Authors: Zhong S.Y. , Dong Y.Y. , Liu D.X. , Xu D.H. , Xiao S.X , Chen H.L. , Kong M.G.
Published: October 2015

Background

Cold atmospheric plasma (CAP) has shown promise for wound healing, although little is understood of the underpinning mechanisms. Little has been reported so far of its potential use in the treatment of immune-mediated diseases such as psoriasis.

Objectives

To study CAP-induced cell death and cytokine release in human keratinocytes as a first assessment of possible CAP use for psoriasis.

Methods

Using a CAP generator free of energetic ions, we observed its effects on keratinocytes in terms of morphology, cell viability and apoptosis, intracellular and mitochondrial reactive oxygen species (ROS), lysosomal integrity and mitochondrial membrane potential; and on secretion and expression of eight cytokines at protein and gene levels.

Results

CAP-induced reduced cell viability, apoptotic death and production of intracellular and mitochondrial ROS in dose-dependent manner. Mitochondrial dysfunction and lysosomal leakage were found in CAP-treated cells. It also induced release of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), and enhanced the mRNA expression of IL-1β, IL-6, IL-8, IL-10, TNF-α, interferon-γ and VEGF. By contrast, IL-12 declined monotonically.

Conclusions

The results suggest that with appropriate control of its dose, physical plasma could induce cell death via apoptotic pathways and enable simultaneous reduction in IL-12. These effects may be used to suppress keratinocyte hyperproliferation and to target T-cell activation to control amplification of inflammation. This provides an initial basis for further studies of CAP as a potential therapeutic option for inflammatory and immune-related diseases in dermatology, including psoriasis.
CpG oligodeoxynucleotides potentiate the antitumor activity of anti‐BST2 antibody
Authors: Hiramatsu Kosuke , Serada Satoshi , Kobiyama Kouji , Nakagawa Satoshi , Morimoto Akiko , Matsuzaki Shinya , Ueda Yutaka , Fujimoto Minoru , Yoshino Kiyoshi , Ishii Ken J. , Enomoto Takayuki , Kimura Tadashi , Naka Tetsuji
Published: October 2015

Numerous monoclonal antibodies (mAb) targeting tumor antigens have recently been developed. Antibody‐dependent cellular cytotoxicity (ADCC) and antibody‐dependent cellular phagocytosis (ADCP) via effector cells such as tumor‐infiltrating natural killer (NK) cells and macrophages are often involved in mediating the antitumor activity of mAb. CpG oligodeoxynucleotides (ODN) have a potent antitumor activity and are considered to increase tumor infiltration of NK cells and macrophages. Our group previously reported significant antitumor activity of anti‐bone marrow stromal antigen 2 (BST2) mAb against BST2‐positive endometrial cancer cells through ADCC. In this study, we evaluated the synergistic antitumor activity of combination therapy with anti‐BST‐2 mAb and CpG ODN using SCID mice and elucidated the mechanisms underlying this activity. Anti‐BST2 mAb and CpG ODN monotherapy had a significant dose‐dependent antitumor activity (P = 0.0135 and P = 0.0196, respectively). Combination therapy with anti‐BST2 mAb and CpG ODN had a significant antitumor activity in SCID mice (P < 0.01), but not in NOG mice. FACS analysis revealed significantly increased numbers of NK cells and macrophages in tumors treated with a combination of anti‐BST2 mAb and CpG ODN and with CpG ODN alone in SCID mice (P < 0.05 and P < 0.01, respectively). These results suggested that the combination therapy with anti‐BST2 mAb and CpG ODN has a significant antitumor activity and induces tumor infiltration of NK cells and macrophages. Combination therapy with CpG ODN and anti‐BST2 mAb or other antitumor mAb depending on ADCC may represent a new treatment option for cancer.
How does human T‐lymphotropic virus type 1 cause central nervous system disease? The importance of cross‐talk between infected T cells and astrocytes
Authors: Yamano Yoshihisa
Published: October 2015

Human T‐lymphotropic virus type 1 (HTLV‐1) can cause HTLV‐1‐associated myelopathy/tropical spastic paraparesis and adult T cell leukemia/lymphoma. The main feature of HTLV‐1‐associated myelopathy/tropical spastic paraparesis pathogenesis is a virus‐induced hyperactive immune response that causes chronic inflammation in the central nervous system (CNS), but the question remains: what is the mechanism by which HTLV‐1 deregulates the immune response and induce chronic inflammation? While T cell infiltrates in the CNS include HTLV‐1‐infected cells, HTLV‐1 does not appear to infect the neuronal cells themselves. It has been established that HTLV‐1 is a unique virus that mainly infects CD4+ helper T cells. We recently showed that HTLV‐1 heavily infects CCR4+ cells, which are known to include regulatory T cells. We showed that HTLV‐1 induces a Th1‐like state in these CCR4+ cells through T‐bet expression. We have also found that CXCL10 plays an important role in a positive feedback loop that maintains inflammation in the CNS. Astrocytes, which were shown to be the main producers of CXCL10 in the CNS, are another key player in the loop. To complete the picture, we showed that the infected CCR4+ Th1‐like T cells produce interferon‐γ, which is what stimulates astrocytes to produce CXCL10. Now we have a much better understanding of the molecular mechanisms at play in HTLV‐1‐associated myelopathy/tropical spastic paraparesis pathogenesis, and clearly CCR4+ cells are a significant contributor to the inflammatory pathways. Thus, we are currently carrying out a phase I/IIa clinical trial to test the effects and safety of a therapy that uses antibody‐dependent cell‐mediated cytotoxicity to target CCR4+ cells.
Environmental Objects for Authoring Procedural Scenes
Authors: Grosbellet Francois , Peytavie Adrien , Guérin Éric , Galin Éric , Mérillou Stéphane , Benes Bedrich
Published: October 2015

We propose a novel approach for authoring large scenes with automatic enhancement of objects to create geometric decoration details such as snow cover, icicles, fallen leaves, grass tufts or even trash. We introduce environmental objects that extend an input object geometry with a set of procedural effects that defines how the object reacts to the environment, and by a set of scalar fields that defines the influence of the object over of the environment. The user controls the scene by modifying environmental variables, such as temperature or humidity fields. The scene definition is hierarchical: objects can be grouped and their behaviours can be set at each level of the hierarchy. Our per object definition allows us to optimize and accelerate the effects computation, which also enables us to generate large scenes with many geometric details at a very high level of detail. In our implementation, a complex urban scene of 10 000 m2, represented with details of less than 1 cm, can be locally modified and entirely regenerated in a few seconds.
Coordinated Crowd Simulation With Topological Scene Analysis
Authors: Barnett Adam , Shum Hubert P. H. , Komura Taku
Published: October 2015

This paper proposes a new algorithm to produce globally coordinated crowds in an environment with multiple paths and obstacles. Simple greedy crowd control methods easily lead to congestion at bottlenecks within scenes, as the characters do not cooperate with one another. In computer animation, this problem degrades crowd quality especially when ordered behaviour is needed, such as soldiers marching towards a castle. Similarly, in applications such as real‐time strategy games, this often causes player frustration, as the crowd will not move as efficiently as it should. Also, planning of building would usually require visualization of ordered evacuation to maximize the flow. Planning such globally coordinated crowd movement is usually labour intensive. Here, we propose a simple solution that is easy to use and efficient in computation. First, we compute the harmonic field of the environment, taking into account the starting points, goals and obstacles. Based on the field, we represent the topology of the environment using a Reeb Graph, and calculate the maximum capacity for each path in the graph. With the harmonic field and the Reeb Graph, path planning of crowd can be performed using a lightweight algorithm, such that any blocking of one another's paths is minimized. Comparing to previous methods, our system can synthesize globally coordinated crowd with smooth and efficient movement. It also enables control of the crowd with high‐level parameters such as the degree of cooperation and congestion. Finally, the method is scalable to thousands of characters with minimal impact to computation time. It is best applied in interactive crowd synthesis systems such as animation designs and real‐time strategy games.
Comparison of heuristic approaches to the generalized tree alignment problem
Authors: Ford Eric , Wheeler Ward C.
Published: October 2015

Two commonly used heuristic approaches to the generalized tree alignment problem are compared in the context of phylogenetic analysis of DNA sequence data. These approaches, multiple sequence alignment + phylogenetic tree reconstruction (MSA+TR) and direct optimization (DO), are alternative heuristic procedures used to approach the nested NP‐Hard optimizations presented by the phylogenetic analysis of unaligned sequences under maximum parsimony. Multiple MSA+TR implementations and DO were compared in terms of optimality score (phylogenetic tree cost) over multiple empirical and simulated datasets with differing levels of heuristic intensity. In all cases examined, DO outperformed MSA+TR with average improvement in parsimony score of 14.78% (5.64–52.59%).
Predictors of low diabetes risk perception in a multi‐ethnic cohort of women with gestational diabetes mellitus
Authors: Mukerji G. , Kainth S. , Pendrith C. , Lowe J. , Feig D. S. , Banerjee A. T. , Wu W. , Lipscombe L. L.
Published: October 2015

Aim

To determine what proportion of women with gestational diabetes underestimate their diabetes risk and identify factors associated with low diabetes risk perception.

Methods

Participants included pregnant adult women with gestational diabetes between 2009 and 2012 across seven diabetes clinics in Ontario, Canada. Data were collected through chart review and a survey that included a diabetes risk perception question.

Results

Of the 614 of 902 women (68% response rate) with gestational diabetes, 89% correctly responded that gestational diabetes increases the risk for developing diabetes. However, 47.1% of women perceived themselves to be at low risk for developing diabetes within 10 years. On multivariable analysis, BMI < 25 kg/m2, absent previous gestational diabetes history, absent diabetes family history and absent insulin use were appropriately associated with low diabetes risk perception. However, compared with Caucasian ethnicity, high‐risk ethnicity (Aboriginal, Latin American, West Indian, South Asian, Middle Eastern, Filipino, Black, Pacific Islander) [odds ratio (OR) 2.07; 95% CI 1.30–3.31] and East and South East Asian ethnicity (OR 2.01; 1.10–3.67) were associated with low diabetes risk perception. After further adjustment for immigration, only high‐risk ethnicity remained a predictor of low diabetes risk perception (OR 1.86; 1.09–3.19), whereas East and South East Asian ethnicity did not (OR 1.67; 0.86–3.22).

Conclusions

Although the majority of women recognized gestational diabetes as a risk factor for diabetes, almost half underestimated their personal high diabetes risk despite prenatal care. Furthermore, women from high‐risk ethnic groups were more likely to underestimate their risk, even after adjusting for immigration. Interventions tailored to these groups are necessary to enhance perceived diabetes risk.
Giant Hydatid Cyst of the Interventricular Septum
Authors: Parakh Neeraj , Jagia Priya , Hote Milind , Arava Sudhir
Published: October 2015

Mini‐Abstract

This case illustrates one of the largest reported hydatid cyst of the interventricular septum that almost obliterated both ventricular cavities. Diagnosis of hydatid cyst was confirmed on echocardiography, cardiac MRI, CT chest, and postoperative histopathology.
Effects of reduced summer flows on the brook trout population and temperatures of a groundwater‐influenced stream
Authors: Nuhfer Andrew J. , Zorn Troy G. , Wills Todd C.
Published: October 2015

Withdrawal of water from streams and groundwater is increasing in Midwestern North America and is a potential threat to coldwater fishes. We examined the effects of summer water withdrawals on brook trout Salvelinus fontinalis populations and water warming rates by diverting 50–90% of summer baseflow from a 602‐m treatment zone (TZ) in a groundwater‐influenced Michigan stream during 1991–1998. We compared density of brook trout in fall, and spring‐to‐fall growth and survival of brook trout, between the TZ and an adjacent reference zone (RZ) whose flows were not altered. Flow reductions had no significant effects on the density of brook trout in fall or spring‐to‐fall survival of brook trout. However, spring‐to‐fall growth of brook trout in the TZ declined significantly when 75% flow reductions occurred. Cold upstream temperatures and the relatively short study reach kept thermal habitat conditions excellent for brook trout in the TZ throughout the dewatering experiments. These findings suggest that brook trout can tolerate some seasonal loss of physical habitat if temperature conditions remain suitable. In summer 1999, we experimentally assessed the influence of flow reduction on the warming rate through the TZ by diverting from 0% to 90% of flow around the TZ in 3‐ or 4‐day trials on a randomised schedule. Average daily temperature increased exponentially as stream flows declined from normal summer levels. Our findings suggest the risk of trout habitat loss from dewatering is potentially large and proportional to the magnitude of withdrawal, especially as thermal conditions approach critical levels for trout.
Are lampreys homebodies? Studying ammocoetes with open population models
Authors: Evans Thomas M
Published: October 2015

Larval lampreys (ammocoetes) are assumed to be sedentary and have restricted movements, but their movement is still poorly understood. Using elastomer implants, ammocoetes of two different species of lampreys (Lethenteron appendix and Petromyzon marinus) in two streams were tagged with permanent, unique marks (N = 1035) and resampled once a month from June 2014 until October 2014. Some individuals were recaptured during every sampling event (N = 3, 0.3%). However, most animals were never recaptured after being tagged (N = 700, 67%) or were captured only once (N = 213, 21%). The apparent survival (ϕ) varied in response to time and grouping variables at both sites (0.25–0.86), but the probability of capture (P) did not vary as much (0.41–0.85). Differences were detected between sites, with ϕ being higher for L. appendix at Dyke Creek, a Genesee River tributary. Whether differences were caused by site‐specific details or species differences is unclear. At Dyke Creek, where age could be partially established from length‐frequency histograms, ϕ was higher for 1 year old than for older animals. At Oquaga Creek (where P. marinus were captured), ϕ was highly variable (0.11–0.72) and was lowest in the fall sampling (September–October). The P was similar at both sites (0.5–0.6) and across times and groups, even when it was significant to the model. Understanding the movement of ammocoetes will help conserve and control lampreys.
Abundance and generalisation in mutualistic networks: solving the chicken‐and‐egg dilemma
Authors: Fort Hugo , Vázquez Diego P. , Lan Boon Leong
Published: October 2015

A frequent observation in plant–animal mutualistic networks is that abundant species tend to be more generalised, interacting with a broader range of interaction partners than rare species. Uncovering the causal relationship between abundance and generalisation has been hindered by a chicken‐and‐egg dilemma: is generalisation a by‐product of being abundant, or does high abundance result from generalisation? Here, we analyse a database of plant–pollinator and plant–seed disperser networks, and provide strong evidence that the causal link between abundance and generalisation is uni‐directional. Specifically, species appear to be generalists because they are more abundant, but the converse, that is that species become more abundant because they are generalists, is not supported by our analysis. Furthermore, null model analyses suggest that abundant species interact with many other species simply because they are more likely to encounter potential interaction partners.
Evaluating Content Alignment in Computerized Adaptive Testing
Authors: Wise Steven L. , Kingsbury G. Gage , Webb Norman L.
Published: October 2015

The alignment between a test and the content domain it measures represents key evidence for the validation of test score inferences. Although procedures have been developed for evaluating the content alignment of linear tests, these procedures are not readily applicable to computerized adaptive tests (CATs), which require large item pools and do not use fixed test forms. This article describes the decisions made in the development of CATs that influence and might threaten content alignment. It outlines a process for evaluating alignment that is sensitive to these threats and gives an empirical example of the process.
Reliability, Dimensionality, and Internal Consistency as Defined by Cronbach: Distinct Albeit Related Concepts
Authors: Davenport Ernest C. , Davison Mark L. , Liou Pey‐Yan , Love Quintin U.
Published: October 2015

This article uses definitions provided by Cronbach in his seminal paper for coefficient α to show the concepts of reliability, dimensionality, and internal consistency are distinct but interrelated. The article begins with a critique of the definition of reliability and then explores mathematical properties of Cronbach's α. Internal consistency and dimensionality are then discussed as defined by Cronbach. Next, functional relationships are given that relate reliability, internal consistency, and dimensionality. The article ends with a demonstration of the utility of these concepts as defined. It is recommended that reliability, internal consistency, and dimensionality each be quantified with separate indices, but that their interrelatedness be recognized. High levels of unidimensionality and internal consistency are not necessary for reliability as measured by α nor, more importantly, for interpretability of test scores.
Monitoring the John Cunningham virus throughout natalizumab treatment in multiple sclerosis patients
Authors: Domínguez‐Mozo M. I. , García‐Montojo M. , Arias‐Leal A. , García‐Martínez Á. , Santiago J. L. , Casanova I. , Galán V. , Arroyo R. , Fernández‐Arquero M. , Alvarez‐Lafuente R.
Published: October 2015

Background and purpose

Progressive multifocal leukoencephalopathy (PML) cases have arisen amongst multiple sclerosis patients treated with natalizumab. Our objective was to gain a better understanding of the mechanisms that underlie the John Cunningham virus (JCV) infection which causes PML.

Methods

A study was made of (i) the quarterly JCV DNA levels in peripheral blood mononuclear cells (PBMCs), serum and urine samples in 100 multiple sclerosis patients during their natalizumab treatment (3–39 months), (ii) the association between human leukocyte antigen (HLA) class II and the previous viral detection and (iii) the identification of the JCV variants in those patients suspected of having PML.

Results

(i) JCV DNA in PBMCs and/or serum was detected in 23% of our cohort. Patients with an intermittent JCV excretion in urine had a significant increase of the viral load and prevalence in this compartment during natalizumab treatment. (ii) The frequency of the DRB1*07/DQA1*02:01/DQB1*02:02 haplotype tended to be higher in patients with detectable versus undetectable JCV DNA in PBMCs (Pcorrected = 0.108). (iii) The variants in PBMCs and serum of the non‐PML patient matched the archetype. In the patient with non‐fatal PML, the archetype and the same neurotropic variant in PBMCs, serum and cerebrospinal fluid was identified at the time PML was diagnosed, whereas in the patient with a worse PML prognosis, four neurotropic variants in the three previous compartments were found by the PML diagnosis.

Conclusions

The detection of the neurotropic variant in blood during natalizumab treatment could be critical in the prevention of the development of severe PML, since this variant appears simultaneously with the clinical symptoms of PML and mutates quickly.
Relationship between ultrasonographic nerve morphology and severity of diabetic sensorimotor polyneuropathy
Authors: Arumugam T. , Razali S. N. O. , Vethakkan S. R. , Rozalli F. I. , Shahrizaila N.
Published: October 2015

Background and purpose

In the current study, the aim was to characterize the nerve ultrasound cross‐sectional areas (CSAs) of type 2 diabetic patients with diabetic sensorimotor polyneuropathy (DSP) of different severities.

Methods

A hundred symptomatic DSP patients and 40 age‐matched healthy controls were prospectively recruited. DSP severity was ascertained through the Toronto Clinical Scoring System (TCCS). Nerve electrophysiology and ultrasound were performed on both lower limbs and the non‐dominant upper limb.

Results

The sural nerve was inexcitable in 19.1% of mild, 40.0% of moderate and 69.0% of severe DSP groups. In contrast, CSAs were measurable in all nerves of DSP patients and were significantly larger compared to controls. Patients with severe DSP had significantly larger ulnar, peroneal, tibial and sural nerves compared to mild DSP patients. By receiver operating characteristic curve analysis, the cut‐off value for the sural nerve at 2 mm2 was a good discriminator (area under the curve 0.88) between the presence and absence of DSP (sensitivity 0.90; specificity 0.74) but performed less well in discriminating between the severity of DSP (cut‐off 2.75 mm2; area under the curve 0.62; sensitivity 0.59; specificity 0.73). Significant correlations were demonstrated between TCSS scores, most neurophysiology parameters and CSAs of the ulnar, peroneal, tibial and sural nerves.

Conclusion

Nerve ultrasound in DSP reveals enlarged CSAs and these changes worsen with increasing disease severity, thus serving as a useful diagnostic tool especially when neurophysiology is unrevealing.
Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication
Authors: Verrotti A. , Laino D. , Rinaldi V. E. , Suppiej A. , Giordano L. , Toldo I. , Margari L. , Parisi P. , Rizzo R. , Matricardi S. , Cusmai R. , Grosso S. , Gaggero R. , Zamponi N. , Pavone P. , Capovilla G. , Rauchenzauner M. , Cerminara C. , Di Gennaro G. , Esposito M. , Striano P. , Savasta S. , Coppola G. , Siliquini S. , Operto F. , Belcastro V. , Ragona F. , Marseglia G. L. , Spalice A.
Published: October 2015

Background and purpose

Our aim was to describe the clinical and electrical features and the long‐term evolution of childhood occipital epilepsy of Gastaut (COE‐G) in a cohort of patients and to compare long‐term prognosis between patients with and without other epileptic syndromes.

Methods

This was a retrospective analysis of the long‐term outcome of epilepsy in 129 patients withCOE‐G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1−23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome.

Results

Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolatedCOE‐G; group B with other epileptic syndromes associated withCOE‐G. The most significant (P< 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow‐up, the percentage of seizure‐free patients was significantly higher in group A than in group B.

Conclusions

Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typicalCOE‐G symptoms with other types of seizure could be related to a poor epilepsy outcome.
Peripheral neuropathy associated with levodopa–carbidopa intestinal infusion: a long‐term prospective assessment
Authors: Merola A. , Romagnolo A. , Zibetti M. , Bernardini A. , Cocito D. , Lopiano L.
Published: October 2015

Background and purpose

Subacute and chronic peripheral neuropathies (PNP) have been reported in Parkinson's disease (PD) patients treated with levodopa/carbidopa intestinal gel infusion (LCIG), although several aspects of their incidence and pathogenesis still remain to be clarified. This study main objective is to prospectively report the 2‐year incidence of PNP in patients treated with LCIG.

Methods and results

The clinical, hematological, nutritional and electrophysiological assessments of 33 consecutive patients have been prospectively collected and evaluated. At baseline (before the start of LCIG therapy), 3/33 (9%) patients showed symptomatic PNP and 7/33 (21%) subclinical PNP. During a follow‐up of 24.36 ± 12.18 months, 2/23 patients with normal baseline clinical‐electrophysiological assessment developed a subacute PNP, 2/23 developed a chronic PNP and 7/23 developed a subclinical PNP. LCIG was immediately halted in the subacute cases, while the infusion therapy was not interrupted in chronic and subclinical forms. All PNP were supplemented with vitamin B1 and B12, showing a clinical improvement and/or substantial stability at the following evaluations. Higher levodopa‐equivalent daily dose (P: 0.024) and homocysteine levels (P: 0.041) were found in chronic PNP, while no correlations were observed with vitamin B12, folate and UPDRS values. A trend towards BMI reduction was observed in both PNP and unaffected subjects and one patient developed a symptomatic PNP associated with a relevant weight loss.

Conclusions

Serial clinical‐electrophysiological evaluations are mandatory in patients treated with LCIG, given the possible risk of subacute and chronic PNP. No clear causative factors has been recognized in the subacute forms, whilst homocysteine‐mediated neurotoxicity seems to underlie the pathogenesis of chronic forms.
Geographies of Flexible Citizenship
Authors: Studemeyer Catherine Cottrell
Published: October 2015

This article provides an overview of the literature on “flexible citizenship,” a concept of the ways in which people seek out and use multiple citizenships to navigate transnational geographies for securing lifestyles and maximizing potential opportunities in a dynamic interconnected world. I argue that in order to deepen our understanding of the ways in which individuals perceive and use their citizenship(s) to “respond fluidly and opportunistically” to the constantly changing contemporary world, we need to broaden our approach to flexible citizenship, understanding it as both a “logic of capitalist accumulation” (Ong, , p. 6) as well as a logic of pursuing less tangible, less quantifiable life goals relating to lifestyle, identity, and everyday practices. First, I review the developments in theoretical approaches to citizenship in recent decades, exploring the importance of flexibility to understanding citizenship in contemporary contexts. I continue by highlighting selected studies that demonstrate how flexible understandings of citizenship are used to accumulate capital for the purpose of mitigating against economic and political uncertainty. I conclude by exploring newer research on the ways in which flexible citizenship can include other logics than those of financial and political security and how combining these two perspectives of flexible citizenship can advance our understandings of citizenship, transnationalism, and identity in a global and globalizing world.
Ex vivo construction of a novel model of bioengineered bladder mucosa: A preliminary study
Authors: Jaimes‐Parra Boris D , Valle‐Díaz de la Guardia Francisco , Arrabal‐Polo Miguel Á , Herrera‐Imbroda Bernardo , Lara María F , Machuca‐Santa‐Cruz Francisco‐Javier , Campos Antonio , Alaminos Miguel , Crespo Pascual V , Garzón Ingrid
Published: October 2015

Objective

To generate and to evaluate ex vivo a novel model of bioengineered human bladder mucosa based on fibrin‐agarose biomaterials.

Methods

We first established primary cultures of stromal and epithelial cells from small biopsies of the human bladder using enzymatic digestion and selective cell culture media. Then, a bioengineered substitute of the bladder lamina propria was generated using cultured stromal cells and fibrin‐agarose scaffolds, and the epithelial cells were then subcultured on top to generate a complete bladder mucosa substitute. Evaluation of this substitute was carried out by cell viability and histological analyses, immunohistochemistry for key epithelial markers and transmission electron microscopy.

Results

The results show a well‐configured stroma substitute with a single‐layer epithelium on top. This substitute was equivalent to the control bladder mucosa. After 7 days of ex vivo development, the epithelial layer expressed pancytokeratin, and cytokeratins CK7, CK8 and CK13, as well as filaggrin and ZO‐2, with negative expression of CK4 and uroplakin III. A reduction of the expression of CK8, filaggrin and ZO‐2 was found at day 14 of development. An immature basement membrane was detected at the transition between the epithelium and the lamina propria, with the presence of epithelial hemidesmosomes, interdigitations and immature desmosomes.

Conclusions

The present results suggest that this model of bioengineered human bladder mucosa shared structural and functional similarities with the native bladder mucosa, although the epithelial cells were not fully differentiated ex vivo. We hypothesize that this bladder mucosa substitute could have potential clinical usefulness after in vivo implantation.
Validation of an educational program balancing surgeon training and surgical quality control during robot‐assisted radical prostatectomy
Authors: Fujimura Tetsuya , Menon Mani , Fukuhara Hiroshi , Kume Haruki , Suzuki Motofumi , Yamada Yuta , Niimi Aya , Nakagawa Tohru , Igawa Yasuhiko , Homma Yukio
Published: October 2015

Objectives

To establish a mentoring program that allows novice surgeons to use robotics while maintaining surgical quality during robot‐assisted radical prostatectomy.

Methods

A total of 242 cases of robot‐assisted radical prostatectomy for patients with localized prostate cancer were considered for this study. Each novice surgeon carried out a step‐by‐step robot‐assisted radical prostatectomy procedure by following technical checkpoints and time limits that were established on the basis of previous surgical performance by a mentor. If technical checkpoints could not be accomplished, or the times were being exceeded, a mentor replaced the novice surgeon to finish the operative step or the surgery. Furthermore, if total blood loss exceeded 500 mL, a mentor completed the surgery. The primary end‐point was the number of cases required for a new surgeon to successfully complete the entire robot‐assisted radical prostatectomy procedure. Clinicopathological outcomes and any cases that deviated more than the standard deviation were also analyzed.

Results

Median patient age, serum prostate‐specific antigen level (ng/mL), and Gleason score at diagnosis were 68 years, 7.6 and 7, respectively. Mean console and total operative times were 184 and 237 min, respectively. Mean perioperative blood loss was 300 mL. Seven out of eight new surgeons finished the total procedure after 10.7 cases (range 8–12). Four cases (1.7%) exceeded perioperative total blood loss and operative time. Positive surgical margin rates for total, T2, and T3 were 22, 9.3 and 47%, respectively. Positive surgical margin localized at bladder neck 19%, lateral lobe 39%, apex 32% and peripheral fat 9.4%.

Conclusions

Herein we demonstrate an institutional mentoring program that effectively balances surgeon robot‐assisted radical prostatectomy training and surgical quality control.
Regulatory T‐cell neutralization in mice during filariasis helps in parasite clearance by enhancing T helper type 17‐mediated pro‐inflammatory response
Authors: Pathak Manisha , Sharma Pankaj , Sharma Aditi , Verma Meenakshi , Srivastava Mrigank , Misra‐Bhattacharya Shailja
Published: October 2015

Lymphatic filariasis leads to profound impairment of parasite‐specific T helper type 1 (Th1) and Th2 immune responses and significantly increases the expression of regulatory networks and regulatory effectors like transforming growth factor‐β, CD25, cytotoxic T‐lymphocyte antigen 4, glucocorticoid‐induced tumour necrosis factor receptor (GITR) and regulatory T (Treg) cells, which together play an important role in immunosuppression. While Treg cells suppress the activity of effector cells, monocyte dysfunction, characterized by an alternatively activated immunoregulatory phenotype, is one hypothesis that explains the lack of an antigen‐specific T‐cell response in infected individuals. In the present study, we administered neutralizing antibodies against the Treg cell‐associated markers CD25 and GITR and observed its effects on filaria‐induced immunosuppression. Our results show that administration of anti‐CD25 and anti‐GITR in infected animals not only arrested the accumulation of Treg cells and reduced arginase activity, but also led to an increase in the percentages of Th17 cells in the secondary lymphoid organs of mice. Elevated levels of interferon‐γ and decreased levels of interleukin‐10 were also noted in the culture supernatants of mouse splenocytes that were treated with neutralizing antibodies. Furthermore, treatment with neutralizing antibodies enhanced the expression of inducible nitric oxide synthase on host macrophages and CD40 on host dendritic cells with concomitant decreased expression of alternative activation markers Arg1, Ym1 and Fizz1, which together lead to reduced parasite burden in treated animals. In summary, administration of neutralizing antibodies helps in breaking the regulatory network in mice and limits parasite‐induced immunosuppression at the earliest host–parasite interface.
Fc receptor inside‐out signaling and possible impact on antibody therapy
Authors: Brandsma Arianne M. , Jacobino Shamir R. , Meyer Saskia , ten Broeke Toine , Leusen Jeanette H. W.
Published: October 2015

Fc receptors (FcR) are expressed on immune cells and bind to the Fc tail of antibodies. This interaction is essential for FcR‐mediated signaling and triggering of cellular effector functions. FcR activation is tightly regulated to prevent immune responses by non‐antigen bound antibodies or in the absence of ‘danger signals’. FcR activity may be modulated at the plasma membrane via cross‐talk with integrins. In addition, cytokines at the site of infection/inflammation can increase FcR avidity, a process referred to as inside‐out signaling. This regulatory mechanism has been described for FcγRI (CD64), FcγRIIa (CD32a), and FcαRI (CD89) and is also well‐known for integrins. Key cellular events during inside‐out signaling are (de)phosphorylation, clustering, cytoskeleton rearrangements, and conformational changes. The latter can be studied with antibodies that specifically recognize epitopes exposed by the active (high affinity) or inactive (low affinity) state of the FcR. These antibodies are important tools to investigate the role of FcR activation in disease settings. Research on FcR has gained momentum with the rise of monoclonal antibodies (mAb) entering the clinic for the treatment of cancer and other diseases. The clinical outcome of mAb therapy may be improved by increasing FcR avidity by cytokine stimulation.
Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling
Authors: Getahun Andrew , Cambier John C.
Published: October 2015

Receptors for immunoglobulin Fc regions play multiple critical roles in the immune system, mediating functions as diverse as phagocytosis, triggering degranulation of basophils and mast cells, promoting immunoglobulin class switching, and preventing excessive activation. Transmembrane signaling associated with these functions is mediated primarily by two amino acid sequence motifs, ITAMs (immunoreceptor tyrosine‐based activation motifs) and ITIMs (immunoreceptor tyrosine‐based inhibition motifs) that act as the receptors’ interface with activating and inhibitory signaling pathways, respectively. While ITAMs mobilize activating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol‐lipid phosphatases. In this review, we will discuss our current understanding of signaling by these receptors/motifs and their sometimes blurred lines of function.