bluuebunny/crossref_metadata_2025 huggingface dataset:
Going Barefoot in Warsaw during the First World War
Authors: Blobaum Robert
Published: December 2012

This article attempts to demonstrate how an entirely unexplored and seemingly unimportant episode, at least to grand historical narratives, can open up multiple lines of inquiry. In the course of my research on everyday life in Warsaw during the First World War, I came across an intriguing phenomenon—one might even call it a movement—of going “barefoot” (boso in Polish) during the last two years of the war. Initiated by students from Warsaw’s institutions of higher education as a means of symbolic protest against collapsed living standards, the barefoot movement would quickly spread to other groups. As it did, it generated a discourse that revealed existing cultural, political, ethnic, social, and gender-based tensions among an urban population made destitute by the exactions of the Great War. Having mined Warsaw’s daily press for any kind of reference to the barefoot movement, I have attempted in these pages to make some sense of this fleeting phenomenon by linking analysis of social and political unrest, metropolitan cultural debates, and the quotidian economic realities of wartime.
Hollywood Peeks
Authors: Parvulescu Constantin , Copilaş Emanuel
Published: December 2012

In socialist Romania of the mid-1980s, workers’ clubs, theaters, student centers, opera houses, and even philharmonics used the new medium of the videocassette to organize film-viewing venues exhibiting pirated cinematic material. They were called videotheques and sold tens of thousands of admission tickets to an audience hungry for Western commercial films. This article studies the development of this quasi-legal and hybrid economic experiment. It describes its operation, analyzes its spectatorship, the alternative public spheres and patterns of resistance it produced, and the reaction of the Communist authorities, revealing the politically subversive dimension of entertainment consumption in socialist economies.
Solar-powered hybrid heating/adsorption cooling device: design and experimental test
Authors: González Manuel I , Serna Andrés , Martínez-Mayo Rodrigo , Valdés Rolando , Lucio Jesús H , Rodríguez Luis R
Published: December 2012

A new class of hybrid (heating and cooling) solar collector has been designed, built and tested. The collector combines an adsorption generator and a heat removal tubing. The tubing speeds up the evaporation stage of the cooling cycle and can also be used to deliver hot water. A small prototype (0.97 m2collection area) has been incorporated to an installation, which was tested in Burgos (northern Spain, 42°20′ N, 3°40′ W, 840 m above sea level). Two operation modes (summer and winter) are allowed. In summer mode, the installation delivers and stores domestic hot water and cold water; solar COP averaged 0.13 in our experimental campaign, and domestic hot water production was 3.1 MJ per day. When domestic hot water production is disabled, the average solar COP is reduced by 30%. In winter mode, domestic hot water and hot water for space heating are produced; combined production reached 55% of average daily solar radiation.
Sequential design of multioverlapping controllers for structural vibration control of tall buildings under seismic excitation
Authors: Karimi Hamid R , Palacios-Quiñonero Francisco , Rossell Josep M , Rubió-Massegú Josep
Published: December 2012

In this article, a computationally effective strategy to obtain multioverlapping controllers via the inclusion principle is applied to design a state-feedback multioverlapping linear-quadratic regulator controller for a 20-story building. The proposed semidecentralized controller only requires state information of neighboring stories to compute the corresponding control actions. This particular information exchange configuration allows introducing a dramatic reduction in the transmission range required for a wireless implementation of the communications system. More specifically, just a one-story transmission range is required by the proposed multioverlapping controller, while a full-building transmission range would be necessary in a classical centralized design. From a computational point of view, the presented design strategy only involves the actual computation of a reduced set of low-dimension controllers. The numerical simulations indicate that despite the simplified low-dimension design and the severe information exchange constraints, the proposed semidecentralized multioverlapping controller achieves a surprisingly high level of seismic attenuation when compared with the centralized linear-quadratic regulator controller.
Perineal Nodular Induration (“Biker’s Nodule”)
Authors: Khedaoui Radia , Martín-Fragueiro Luz M. , Tardío Juan C.
Published: December 2012

Perineal nodular induration (PNI) is a fibroblastic pseudotumor that presents almost exclusively in male cyclists. It develops in the soft tissues of the perineum immediately posterior to the scrotum, as a bilateral or single, central or lateralized mass. Although well known to sport medicine specialists, it is a scarcely documented entity in the pathology literature. We present 2 cases of PNI with fine-needle aspiration cytology and immunohistochemistry. They consisted of a paucicellular fibroblastic proliferation containing CD34-reactive spindle and epithelioid cells, small foci of fibrinoid degeneration, numerous blood vessels, and entrapped groups of mature fat cells. Our cases show that the histopathological features of PNI are more varied than those previously described and its immunohistochemical profile is wider. A central cystic focus and a zonal pattern are not consistent features of this entity. The lesional cells can express CD34, a hitherto unreported immunohistochemical finding.
Recurrent Histiocytic Necrotizing Lymphadenitis With a Long Latency in a Patient With Autoimmunity
Authors: Bogusz Agata M. , Bhargava Parul
Published: December 2012

Kikuchi–Fujimoto disease (KFD), a histiocytic necrotizing lymphadenitis (HNL), characteristically presents as cervical lymphadenopathy in young Asian women. Most resolve spontaneously with rare recurrences described. We report a patient with biopsy-proven recurrence of KFD-like HNL after almost 8 years and analyze 65 additional published cases with recurrences. While those with recurrences similarly affect young (average age = 27 years), Asian (80%) women (76%), 73% had multiple sites of involvement and 32% of those tested had underlying autoimmune conditions. Our case is unusual with respect to the following: (a) Age: 50 years, the oldest among the reported patients with recurrences. (b) Race: African descent, with only 3 others reported with recurrent HNL. Of these 4 cases, 2 had underlying autoimmunity. (c) Underlying condition: Her clinical and laboratory features were best felt to represent Sjögren’s syndrome (SjS). Only 2 other cases of SjS-associated HNL have been reported; in 2 recently reported cases SjS developed subsequently.
Intrascrotal Multiple Neurofibromas Unassociated With Neurofibromatosis
Authors: Mohammed Raji Hussain , Hussein Yaser R.
Published: December 2012

We report the case of a 33-year-old male with multiple intrascrotal neurofibromas not associated with neurofibromatosis, treated by surgical excision.
NAL-NL2 Empirical Adjustments
Authors: Keidser Gitte , Dillon Harvey , Carter Lyndal , O’Brien Anna
Published: December 2012

NAL-NL1, the first procedure from the National Acoustic Laboratories (NAL) for prescribing nonlinear gain, was a purely theoretically derived formula aimed at maximizing speech intelligibility for any input level of speech while keeping the overall loudness of speech at or below normal loudness. The formula was obtained through an optimization process in which speech intelligibility and loudness were predicted from selected models. Using updated models and applying some revisions to the derivation process, a theoretically derived NAL-NL2 formula was obtained in a similar way. Further adjustments, directed by empirical data collected in studies using NAL-NL1 as the baseline response, have been made to the theoretically derived formula. Specifically, empirical data have demonstrated that (a) female hearing aid users prefer lower overall gain than male users; (b) new hearing aid users with more than a mild hearing loss prefer increasingly less gain with increasing degree of hearing loss than experienced hearing aid users, and require up to 2 years to adapt to gain levels selected by experienced hearing aid users; (c) unilaterally and bilaterally fitted hearing aid users prefer overall gain levels that vary less than estimated by the bilateral correction factor; (d) adults prefer lower overall gain than children; and (e) people with severe/profound hearing loss prefer lower compression ratios than predicted when fitted with fast-acting compression. The literature and data leading to these conclusions are summarized and discussed in this article, and the procedure for implementing the adjustments to the theoretically derived NAL-NL2 formula is described.
Observations From a Musician With Hearing Loss
Authors: Einhorn Richard
Published: December 2012

Extensive personal experience with professional recording and audio signal processing technology has enabled the author to continue his music career after experiencing sudden sensorineural hearing loss. The iPhone™ is one such device that has been found useful for many music and general listening situations that would otherwise be intractable. Additional techniques and technologies are described that the author has found useful for specific situations, including music composition, rehearsal, and enjoyment.
Childhood Predictors of Criminal Offending
Authors: Young Susan , Taylor Eric , Gudjonsson Gisli
Published: December 2012

Objective: To examine the relative contribution of hyperactivity, conduct, and emotional problems in predicting criminal offending. Method: In all, 173 boys aged 6 to 8 years (assessed for hyperactivity, conduct, and emotional problems) were followed up 19 years later by examining criminal offense histories. Results: Significant main effects for total and violent convictions were found, the strongest being for violent criminal offenses. Conduct problems predicted general offending (irrespective of the type of conviction), whereas emotional problems were the single best predictor of violent convictions. Hyperactivity was not a significant predictor in the models. Conclusion: The findings provide insight into the developmental mechanisms that mediate criminal behavior by showing that childhood emotional problems independently contribute to the risk of violent offending in later life.
The Relation Between Inattentive and Hyperactive/Impulsive Behaviors and Early Mathematics Skills
Authors: Sims Darcey M. , Purpura David J. , Lonigan Christopher J.
Published: December 2012

Objective: Despite strong evidence that inattentive and hyperactive/impulsive behaviors are associated with mathematical difficulties in school-age children, little research has been conducted to examine the link between these constructs before the start of formal education. The purpose of this study was to examine how different manifestations of inattentive and hyperactive/impulsive behaviors, as measured by different assessment tools, are related to early mathematics skills in preschoolers. Method: Eighty-two preschool children completed a measure of early mathematics and the Continuous Performance Test (CPT). Teachers rated children’s behaviors using the Conners’ Teacher Rating Scale–15 Item. Sixty-five of these children completed mathematics assessments 1 year later. Results: Teacher ratings of inattention were uniquely related to concurrent early mathematics skills, whereas CPT errors were uniquely predictive of early mathematics skills 1 year later. Conclusion: Findings have implications for the understanding and assessment of behavior problems that are associated with early mathematics difficulties.
Coping Self-Efficacy Mediates the Association Between Child Abuse and ADHD in Adulthood
Authors: Singer Michael J. , Humphreys Kathryn L. , Lee Steve S.
Published: December 2012

Objective: To investigate whether individual differences in coping self-efficacy mediated the association of child abuse and symptoms of ADHD in young adults. Method: Self-reported measures of coping self-efficacy, child abuse, and ADHD were obtained from 66 adults. Results: Adults who reported childhood physical or sexual abuse (prior to the age of 17) had significantly higher levels of ADHD than those who did not. Individual differences in coping self-efficacy fully mediated the association between child abuse and ADHD symptoms in adulthood, such that individuals who endorsed child abuse had lower coping self-efficacy, and coping self-efficacy negatively predicted ADHD symptoms. Discussion: The findings suggest a potential causal mechanism by which childhood physical and sexual abuse may result in ADHD symptoms later in life. Interventions that improve coping skills may be useful in preventing later ADHD symptoms among adults with a childhood history of physical and sexual abuse.
Modelling and experimental validation of dynamic characteristics of porous-walled air film for non-contact conveyor system
Authors: Zhong Wei , Li Xin , Liu Fanghua , Lu Daohua , Tao Guoliang , Kagawa Toshiharu
Published: December 2012

Air film conveyors equipped with porous pads have been developed to bring the liquid crystal display into a non-contact state during transportation process. In this study, a theoretical model of one porous-walled radial flow, considering the effects of velocity slip at the surface of the porous medium, is established within a representative region, and its validity is verified by vibrating a moveable plate close to the porous surface to conduct investigations on pressure dynamic response. Due to the air damping effects, an apparent pressure hysteresis is observed when the air film subjected to periodic sinusoidal squeeze, and particularly for a given gap thickness, the pressure show approximate proportion to the squeezing velocities. A slip coefficient valued 0.004 is determined and applied to the theoretical model to study the air damping characteristics. In accordance with the experimental results, it is found that the air damping is greatly affected by the region radius, but little by the supply flow rate. Also, it is confirmed that the velocity slip is capable of inhibiting the damping effect. Moreover, free-decay oscillation of a suspended workpiece is inspected. The results indicate that the oscillating amplitude continuously attenuates until the workpiece finally becomes stable, and any change to the region radius or the supply flow rate can exert direct or indirect impact on the decay speed.
Incorporation of deformation in a lubrication analysis for automotive piston skirt–liner system
Authors: Ning Lipu , Meng Xianghui , Xie Youbai
Published: December 2012

A numerical study for the piston skirt–liner system lubrication is conducted to consider the effects of deformation of the piston skirt and the liner. This study incorporates the thermal and the elastic deformation of the piston skirt and the cylinder liner, and the piston skirt deformations due to the combustion pressure and the piston inertia. The piston dynamics, the oil film pressure and thickness, and the friction loss of the piston skirt–liner system are analyzed. The results show that the deformations all play important roles in the piston skirt–liner lubrication. Considering the deformations of the piston skirt and the cylinder liner is beneficial to the prediction of piston skirt–liner lubrication more accurately.
Measuring party positions in Europe
Authors: Bakker Ryan , de Vries Catherine , Edwards Erica , Hooghe Liesbet , Jolly Seth , Marks Gary , Polk Jonathan , Rovny Jan , Steenbergen Marco , Vachudova Milada Anna
Published: December 2012

This article reports on the 2010 Chapel Hill expert surveys (CHES) and introduces the CHES trend file, which contains measures of national party positioning on European integration, ideology and several European Union (EU) and non-EU policies for 1999−2010. We examine the reliability of expert judgments and cross-validate the 2010 CHES data with data from the Comparative Manifesto Project and the 2009 European Elections Studies survey, and explore basic trends on party positioning since 1999. The dataset is available at the CHES website.
The −344C/T polymorphism in the CYP11B2 gene is associated with essential hypertension in the Chinese
Authors: Li Weixing , Liu Chibo
Published: December 2012

Background:

It has been suggested that the −344C/T polymorphism in the CYP11B2 gene is involved in the development of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the association of −344C/T polymorphism in the CYP11B2 gene with hypertension risk in the Chinese population.

Methods:

Published literature from PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang data were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a fixed or random effects model.

Results:

A total of 29 studies (8482 cases/8560 controls) were included in the final meta-analysis. Overall, there was a significant association between −344T/C polymorphism in the CYP11B2 gene and hypertension in the Chinese (heterogeneous co-dominant model: OR=1.10, 95% CI=1.03–1.17, I2=12.7%, p for heterogeneity=0.271; dominant model: OR=1.11, 95% CI=1.02–1.20, I2=32.1%, p for heterogeneity=0.051; allelic model: OR=1.08, 95% CI 1.01–1.16, p for heterogeneity=0.006). In the stratified analysis, the effect size was significant only in the Han Chinese (heterogeneous co-dominant model: OR=1.11, 95% CI=1.03–1.20, I2=0.0%, p for heterogeneity=0.745; dominant model: OR=1.11, 95% CI=1.02–1.21, I2=18.1%, p for heterogeneity=0.299; allelic model: OR=1.09, 95% CI 1.00–1.18, p=0.028), but not in the minority Chinese.

Conclusions:

Our study suggested that the −344T/C polymorphism in the CYP11B2 gene was significantly associated with hypertension in the Chinese population, especially in the Han Chinese.
Developmental expression patterns for angiotensin receptors in mouse skin and brain
Authors: Yu Li , Shao Chunhong , Gao Lie
Published: December 2012

Two G-protein-coupled receptors, angiotensin type 1 receptor (AT1R) and type 2 receptor (AT2R), mediate the majority of angiotensin II (Ang II) effects. It has long been believed that the AT2R is reduced to extremely low levels in adulthood but is abundantly expressed in the fetus. However, recent data from rats and mice do not support this notion. Employing Western blot analysis, we found a gradual increase in AT2R protein expression from fetal life to adulthood in brain, heart, lung, liver, and kidney. The reason for the discrepancy between our observations and the conventional concept is unknown. Evidence supporting a regression of the AT2R during maturation is derived largely from autoradiographic signals that were confined to the outline of fetal rats, implying that the previously reported high AT2R expression in the fetus might be valid only for skin. We therefore hypothesized that the ontogeny of angiotensin receptors in skin is opposite that in other organs. In the current experiment, we employed Western blot analysis to compare AT2R and AT1R protein expressions in skin with that in the brainstem of fetal and adult mice. Fetal brainstem expressed lower AT2R and higher AT1R protein compared to adult brainstem (AT2R/GAPDH: 0.08 ± 0.2 in fetus vs 7.6 ± 0.9 in adult, p < 0.05; AT1R/GAPDH: 5.9 ± 0.8 in fetus vs 0.7 ± 0.3 in adult, p < 0.05). In contrast, fetal skin expresses higher AT2R and lower AT1R protein compared to adult skin (AT2R/GAPDH: 0.95 ± 0.4 in fetus vs 0.04 ± 0.2 in adult, p < 0.05; AT1R/GAPDH: 0.6 ± 0.2 in fetus vs 2.1 ± 0.5 in adult, p < 0.05). This expression profile was also confirmed by immunofluorescence. Using real-time RT-PCR, we could not detect any significant differences in mRNA of these two receptors in brainstem between fetal and adult mice. However, we found a higher AT2R mRNA and lower AT1R mRNA in the fetal skin compared to adult skin. The above results confirm our hypothesis that skin displays an expression profile of angiotensin receptors opposite that of other organs during development, suggesting that the currently held view concerning AT2R maturation is suitable only for skin. In other organs and tissues, adults express higher AT2R protein than does the fetus.
Outcomes of Endovascular Aneurysm Repair With 2 Different Endograft Systems With Suprarenal Fixation in Patients With Hostile Infrarenal Aortic Anatomy
Authors: Antoniou George A. , Georgiadis George S. , Glancz Laurence , Delbridge Michael , Murray David , Smyth J. Vincent , Lazarides Miltos K. , Serracino-Inglott Ferdinand
Published: December 2012

Objective:

To evaluate 2 different aortic endograft systems with suprarenal fixation in patients with unfavorable neck morphology.

Methods:

A prospective observational study assigning patients with abdominal aortic aneurysm with unfriendly neck anatomy treated with 2 different endograft systems (Endurant and Zenith) was conducted. The log-rank test was applied to investigate the differences in cumulative outcome parameters.

Results:

Successful endograft implantation was achieved in all patients. Requirement for troubleshooting techniques was similar in the 2 groups ( P = .156 and P = .081, respectively). In-hospital procedure-related morbidity occurred in 7 patients (Zenith vs Endurant, P = .690). Freedom from any type of endoleak and overall mortality did not differ significantly between the groups (log-rank test, P = .068 and P = .087). Reinterventions were more commonly required in the Zenith group (log-rank rest, P = .041), and were all nongraft/aneurysm-related.

Conclusions:

Similar performances of the Zenith and the Endurant endograft systems were demonstrated.
Spontaneous Dissection of the External Iliac Artery Secondary to Golf Club Manufacturing
Authors: Yoong S. , Heyes G. , Davison G. W. , Hannon R. , O’Donnell M. E.
Published: December 2012

Spontaneous dissection of the external iliac artery in the absence of aortic disease is extremely uncommon. We report the conservative treatment of a 46-year-old male patient who presented with acute left lower limb ischemia due to an isolated dissection of the external iliac artery secondary to repetitive swinging movements during golf club manufacturing. Although syndromes of nonatherosclerotic vascular disease secondary to repetitive movements in high-level athletic activity have been previously described in cyclists, long distance runners, and rugby players, we believe this to be the first occupational case associated with golf.
Patterns of Visceral and Renal Artery Involvement in Type B Aortic Dissections
Authors: Ravichandran Pranavi , Harrington David M. , Lovell Marge B. , Harris Jeremy R. , DeRose Guy , Forbes Thomas L.
Published: December 2012

Objective:

The main objective of this study was to describe the visceral and renal vessel involvement and the outcomes in thoracic dissections.

Methods:

Computed tomography scans of 39 patients were reviewed (30 type B, 9 type A). Visceral and renal arteries were recorded as perfused by the true lumen (TL) or false lumen (FL). Radiologic follow-up was 3.3 years (range 0-10).

Results:

A total of 156 vessels were analyzed, and 49 (31%) were supplied by the FL. The most common patterns were FL supply of a renal artery (RA) with the visceral arteries and contralateral RA from the TL. In the follow-up, branch vessel compromise occurred in 12 vessels and was more likely to occur when supplied by the FL ( P = .01). About 75% of the patients with at least 2 vessels supplied by the FL demonstrated aortic dilatation.

Conclusions:

Branch vessel occlusion is more likely in the vessels supplied by the FL. Aortic dilatation occurred more frequently when 2 or more vessels were supplied by the FL.
Education Versus Learning
Authors: Adamson Craig W. , Bailie John W.
Published: December 2012

Increasing numbers of adults are returning to a diverse array of higher education settings. Institutions that serve this population must consider the meaning of education to these students, their needs, and the modes of instruction most likely to meet those needs. Approaches to education have historically tended toward mechanistic and routine-oriented learning. However, adult learning is best accomplished through more flexible, collaborative, and transformative processes. Adult learning literature over the last several decades has offered challenges and insights into these two approaches. This literature has been rich in its exploration of diverse ideological and conceptual concerns related to the desire to create a more empowering and transformative experience of learning. This article provides a brief historical overview of education and learning as concepts with a focus on the insights of recent adult learning scholarship. The authors will also discuss how the emerging field of restorative practices offers new perspectives on these approaches. As a field that has developed independently of adult learning scholarship, but shares many of its commitments, restorative practices offer a fresh view on adult learning scholarship.
Behind the Resume
Authors: Wang Michelle , Yorks Lyle
Published: December 2012

This article provides an account of how presentational, or expressive, ways of knowing has been used in career planning classes in a community college located in large urban area. Career planning, and resume preparation, is often framed as a very instrumental process. However, as the inquiry described in this article demonstrates, developing a resume can be an opportunity for engaging in self-reflective practices. Using image drawing, poetry, metaphor, and similes challenged many students’ self-perceptions, brought into conscious awareness how their meaning schemes shaped their actions, and deepened their self-awareness.
Perceived Changes in Health and Interactions With “the Paracetamol Force”
Authors: Goodwin Robin , Polek Ela , Goodwin Kinga
Published: December 2012

Recent European Union expansion has permitted new, but complex, health interactions for migrants. This study examined perceived changes in health and interactions with the British National Health Service among new Polish migrants. In a mixed methods sequential study, questionnaires were administered at Time 1 ( n = 418), Time 2 ( n = 222), and Time 3 ( n = 214). Thirty respondents participated in interviews 6 months after arrival; 25 of these were interviewed 1 year later. Age, psychological and cognitive resources, social support, discrimination, and economic status predicted perceived health changes. Interviews revealed cultural differences in treatment procedures and the role of social networks in health service expectations.
Accrual by groups in trials with discrete-time survival endpoints
Authors: Jóźwiak Katarzyna , Moerbeek Mirjam
Published: December 2012

Background

In many fields of science, event status is often recorded in intervals or at discrete points in time and can be investigated in experimental settings. Conducting such trials requires thorough planning before they are actually performed.

Purpose

To investigate accrual by groups in a trial with discrete-time survival endpoints and to describe how to choose the number of accrual groups, the size of the accrual groups, and the duration of the trial to achieve a sufficient power level.

Methods

In trials with multiple time periods, the event status is recorded at the end of each period, but the event may occur at any time between the time points the measurements are taken. Therefore, time is recorded discretely, but the underlying process is continuous. To find the risk of event occurrence in each time interval, a continuous-time survival function is used and the generalized linear model is applied.

Results

It is observed that the combination of the number of accrual groups, the size of the accrual groups, and the duration of the trial that gives a sufficient power level depends on the shape of the continuous-time survival function, the proportion of subjects who have experienced the event after a fixed number of time periods, and the size of the treatment effect.

Limitations

The results of the study are only presented graphically, because there is no simple closed-form expression for finding the variance of the treatment effect. The authors provide MATLAB software to perform the power calculations.

Conclusions

More subjects should be recruited in each accrual group or more accrual groups should be included if the effect size or the proportion of the subjects who have experienced the event after a fixed number of time periods decreases, or the probability of the event occurrence is concentrated toward the end of the study duration.
In vivo confocal microscopic evaluation of corneal Langerhans cell density, and distribution and evaluation of dry eye in rheumatoid arthritis
Authors: Marsovszky László , Resch Miklós D , Németh János , Toldi Gergely , Medgyesi Erzsébet , Kovács László , Balog Attila
Published: December 2012

Corneal Langerhans cells (LCs) offer the opportunity to gain insight into the activity of the innate immunity. We examined the density and the distribution of LCs and compared the results with dry-eye parameters in rheumatoid arthritis (RA). Fifty-two RA patients with various degrees of disease activity and 24 healthy subjects were enrolled. Peripheral and central LC number and morphology were assessed with in vivo laser confocal microscopy. In addition, ocular surface disease index (OSDI), lid parallel conjunctival folds, Schirmer test, and tear break-up time (TBUT) were evaluated. The prevalence of central and peripheral LC, and the central LC morphology values (LCM) were higher than normal in RA. Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti-TNF or glucocorticosteroid (GCS) therapy exhibited normal LCM, and normal central and peripheral LC density. OSDI was higher and TBUT was lower than normal in RA. The alteration of LC in RA suggests an active inflammatory process in the cornea, which may reflect an increased activation state of the innate immune system—even in inactive stages of RA and without ocular symptoms. The results also indicate ocular effects of GCS therapy in RA.
Palliative care in COPD patients: is it only an end-of-life issue?
Authors: Carlucci Annalisa , Guerrieri Aldo , Nava Stefano
Published: December 2012

The presence of acute or chronic respiratory failure is often seen as a terminal phase of chronic obstructive pulmonary disease. A great variability in end-of-life practice is observed in these patients mainly because physicians are not always able to correctly predict survival. There is a need for a clear discussion about decision making earlier than when acute respiratory failure ensues. Indeed, a perceived poor quality of life does not necessarily correlate with a clear willingness to refuse invasive or noninvasive mechanical ventilation. It has been suggested to start palliative care earlier, together with curative and restorative care, when there is an increased intensity of symptoms. The patients eligible for palliative care are those complaining of breathlessness, pain, fatigue and depression, which in some studies accounted for a prevalence much higher than 50%. Among comfort measures for palliation, oxygen is frequently prescribed even when the criteria for long-term home oxygen therapy are not met; however, when compared with air, no benefits on dyspnoea have been found. The only drug with a proven effect on dyspnoea is morphine, but not when it is delivered with a nebuliser. Finally, noninvasive ventilation may be used only as a comfort measure for palliation to maximise comfort by minimising adverse effects.
Pulmonary hypertension in left heart disease
Authors: Guazzi Marco , Galiè Nazzareno
Published: December 2012

Pulmonary hypertension (PH) is a frequent complication of left heart disease arising from a wide range of cardiac disorders. In the clinical classification, PH associated with left heart disease is classified as Group 2, which includes left heart systolic dysfunction, left heart diastolic dysfunction and left heart valvular disease. In the past, rheumatic mitral valve disease was the most common cause of PH in left heart disease; however, today it is more likely to be associated with hypertensive and/or ischaemic heart disease.

As the incidence of these conditions is increasing, the number of patients presenting with PH is also increasing and, today, left heart disease represents the most frequent cause of PH. The development of PH in patients with left heart disease is associated with poor prognosis. However, despite the increasingly large number of patients affected and the impact of PH on outcome, there are currently no specific treatment options for these patients.

This review gives an overview of the pathophysiology and epidemiology of PH associated with left heart disease, and discusses the challenges associated with its management and treatment.
Pulmonary arterial hypertension associated with congenital heart disease
Authors: D'Alto Michele , Mahadevan Vaikom S.
Published: December 2012

Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD), with most cases occurring in patients with congenital cardiac shunts. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodelling and dysfunction, resulting in a progressive rise in pulmonary vascular resistance and increased pressures in the right heart. Eventually, reversal of the shunt may arise, with the development of Eisenmenger's syndrome, the most advanced form of PAH-CHD.

The prevalence of PAH-CHD has fallen in developed countries over recent years and the number of patients surviving into adulthood has increased markedly. Today, the majority of PAH-CHD patients seen in clinical practice are adults, and many of these individuals have complex disease or received a late diagnosis of their defect. While there have been advances in the management and therapy in recent years, PAH-CHD is a heterogeneous condition and some subgroups, such as those with Down's syndrome, present particular challenges.

This article gives an overview of the demographics, pathophysiology and treatment of PAH-CHD and focuses on individuals with Down's syndrome as an important and challenging patient group.
Pathways in pulmonary arterial hypertension: the future is here
Authors: Sitbon Olivier , Morrell NicholasW.
Published: December 2012

It is well established that the endothelin, nitric oxide and prostacyclin pathways play an important role in the development of pulmonary arterial hypertension (PAH). Indeed, the therapeutic options currently available for the management of PAH all act on one of these mechanistic pathways.

However, this is an exciting time for both clinicians and scientists, as increased understanding of the mechanisms involved in the pathogenesis and progression of PAH has resulted in the development of a number of novel therapeutic options.

This article highlights how the introduction of new compounds such as macitentan, riociguat and selexipag, which act on the endothelin, nitric oxide and prostacyclin pathways, respectively, have the potential to further improve the prognosis for patients with PAH.
Early detection and management of pulmonary arterial hypertension
Authors: Humbert Marc , Gerry Coghlan J. , Khanna Dinesh
Published: December 2012

The long-term prognosis for patients with pulmonary arterial hypertension (PAH) remains poor, despite advances in treatment options that have been made in the past few decades. Recent evidence suggests that World Health Organization functional class I or II patients have significantly better long-term survival rates than patients in higher functional classes, thus providing a rationale for earlier diagnosis and treatment of PAH. However, early diagnosis is challenging and there is frequently a delay between symptom onset and diagnosis. Screening programmes play an important role in PAH detection and expert opinion favours echocardiographic screening of asymptomatic patients who may be predisposed to the development of PAH (i.e.those with systemic sclerosis or sickle cell disease), although current guidelines only recommend annual echocardiographic screening in symptomatic patients. This article reviews the currently available screening programmes, including their limitations, and describes alternative screening approaches that may identify more effectively those patients who require right heart catheterisation for a definitive PAH diagnosis.
The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD – a monozygotic twin study
Authors: Hall Timothy , Galletly Cherrie , Clark C Richard , Veltmeyer Melinda , Metzger Linda J , Gilbertson Mark W , Orr Scott P , Pitman Roger K , McFarlane Alexander
Published: December 2012

Background

PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD.

Methods

Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins.

Results

There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD.

Conclusions

These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.
Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans
Authors: Sutphin George L , Bishop Emma , Yanos Melana E , Moller Richard M , Kaeberlein Matt
Published: December 2012

Background

The longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend life span by targeting pathways with a defined role in the aging process. On the environmental side, the molecular mechanisms responsible for the positive influence of interventions such as dietary restriction are being explored. The environment experienced by humans in modern societies already contains countless compounds that may influence longevity. Understanding the role played by common compounds that substantially affect the aging process will be critical for predicting and interpreting the outcome of introducing new interventions. Caffeine is the most widely used psychoactive drug worldwide. Prior studies in flies, worms, and mice indicate that caffeine may positively impact age-associated neurodegenerative pathology, such as that observed in Alzheimer’s disease.

Results

Here we report that caffeine is capable of extending life span and improving healthspan in Caenorhabditis elegans, a finding that is in agreement with a recently published screen looking for FDA-approved compounds capable of extending worm life span. Life span extension using caffeine displays epistatic interaction with two known longevity interventions: dietary restriction and reduced insulin signaling. Caffeine treatment also delays pathology in a nematode model of polyglutamine disease.

Conclusions

The identification of caffeine as a relevant factor in aging and healthspan in worms, combined with prior work in both humans and rodents linking caffeine consumption to reduced risk of age-associated disease, suggests that caffeine may target conserved longevity pathways. Further, it may be important to consider caffeine consumption when developing clinical interventions, particularly those designed to mimic dietary restriction or modulate insulin/IGF-1-like signaling. The positive impact of caffeine on a worm model of polyglutamine disease suggests that chronic caffeine consumption may generally enhance resistance to proteotoxic stress and may be relevant to assessing risk and developing treatments for human diseases like Alzheimer’s and Huntington’s disease. Future work addressing the relevant targets of caffeine in models of aging and healthspan will help to clarify the underlying mechanisms and potentially identify new molecular targets for disease intervention.
Editorial: Space flight modifies T cell activation—role of microgravity
Authors: Sonnenfeld Gerald
Published: December 2012

Discussion of evidence that microgravity may have a direct effect on the immune system.
Mouse zygote-specific proteasome assembly chaperone important for maternal-to-zygotic transition
Authors: Shin Seung-Wook , Shimizu Natsumi , Tokoro Mikiko , Nishikawa Satoshi , Hatanaka Yuki , Anzai Masayuki , Hamazaki Jun , Kishigami Satoshi , Saeki Kazuhiro , Hosoi Yoshihiko , Iritani Akira , Murata Shigeo , Matsumoto Kazuya
Published: December 2012

During the maternal-to-zygotic transition (MZT), maternal proteins in oocytes are degraded by the ubiquitin–proteasome system (UPS), and new proteins are synthesized from the zygotic genome. However, the specific mechanisms underlying the UPS at the MZT are not well understood. We identified a molecule named zygote-specific proteasome assembly chaperone (ZPAC) that is specifically expressed in mouse gonads, and expression of ZPAC was transiently increased at the mouse MZT. ZPAC formed a complex with Ump1 and associated with precursor forms of 20S proteasomes. Transcription of ZPAC genes was also under the control of an autoregulatory feedback mechanism for the compensation of reduced proteasome activity similar to Ump1 and 20S proteasome subunit gene expression. Knockdown of ZPAC in early embryos caused a significant reduction of proteasome activity and decrease in Ump1 and mature proteasomes, leading to accumulation of proteins that need to be degraded at the MZT and early developmental arrest. Therefore, a unique proteasome assembly pathway mediated by ZPAC is important for progression of the mouse MZT.
In vivo genetic manipulation of cortical progenitors in gyrencephalic carnivores using in utero electroporation
Authors: Kawasaki Hiroshi , Toda Tomohisa , Tanno Kaori
Published: December 2012

Brain structures such as the outer subventricular zone (OSVZ) and the inner fiber layer (IFL) in the developing cerebral cortex are especially prominent in higher mammals. However, the molecular mechanisms underlying the formation of the OSVZ are still largely unknown, mainly because genetic manipulations that can be applied to the OSVZ in higher mammals had been poorly available. Here we developed and validated a rapid and efficient genetic manipulation technique for germinal zones including the OSVZ using in utero electroporation in developing gyrencephalic carnivore ferrets. We also determined the optimal conditions for using in utero electroporation to express transgenes in germinal zones. Using our electroporation procedure, the morphology of GFP-positive cells in the OSVZ was clearly visible even without immunostaining, and multiple genes were efficiently co-expressed in the same cells. Furthermore, we uncovered that fibers, which seemed to correspond to those in the IFL of monkeys, also existed in ferrets, and were derived from newly generated cortical neurons. Our technique promises to be a powerful tool for investigating the fundamental mechanisms underlying the formation and abnormalities of the cerebral cortex in higher mammals.
Capicua regulates proliferation and survival of RB-deficient cells in Drosophila
Authors: Krivy Kate , Bradley-Gill Mary-Rose , Moon Nam-Sung
Published: December 2012

Mutations in rbf1, the Drosophila homologue of the RB tumour suppressor gene, generate defects in cell cycle control, cell death, and differentiation during development. Previous studies have established that EGFR/Ras activity is an important determinant of proliferation and survival in rbf1 mutant cells. Here, we report that Capicua (Cic), an HMG box transcription factor whose activity is regulated by the EGFR/Ras pathway, regulates both proliferation and survival of RB-deficient cells in Drosophila. We demonstrate that cic mutations allow rbf1 mutant cells to bypass developmentally controlled cell cycle arrest and apoptotic pressure. The cooperative effect between Cic and RBF1 in promoting G1 arrest is mediated, at least in part, by limiting Cyclin E expression. Surprisingly, we also found evidence to suggest that cic mutant cells have decreased levels of reactive oxygen species (ROS), and that the survival of rbf1 mutant cells is affected by changes in ROS levels. Collectively, our results elucidate the importance of the crosstalk between EGFR/Ras and RBF1 in coordinating cell cycle progression and survival.
Association of β-catenin with P-Smad3 but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1
Authors: Tian Xinrui , Zhang Jianlin , Tan Thian Kui , Lyons J. Guy , Zhao Hong , Niu Bo , Lee So Ra , Tsatralis Tania , Zhao Ye , Wang Ya , Cao Qi , Wang Changqi , Wang Yiping , Lee Vincent W. S. , Kahn Michael , Zheng Guoping , Harris David C. H.
Published: December 2012

Transforming growth factor β1 (TGF-β1) is known to be both anti-inflammatory and profibrotic. Cross-talk between TGF-β/Smad and Wnt/β-catenin pathways in epithelial–mesenchymal transition (EMT) suggests a specific role for β-catenin in profibrotic effects of TGF-β1. However, no such mechanistic role has been demonstrated for β-catenin in the anti-inflammatory effects of TGF-β1. In the present study, we explored the role of β-catenin in the profibrotic and anti-inflammatory effects of TGF-β1 by using a cytosolic, but not membrane, β-catenin knockdown chimera (F-TrCP-Ecad) and the β-catenin/CBP inhibitor ICG-001. TGF-β1 induced nuclear Smad3/β-catenin complex, but not β-catenin/LEF-1 complex or TOP-flash activity, during EMT of C1.1 (renal tubular epithelial) cells. F-TrCP-Ecad selectively degraded TGF-β1-induced cytoplasmic β-catenin and blocked EMT of C1.1 cells. Both F-TrCP-Ecad and ICG-001 blocked TGF-β1-induced Smad3/β-catenin and Smad reporter activity in C1.1 cells, suggesting that TGF-β1-induced EMT depends on β-catenin binding to Smad3, but not LEF-1 downstream of Smad3, through canonical Wnt. In contrast, in J774 macrophages, the β-catenin level was low and was not changed by interferon-γ (IFN-γ) or lipopolysaccharide (LPS) with or without TGF-β1. TGF-β1 inhibition of LPS-induced TNF-α and IFN-γ-stimulated inducible NO synthase (iNOS) expression was not affected by F-TrCP-Ecad, ICG-001 or by overexpression of wild-type β-catenin in J774 cells. Inhibition of β-catenin by either F-TrCP-Ecad or ICG-001 abolished LiCl-induced TOP-flash, but not TGF-β1-induced Smad reporter, activity in J774 cells. These results demonstrate for the first time that β-catenin is required as a co-factor of Smad in TGF-β1-induced EMT of C1.1 epithelial cells, but not in TGF-β1 inhibition of macrophage activation. Targeting β-catenin may dissociate the TGF-β1 profibrotic and anti-inflammatory effects.