bluuebunny/crossref_metadata_2025 huggingface dataset:
Extremes in Otolaryngology Resident Surgical Case Numbers
Authors: Rosenberg Tara L. , Franzese Christine B.
Published: May 2012

Objective

Understand (1) significance between minimum, mean, and maximum case numbers for otolaryngology resident surgical procedures; (2) weaknesses of Accreditation Council for Graduate Medical Education (ACGME) resident case log system contributing to inaccurate data/case inflation; and (3) when excessive case load may transform education into service.

Study Design

Cross‐sectional survey using a national database.

Setting

Academic otolaryngology residency programs.

Subjects/Methods

Review of otolaryngology resident national data reports from ACGME resident case log system performed from 2004 to 2010. Minimum, mean, standard deviation, and maximum values for total number of resident surgeon cases and for specific surgical procedures were compared. Case unbundling, resident data entry habits, and tracked vs untracked Current Procedural Terminology (CPT) codes were reviewed.

Results

Mean total number of resident surgeon cases remained constant (1699.5 ± 424.2 to 1772.2 ± 517). Minimum total number of cases ranged from 730 to 811 (approaching 2 standard deviations below the mean). Zero was reported as the minimum case number for some procedures. Maximum for total number of cases increased (3559 to 4857) and surpassed the mean by 4 to 5 standard deviations. Some procedures have maximums greater than 11 standard deviations above the mean. The authors identified untracked CPT codes and variations in resident case log documentation habits.

Conclusions

Large differences between the minimum, mean, and maximum resident surgeon case numbers exist. Establishing minimum case number requirements for otolaryngology residents should be considered. Educational benefit derived from excessive case load is unclear. Critical examination of the ACGME resident case log system and resident documentation habits is needed to improve accuracy of reporting.
The Effects of Systemic, Topical, and Intralesional Steroid Treatments on Apoptosis Level of Nasal Polyps
Authors: Kapucu Burak , Cekin Engin , Erkul Bulent Evren , Cincik Hakan , Gungor Atila , Berber Ufuk
Published: May 2012

Objective

The purpose of this study was to compare the apoptotic responses to systemic, topical, and intrapolyp injection of glucocorticoid with no treatment in nasal polyps.

Study Design

Prospective, randomized controlled study.

Setting

Tertiary training hospital.

Subjects and Methods

The study was performed on 48 patients with nasal polyposis in the Department of Otorhinolaryngology between 2008 and 2009. Patients were assigned to 1 of 4 groups of 12 patients. Group A was treated with oral methylprednisolone 1 mg/kg/d, and the dose was tapered gradually. Group B received 0.3 mL triamcinolone acetonide (40 mg/mL), which was injected into polyp tissue. Group C was treated with topical 55 µg triamcinolone acetonide 2 times daily for 1 month. Group D received no medication. Samples were collected endoscopically after the seventh day for groups A and B, the first month for group C, and the first visit for group D. Apoptotic indexes were determined using the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling method.

Results

Statistically significant differences in apoptotic index were found between each steroid‐medicated group and the control group (PD‐A =. 0001; PD‐B =. 003; PD‐C =. 026) and between groups A and C (PA‐C =. 012). Group B did not differ significantly from either group A or C (PA‐B =. 11; PB‐C =. 75).

Conclusions

The apoptotic index in nasal polyps treated with systemic, topical, and intrapolyp injection forms of glucocorticoids was higher than that in the control group. Systemic steroid treatment induced the most apoptosis.
Intracolleague Aggression in a Group of Dutch Prison Workers
Authors: Bogaerts Stefan , van der Laan André M.
Published: May 2012

This study examined workplace aggression among a Dutch group of 174 prison workers at 10 penitentiaries in the Netherlands. The purpose of the study was to investigate the main and interaction effects of Type D personality and violence on posttraumatic stress disorder (PTSD). The results showed a significant interaction effect between the type of violence and Type D personality. Physically violated Type D individuals achieved the highest average score on the PTSD scale. Type D personality was found to have a strong main effect on PTSD.
A re-examination of the empirical performance of the Longstaff and Schwartz two-factor term structure model using real yield data
Authors: Faff Robert , Treepongkaruna Sirimon
Published: May 2012

In this study, we apply the Longstaff and Schwartz (1992) two-factor term structure model to real yields across eight countries. As such, we improve on many prior studies that have inappropriately tested this formulation using nominal yield data. We use the generalized method of moments to test the cross-sectional restrictions imposed by the Longstaff and Schwartz model, as well as the Cox–Ingersoll–Ross one-factor model. Further, we compare the forecasting ability from both models. Our findings support the superiority of the two-factor model. We confirm general reliability of prior research in this area, despite the unfortunate reliance on nominal data in such earlier tests.
Modeling the tribological abrasive wear behavior of woven composite materials using the planning design experimentation approach
Authors: Zenasni R , Hebbar A , Olay Jaime Vina
Published: May 2012

This article addresses the experimental characterization of the abrasive wear of two woven fabric carbon fiber and glass fiber composite materials, taking into account the effect of moisture absorption. The composite materials were tested to three level loadings and two sliding speeds. The abrasive used was dry sand of size 0.6 µm, and the time of wear testing was 10 min. In order to study the effects of moisture on wear behavior, another series of samples was introduced into the tank of water during a period of 40 days at ambient temperature. The planning design experimentation approach was applied to obtain a mathematical model taking into account the influencing parameters on the wear behavior of the composites. The wear results have shown that for a higher turn speed and a load, the loss of matter increases. In the case of samples exposed to water absorption, the wear rate increases more than the dry samples. The micrographs of the surface of the samples tested were taken in order to characterize the wear mechanism.
Disparities in Health Status and Health Care Access and Use Among Older American Indians and Alaska Natives and Non-Hispanic Whites in California
Authors: Kim Giyeon , Bryant Ami N. , Goins R. Turner , Worley Courtney B. , Chiriboga David A.
Published: May 2012

Objectives:

The present study compared the characteristics of health status and health care access and use among older American Indians and Alaska Natives (AIANs) to those of non-Hispanic Whites (NHWs).

Methods:

Data were drawn from the 2009 California Health Interview Survey, with a total of 17,156 adults aged 60 and older (198 AIANs and 16,958 NHWs) analyzed.

Results:

Older AIANs reported poorer physical and mental health than did NHWs. AIANs were less likely than NHWs to see a medical doctor and have a usual source of medical care and were more likely than NHWs to delay getting needed medical care and report difficulty understanding the doctor at their last visit.

Discussion:

These findings highlight the vulnerability and unmet health care needs of older AIANs. More research on the older AIAN population is clearly needed to document their health care needs in order to better inform efforts to reduce health disparities.
Metapsychics in Spain
Authors: Mülberger Annette , Balltondre Mónica
Published: May 2012

The present article deals with a kind of parapsychology called metapsychics ( metapsíquica) as conceived and practised in Spain between 1923 and 1925. First we focus on the reception of a treatise by Richet that evoked both support (Ferrán) and criticism (Mira). Then we examine some experiments on clairvoyance performed at the Marquis of Santa Cara’s home, dealing chiefly with the rise and fall of a case of prodigious vision. The analysis gives special attention to the question of how metapsychics was understood and to which discussions it gave rise. The authors argue that the project of metapsychics must be understood within a frame of two tendencies, namely, the increasing popularization and the demarcation of science that were under way in modern society.
Preparation of new phenylethynyl terminated imide oligomers from pyromellitic dianhydride
Authors: Wang Wei , Zhou Hongwei , Jin Zhuomin , Dang Guodong , Chen Chunhai
Published: May 2012

Phenylethenyl end-capped imide oligomers based on pyromellitic dianhydride (PMDA), 2, 5-bis(4-aminophenoxy)-biphenyl ( p-TPEQ) and 4-phenylethynylphthalic anhydride (PEPA) were prepared. The thermal properties and melt viscosity of oligomers were investigated by differential scanning calorimetry, thermogravimetric analysis and rheological studies, respectively. The oligomers bearing pendant phenyl groups exhibited much lower melt viscosities than PETI-5, and provided broader processing window. Thermal curing processing was monitored by Fourier transform infrared spectrometry, crosslink reaction of phenylethynyl end group completed at 370 °C in 20 min. Glass transition temperatures of cured oligomers determined by DMA were about 273 to 330 °C, which was much higher than PETI-5. In addition, these cured imide oligomers exhibited excellent tensile properties with strength about 100 MPa and modulus more than 2 GPa. Finally, the films cured by oligo-6 were aged at 177 °C for different times and they still exhibited excellent thermo-oxidative stabilities after aging. It is concluded that using inexpensive PMDA not only lowers the cost, but also increases the glass transition temperature after curing. The excellent properties of these phenylethynyl end-capped imide oligomers demonstrate a promising potential for future aerospace applications.
Common Patterns of Prediction of Literacy Development in Different Alphabetic Orthographies
Authors: Caravolas Markéta , Lervåg Arne , Mousikou Petroula , Efrim Corina , Litavský Miroslav , Onochie-Quintanilla Eduardo , Salas Naymé , Schöffelová Miroslava , Defior Sylvia , Mikulajová Marína , Seidlová-Málková Gabriela , Hulme Charles
Published: May 2012

Previous studies have shown that phoneme awareness, letter-sound knowledge, rapid automatized naming (RAN), and verbal memory span are reliable correlates of learning to read in English. However, the extent to which these different predictors have the same relative importance in different languages remains uncertain. In this article, we present the results from a 10-month longitudinal study that began just before or soon after the start of formal literacy instruction in four languages (English, Spanish, Slovak, and Czech). Longitudinal path analyses showed that phoneme awareness, letter-sound knowledge, and RAN (but not verbal memory span) measured at the onset of literacy instruction were reliable predictors, with similar relative importance, of later reading and spelling skills across the four languages. These data support the suggestion that in all alphabetic orthographies, phoneme awareness, letter-sound knowledge, and RAN may tap cognitive processes that are important for learning to read.
Interpolation between spatial frameworks: An application of process convolution to estimating neighbourhood disease prevalence
Authors: Congdon Peter
Published: May 2012

Health data may be collected across one spatial framework (e.g. health provider agencies), but contrasts in health over another spatial framework (neighbourhoods) may be of policy interest. In the UK, population prevalence totals for chronic diseases are provided for populations served by general practitioner practices, but not for neighbourhoods (small areas of circa 1500 people), raising the question whether data for one framework can be used to provide spatially interpolated estimates of disease prevalence for the other. A discrete process convolution is applied to this end and has advantages when there are a relatively large number of area units in one or other framework. Additionally, the interpolation is modified to take account of the observed neighbourhood indicators (e.g. hospitalisation rates) of neighbourhood disease prevalence. These are reflective indicators of neighbourhood prevalence viewed as a latent construct. An illustrative application is to prevalence of psychosis in northeast London, containing 190 general practitioner practices and 562 neighbourhoods, including an assessment of sensitivity to kernel choice (e.g. normal vs exponential). This application illustrates how a zero-inflated Poisson can be used as the likelihood model for a reflective indicator.
Spatial health effects analysis with uncertain residential locations
Authors: Reich Brian J , Chang Howard H , Strickland Matthew J
Published: May 2012

Spatial epidemiology has benefited greatly from advances in geographic information system technology, which permits extensive study of associations between various health responses and a wide array of socio-economic and environmental factors. However, many spatial epidemiological datasets have missing values for a substantial proportion of spatial variables, such as the census tract of residence of study participants. The standard approach is to discard these observations and analyze only complete observations. In this article, we propose a new hierarchical Bayesian spatial model to handle missing observation locations. Our model utilizes all available information to learn about the missing locations and propagates uncertainty about the missing locations throughout the model. We show via a simulation study that this method can lead to more efficient epidemiological analysis. The method is applied to a study of the relationship between fine particulate matter and birth outcomes is southeast Georgia, where we find smaller posterior variance for most parameters using our missing data model compared to the standard complete case model.
Chronic Pain in the Outpatient Palliative Care Clinic
Authors: Merlin Jessica S. , Childers Julie , Arnold Robert M.
Published: May 2012

Chronic pain is common. Many patients with cancer and other life-limiting illnesses have chronic pain that is related to their disease, and some have comorbid chronic nonmalignant chronic pain. As palliative care continues to move upstream and outpatient palliative care programs develop, palliative care clinicians will be called upon to treat chronic pain. Chronic pain differs from acute pain in the setting of advanced disease and a short prognosis in terms of its etiology, comorbidities—especially psychiatric illness and substance abuse—and management. To successfully care for these patients, palliative care providers will need to learn new clinical competencies. This article will review chronic pain management core competencies for palliative care providers.
Mortality of Patients With Cancer Admitted to Intensive Care Unit
Authors: Ñamendys-Silva Silvio A. , González-Herrera María O. , Herrera-Gómez Angel
Published: May 2012

Outcomes of critically ill cancer patients admitted to the intensive care unit (ICU) had improved; it could be associated with medical advances in critical care, introduction of new anticancer treatments, and better supportive care. Recent reports have described ICU mortality for critically ill cancer patients ranged from 15.9% to 32%. During the period 2007 to 2011, a total of 1418 critically ill cancer patients were admitted to our ICU with a mortality rate lower (17.5%) than that reported by other centers. The ICUs around the world should consider the improvement in the prognosis of critically ill cancer patients who require critical care and they should not be denied ICU admission only on the basis of a patient having cancer.
Impact of Patient and Caregiver Transfer Training Provided by a Physical Therapist in the Hospice Setting
Authors: Turner Fernette , Seiger Cindy , Devine Nancy
Published: May 2012

Background:

As patients in hospice become increasingly dependent upon caregivers, physical therapy interventions can minimize the risk of injury to the patient or caregiver that may occur during transfers between surfaces.

Case Description:

A 68-year-old male hospice patient was referred to physical therapy for strengthening and transfer training after a fall that resulted in the patient remaining in bed for 5 weeks due to an increased fear of falling. Treatments focused on caregiver training for correct transfer techniques.

Outcome:

During 10 treatment sessions, the patient and caregiver became independent and safe with all transfers. Although the patient’s health declined, his risk for and fear of falling decreased. Confidence with transfers improved for the patient and caregiver.

Discussion:

Physical therapy “benefits were immeasurable” for the patient and caregiver by teaching them how to safely perform patient transfers with reduced risk of injury.
Perceptions and Attitudes About Hospice and Palliative Care Among Community-Dwelling Older Adults
Authors: Manu Erika , Mack-Biggs Terri L. , Vitale Caroline A. , Galecki Andrej , Moore Tisha , Montagnini Marcos
Published: May 2012

It is expected that the American geriatric population will have an increased need for hospice and palliative care services over the next few decades. We surveyed 187 community dwelling older adults about several aspects related to end-of-life (EOL) care. Participants were much more familiar with the term hospice than palliative care. In general, they had positive attitudes towards hospice and palliative care. Although experience caring for a dying relative was common, it wasn't associated with better attitudes towards hospice and palliative care or better familiarity with these terms. Familiarity with the term palliative care was associated with better attitudes towards EOL care. Our findings highlight the need for enhanced end-of-life care education among older adults, and reinforce the need for further research in this area.
Risk Factors Related to Suicidal Ideation and Attempted Suicide
Authors: Chung Sung Suk , Joung Kyoung Hwa
Published: May 2012

Suicidal trends and related characteristics such as sociodemographic factors, psychological factors, and health behaviors can differ between countries. This study investigated the predictors of suicidal ideation and attempted suicide including health behaviors among American and Korean youth from two national representative data sets. In both countries, depression was the most predominant predictor to suicidal ideation and attempted suicide. Unique predictors of suicidal youth in each country were also found. In America, attempted suicide was predicted by poor body image, whereas in Korea attempted suicide was predicted by medical diagnosis such as asthma, concern about weight, and alcohol consumption. The value of our approach lies in the comparative analysis of analogous and unique characteristics of suicidal youths in these two huge data sets from different countries. These results should be helpful for school and mental health care providers to plan interventions for youth at risk of suicide to prevent suicidal completion in these nations.
Leveraging Rebranding of ‘Unattractive’ Nation Brands to Stimulate Post-Disaster Tourism
Authors: Amujo Olusanmi C. , Otubanjo Olutayo
Published: May 2012

This paper presents insights on how to rebrand a nation with a negatively viewed brand name and identity caused by disaster, atrocity or political upheaval, to stimulate tourism. Following a review of the literature, the authors conceptualise the notion of negatively viewed nation brand and propose a positioning model for rebranding negatively viewed nation brand identity. The study reveals that nation brand association and identity redeployment in post genocide or natural disaster are critical resources for an effective nation rebranding exercise. The study provides insights on how tourism marketers can successfully leverage nation rebranding to stimulate tourism in the aftermath of a disaster. It proposes a theoretical framework for nation rebranding in post atrocity in emerging markets.
Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticosteroids in gastrointestinal graft-versus-host disease
Authors: Rodriguez-Otero Paula , Porcher Raphael , Peffault de Latour Régis , Contreras Margarita , Bouhnik Yoram , Xhaard Aliénor , Andreoli Annalisa , Ribaud Patricia , Kapel Nathalie , Janin Anne , Socié Gérard , Robin Marie
Published: May 2012

Diagnosis of gastrointestinal GVHD (GI-GVHD) is based on clinical symptoms and histologic findings. No biomarkers predicting responses to treatment are routinely available even though 30% to 50% of patients will not respond to corticosteroids. In this study, we aimed to evaluate fecal calprotectin, α-1-antitrypsin (α1-AT), and elastase at the time of first symptoms as diagnostic and prognostic tools for GI-GVHD in 72 consecutive patients, of whom 51 developed GI-GVHD. The prognostic value of markers was evaluated by their association with complete response (CR) and steroid-resistant (SR) GVHD. Calprotectin and α1-AT concentrations increased with GI-GVHD initial stages but patients with initial stage 1 GI-GVHD had similar marker levels to patients without GI-GVHD, so sensitivity to diagnose GI-GVHD was weak. In contrast, calprotectin and α1-AT were predictors for SR-GVHD and CR. Multiple regression modeling identified calprotectin and α1-AT concentration as independently predicting SR-GVHD together with initial stage > 2 GI-GVHD. Our results showed that fecal calprotectin and α1-AT levels at the time of diagnosis are predictive for responses to treatment but are not diagnostic markers for initial stage 1 to 3 GI-GVHD.
GeSICA: Genome segmentation from intra-chromosomal associations
Authors: Liu Lin , Zhang Yiqian , Feng Jianxing , Zheng Ning , Yin Junfeng , Zhang Yong
Published: May 2012

Background

Various aspects of genome organization have been explored based on data from distinct technologies, including histone modification ChIP-Seq, 3C, and its derivatives. Recently developed Hi-C techniques enable the genome wide mapping of DNA interactomes, thereby providing the opportunity to study genome organization in detail, but these methods also pose challenges in methodology development.

Results

We developed Genome Segmentation from Intra Chromosomal Associations, or GeSICA, to explore genome organization and applied the method to Hi-C data in human GM06990 and K562 cells. GeSICA calculates a simple logged ratio to efficiently segment the human genome into regions with two distinct states that correspond to rich and poor functional element states. Inside the rich regions, Markov Clustering was subsequently applied to segregate the regions into more detailed clusters. The binding sites of the insulator, cohesion, and transcription complexes are enriched in the boundaries between neighboring clusters, indicating that inferred clusters may have fine organizational features.

Conclusions

Our study presents a novel analysis method, known as GeSICA, which gives insight into genome organization based on Hi-C data. GeSICA is open source and freely available at: http://web.tongji.edu.cn/~zhanglab/GeSICA/
The fetomaternal interface in the placenta of three species of armadillos (Eutheria, Xenarthra, Dasypodidae)
Authors: Rezende Lorenna C , Barbeito Claudio G , Favaron Phelipe O , Mess Andrea , Miglino Maria A
Published: May 2012

Background

Placental characters vary among Xenarthra, one of four supraordinal clades of Eutheria. Armadillos are known for villous, haemochorial placentas similar to humans. Only the nine-banded armadillo has been well studied so far.

Methods

Placentas of three species of armadillos were investigated by means of histology, immunohistochemistry including proliferation marker, and transmission and scanning electron microscopy.

Results

The gross anatomy differed: Euphractus sexcinctus and Chaetophractus villosus had extended, zonary placentas, whereas Chaetophractus vellerosus had a disk. All taxa had complex villous areas within the maternal blood sinuses of the endometrium. Immunohistochemistry indicated the validity of former interpretations that the endothelium of the sinuses was largely intact. Tips of the villi and the columns entering the maternal tissue possessed trophoblast cell clusters with proliferation activity. Elsewhere, the feto-maternal barrier was syncytial haemochorial with fetal vessels near the surface.

Conclusions

Differences among armadillos occurred in regard to the extension of the placenta, whereas the fine structure was similar. Parallels to the human suggest that armadillos are likely to be useful animal models for human placentation.
Platelet-Activating Factor Antagonists Decrease Follicular Dendritic-Cell Stimulation of Human B Lymphocytes
Authors: Halickman Isaac , Bastien Yolande , Zhuang Qianli , Mazer Monty B , Toledano Baruch , Mazer Bruce D
Published: May 2012

Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA) gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10-6to 10-8M) inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6to 10-8M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA) from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.
Potential Adverse and Allergic Reactions from Complementary and Alternative Medicine and Dietary Supplements
Authors: Wong H.C. George
Published: May 2012

Complementary and alternative medicine and dietary supplements are often used by patients. A detailed examination of each preparation used by four patients was carried out. Seven such preparations with the potential to cause bleeding, cardiovascular and central nervous system side effects, and allergic food reactions are described. They were taken by both Asian and Caucasian patients, were purchased locally, and were used for allergic and nonallergic disorders. Inquiry into their use is important to prevent potential adverse and allergic reactions. There should be a higher standard of regulation for such products.
Mechanisms of Degranulation in Neutrophils
Authors: Lacy Paige
Published: May 2012

Neutrophils are critical inflammatory cells that cause tissue damage in a range of diseases and disorders. Being bone marrow-derived white blood cells, they migrate from the bloodstream to sites of tissue inflammation in response to chemotactic signals and induce inflammation by undergoing receptor-mediated respiratory burst and degranulation. Degranulation from neutrophils has been implicated as a major causative factor in pulmonary disorders, including severe asphyxic episodes of asthma. However, the mechanisms that control neutrophil degranulation are not well understood. Recent observations indicate that granule release from neutrophils depends on activation of intracellular signalling pathways, including β-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, thesrcfamily of tyrosine kinases, and the tyrosine phosphatase MEG2. Some of these observations suggest that degranulation from neutrophils is selective and depends on nonredundant signalling pathways. This review focuses on new findings from the literature on the mechanisms that control the release of granule-derived mediators from neutrophils.
Maternal Smoking in Pregnancy: Do the Effects on Innate (Toll-Like Receptor) Function Have Implications for Subsequent Allergic Disease?
Authors: Prescott Susan L. , Noakes Paul S.
Published: May 2012

Subtle increases in immaturity of immune function in early infancy have been implicated in the rising susceptibility to allergic disease, particularly relative impairment of type 1 interferon (IFN)-γ responses in the neonatal period. Although genetic predisposition is a clear risk factor, the escalating rates of allergic disease in infancy suggest that environmental factors are also implicated. We previously showed that maternal smoking in pregnancy may impair neonatal IFN-γ responses. Our more recent studies now indicate that this common avoidable toxic exposure is also associated with attenuation of innate immune function, with attenuated Toll-like receptor (TLR)-mediated microbial responses (including TLR-2, -3, -4, and -9 responses). Most notably, the effects were more marked if the mothers were also allergic. In this review, we discuss the significance of these observations in the context of the emerging hypothesis that variations in TLR function in early life may be implicated in allergic propensity. There is now growing evidence that many of the key pathways involved in subsequent T-cell programming and regulation (namely, antigen-presenting cells and regulatory T cells) rely heavily on microbe-driven TLR activation for maturation and function. Factors that influence the function and activity of these innate pathways in early life may contribute to the increasing predisposition for allergic disease. Although "cleaner" environments have been implicated, here we explore the possibility that other common environmental exposures (such as maternal smoking) could also play a role.
Progress and Challenges in the Understanding of Chronic Urticaria
Authors: Ferrer Marta , Kaplan Allen P
Published: May 2012

Chronic urticaria is a skin disorder characterized by transient pruritic weals that recur from day to day for 6 weeks or more. It has a great impact on patients' quality of life. In spite of this prevalence and morbidity, we are only beginning to understand its physiopathology and we do not have a curative treatment. Moreover, a patient with chronic urticaria may undergo extensive laboratory evaluations seeking a cause only to be frustrated when none is found. In recent years there have been significant advances in our understanding of some of the molecular mechanisms responsible for hive formation. The presence and probable role of IgG autoantibodies directed against epitopes expressed on the alpha-chain of the IgE receptor and to lesser extent, to IgE in a subset of patients is generally acknowledged. These autoantibodies activate complement to release C5a, which augments histamine release, and IL4 and leukotriene C4 are released as well. A perivascular cellular infiltrate results without predominance of either Th1 or Th2 lymphocyte subpopulations. Basophils of all chronic urticaria patients (autoimmune or idiopathic) are hyperresponsive to serum, regardless of source, but poorly responsive to anti IgE. In this review we will summarize the recent contributions to this field and try to provide insights to possible future directions for research on this disease.
Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors
Authors: Peters Paul J , Duenas-Decamp Maria J , Sullivan W Matthew , Brown Richard , Ankghuambom Chiambah , Luzuriaga Katherine , Robinson James , Burton Dennis R , Bell Jeanne , Simmonds Peter , Ball Jonathan , Clapham Paul R
Published: May 2012

Background

HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node.

Results

R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542), but with increased resistance to the anti-CD4 monoclonal antibody (mab), Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120.

Conclusion

Variation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.
Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration
Authors: Tervo Hanna-Mari , Goffinet Christine , Keppler Oliver T
Published: May 2012

Background

The development of an immunocompetent, genetically modified mouse model to study HIV-1 pathogenesis and to test antiviral strategies has been hampered by the fact that cells from native mice do not or only inefficiently support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse T-cell lines fail to express viral proteins, but the underlying replication barrier has thus far not been unambiguously identified. Here, we performed a kinetic and quantitative assessment of consecutive steps in the early phase of the HIV-1 replication cycle in T-cells from mice and humans.

Results

Both T-cell lines and primary T-cells from mice harbor a severe post-entry defect that is independent of potential species-specTR transactivation. Reverse transcription occurred efficiently following VSV-G-mediated entry of virions into mouse T-cells, and abundant levels of 2-LTR circles indicated successful nuclear import of the pre-integration complex. To probe the next step in the retroviral replication cycle, i.e. the integration of HIV-1 into the host cell genome, we established and validated a nested real-time PCR to specifically quantify HIV-1 integrants exploiting highly repetitive mouse B1 elements. Importantly, we demonstrate that the frequency of integrant formation is diminished 18- to > 305-fold in mouse T-cell lines compared to a human counterpart, resulting in a largely abortive infection. Moreover, differences in transgene expression from residual vector integrants, the transcription off which is cyclin T1-independent, provided evidence for an additional, peri-integrational deficit in certain mouse T-cell lines.

Conclusion

In contrast to earlier reports, we find that mouse T-cells efficiently support early replication steps up to and including nuclear import, but restrict HIV-1 at the level of chromosomal integration.
The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients
Authors: Van Rompaey Bart , Elseviers Monique M , Van Drom Wim , Fromont Veronique , Jorens Philippe G
Published: May 2012

Introduction

This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium. Two research questions were formulated. First, does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU? Second, does the use of earplugs during the night improve the quality of sleep in the ICU?

Methods

A randomized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night. The researchers were blinded during data collection. Assignment was performed by an independent nurse researcher using a computer program. Eligible patients had an expected length of stay in the ICU of more than 24 hours, were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10. Delirium was assessed using the validated NEECHAM scale, sleep perception was reported by the patient in response to five questions.

Results

The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients. A vast improvement was shown by a Hazard Ratio of 0.47 (95% confidence interval (CI) 0.27 to 0.82). Also, patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs. After the first night in the ICU, patients sleeping with earplugs reported a better sleep perception.

Conclusions

Earplugs may be a useful instrument in the prevention of confusion or delirium. The beneficial effects seem to be strongest within 48 hours after admission. The relation between sleep, sound and delirium, however, needs further research.

Trial registration

Current Controlled Trials ISRCTN36198138
The Effects of Tax Shocks on Output: Not So Large, But Not Small Either
Authors: Perotti Roberto
Published: May 2012

I argue that, on theoretical grounds, the discretionary component of taxation should be allowed to have different effects than the automatic response of tax revenues to macroeconomic variables. Based on a novel dataset, I show two results. First, responses to a tax shock that allow for a distinction between the discretionary and the endogenous components of tax changes are about halfway between the large effects estimated by Romer and Romer (2010) and the smaller effects estimated, for instance, by Favero and Giavazzi (2012) or Blanchard and Perotti (2002). Second, there is almost no statistically significant evidence of anticipation effects. (JEL E23, E62, H22, H24, H25, K34)
Fiscal Policy Multipliers on Subnational Government Spending
Authors: Clemens Jeffrey , Miran Stephen
Published: May 2012

Balanced budget requirements lead to substantial pro-cyclicality in state government spending, with the stringency of a state's rules driving the pace at which it must adjust to shocks. We show that fiscal institutions can generate natural experiments in deficit-financed spending that are informative regarding fiscal stabilization policy. Alternative sources of variation in subnational fiscal policy often implicitly involve “windfall” financing, which precludes any effect of future debt or taxation on current consumption and investment. Consistent with a role for these “Ricardian” effects, our estimates are smaller than those in related studies, implying an on-impact multiplier below 1. (JEL C51, E32, E62, H72)
The Stiff Is Moving—Conjugate Direction Frank-Wolfe Methods with Applications to Traffic Assignment*
Authors: Mitradjieva Maria , Lindberg Per Olov
Published: May 2012

We present versions of the Frank-Wolfe method for linearly constrained convex programs, in which consecutive search directions are made conjugate. Preliminary computational studies in a MATLAB environment applying pure Frank-Wolfe, conjugate direction Frank-Wolfe (CFW), bi-conjugate Frank-Wolfe (BFW), and “partanized” Frank-Wolfe methods to some classical Traffic Assignment Problems show that CFW and BFW compare favorably to the other methods. This spurred a more detailed study, comparing our methods to an origin-based algorithm. This study indicates that our methods are competitive for accuracy requirements ensuring link flow stability. We also show that CFW is globally convergent. We further point at independent studies by other researchers that show that our methods compare favorably with recent bush-based and gradient projection algorithms on computers with several cores.
On the crossing number of semiadequate links
Authors: Stoimenow Alexander
Published: May 2012

The concept of adequacy of a link was introduced to determine
its crossing number. We give crossing number estimates for the
(much larger) class of semiadequate links, in particular improving
the previously known estimates for positive links. We also give
examples showing that semiadequacy may not be attained in
minimal crossing number diagrams. Our approach uses the
description of links of a given canonical genus, and is related
to skein invariants, the signature, the new concordance
invariants, and hyperbolic volume. It allows to settle the
A/B-adequacy status of many examples, including all knots
up to 10 crossings. As two applications, we describe generic
alternating and positive knots of given genus, determining
the asymptotical behaviour of the number of such knots, and
classify Seifert fibered, and therewith also hyperbolic,
Montesinos links.
On the existence of non-trivial finitely injective modules
Authors: Guil Asensio Pedro A. , Izurdiaga Manuel C. , Torrecillas Blas
Published: May 2012

We develop a technique to construct finitely injective modules which
are non-trivial, in the sense that they are not direct sums of
injective modules. As a consequence, we prove that a ring R is
left noetherian if and only if each finitely injective left
R-module is trivial, thus answering an open question posed by
Salce.
The composite nature of the interaction between nuclear receptors EcR and DHR38
Authors: Zoglowek Anna , Orłowski Marek , Pakuła Szymon , Dutko-Gwóźdź Joanna , Pajdzik Dorota , Gwóźdź Tomasz , Rymarczyk Grzegorz , Wieczorek Elżbieta , Dobrucki Jurek , Dobryszycki Piotr , Ożyhar Andrzej
Published: May 2012

Ecdysteroids coordinate essential biological processes in Drosophila through a complex of two nuclear receptors, the ecdysteroid receptor (EcR) and the ultraspiracle protein (Usp). Biochemical experiments have shown that, in contrast to Usp, the EcR molecule is characterized by high intramolecular plasticity. To investigate whether this plasticity is sufficient to form EcR complexes with nuclear receptors other than Usp, we studied the interaction of EcR with the DHR38 nuclear receptor. Previous in vitro experiments suggested that DHR38 can form complexes with Usp and thus disrupt Usp-EcR interaction with the specific hsp27pal response element. This article provides the experimental evidence that EcR is able to form complexes with DHR38 as well. The recombinant DNA-binding domains (DBDs) of EcR and DHR38 interact specifically on hsp27pal. However, the interaction between the receptors is not restricted to their isolated DBDs. We pre\xadsent data that indicate that the full-length EcR and DHR38 can also form specific complexes within the nuclei of living cells. This interaction is mediated by the hinge region of EcR, which was recently classified as an intrinsically disordered region. Our results indicate that DHR38 might modulate the activity of the Usp-EcR heterodimer by forming complexes with both of its components.
Rab1 interacts directly with the β2-adrenergic receptor to regulate receptor anterograde trafficking
Authors: Hammad Maha M. , Kuang Yi-Qun , Morse Alexa , Dupré Denis J.
Published: May 2012

Very little is understood about the trafficking of G protein-coupled receptors (GPCRs) from the endoplasmic reticulum (ER) to the plasma membrane. Rab guanosine triphosphatases (GTPases) are known to participate in the trafficking of various GPCRs via a direct interaction during the endocytic pathway, but whether this occurs in the anterograde pathway is unknown. We evaluated the potential interaction of Rab1, a GTPase known to regulate β2-adrenergic receptor (β2AR) trafficking, and its effect on export from the ER. Our results show that GTP-bound Rab1 interacts with the F(x)6LL motif of β2AR. Receptors lacking the interaction motif fail to traffic properly, suggesting that a direct interaction with Rab1 is required for β2AR anterograde trafficking.
Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2
Authors: Esterházy Daria , Akpinar Pinar , Stoffel Markus
Published: May 2012

The pancreatic β-cell surface protein Tmem27 is promotes the preservation of functional β-cell mass. It is a selective substrate of the protease Bace2, yet the intramolecular features of Tmem27 that regulate its processing by this sheddase have not been characterized. In particular, the importance of homodimerization, glycosylation, trafficking to the plasma membrane (PM), the existence of multiple cleavage sites, and the amino acid residues that govern these features are currently unknown. Using Tmem27 mutational analysis and multiple biochemical approaches, we here show that Tmem27 dimerization is a dynamic process mediated by its intracellular cysteine residue and that prevents Tmem27 cleavage, that extracellular asparagine glycosylation is essential for Tmem27 trafficking to the PM and its processing by Bace2, that the amount of Tmem27 at the PM is proportional to its total cell levels upon glucose stimulation and Bace2 inhibition, and that the double phenylalanine motif in the Tmem27 cleavage site is an intramolecular Bace2 inhibitor. These findings define structural properties of Tmem27 that affect the susceptibility to its protease Bace2 and have implications for the efficiency with which Tmem27 and other Bace2 substrates are cleaved in normal and disease states.
New ketomethylene inhibitor analogues: synthesis and assessment of structural determinants for N-domain selective inhibition of angiotensin-converting enzyme
Authors: Sharma Rajni K. , Douglas Ross G. , Louw Stefan , Chibale Kelly , Sturrock Edward D.
Published: May 2012

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase containing two homologous domains. While the C-domain plays a major role in blood pressure regulation, the N-domain hydrolyzes the antifibrotic agent N-acetyl-Ser-Asp-Lys-Pro. Thus, N-domain selective (N-selective) inhibitors could be useful in the treatment of conditions relating to excessive tissue fibrosis. New keto-ACE analogues were designed that contained functionalities considered important for N-selective inhibitor RXP407 binding, namely, a P2 Asp, N-acetyl group, and C-terminal amide. Such functionalities were incorporated to assess the structural determinants for N-selective binding in a novel inhibitor template. Inhibitors containing a C-terminal amide and modified P2′ group were poor inhibitors of the N-domain, with several of these displaying improved inhibition of the C-domain. Molecules with both a C-terminal amide and P2 Asp were also poor inhibitors and not N-selective. Compounds containing a free C-terminus, a P2 Asp and protecting group displayed a change of more than 1000-fold N-selectivity compared with the parent molecule. Molecular docking models revealed interaction of these P2 groups with S2 residues Tyr369 and Arg381. This study emphasizes the importance of P2 functionalities in allowing for improved N-selective binding and provides further rationale for the design of N-selective inhibitors, which could be useful in treating tissue fibrosis.