bluuebunny/crossref_metadata_2025 huggingface dataset:
Compadrazgo
Authors: Gill-Hopple Kathy , Brage-Hudson Diane
Published: January 2012

Compadrazgo, “coparenthood,” is a traditional ritual fictive kinship system that provides a network of mutually supportive relationships in the Mexican American culture. A literature search of CINAHL, Medline, PsychoInfo, and Web of Science was used to identify peer-reviewed journals and original sources. Keywords included comadre, compadrazgo, fictive kin, social support, Mexican, and Mexican American. Additional resources were identified through a focused review of references. Findings from this study indicate knowledge about compadrazgo, is limited to the social organization, historical practices, and a preliminary description of the compadres role. Minimal information is available about the relationship between compadrazgo, and health, and variations in roles and responsibilities of compadrazgo, participants. Frequency of enactment of compadrazgo, responsibilities and barriers to the enactment of social support by compadres remain unknown. Variations in practice have not been explored. Nursing implication include the recommended ways that compadrazgo, can be encouraged or promoted in patient care.
Simulating REAL LIVES
Authors: Bachen Christine M. , Hernández-Ramos Pedro F. , Raphael Chad
Published: January 2012

In response to an increasingly interdependent world, educators are demonstrating a growing interest in educating for global citizenship. Many definitions of the “good global citizen” value empathy as an especially important disposition for understanding others across national borders and cultural divides. Yet it may be difficult for people to achieve empathy with others who are perceived as psychologically and geographically distant. Can computerized simulation games help foster global empathy and interest in global civic learning? This quasiexperimental classroom study of 301 Northern California high school students in three schools examined the effects of playing REAL LIVES, a simulation game that allows players to inhabit the lives of individuals around the world. Compared with a control group, students who played the simulation game as part of their curriculum expressed more global empathy and greater interest in learning about other countries. Identification with REAL LIVES characters was also positively related to global empathy. These findings support claims that computerized simulations can cultivate important dispositions for global learning and citizenship.
Assessing the Effectiveness of First Step to Success
Authors: Sumi W. Carl , Woodbridge Michelle W. , Javitz Harold S. , Thornton S. Patrick , Wagner Mary , Rouspil Kristen , Yu Jennifer W. , Seeley John R. , Walker Hill M. , Golly Annemieke , Small Jason W. , Feil Edward G. , Severson Herbert H.
Published: January 2012

This article reports on the effectiveness of First Step to Success, a secondary-level intervention appropriate for students in early elementary school who experience moderate to severe behavior problems and are at risk for academic failure. The authors demonstrate the intervention’s short-term effects on multiple behavioral and academic outcomes as delivered off-the-shelf in a variety of classrooms and schools across the country—effects that were mitigated by fidelity of implementation. Furthermore, the authors assess the body of evidence on First Step to Success against the standards for effectiveness and widespread dissemination promulgated by the Society for Prevention Research, thereby suggesting directions for further research.
Do Reasons Matter? The Impact of Opinion Content on Supreme Court Legitimacy
Authors: Farganis Dion
Published: January 2012

Is Supreme Court legitimacy affected by the way justices explain their decisions to the public? Existing work shows a link between legitimacy and case outcomes but often overlooks the impact of opinion content. Using a novel experimental design, the author measures the effect of three different types of judicial arguments on public support for the Court. The results suggest that the rationales used by justices in their opinions can affect institutional legitimacy, but to a lesser degree than conventional wisdom suggests. Taken together with other recent legitimacy research, these findings have important implications and set the stage for follow-up research.
Diversity in Political Institutions and Congressional Responsiveness to Minority Interests
Authors: Minta Michael D. , Sinclair-Chapman Valeria
Published: January 2012

Despite claims that diversity benefits the democratic process, critics question whether increased diversity significantly improves government responsiveness and accountability beyond electoral competition and constituency influence. The authors advance a diversity infrastructure theory to explain why and how minority legislators have kept minority interests on the congressional agenda. Using data on congressional hearings held on civil rights and social welfare from 1951 to 2004, the authors find that despite the decline of national attention to civil rights and social welfare issues in general, increased diversity in the House and to a lesser extent in the Senate is responsible for keeping minority interests on the congressional agenda.
Attack Advertising, the White Decision, and Voter Participation in State Supreme Court Elections
Authors: Gann Hall Melinda , Bonneau Chris W.
Published: January 2012

This project evaluates whether televised attack advertising and less restrictive campaign speech codes brought about by Republican Party of Minnesota v. White (2002) have had adverse effects on citizen participation in state supreme court elections. The authors’ specific focus is on partisan and nonpartisan races from 2002 through 2006. Overall, they find that attack ads and liberalized speech codes actually mobilize rather than demobilize the electorate. These findings highlight the striking similarities between supreme court elections and elections to other important offices. These results also raise questions about the validity of normative accounts of the relationship between citizens and the bench.
Fluorodeoxyglucose-induced allergic reaction: A case report
Authors: Codreanu Ion , Dasanu Constantin A , Weinstein Gregory S , Divgi Chaitanya
Published: January 2012

The number of diagnostic positron emission tomography/computed tomography (PET/CT) procedures performed in the USA and worldwide is rapidly increasing. Although the benefits of these procedures are obvious, the increasing use of radiopharmaceuticals requires a better understanding of potential adverse affects and their proper management. We present herein the first report of an allergic reaction to fluorodeoxyglucose in the setting of repeated PET/CT scans for restaging purposes in a patient with pyriform sinus cancer.
Social Ecological Approaches to Individuals and Their Contexts
Authors: Golden Shelley D. , Earp Jo Anne L.
Published: January 2012

Social ecological models that describe the interactive characteristics of individuals and environments that underlie health outcomes have long been recommended to guide public health practice. The extent to which such recommendations have been applied in health promotion interventions, however, is unclear. The authors developed a coding system to identify the ecological levels that health promotion programs target and then applied this system to 157 intervention articles from the past 20 years of Health Education & Behavior. Overall, articles were more likely to describe interventions focused on individual and interpersonal characteristics, rather than institutional, community, or policy factors. Interventions that focused on certain topics (nutrition and physical activity) or occurred in particular settings (schools) more successfully adopted a social ecological approach. Health education theory, research, and training may need to be enhanced to better foster successful efforts to modify social and political environments to improve health.
Renaming the past in post-Nazi Germany: insights into the politics of street naming in Mannheim and Potsdam
Authors: Azaryahu Maoz
Published: January 2012

The critical turn in the study of toponymy has drawn attention to the politics of place-naming practices and to how place names are embedded into systems of meaning and partake in social and ideological discourses. A measure of historical revision, the commemorative renaming of streets in the context of regime change is a common strategy employed to signify the break with the past. This article juxtaposes patterns of renaming the past in two German cities from 1945 through 1950 as an aspect of the democratic reconstruction of post-Nazi Germany. The moderate pattern applied in Mannheim represented a restorative approach and signified continuity with the pre-1933 Weimar Republic. The radical pattern applied in communist-controlled Potsdam represented the future-oriented approach of socialist transformation. At one level, the investigation explores patterns of commemorative renaming of streets in two German provincial cities after the collapse of Nazi Germany. At another, the juxtaposition of two patterns of renaming the past in post-Nazi Germany offers insights into large-scale renaming of streets as a ritual of revolution that, involving different interests and priorities introduces major political shifts and the ideological reorientation of society they entail into urban namescapes.
Competitive Balance in the Eyes of the Sports Fan
Authors: Bowman R. Alan , Lambrinos James , Ashman Thomas
Published: January 2012

There are many measures of competitive balance in the sports economics literature, each with their strengths and weaknesses. This study uses point spreads to measure competitive balance which has the advantages that they are prospective rather than retrospective and that they are determined by the sports fans and not just the outcome of a game. A total of six measures of competitive balance are developed from point spreads. These measures show a general trend toward improvement in competitive balance in the National Basketball Association over the past 20 years with no clear trend emerging for competitive balance in the National Football League.
Policy Timing and Footballers' Incentives
Authors: Lenten Liam J.A. , Libich Jan , Stehlík Petr
Published: January 2012

Assessing the effect of the timing and sequencing of various policy regimes on optimizing agent behavior is both important and difficult. To offer some insights, this article examines a timing decision from sports. The penalty shootout in football (soccer) has long been seen as problematic, among other reasons because it creates incentives for excessively cautious play during extra time. One proposal to alleviate this has been to alter the timing, and stage the shootout before (rather than after) extra time with the result binding only if the subsequent extra time offers no resolution. Carrillo’s (2007) theoretical model shows that since the effect of this rule change is ambiguous in theory, the proposal’s desirability needs to be assessed empirically. Using a comprehensive match data set, the authors compare scoring outcomes of various treatment and control groups, whereby the former simulate closely players' incentives from the proposed rule change, and the latter represent the current timing. Most importantly, the authors examine how extra time scoring probabilities depend on a goal being scored in the first 5 (or 15) min of extra time. Their estimates suggest that bringing the shootout before extra time would substantially alter the players' incentives in extra time and produce more overall attacking play. Quantitatively, the rule change is predicted to increase the odds of extra time scoring about threefold. Specifically, for the FIFA World Cup and the UEFA club competitions, the probability of scoring in extra time is estimated to increase on average by 45–60%, depending on various factors such as the result in regulation time, balancedness of the teams, and home ground advantage. In summary, all these results suggest that the case for trialing the proposed rule is strong. More generally, they highlight the incentive channels through which sequencing of policies may determine their effectiveness.
Exploring the Relationship Between Intercollegiate Athletic Expenditures and Team On-Field Success Among NCAA Division I Institutions
Authors: Jones Willis A.
Published: January 2012

In recent years, there has been increased research exploring the relationship between college/university intercollegiate athletic expenditures and team on-field success. Scope and methodological limitations of this previous research, however, suggest the need for further empirical research in this area. This study uses regression analyses with time and institutional fixed effects and several control variables to investigate the relationship between college/university athletic department expenditures and overall athletic department on-field success. The findings indicate that institutional athletic expenditures are strongly correlated with team on-field performance among Football Bowl Subdivision (FBS) institutions but not among non-FBS institutions.
Immediate Effects of On-The-Job Training and Its Intensity
Authors: Nutting Andrew W.
Published: January 2012

National Basketball Association home teams produce more defense and more wins the more consecutive games they play at home, suggesting home games serve as on-the-job training for future games during the same homestand. Home teams produce less defense and fewer wins the more days off during a homestand, suggesting training intensity increases productivity. A possible explanation is that teams develop communication skills specific to their home environments and/or adapt to referee bias toward home teams as homestands progress. Homestand training significantly weakens as the season progresses. Visiting teams show similar, but weaker, training effects with respect to roadtrip length and productivity.
Iron Deficiency in Athletes
Authors: Rowland Thomas
Published: January 2012

Adequate body stores of iron are necessary for optimal endurance exercise performance. Severe iron depletion resulting in overt iron-deficiency anemia clearly depresses endurance fitness, but it is not clear if milder degrees of iron deficiency (low serum ferritin with normal hemoglobin levels) impair physical capacity. The question is an important one for athletes, particularly females, who are particularly prone to iron deficiency without anemia. This review examines research data, in both animals and humans, which have addressed this issue. Constructing guidelines based on this often-conflicting body of information is difficult. Routine screening is advocated for at-risk athletes, particularly elite-level female competitors in distance sports, and, although controversial, many authorities recommend iron treatment for athletes with hypoferritemia (ferritin <12-20 ng/mL), even without overt anemia. However, “blind” supplementation with oral iron by athletes is not recommended.
Arguing for Amnesty
Authors: Bosniak Linda
Published: January 2012

This commentary addresses scholars and activists in liberal national states who advocate on behalf of undocumented immigrants, and offers some reflections on some of the intellectual and political challenges we encounter. I will suggest that the nature of our standard arguments on behalf of immigrants can sometimes give too much ground to current social conditions, and that we may – in our efforts to remain immediately policy-relevant – relinquish the opportunity to develop more fundamental social criticism of existing immigration relations.
Repeated oral administration of lipopolysaccharide from Escherichia coli 0111:B4 modulated humoral immune responses in periparturient dairy cows
Authors: Ametaj Burim N , Sivaraman Shanti , Dunn Suzanna M , Zebeli Qendrim
Published: January 2012

The objective of this study was to evaluate the effects of repeated oral exposure to LPS on humoral immune responses of periparturient dairy cows. Sixteen Holstein cows were assigned to two treatment groups 2 wk before the expected day of parturition. Cows were administered orally, twice weekly at wk −2, −1 and +1 around parturition, with the following treatments: 3 ml saline; or 3 ml of saline containing LPS from Escherichia coli 0111:B4. The amount of LPS administered during wk −2, −1, and +1 was 0.01, 0.05, or 0.1 µg/kg body weight, respectively. Multiple blood samples were collected by jugular vein and various immune and clinical variables were measured. Results indicated that, on one hand, concentrations of plasma IgG anti-LPS Abs decreased ( P < 0.01) and those of IgM anti-LPS Abs increased ( P < 0.01) in cows treated with oral LPS. On the other hand, there were no overall differences ( P > 0.05) in the concentrations of serum amyloid A, LPS-binding protein, haptoglobin, cortisol, IgA anti-LPS Abs in the plasma, feed intake, body temperature and rumen contractions rate between the control and treatment groups. To our knowledge, this study is the first to show that repeated oral administration with LPS from E. coli 0111:B4 has the potential to stimulate humoral immune responses in periparturient dairy cows.
A Study of the Proximal Wedge Shelf Osteotomy for Correction of Large IM Angle HAV Deformity
Authors: Fabrikant Jerry M. , Colarco Justin
Published: January 2012

Many procedures have been identified to correct hallux abducto valgus deformity of the foot. Due to surgical skill level, complexity, and risk of complications, more procedures have been defined for distal than proximal correction. The senior author has used an alternative proximal procedure to correct larger hallux abducto valgus deformities, which may prove to be as effective as traditional procedures. The purpose of this study was to examine the short-term clinical and radiographic results of the proximal wedge shelf osteotomy and evaluate its potential as a satisfactory option for correction of larger bunion deformities. The study revealed many positive outcomes as measured radiographically in preoperative and postoperative hallux abductus, intermetatarsal and metatarsal elevation/declination angles, and clinically by first metatarsophalangeal joint scores and patients’ subjective postoperative responses. From a review of the literature and results of the study, the authors conclude that the wedge shelf osteotomy can be used as an effective alternative for correcting larger bunion deformities with an intermetatarsal angle as large as 20° and a hallux valgus angle up to 38°. The advantages of this procedure include ability to correct in more than one plane, good bone-to-bone contact, and ease of fixation with 2 screws in an easily visible dorsal-to-plantar area. Disadvantages include the technical challenge of the procedure and its learning curve and some shortening of the first metatarsal.

Levels of Evidence: Therapeutic Level IV
The Postoperative COFAS End-Stage Ankle Arthritis Classification System
Authors: Krause Fabian G. , Di Silvestro Matthew , Penner Murray J. , Wing Kevin J. , Glazebrook Mark A. , Daniels Timothy R. , Lau Johnny T. C. , Younger Alastair S. E.
Published: January 2012

End-stage an kle arthritis is operatively treated with numerous designs of total an kle replacement and different techniques for an kle fusion. For superior comparison of these procedures, outcome research requires a classification system to stratify patients appropriately. A postoperative 4-type classification system was designed by 6 fellowship-trained foot and an kle surgeons. Four surgeons reviewed blinded patient profiles and radiographs on 2 occasions to determine the interobserver and intraobserver reliability of the classification. Excellent interobserver reliability (κ = .89) and intraobserver reproducibility (κ = .87) were demonstrated for the postoperative classification system. In conclusion, the postoperative Canadian Orthopaedic Foot and Ankle Society (COFAS) end-stage an kle arthritis classification system appears to be a valid tool to evaluate the outcome of patients operated for end-stage an kle arthritis.
A Proposed Treatment Algorithm for Midfoot Charcot Arthropathy
Authors: Smith W. Bret , Moore Chris A.
Published: January 2012

Charcot arthropathy (CA) is an insidious, destructive, and disabling pathology of the foot and ankle. Efficient and effective treatment is therefore required to improve clinical outcomes and to reduce overall mortality risk. The purpose of this case series report is to propose a treatment algorithm for correcting deformity and restoring a plantigrade, shoeable foot in patients with midfoot CA. While there is no clear evidence in the literature favoring either internal or external fixation methods, it may be appropriate to use both techniques during most deformity correction cases. Depending on the presence of ulceration, single-stage and multi-stage reconstruction with either biplanar or aggressive resection can effectively address the presentation of nonviable tissue and a wide degree of variable deformity. Following midfoot reduction, medial column plating and circular external frame can be used together to effectively stabilize and protect the correction and construct. In all cases, the aim is to immediately place the patient into a Charcot Restraint Orthotic Walker boot, with the ultimate goal of transitioning to diabetic shoeing as quickly as possible.
Platelet-Rich Plasma Treatment in Symptomatic Patients With Knee Osteoarthritis
Authors: Gobbi Alberto , Karnatzikos Georgios , Mahajan Vivek , Malchira Somanna
Published: January 2012

Background: With increasing frequency, platelet-rich plasma (PRP) preparations have been used to treat cartilage lesions to regenerate tissue homeostasis and retard the progression of knee osteoarthritis (OA).

Purpose: To determine the effectiveness of intra-articular PRP injections in active patients with knee OA and to evaluate clinical outcomes in patients with and without previous surgical treatment for cartilage lesions.

Study Design: Case series.

Materials and Methods: Fifty patients with knee OA were followed for a minimum of 12 months. All were treated with 2 intra-articular injections of autologous PRP. Twenty-five patients had undergone a previous operative intervention for cartilage lesions, whereas 25 had not. Operated patients had undergone either cartilage shaving or microfracture. Multiple evaluative scores were collected at pretreatment and at 6 and 12 months posttreatment. The required sample of patients was determined beforehand by using statistical power analysis; International Knee Documentation Committee (subjective) score was defined as the primary parameter. A P value of less than 0.05 was considered statistically significant. General linear model–repeated measure test evaluated within-time improvement for each variable for all patients. Post hoc test with Bonferroni adjustment for multiple comparisons was performed to investigate the significance in improvement within time evaluations for each variable for the total sample. The differences in improvement between operated and nonoperated patients were also investigated, as were those between sexes.

Results: All patients showed significant improvement in all scores at 6 and 12 months ( P < 0.01) and returned to previous activities. No significant difference in improvement was found between the evaluated subgroups ( P < 0.01).

Conclusions: The PRP treatment showed positive effects in patients with knee OA. Operated and nonoperated patients showed significant improvement by means of diminishing pain and improved symptoms and quality of life.

Clinical Relevance: There are only a few studies of PRP treatment for cartilage on osteoarthritic knees. Different PRP products might be more or less appropriate to treat different types of tissues and pathologies. The clinical efficacy of PRP remains under debate, and a standardized protocol has not yet been established.
The Psychological Weight of Weight Stigma
Authors: Major Brenda , Eliezer Dina , Rieck Heather
Published: January 2012

The authors theorized that overweight individuals experience social identity threat in situations that activate concerns about weight stigma, causing them to experience increased stress and reduced self-control. To test these predictions, women who varied in body mass index (BMI) gave a speech on why they would make a good dating partner. Half thought they were videotaped (weight visible); the remainder thought they were audiotaped (weight not visible). As predicted, higher BMI was associated with increased blood pressure and poorer performance on a measure of executive control when weight was visible and concerns about stigma were activated but not when weight was not visible. Compared to average weight women, overweight women also reported more stress-related emotions when videotaped versus audiotaped. Findings suggest that weight stigma can be detrimental to mental and physical health and deplete self-regulatory resources necessary for weight control.
Importance of characteristics and modalities of physical activity and exercise in defining the benefits to cardiovascular health within the general population: recommendations from the EACPR (Part I)
Authors: Vanhees L , De Sutter J , Geladas N , Doyle F , Prescott E , Cornelissen V , Kouidi E , Dugmore D , Vanuzzo D , Börjesson M , Doherty P
Published: January 2012

Over the last decades, more and more evidence is accumulated that physical activity (PA) and exercise interventions are essential components in primary and secondary prevention for cardiovascular disease. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit in achieving cardiovascular health. The present paper, as the first of a series of three, will make specific recommendations on the importance of these characteristics for cardiovascular health in the population at large. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and the individual member of the public. Based on previous and the current literature, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and exercise.
The Certified Asthma Educator (AE-C)
Authors: Cataletto Mary , Abramson Stuart , Meyerson Karen , Arney Traci , Bollmeier Suzanne , Dennis Rose , Hargrove Joyce Keith , Harver Andrew , Wissing Dennis , Williams Dennis ,   on behalf of theBoard of Directors of the National Asthma Educator Certification Board
Published: January 2012

Introduction: The Centers for Disease Control and Prevention report that the number of individuals with asthma in the United States has increased by 4.3 million, or 12.3%, between 2001 and 2009, creating an increasing burden on our health care system. Effective patient education is a key component of asthma management. The National Asthma Educator Certification Board (NAECB) promotes “optimal asthma management and quality of life by advancing excellence in asthma education through the Certified Asthma Educator process.” Methods: Following completion of the asthma educator certification examination, applicants were invited to participate in a voluntary, anonymous Web-based survey. The survey was developed and approved by the Executive and Research Committees of the NAECB, with the objective of reviewing the experience of applicants seeking initial certification and of those seeking recertification. Results: Completed surveys were obtained from 988 applicants. Seventy-six percent of respondents were first-time test takers; the remaining respondents were repeat test takers. Eighty percent reported having passed the examination. Approximately 85% felt that the time allotted for the examination was “just right”; the level of difficulty was “ just right” for 65% of the respondents, and the clarity of the examination questions was rated as “good” or “excellent” by 72% of the respondents. Seventy-two percent responded that the examination reflected the role of the asthma educator and 88.1% would recommend the examination to others interested in asthma education. Open-ended responses highlighted benefits and barriers. Discussion: The asthma educator certification examination is reflective of the professional responsibilities of the asthma educator. Benefits and barriers are discussed in the context of published literature.
Patient Preferences in Choosing a Primary Care Physician
Authors: Mercado Francis , Mercado Margaret , Myers Nancy , Hewit Michael , Haller Nairmeen Awad
Published: January 2012

Background and Aims: Studies have identified factors important to patients in consideration of a primary care physician (PCP). Few have explored relevant differences in choosing between family medicine (FM) and internal medicine (IM) physicians. The objective of this study was to identify differences in rating of factors perceived to be important to racially diverse FM and IM patients in the selection of a PCP, and to determine patient knowledge of PCP training. Settings, Design, Methods, and Material: This observational study used self-administered questionnaires to obtain information from adult participants at 2 continuity clinics, FM and IM. Participants rated 16 factors on their importance in selecting a PCP. Demographics and information regarding participants’ knowledge of PCP training were collected. Statistical Analyses Used and Results: 857 surveys were completed. Data were analyzed using descriptive statistics, Student t test, χ2, and multivariate logistic regression. Sixty-five percent and 32% of participants were Caucasian or African American, respectively. Combined responses from both clinics revealed g ood patient care as the factor ranked highest in importance for selecting a PCP, followed by good communication skills. Forty-eight percent and 35% of FM and IM participants, respectively, did not know whether their PCP was trained in IM or FM. More than 50% of participants were not familiar with the scope of their physicians’ practice. Conclusions: Our results suggest that good patient care and communication are similarly important to all patients, regardless of race. Practices should maintain focus on these qualities, as well as on patient education regarding the relevant differences between FM and IM physicians. Results from this study are consistent with prior research on these issues in more racially homogenous populations.
Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies
Authors: Barcellini Wilma , Zaja Francesco , Zaninoni Anna , Imperiali Francesca Guia , Battista Marta Lisa , Di Bona Eros , Fattizzo Bruno , Consonni Dario , Cortelezzi Agostino , Fanin Renato , Zanella Alberto
Published: January 2012

This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary autoimmune hemolytic anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼ 90% at months +6 and +12; the response was better in warm autoimmune hemolytic anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼ 50%) and duration compared with the patient's past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immunomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708.
RNAi screening of the kinome with cytarabine in leukemias
Authors: Tibes Raoul , Bogenberger James M. , Chaudhuri Leena , Hagelstrom R. Tanner , Chow Donald , Buechel Megan E. , Gonzales Irma M. , Demuth Tim , Slack James , Mesa Ruben A. , Braggio Esteban , Yin Hongwei H. , Arora Shilpi , Azorsa David O.
Published: January 2012

To identify rational therapeutic combinations with cytarabine (Ara-C), we developed a high-throughput, small-interference RNA (siRNA) platform for myeloid leukemia cells. Of 572 kinases individually silenced in combination with Ara-C, silencing of 10 (1.7%) and 8 (1.4%) kinases strongly increased Ara-C activity in TF-1 and THP-1 cells, respectively. The strongest molecular concepts emerged around kinases involved in cell-cycle checkpoints and DNA-damage repair. In confirmatory siRNA assays, inhibition of WEE1 resulted in more potent and universal sensitization across myeloid cell lines than siRNA inhibition of PKMYT1, CHEK1, or ATR. Treatment of 8 acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) cell lines with commercial and the first-in-class clinical WEE1 kinase inhibitor MK1775 confirmed sensitization to Ara-C up to 97-fold. Ex vivo, adding MK1775 substantially reduced viability in 13 of 14 AML, CML, and myelodysplastic syndrome patient samples compared with Ara-C alone. Maximum sensitization occurred at lower to moderate concentrations of both drugs. Induction of apoptosis was increased using a combination of Ara-C and MK1775 compared with using either drug alone. WEE1 is expressed in primary AML, ALL, and CML specimens. Data from this first siRNA-kinome sensitizer screen suggests that inhibiting WEE1 in combination with Ara-C is a rational combination for the treatment of myeloid and lymphoid leukemias.
Trastuzumab for treatment of refractory/relapsed HER2-positive adult B-ALL: results of a phase 2 GRAALL study
Authors: Chevallier Patrice , Robillard Nelly , Charbonnier Aude , Raffoux Emmanuel , Maury Sebastien , Carras Sylvain , Chabrot Cecile , Fohrer Cecile , Bernard Marc , Blade Jean-Sebastien , Etienne Anne , Talmant Pascaline , Delaunay Jacques , Guillaume Thierry , Mohty Mohamad , Bene Marie-Christine , Ifrah Norbert , Dombret Herve
Published: January 2012

The aim of this phase 2 study was to evaluate the efficacy and safety of trastuzumab, a humanized monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2), for adult patients with relapsed/refractory HER2-positive B-ALL. Fifteen patients, with a median age of 62 years, received trastuzumab according to the schedule approved for breast cancer patients (ie, 4 mg/kg intravenous loading dose followed by 2 mg/kg weekly). The overall response rate was 13% with 2 patients achieving partial response and partial remission cytolytic response, respectively. Two other patients were documented with blast clearance. Only 1 reversible grade 3 cardiac toxic event occurred. This phase 2 study showed that trastuzumab monotherapy can allow for some responses in a very high-risk refractory/relapsed HER2-positive adult B-ALL population. Combination of trastuzumab with chemotherapy or other therapeutic monoclonal antibodies should be tested in the future. This trial was registered at www.clinicaltrials.gov/ct as NCT00724360.
Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity
Authors: Schuurhof Annemieke , Bont Louis , Hodemaekers Hennie M. , de Klerk Arja , de Groot Hanneke , Hofland Regina W. , van de Pol Alma C. , Kimpen Jan L.L. , Janssen Riny
Published: January 2012

Severity of respiratory syncytial virus (RSV) infection ranges widely. To what extent the local immune response is involved in RSV disease pathogenesis and which markers of this response are critical in determining disease severity is still a matter of debate.

The local immune response was studied in nasopharyngeal aspirates (NPAs) during RSV infection. 47 potential markers of disease severity were analysed in a screening cohort of RSV-infected infants with mild disease at home (n=8), hospitalised infants (n=10) and infants requiring mechanical ventilation (n=7). Results were confirmed in a cohort of infants hospitalised for RSV infection (n=200). Finally, genetic validation was studied in a cohort of infants hospitalised for RSV infection (n=465) and healthy controls (n=930).

The concentration of TIMP-1 (tissue inhibitor of metalloproteinase) was higher in the NPAs of hospitalised infants compared with the NPAs of infants at home (1,199versus568 ng·mL−1; p<0.0001). Similar results were found for matrix metalloproteinase (MMP)-3 (765versus370 pg·mL−1; p=0.004). MMP-3 was confirmed as a marker of disease severity in a larger cohort andMMP3gene polymorphism rs522616 was associated with severe RSV infection (OR 0.82, p<0.05).

In conclusion, extracellular matrix proteinases play an important role in the pathogenesis of RSV bronchiolitis.
DNA damage as a molecular link in the pathogenesis of COPD in smokers
Authors: Aoshiba Kazutetsu , Zhou Fang , Tsuji Takao , Nagai Atsushi
Published: January 2012

In this study, we investigated whether DNA double-strand breaks (DSBs) contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD).

We immunofluorescence-stained lung tissue samples obtained from COPD patients, asymptomatic smokers and nonsmokers for markers of DSBs.

The numbers of DSB foci (phosphorylated histone 2AX (γH2AX), phosphorylated ATM (ataxia telangiectasia mutated) substrate and phosphorylated p53-binding protein-1 foci) per cell in alveolar type I and II cells and endothelial cells were higher in the COPD patients than in the asymptomatic smokers and nonsmokers. The lung tissue in which type II cells contained higher numbers of γH2AX foci per cell had higher percentages of type II cells that expressed p16INK4a(p16), phosphorylated nuclear factor (NF)-κB and interleukin (IL)-6, and of alveolar wall cells that expressed active caspase-3. The type II cells that contained higher numbers of γH2AX foci per cell had higher rates of expression of p16, phosphorylated NF-κB, and IL-6. Half of the alveolar wall cells that expressed active-caspase-3 contained γH2AX foci. Type II cells that stained positive for 8-hydroxy-2-deoxyguanosine contained a higher number of γH2AX foci per cell than the type II cells that stained negative.

In conclusion, DSBs, at least in part caused by oxidative stress, appear to contribute to the pathogenesis of COPD by inducing apoptosis, cell senescence and pro-inflammatory responses.
Mechanical properties of asthmatic airway smooth muscle
Authors: Chin Leslie Y.M. , Bossé Ynuk , Pascoe Chris , Hackett Tillie L. , Seow Chun Y. , Paré Peter D.
Published: January 2012

Airway smooth muscle (ASM) is the major effector of excessive airway narrowing in asthma. Changes in some of the mechanical properties of ASM could contribute to excessive narrowing and have not been systematically studied in human ASM from nonasthmatic and asthmatic subjects.

Human ASM strips (eight asthmatic and six nonasthmatic) were studied atin situlength and force was normalised to maximal force induced by electric field stimulation (EFS). Measurements included: passive and active forceversuslength before and after length adaptation, the force–velocity relationship, maximal shortening and force recovery after length oscillation. Force was converted to stress by dividing by cross-sectional area of muscle.

The only functional differences were that the asthmatic tissue was stiffer at longer lengths (p<0.05) and oscillatory strain reduced isometric force in response to EFS by 19% as opposed to 36% in nonasthmatics (p<0.01).

The mechanical properties of human ASM from asthmatic and nonasthmatic subjects are comparable except for increased passive stiffness and attenuated decline in force generation after an oscillatory perturbation. These data may relate to reduced bronchodilation induced by a deep inspiration in asthmatic subjects.
Prognostic value ofTP53,KRASandEGFRmutations in nonsmall cell lung cancer: the EUELC cohort
Authors: Scoccianti Chiara , Vesin Aurélien , Martel Ghislaine , Olivier Magali , Brambilla Elisabeth , Timsit Jean-François , Tavecchio Luca , Brambilla Christian , Field John K. , Hainaut Pierre ,   the European Early Lung Cancer Consortium
Published: January 2012

Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in theTP53,KRASandEGFRgenes.

The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs), 133 adenocarcinomas (ADCs) and seven large cell carcinomas or mixed histologies. Expression of p53 was analysed by immunohistochemistry. DNA was extracted from frozen tumour tissues.

TP53mutations were detected in 48.8% of cases and were more frequent among SCCs than ADCs (p<0.0001).TP53mutation status was not associated with prognosis. G to T transversions, known to be associated with smoking, were marginally more common among patients who developed a second primary lung cancer or recurrence/metastasis (progressive disease).EGFRmutations were almost exclusively found in never-smoking females (p=0.0067).KRASmutations were detected in 18.5% of cases, mainly ADC (p<0.0001), and showed a tendency toward association with progressive disease status.

These results suggest that mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception ofKRASmutation, which may have a prognostic value in ADC.
The European Respiratory Society spirometry tent: a unique form of screening for airway obstruction
Authors: Maio Sara , Sherrill Duane L. , MacNee William , Lange Peter , Costabel Ulrich , Dahlén Sven-Erik , Sybrecht Gerhard W. , Burghuber Otto C. , Stevenson Robin , Tønnesen Philip , Haeussinger Karl , Hedlin Gunilla , Bauer Torsten T. , Riedler Josef , Nicod Laurent , Carlsen Kai-Håkon , Viegi Giovanni
Published: January 2012

In order to raise public awareness of the importance of early detection of airway obstruction and to enable many people who had not been tested previously to have their lung function measured, the European Lung Foundation and the European Respiratory Society (ERS) organised a spirometry testing tent during the annual ERS Congresses in 2004–2009.

Spirometry was performed during the ERS Congresses in volunteers; all participants answered a simple, brief questionnaire on their descriptive characteristics, smoking and asthma. Portable spirometers were freely provided by the manufacturer. Nurses and doctors from pulmonary departments of local hospitals/universities gave their service for free. Lower limit of normal (LLN) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for diagnosing and grading airway obstruction were used.

Of 12,448 participants in six congress cities, 10,395 (83.5%) performed acceptable spirometry (mean age 51.0±18.4 yrs; 25.5% smokers; 5.5% asthmatic). Airway obstruction was present in 12.4% of investigated subjects according to LLN criteria and 20.3% according to GOLD criteria. Through multinomial logistic regression analysis, age, smoking habits and asthma were significant risk factors for airway obstruction. Relative risk ratio and 95% confidence interval for LLN stage I, for example, was 2.9 (2.0–4.1) for the youngest age (≤19 yrs), 1.9 (1.2–3.0) for the oldest age (≥80 yrs), 2.4 (2.0–2.9) for current smokers and 2.8 (2.2–3.6) for reported asthma diagnosis.

In addition to being a useful advocacy tool, the spirometry tent represents an unusual occasion for early detection of airway obstruction in large numbers of city residents with an important public health perspective.
A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation
Authors: Brittan Mairi , Barr Laura , Conway Morris Andrew , Duffin Rodger , Rossi Fiona , Johnston Shonna , Monro Graham , Anderson Niall , Rossi Adriano G. , McAuley Danny F. , Haslett Christopher , Hirani Nik , Dhaliwal Kev , Simpson A. John
Published: January 2012

The co-ordinated recruitment of monocyte subpopulations, neutrophils and regulatory T-cells (Tregs) during the early stages of human acute lung inflammation remains poorly understood. We therefore performed a detailed characterisation of these lineages in the blood and lungs in a model of human acute lung inflammation.

Healthy volunteers inhaled lipopolysaccharide (LPS) or saline (n=6 for each group). Blood was collected at 0, 2, 4, 6 and 8 h and bronchoscopy with bronchoalveolar lavage (BAL) performed at 8 h. Multiparameter flow cytometry was used to characterise monocyte subpopulations, neutrophils and Tregs in the blood and lung.

Inhalation of LPS was associated with significant blood and BAL fluid neutrophilia. Blood populations of monocyte subpopulations and Tregs were unaltered by LPS. In contrast, LPS induced an accumulation of a pulmonary monocyte-like cell (PMLC) population, which was further subdivided into “inducible” CD14++CD16-and “resident” CD14++CD16+subsets. Inducible PMLCs were significantly increased following LPS inhalation (p=0.0046), whereas resident PMLCs were unchanged. In addition, we noted a significant decrease in Tregs in BAL fluid with LPS inhalation (p=0.027).

The early stages of LPS-induced inflammation in humans is characterised by pulmonary accumulation of a novel inducible monocyte-like subpopulation, accompanied by significant changes in both neutrophil and Treg numbers.
Two novel, severe asthma phenotypes identified during childhood using a clustering approach
Authors: Just Jocelyne , Gouvis-Echraghi Rahele , Rouve Sarah , Wanin Stephanie , Moreau David , Annesi-Maesano Isabella
Published: January 2012

Unsupervised cluster analysis has already been used to identify severe phenotypes of childhood asthma, but without taking into account inflammatory markers. The aim of this study was to define independent homogeneous phenotypic clusters of severe asthma in a cohort of asthmatic children.

Cluster analysis was applied to 19 variables from 315 children enrolled in the Trousseau Asthma Program in Paris, France.

Three independent clusters of asthma were identified. Cluster 1, asthma with severe exacerbations and multiple allergies: 103 children had more sensitisations to inhaled allergens and food allergens, more blood eosinophils and basophils, more uncontrolled asthma despite high doses of inhaled corticosteroid and more hospitalisations for exacerbation. Cluster 2, severe asthma with bronchial obstruction: 72 children were significantly older, had the highest body mass index, a lower forced expiratory volume in 1 s, more pronounced blood neutrophils and significantly higher levels of all classes of immunoglobulin (Ig), except IgE. Cluster 3, mild asthma: 140 children did not show statistically significant features.

These results could lead to improved management of severe asthma in children by optimising treatment strategies,i.e.anti-allergic drugs, such as anti-IgE for children with the allergic phenotype, and anti-neutrophil drugs, such as macrolides for those with the obstructive phenotype.