bluuebunny/crossref_metadata_2025 huggingface dataset:
NOx, fuel consumption and time effects of flight path angle during descent
Authors: Turgut Enis T , Usanmaz Oznur
Published: March 2012

Due to factors affecting flight operation and air traffic management, such as air traffic separation, avoidance of traffic from congested areas, or facilitating separation with crossing traffic, as well as environmental constraints, aircraft cannot always use optimum descent profiles and perform stair step descent or low level flight. This leads to vertical flight inefficiencies and thereby an increase in fuel consumption and NO x emissions. In order to address the negative impact of vertical flight inefficiencies, particularly in the descent phase, descending at constant flight path angles has been identified as an efficient approach procedure by aviation organizations and researchers. This procedure is defined as continuous descent approach. In this study, an evaluation of continuous descent approach and various flight path angles, in relation to conventional approaches, is investigated and the comparative results are given in terms of NO x emissions, fuel consumption, and descent duration. As a result, a strong inverse proportion between flight path angle and fuel consumption is found. As expected, an analogous strong inverse relationship is also found for flight path angle and NO x emissions, not only from reduced fuel usage, but also from the changed exhaust gas temperature due to lower power settings thanks to the continuous descent approach. It can also be seen that the descent duration could be less for steeper flight path angles.
Six-degree of freedom active pneumatic table based on time delay control technique
Authors: Sun Jong-Oh , Kim Kwang-joon
Published: March 2012

Precision equipment is sensitive in general to both horizontal and vertical ground vibrations and, thus, equipment manufacturers specify limits on the vibrations of the floor so that such equipment can be operated satisfactorily. When the floor vibrations are unacceptably high, various types of passive or active vibration isolation tables can be used.

A three-degree of freedom active pneumatic table with time delay control was developed for control of heaving, pitching, and rolling motions in a previous study by the authors. The isolation performances achieved were very good for both ground and table excitations in the vertical directions. Limitations of the three-degree of freedom active pneumatic table, however, were that it is vulnerable to excitations of the floor and table in the horizontal directions. Hence, a six-degree of freedom active pneumatic table was required in order to tackle ground and table excitations in the horizontal as well as vertical direction.

In this paper, a study on the six-degree of freedom active pneumatic table supported by four air-springs for both vertical and horizontal vibration control is presented. Its performance is evaluated by ground and table excitation tests. The physical meaning of the singular value decomposition approach in transmissibility analysis on a multi-input/multi-output vibration isolation system is presented using a simple two-degree of freedom example and applied to the actual six-degree of freedom active pneumatic table. It is also shown that settling time in the case of table excitations in both vertical and horizontal directions can be effectively reduced by the proposed six-degree of freedom control.
Comparison between multi-objective and single-objective optimization for the modeling of dynamic systems
Authors: Zakaria Mohd Z , Jamaluddin Hishamuddin , Ahmad Robiah , Loghmanian Sayed MR
Published: March 2012

Modeling input–output data representing a dynamic system is a challenging task when multiple objectives are involved. The developed model needs to be parsimonious yet still adequate. To achieve these goals, two objective functions, i.e. optimum structure and minimum predictive error, need to be satisfied. Most works in system identification only consider one objective function, i.e. minimum predictive error, and the model structure is obtained by trial and error. This paper attempts to establish the needs of a multi-objective optimization algorithm by comparing it with a single-objective optimization algorithm. In this study, two different types of optimization algorithms are used to model a discrete-time system. These are an elitist non-dominated sorting genetic algorithm for multi-objective optimization and a modified genetic algorithm for single-objective optimization. Simulated and real systems data are studied for comparison in terms of model predictive accuracy and model complexity. The results show the advantage of the multi-objective optimization algorithm compared with the single-objective optimization algorithm in developing an adequate and parsimonious model for a discrete-time system.
Response to ustekinumab in a patient with both severe psoriasis and hypertrophic cutaneous lupus
Authors: Winchester D , Duffin K Callis , Hansen C
Published: March 2012

Psoriasis is an autoimmune inflammatory disease that has recently been treated with a novel treatment, ustekinumab, a human monoclonal antibody that targets the Th17 pathway. Discoid lupus is a subset of chronic cutaneous lupus erythematosus. Recent studies have suggested the Th17 pathway may be involved in cutaneous lupus. We present a case of a 41-year-old man with both severe psoriasis and hypertrophic discoid lupus treated with ustekinumab. After three doses of 45 mg subcutaneous injections at day 1, week 4, and week 16, his psoriasis plaques cleared and his hypertrophic discoid lupus plaques showed moderate improvement. Following a fourth dose of 90 mg his lupus plaques showed marked improvement. Ustekinumab may be a promising therapy for this and other forms of cutaneous lupus.
Factors Associated With Undernutrition Among Children in a Rural District of Kelantan, Malaysia
Authors: Whye Lian Cheah , Wan Muda Wan Abdul Mana , Mohd Hussin Zabidi Azhar , Ching Thon Chang
Published: March 2012

The aim of the study was to identify the factors associated with undernutrition indicators in children 5 years and younger in a rural community in Malaysia. A total of 295 children and their carers were selected from community clinics based on a multistage sampling method. Pretested questionnaire, anthropometric measurement, and dietary assessment were used for data collection. There was 69% stunting, 63.4% underweight, 40% wasting, and 26.8% with mid-upper-arm circumference (MUAC) for age below a z score of −2 among children. In all, 10 factors were found to be associated with different indicators of undernutrition. Age was the only factor that had association with all the undernutrition indicators. Total household income and total expenditure showed significant association with underweight. Birth weight was reported to have significant association with underweight, stunting, and low MUAC-for-age. The findings suggest that the factors of undernutrition were different for different indicators of undernutrition and thus give a more comprehensive picture on factors contributing to acute and chronic malnutrition.
Comparing a Pictorial Stroop Task to Viewing Time Measures of Sexual Interest
Authors: Bourke Ashling B. , Gormley Michael J.
Published: March 2012

This study investigated the ability of two viewing time (VT) methodologies and a pictorial Stroop task to differentiate sexual interest in a group of nonoffending heterosexual and homosexual men. The two VT methodologies were investigated given the lack of consistency among published studies supporting this method. The results indicated that the VT methodology in which participants are asked to browse through some images is slightly superior to the method in which participants are asked to rate their attractiveness to the images. The results also indicated that the Pictorial Stroop Task did not adequately differentiate between age categories of sexual interest within the two groups. The results have implications for the methodology used in VT tasks.
The Impact of Persisting Hyperactivity on Social Relationships
Authors: Moyá Jaime , Stringaris Argyris K. , Asherson Philip , Sandberg Seija , Taylor Eric
Published: March 2012

Objective: The purpose of this study was to examine whether persisting hyperactivity into adulthood was associated with impaired family, friendship, and partner relationships or poor coping skills in everyday life. Method: A 20-year community-based follow-up of 6- to 7-year-old boys showing pervasive hyperactivity ( n = 40) and unaffected controls ( n = 25) was conducted. At age 27 years, participants were assessed with detailed interview techniques as well as self-report ratings. Results: ADHD in adulthood was associated with problems in intimate relationships and negotiation skills. Antisocial behavior did not influence the association, but remitting childhood hyperactivity was not associated with social relationship difficulties in adulthood. Conclusion: In an untreated, community-based sample of hyperactive children, the risk for unsatisfactory social relationships is largely confined to those patients who still show ADHD in adulthood. The majority of patients who experience childhood hyperactivity have positive social relationships in adulthood.
Understanding intuition: The case for two forms of intuition
Authors: Dörfler Viktor , Ackermann Fran
Published: March 2012

Since the recent rejuvenation of intuition research within the management literature, significant work has been done on conceptualizing intuition. Whilst remarkable progress has been achieved in many areas of intuition, the role of intuition in creativity remains comparatively under-researched. Through an extensive review of intuition literature, we believe that a reason for this could be that intuition in the management literature is generally conceptualized as judgement. In this article we aim to extend our understanding of intuition in creativity by distinguishing between intuitive judgment and intuitive insight. Strengthening our case, this article builds on two previous research projects. The first focuses on literature-based features of intuition and the second project builds a conceptual model of knowledge types. Further informing the argument is Polanyi’s distinction of focal and subsidiary awareness. These considerations lead us to propose that there are two distinct kinds of intuition – intuitive judgement and intuitive insight.
Computational modelling of polyethylene wear and creep in total hip joint replacements: Effect of the bearing clearance and diameter
Authors: Liu Feng , Fisher John , Jin Zhongmin
Published: March 2012

Computational wear modelling has been improved using a contact area dependent wear law for the conventional ultra-high molecular weight polyethylene used in total hip joint bearings. The current designs of polyethylene bearings tend to use larger diameter heads to achieve improved motion function for patients in clinical practice, but the wear of the bearing may also increase due to the increase in contact area associated with the larger bearings. Additionally, bearing clearance, which is the difference in diameter or radius between the cup and head bearing surfaces, may also play an important role in affecting the wear. This study particularly investigates the effect of bearing clearance on polyethylene wear, for different femoral head diameters, through a parametric study using the computational modelling method. The effect of creep of polyethylene on the contact area and wear was considered, since polyethylene creep can account for a significantly large proportion of volumetric change, particularly during the initial loading stage, and an increase in the contact area. The predicted wear rate was found to be comparable to the experimental wear rate found in independent simulator tests. The polyethylene bearing with decreased bearing clearances led to a substantial increase in the wear rate, particularly when combined with large diameters.
“Without a Net”
Authors: Ramsay J. Russell
Published: March 2012

It is currently recognized that attention deficit/hyperactivity disorder (ADHD) persists into adulthood for more than half of affected individuals. ADHD in adulthood is associated with impairments in most adult roles. Medications are considered an effective treatment for the core symptoms of ADHD. Adjunctive psychosocial treatment, primarily cognitive-behavioral therapy (CBT), is efficacious in cases of residual symptoms and impairments. However, a minority of adults with ADHD may not be able to take medications due to medical contraindications, nonresponse, or intolerable side effects. The goal of this article is to discuss the case of an adult with ADHD who is unable to take medications for ADHD due to cardiac risk. The patient sought a course of CBT for adult ADHD to address difficulties he experienced at work and in his home life. His case illustrates the challenges of and opportunities for CBT for adult ADHD without medications.
Buttock Claudication After Interventional Occlusion of the Hypogastric Artery—A Mid-Term Follow-Up
Authors: Pavlidis Daphne , Hörmann M. , Libicher M. , Gawenda M. , Brunkwall J.
Published: March 2012

Background. Interventional occlusion of the hypogastric artery (HA) can be used for endovascular aneurysm repair (EVAR) in the iliac arteries. Most frequent ischemic complication is buttock claudication (BC). Aim. To investigate the frequency and progression of BC after interventional occlusion of the HA prior to EVAR. Methods. A retrospective analysis was performed in patients with EVAR and occlusion of the HA between September 2004 and August 2010. Acute and persistent BC symptoms were assessed. Results. Fifty-four catheter occlusions of the HA were performed. In 10 cases, claudication could not be evaluated. During a mean follow-up of 17 months, 23 occlusions (52.3%) of the HA showed BC, in 52% symptoms were persistent. Of the 5 patients, 3 patients who underwent bilateral occlusion had BC and in 2 cases, persistent in the follow-up. Conclusion. Buttock claudication after occlusion of the HA prior to EVAR is a frequent complication, which often persists during follow-up. Alternatives that maintain pelvic perfusion should be considered.
An adaptive strategy for assessing regional consistency in multiregional clinical trials
Authors: Chen Joshua , Quan Hui , Gallo Paul , Ouyang Soo P , Binkowitz Bruce
Published: March 2012

Background Unexpected regional difference in treatment effect has been reported in recent multiregional clinical trials (MRCTs). This may cause difficulty in interpreting results and can have regulatory implications such as marketing approvals and/or product labels in various markets. Careful consideration of consistency across regions and appropriate plans to address potential regional difference are necessary at the design stage. However, assessment of consistency in treatment effect is generally not the primary objective, and therefore, when there is no strong a priori reason to expect a regional difference, a MRCT is not usually designed to address the regional consistency. Unexpected regional finding may arise and increase the risk of ambiguous or controversial results at the end of the study.

Purpose To mitigate this risk, we propose an adaptive strategy for regional assessment based upon accumulated blinded data.

Methods If review of accumulated blinded data shows unexpectedly severe imbalance in an intrinsic or extrinsic factor, and further assessment indicates that this factor could be a potential effect modifier as supported by biological plausibility or blinded correlation analysis, a stratified regional analysis controlled for this factor may be specified and documented before database lock.

Results The proposed adaptive strategy can help with the interpretation of unexpected regional finding. A recent trial is used to illustrate the approach.

Limitations Even if the imbalanced factor may appear to explain away the regional difference, establishment of causal effect is usually difficult and requires more involved effort.

Conclusions This approach, by prespecifying the stratified analysis, can reduce the risk of post hoc exaggerated emphases across many possible exploratory analyses and provide greater confidence in the validity of the conclusions. If a causal effect can be established that the apparent regional difference is likely caused by this intrinsic or extrinsic factor, this prespecified analysis can also help guide clinical practice.
Regulatory role of periodontal ligament fibroblasts for innate immune cell function and differentiation
Authors: Konermann Anna , Stabenow Dirk , Knolle Percy A , Held Stefanie AE , Deschner James , Jäger Andreas
Published: March 2012

Innate immunity is crucial for an effective host defense against pathogenic microorganisms in periodontal tissues. As periodontal ligament (PDL) cells synthesize immunomodulatory cytokines, the aim of this in vitro study was to investigate whether these cells can interact with innate immune cells. Resting and inflammatory primed (IL-1β, TNF-α, HMGB1) human PDL cells were co-cultured with human monocyte-derived dendritic cells or macrophages. Migration, phenotypic maturation and modulation of phagocytosis of Porphyromonas gingivalis by immune cells were investigated upon co-culture with PDL cells and/or their released soluble factors. PDL cells interacted with immune cells under both non-inflammatory and inflammatory conditions. Immune cell migration was significantly enhanced by co-culture with PDL cells, which also affected their phenotypic maturation both through cell-cell contact and through released soluble mediators. The dendritic cell maturation markers CD83 and CD86 were upregulated as much as both ‘alternatively activated’ M2 macrophage maturation markers CD23 and CD163. In contrast, the ‘classically activated’ M1 macrophage maturation marker CD64 was downregulated. Finally, PDL cells significantly enhanced the phagocytosis of Porphyromonas gingivalis by immune cells. Our experiments revealed that PDL cells are not only structural elements of the periodontium, but actively influence immune responses by interaction with innate immune cells.
Intramuscular Ketorolac Injections in the Athlete
Authors: Sawyer Gregory A. , Anderson Brett C. , Raukar Neha P. , Fadale Paul D.
Published: March 2012

Background:

Pain control is a factor in the sideline treatment of competitive athletes. Ketorolac injections by team physicians as a pain control measure are seemingly becoming more mainstream, although there have been very little data published on its use.

Hypothesis:

Intramuscular ketorolac injections are being used regularly by orthopaedic surgeons and primary care sports medicine physicians in their care of athletes.

Study Design:

Descriptive epidemiology study.

Methods:

A 19-question survey was generated online for physician members of the American Orthopaedic Society for Sports Medicine, the Arthroscopy Association of North America, and the American Medical Society for Sports Medicine. The survey link was e-mailed, with reminders sent every 1 to 2 weeks, and results were collected from April to June 2011.

Results:

The survey was e-mailed to 6950 physicians, with 1100 respondents completing it (60% orthopaedic surgeons, 40% nonsurgical sports medicine physicians). Approximately 49% use intramuscular ketorolac in the treatment of athletes, primarily at the collegiate and professional levels; 95.8% reported effective pain control after administration; 2.9% reported bleeding complications; and 1.9% reported kidney complications from its use.

Conclusion:

Intramuscular ketorolac injections are used by approximately half of all team physicians in their sideline treatment of competitive athletes.
Apoptotic cell instillation after bleomycin attenuates lung injury through hepatocyte growth factor induction
Authors: Lee Ye-Ji , Moon Changsuk , Lee Seung Hae , Park Hyun-Jeong , Seoh Ju-Young , Cho Min-Sun , Kang Jihee Lee
Published: March 2012

Apoptotic cell clearance by macrophages and neighbouring tissue cells induces hepatocyte growth factor (HGF) secretion. HGF plays a key role in alveolar epithelial regeneration and reconstruction after lung injury. Directin vivoexposure to apoptotic cells enhances HGF production, resulting in attenuation of pulmonary injury.

We investigated the direct effect ofin vivoexposure to apoptotic cells in bleomycin-stimulated lungs (2 days old) on HGF induction. Furthermore, sequential changes of bleomycin-induced HGF production following apoptotic cell instillation related to the changes in inflammatory and fibrotic responses were assessed.

At 2 h after apoptotic cell instillation into bleomycin-stimulated lungs, the levels of HGF mRNA and protein production, and apoptotic cell clearance by alveolar macrophages were enhanced. Furthermore, HGF induction persistently increased following apoptotic cell instillation up to 21 days after bleomycin treatment. Apoptotic cell instillation attenuated bleomycin-induced pro-inflammatory mediator production, inflammatory cell recruitment and total protein levels. Apoptotic cell instillation also induced antiapoptotic and antifibrotic effects. These anti-inflammatory and antiapoptotic effects could be reversed by co-administration of HGF-neutralising antibody.

These findings indicate thatin vivoexposure to apoptotic cells enhances transcriptional HGF production in bleomycin-stimulated lungs, resulting in attenuation of lung injury and fibrosis.
Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury
Authors: Chimenti Laura , Luque Tomás , Bonsignore Maria R. , Ramírez José , Navajas Daniel , Farré Ramon
Published: March 2012

Bone marrow-derived mesenchymal stem cells (MSCs) reduce acute lung injury in animals challenged by bleomycin or bacterial lipopolysaccaride. It is not known, however, whether MSCs protect from ventilator-induced lung injury (VILI).

This study investigated whether MSCs have a potential role in preventing or modulating VILI in healthy rats subjected to high-volume ventilation.

24 Sprague–Dawley rats (250–300 g) were subjected to high-volume mechanical ventilation (25 mL·kg−1). MSCs (5×106) were intravenously or intratracheally administered (n=8 each) 30 min before starting over-ventilation and eight rats were MSC-untreated. Spontaneously breathing anesthetised rats (n=8) served as controls. After 3 h of over-ventilation or control the animals were sacrificed and lung tissue and bronchoalveolar lavage fluid (BALF) were sampled for further analysis.

When compared with controls, MSC-untreated over-ventilated rats exhibited typical VILI features. Lung oedema, histological lung injury index, concentrations of total protein, interleukin-1β, macrophage inflammatory protein-2 and number of neutrophils in BALF and vascular cell adhesion protein-1 in lung tissue significantly increased in over-ventilated rats. All these indices of VILI moved significantly towards normalisation in the rats treated with MSCs, whether intravenously or intratracheally. Both local and systemic pre-treatment with MSCs reduced VILI in a rat model.
Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes
Authors: Reddy Taryn L. , Tominaga Masaki , Hansell David M. , von der Thusen Jan , Rassl Doris , Parfrey Helen , Guy Suzy , Twentyman Orion , Rice Alexandra , Maher Toby M. , Renzoni Elisabetta A. , Wells Athol U. , Nicholson Andrew G.
Published: March 2012

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterised by predominantly upper lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls. The aim of this study was to review cases fulfilling published imaging and histological criteria, and identify any common clinical features that may suggest an underlying aetiology for a condition that has previously been regarded as idiopathic.

Of 12 patients (seven females, median age 57 yrs), the presenting symptoms were shortness of breath (11 out of 12 patients) and dry cough (six out of 12 patients). Seven patients reported recurrent infections during the course of their disease. Five demonstrated nonspecific autoantibody positivity. Two patients had a family history of interstitial lung disease (ILD).

High-resolution computed tomography features of lung disease remote from the pleuroparenchymal changes were present in six out of 12 patients (coexistent fibrosis, n=5; bronchiectasis, n=1). Of seven patients with tissue sampled from the lower lobes, four patients showed less intense PPFE changes (one with additional features of hypersensitivity pneumonitis) and three showed usual interstitial pneumonia.

PPFE is a distinct clinicopathological entity, with clinical data suggesting a link to recurrent pulmonary infection. Genetic and autoimmune mechanisms may also contribute to the development of these changes. PPFE may also present with more diffuse involvement than previously reported, and coexist with different patterns of ILD.
Natural course of sleep-disordered breathing after acute myocardial infarction
Authors: Buchner Stefan , Greimel Tanja , Hetzenecker Andrea , Luchner Andreas , Hamer Okka W. , Debl Kurt , Poschenrieder Florian , Fellner Claudia , Riegger Günter A.J. , Pfeifer Michael , Arzt Michael
Published: March 2012

The aim of this study was to test whether an improvement of left ventricular ejection fraction (EF) in the early phase after acute myocardial infarction is associated with a reduction of the severity of central and obstructive sleep apnoea.

40 consecutive patients with acute myocardial infarction underwent polysomnography and cardiovascular magnetic resonance imaging within 5 days and 12 weeks after the event to assess sleep apnoea and cardiac function. We stratified the sample in patients who improved their left ventricular EF within 12 weeks by ≥5% (improved EF group, ΔEF 9±1%, n=16) and in those who did not (unchanged EF group, ΔEF -1±1%, n=24).

Prevalence of sleep apnoea (≥15 apnoea and hypopnoea events·h−1) within ≤5 days after myocardial infarction was 55%. Apnoea and hypopnoea events·h−1were significantly more reduced in the improved EF group compared with the unchanged EF group (-10±3versus1±3 events·h−1; p=0.036). This reduction was based on a significant alleviation of obstructive events (-7±2versus4±3 events·h−1; p=0.009), while the reduction of central events was similar between groups (p=0.906).

An improvement of cardiac function early after myocardial infarction is associated with an alleviation of sleep apnoea. This finding suggests that re-evaluation of treatment indication for sleep apnoea is needed when a change in cardiac function occurs.
High-altitude treatment in atopic and nonatopic patients with severe asthma
Authors: Rijssenbeek-Nouwens Lucia H. , Fieten Karin B. , Bron Adriaan O. , Hashimoto Simone , Bel Elisabeth H. , Weersink Els J.
Published: March 2012

The beneficial effects of high-altitude treatment in asthma have been attributed to allergen avoidance. Recent evidence shows that this treatment also improves airway inflammation in nonallergic patients. We hypothesised that high-altitude treatment is clinically equally effective in patients with severe refractory asthma, with or without allergic sensitisation.

In a prospective observational cohort study, 137 adults with severe refractory asthma (92 with allergic sensitisation), referred for high-altitude (1,600 m) treatment in Davos, Switzerland, were consecutively included. We measured asthma control (Asthma Control Questionnaire (ACQ)), asthma-related quality of life (Asthma-Related Quality of Life Questionnaire (AQLQ)), sino-nasal symptoms (Sino-Nasal Outcome Test (SNOT-20)), medication requirement, postbronchodilator (post-BD) forced expiratory volume in 1 s (FEV1), 6-min walking distance (6MWD), total immunoglobulin (Ig)E, blood eosinophils and exhaled nitric oxide fraction (FeNO) at admission and after 12 weeks.

Sensitised and nonsensitised patients showed similar improvements in ACQ (-1.4 and -1.5, respectively; p=0.79), AQLQ (1.6 and 1.5, respectively; p=0.94), SNOT-20 (-0.7 and -0.5, respectively; p=0.18), post-BD FEV1(6.1% and 5.8% pred, respectively; p=0.87), 6MWD (+125 m and +147 m, respectively; p=0.43) and oral steroids (40%versus44%, respectively; p=0.51). Sensitised patients showed a larger decrease in total IgE, blood eosinophils andFeNO.

High-altitude treatment improves clinical and functional parameters, and decreases oral corticosteroid requirement in patients with severe refractory asthma, irrespective of allergic sensitisation.
Exercise testing to predict outcome in idiopathicversusassociated pulmonary arterial hypertension
Authors: Deboeck Gaël , Scoditti Cristina , Huez Sandrine , Vachiéry Jean-Luc , Lamotte Michel , Sharples Linda , Melot Christian , Naeije Robert
Published: March 2012

We tested the ability of exercise testing to predict not only survival, but also time to clinical worsening (TTCW) in idiopathicversusassociated pulmonary arterial hypertension (PAH).

136 patients with PAH (85 idiopathic and 51 with associated conditions) underwent cardiopulmonary exercise testing and a 6-min walk test. Death or transplantation, and clinical worsening events were recorded.

32 patients died and four had lung transplantation. In a univariate analysis, PAH patients survival was associated with oxygen uptake (V′O2) at peak exercise and at the anaerobic threshold, ventilatory equivalent for carbon dioxide (minute ventilation (V′E)/carbon dioxide production (V′CO2) at the anaerobic threshold (at)),V′E/V′CO2slope and distance walked. TTCW was associated with peakV′O2andV′O2,at,V′E/V′CO2,at, end-tidal carbon dioxide tension measured at the anaerobic threshold, peak oxygen pulse, increase in oxygen pulse and distance walked. In a multivariable analysis, distance walked andV′E/V′CO2,atpredicted survival, and only peakV′O2predicted TTCW. The receiver operating characteristic curve-derived cut-off values were 305 m for the 6-min walk distance, 54 forV′E/V′CO2,atand 11.6 mL·kg−1·min for peakV′O2. In the subgroup with associated PAH, no variable independently predicted either survival or clinical worsening.

We conclude that several exercise variables predict survival and clinical stability in idiopathic PAH. Exercise variables are less accurate predictors of outcome in associated PAH.
Patient-reported treatment burden of chronic immune thrombocytopenia therapies
Authors: Brown T Michelle , Horblyuk Ruslan V , Grotzinger Kelly M , Matzdorff Axel C , Pashos Chris L
Published: March 2012

Background

Chronic immune thrombocytopenia (ITP) is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy.

This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP.

Methods

A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress), and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS), intravenous immunoglobulin (IVIg), anti-D immunoglobulin (anti-D), rituximab (RT), and splenectomy (SPL), as well as for other patient-referenced therapies (captured as "other").

Results

The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71), and 68% reported a typical low platelet count of < 50,000/μL. Current or past treatment with CS was reported by 92% (n = 542) of patients, 56% (n = 322) for IVIg, 36% (n = 209) for anti-D, 36% (n = 213) for RT, and 39% (n = 227) for SPL. A substantial proportion of CS-treated patients reported side effects (98%, P < 0.05), were highly bothered by their side effects (53.1%, P < 0.05), and reported the need to stop or reduce treatment due to side effects (37.8%, P < 0.05). Among patients reporting side effects of treatment, significant associations were noted for the number of side effects, aggregate bother of reported side effects, and the need to stop or reduce treatment (all P < 0.05).

Conclusions

Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.
Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature
Authors: Davidson Tom B , Sanchez-Lara Pedro A , Randolph Linda M , Krieger Mark D , Wu Shi-Qi , Panigrahy Ashok , Shimada Hiroyuki , Erdreich-Epstein Anat
Published: March 2012

Background

Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the NF2 gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient.

Case presentation

We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including NF2 and MN1 (meningioma 1).

Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing NF2 were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed MN1, PITPNB and TTC28. MN1, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (TEL/MN1) in human myeloid leukemias. Interestingly, Mn1-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with murine and human cleft palate. This suggests that deletion of MN1 in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities.

Conclusions

Thus, our report describes a NF2-adjacent chromosome 22q12.2 deletion syndrome and is the first to report association of MN1 deletion with abnormal craniofacial development and/or cleft palate in humans.
Clinical decision-making: midwifery students' recognition of, and response to, post partum haemorrhage in the simulation environment
Authors: Scholes Julie , Endacott Ruth , Biro MaryAnne , Bulle Bree , Cooper Simon , Miles Maureen , Gilmour Carole , Buykx Penny , Kinsman Leigh , Boland Rosemarie , Jones Jan , Zaidi Fawzia
Published: March 2012

Background

This paper reports the findings of a study of how midwifery students responded to a simulated post partum haemorrhage (PPH). Internationally, 25% of maternal deaths are attributed to severe haemorrhage. Although this figure is far higher in developing countries, the risk to maternal wellbeing and child health problem means that all midwives need to remain vigilant and respond appropriately to early signs of maternal deterioration.

Methods

Simulation using a patient actress enabled the research team to investigate the way in which 35 midwifery students made decisions in a dynamic high fidelity PPH scenario. The actress wore a birthing suit that simulated blood loss and a flaccid uterus on palpation. The scenario provided low levels of uncertainty and high levels of relevant information. The student's response to the scenario was videoed. Immediately after, they were invited to review the video, reflect on their performance and give a commentary as to what affected their decisions. The data were analysed using Dimensional Analysis.

Results

The students' clinical management of the situation varied considerably. Students struggled to prioritise their actions where more than one response was required to a clinical cue and did not necessarily use mnemonics as heuristic devices to guide their actions. Driven by a response to single cues they also showed a reluctance to formulate a diagnosis based on inductive and deductive reasoning cycles. This meant they did not necessarily introduce new hypothetical ideas against which they might refute or confirm a diagnosis and thereby eliminate fixation error.

Conclusions

The students response demonstrated that a number of clinical skills require updating on a regular basis including: fundal massage technique, the use of emergency standing order drugs, communication and delegation of tasks to others in an emergency and working independently until help arrives. Heuristic devices helped the students to evaluate their interventions to illuminate what else could be done whilst they awaited the emergency team. They did not necessarily serve to prompt the students' or help them plan care prospectively. The limitations of the study are critically explored along with the pedagogic implications for initial training and continuing professional development.
Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis
Authors: Malfettone Andrea , Saponaro Concetta , Paradiso Angelo , Simone Giovanni , Mangia Annita
Published: March 2012

Background

Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2.

Methods

We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index.

Results

Grade 2 subgroup analysis showed that the PVI (p = 0.023) and the loss of membranous NHERF1 (p = 0.028) were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000). Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively). Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000), and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level.

Conclusions

The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors.
miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10
Authors: Chen Yating , Zhang Jin , Wang Huijun , Zhao Jiayi , Xu Cheng , Du Yingying , Luo Xin , Zheng Fengyun , Liu Rui , Zhang Hongwei , Ma Duan
Published: March 2012

Background

miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. HOXA10 however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because HOXA10 is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type.

Methods

Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including HOXA10. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student"s t-test.

Results

Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. HOXA10, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of HOXA10 both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of HOXA10.

Conclusions

In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. HOXA10 is a target gene for miR-135a in breast cancer cells and overexpression of HOXA10 can partially reverse the miR-135a invasive phenotype.
Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis
Authors: Barrière Guislaine , Riouallon Alain , Renaudie Joël , Tartary Michel , Rigaud Michel
Published: March 2012

Background

Epithelial mesenchymal transition (EMT) is a crucial event likely involved in dissemination of epithelial cancer cells. This process enables them to acquire migratory/invasive properties, contributing to tumor and metastatic spread. To know if this event is an early one in breast cancer, we developed a clinical trial. The aim of this protocol was to detect circulating tumor cells endowed with mesenchymal and/or stemness characteristics, at the time of initial diagnosis. Breast cancer patients (n = 61), without visceral or bone metastasis were enrolled and analysis of these dedifferentiated circulating tumor cells (ddCTC) was realized.

Methods

AdnaGen method was used for enrichment cell selection. Then, ddCTC were characterized by RT-PCR study of the following genes: PI3Kα, Akt-2, Twist1 (EMT markers) and ALDH1, Bmi1 and CD44 (stemness indicators).

Results

Among the studied primary breast cancer cohort, presence of ddCTC was detected in 39% of cases. This positivity is independant from tumor clinicopathological factors apart from the lymph node status.

Conclusions

Our data uniquely demonstrated that in vivo EMT occurs in the primary tumors and is associated with an enhanced ability of tumor cells to intravasate in the early phase of cancer disease. These results suggest that analysis of circulating tumor cells focused on cells showing mesenchymal or stemness characteristics might facilitate assessment of new drugs in clinical trials.
Existence of the rdl mutant alleles among the anopheles malaria vector in Indonesia
Authors: Asih Puji BS , Syahrani Lepa , Rozi Ismail EP , Pratama Nandha R , Marantina Sylvia S , Arsyad Dian S , Mangunwardoyo Wibowo , Hawley William , Laihad Ferdinand , Shinta  , Sukowati Supratman , Lobo Neil F , Syafruddin Din
Published: March 2012

Background

The gamma-aminobutyric acid (GABA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide. GABA-receptors, with a naturally occurring amino acid substitution, A302S/G in the putative ion-channel lining region, confer resistance to cyclodiene insecticides that includes aldrin, chlordane, dieldrin, heptachlor, endrin and endosulphan.

Methods

A total of 154 mosquito samples from 10 provinces of malaria-endemic areas across Indonesia (Aceh, North Sumatra, Bangka Belitung, Lampung, Central Java, East Nusa Tenggara, West Nusa Tenggara, West Sulawesi, Molucca and North Molucca) were obtained and identified by species, using morphological characteristic. The DNA was individually extracted using chelex-ion exchanger and the DNA obtained was used for analyses using sequencing method.

Results

Molecular analysis indicated 11% of the total 154 Anopheles samples examined, carried Rdl mutant alleles. All of the alleles were found in homozygous form. Rdl 302S allele was observed in Anopheles vagus (from Central Java, Lampung, and West Nusa Tenggara), Anopheles aconitus (from Central Java), Anopheles barbirostris (from Central Java and Lampung), Anopheles sundaicus (from North Sumatra and Lampung), Anopheles nigerrimus (from North Sumatra), whereas the 302 G allele was only found in Anopheles farauti from Molucca.

Conclusion

The existence of the Rdl mutant allele indicates that, either insecticide pressure on the Anopheles population in these areas might still be ongoing (though not directly associated with the malaria control programme) or that the mutant form of the Rdl allele is relatively stable in the absence of insecticide. Nonetheless, the finding suggests that integrated pest management is warranted in malaria-endemic areas where insecticides are widely used for other purposes.
Effects of Corni fructus on ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of allergic asthma
Authors: Kim Seung-Hyung , Kim Bok-Kyu , Lee Young-Cheol
Published: March 2012

Background

Allergic asthma is a chronic inflammatory lung disease that is characterized by airway hyperresponsiveness (AHR) to allergens, airway oedema, increased mucus secretion, excess production of T helper-2 (Th2) cytokines, and eosinophil accumulation in the lungs. Corni fructus (CF) is a fruit ofCornus officinalisSieb. Et. Zucc. (Cornaceae) and has been used in traditional Korean medicine as an anti-inflammatory, analgesic, and diuretic agent. To investigate the anti-asthmatic effects of CF and their underlying mechanism, we examined the influence of CF on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma.

Methods

In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA) by intraperitoneal (i.p.), intratracheal (i.t.) injections and intranasal (i.n.) inhalation of OVA. We investigated the effect of CF on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, and OVA-specific immunoglobulin E (IgE) production.

Results

The CF-treated groups showed suppressed eosinophil infiltration, allergic airway inflammation, and AHR via reduced production of interleuin (IL) -5, IL-13, and OVA-specific IgE.

Conclusions

Our data suggest that the therapeutic effects of CF in asthma are mediated by reduced production of Th2 cytokines (IL-5), eotaxin, and OVA-specific IgE and reduced eosinophil infiltration.