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Eosinophils are multifunctional leukocytes that increase in various tissues in a variety of disorders. Locally, they can be involved in the initiation and propagation of diverse inflammatory responses. In this review, the clinical association of eosinophils with diseases of the skin, lung and gastrointestinal tract is summarized. An approach to determining the causal role of eosinophils in these diseases is presented. Recent findings concerning molecular diagnosis, etiology and treatment are discussed.
Eosinophils are multifunctional leukocytes implicated in the pathogenesis of numerous inflammatory processes including infections (parasitic helminths, bacterial and viral), non-specific tissue injury, malignancy, and allergic diseases.1 In response to a variety of stimuli, eosinophils are recruited from the circulation into the tissue where they modulate immune responses through muliple mechanisms. Triggering of eosinophils by cytokines, immunoglobulins, and complement can lead to the release of an array of proinflammatory cytokines, such as chemokines, interleukins (e.g. IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-16, IL-18), transforming growth factor (TGF)-α/β, lipid mediators such as platelet-activating factor (PAF) and leukotriene (LT)C4, free radicals, and mitochondrial DNA. These molecules have proinflammatory effects that include upregulation of adhesion systems, modulation of cellular trafficking, regulation of vascular permeability, mucus secretion, and smooth muscle constriction. In addition, eosinophils can initiate adaptive immunity by acting as antigen-presenting cells and secreting T helper cell chemokines. Furthermore, eosinophils can serve as major effector cells inducing tissue damage and dysfunction by releasing cytotoxic granule proteins, inflammatory lipid mediators and mitochondrial DNA.1 In this chapter, we summarize the association of eosinophils with diseases involving three tissues, the skin, respiratory tract, and gastrointestinal (GI) tract. Focusing on clinical data, we discuss differential disease diagnosis, therapy and pathogenesis. A more detailed discussion of disease mechanisms and the detailed results of early eosinophil-targeted novel therapy are provided in another review in this issue.2
Eosinophil infiltration is found in a broad spectrum of skin disorders (Table 1).3 It is a characteristic feature of allergic diseases or parasitic infestations, but it is also observed in autoimmune diseases, hematologic diseases, as well as in association with tumors, and bacterial or viral infections. Depending upon the disease, eosinophils can be the predominant cell infiltrate such as in eosinophilic cellulitis or can be part of a mixed inflammatory infiltrate in the dermis such as in eczematous reactions. Eosinophils may infiltrate the epidermis presenting as eosinophilic spongiosis in particular in autoimmune bullous diseases, insect bite reactions or acute contact dermatitis. Eosinophil infiltration of the deep dermis and subcutaneous fat tissue can be observed in eosinophilic cellulitis, parasitic infections, erythema nodosum, vasculitis, or lymphomas. Peripheral blood eosinophilia may be associated with tissue eosinophilia, e.g. in drug reactions with eosinophilia and systemic symptoms (DRESS), atopic dermatitis, or bullous pemphigoid.
In hematoxylin and eosin stained skin specimens, eosinophils are noticeable as round shaped cells stuffed with coarse eosinophil granules. In subacute and chronic eczematous lesions, disrupted oval shaped eosinophils may also be found. Extracellular deposits of granular proteins can be detected in varying amounts either as separate little granules or as a thin coating on collagen bundles. The latter are called flame figures and can typically be seen in eosinophilic cellulitis. Immunofluorescence staining using antibodies directed against eosinophilic cationic protein (ECP) or major basic protein (MBP) allows a more sensitive detection of eosinophils and extracellular granular protein depositions compared with hematoxylin and eosin staining.
Eosinophils do not enter the skin under physiological states. Mechanistically, cutaneous eosinophilia can be from a primary problem internal to the eosinophil or may be caused by stimuli outside the cell.3 In either case, increased production, recruitment and/or survival of eosinophils is likely. Hematologic disorders affecting multipotent or pluripotent hematopoietic stem cells may involve the eosinophil lineage. In these diseases, mutations that represent intrinsic defects in eosinophils cause eosinophil proliferation and tissue infiltration including the skin. Cutaneous manifestations are described as multiple erythematous papules, plaques and nodules, or generalized erythematous maculopapular eruptions often associated with pruritus. By means of cytogenetic and molecular techniques, a number of diseases formerly defined as idiopathic hypereosinophilic syndrome (HES) can now be classified as separate entities. Clonal eosinophilia is often associated with rearrangements involving the genes of the platelet-derived growth factors A and B (PDGFRA, PDGFRB) resulting in increased tyrosine kinase activity.4 Notably, patients with HES due to the fusion of the PFGFRA and FIP1L1 genes respond to imatinib therapy.4
More commonly, extrinsic eosinophilic disorders are observed, in which skin eosinophilia is due to cytokine release by either T cells or tumor cells. Cytokines involved in the development of skin eosinophilia include interleukin (IL-)-3, IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF). The expression of IL-5 in association with eosinophilic skin disorders has been reported in atopic dermatitis,5, 6 exanthematous drug reactions, 7 urticaria,8 episodic angioedema with eosinophilia,9 bullous pemphigoid,10 eosinophilic fasciitis,11 eosinophilic folliculitis,12 cutaneous T cell lymphoma,13 eosinophilic cellulitis14 and HES with skin involvement.15 IL-3 expression has been detected in blister fluids of bullous pemphigoid.16 In Langerhans cell histiocytosis17 as well as in atopic dermatitis, atopy patch test reactions and cutaneous late phase reactions, the expression of both IL-3 and GM-CSF has been shown.16, 18 Expression of the chemokine eotaxin has been observed in atopic dermatitis,19 drug reactions,20 autoimmune-blistering diseases like dermatitis herpetiformis and bullous pemphigoid,21 parasitic dermatoses,22 eosinophilic folliculitis,12 but also lymphomas, (e.g. cutaneous T cell lymphoma) and Hodgkin's disease.23 The functional role of eosinophils in the pathogenesis of skin diseases remains largely unknown. Depending on the skin disease, a role in host defense, immunoregulation and/or remodeling and fibrosis can be assumed. Specific cutaneous eosinophilic disorders are described below.
As the name implies, Wells syndrome is characterized by an intense infiltration of eosinophils, extracellular granule deposition and flame figures in the dermis. Patients present with recurrent episodes of acute pruritic dermatitis, seldom with blisters, painful edematous swellings or persistent urticarial eruptions.24 An increased expression of IL-5 has been reported in a number of cases. The cause is not known, but some patients developed eosinophilic cellulitis in association with hematological disorders, infections, or anti-TNF-alpha therapy. Corticosteroids are usually helpful in Wells syndrome. Eosinophilic cellulitis may also occur as a cutaneous manifestation of HES. Other skin manifestations of HES are erythematous macules, papules or nodules, blisters, necrosis, ulcerations, purpura, lichenoid eruptions or urticarial lesions, and pruritus. The skin is affected in 37% of HES patients.25 Anti-IL-5 antibody therapy was shown to improve skin symptoms in HES patients.26 In a subgroup of patients with HES, IL-5 producing clonal T cells has been identified. These T cells often exhibit an abnormal phenotype in as far as they have an either higher, lower or absent expression of lineage-associated markers. Those patients usually present with cutaneous symptoms.27
EPF presents as annular clusters of sterile follicular papules and pustules predominantly on the face and trunk that heal with postinflammatory hyperpigmentation but tend to recur periodically.28 The histology shows a dense follicular and perifollicular infiltrate of eosinophils and scattered lymphocytes, and sometimes follicle destruction. The classic type of EPF affects immunocompetent subjects. Meanwhile two other subtypes of EPF have been identified. Infancy-associated EPF often involves the scalp. More commonly, EPF is seen in context with immunosuppression. EPF has been reported in association with infections, in particular AIDS, medications, autoimmune diseases, as well as autologous peripheral blood stem cell and allogeneic bone marrow transplantation. A pathogenic role for eosinophils in response to fungi (Malassezia), demodex mites and bacteria has been suggested.
Despite various cutaneous and histopathological presentations of drug reactions (e.g. maculopapular rashes, erythema multiforme, acute generalized exanthematous pustulosis, pseudolymphomatous and granulomatous drug reactions), the presence of eosinophils in the skin is a quite striking finding.29 DRESS, also named hypersensitivity syndrome, presents with an acute, severe skin eruption that may develop from a maculopapular rash into erythroderma, as well as with fever, lymphadenopathy, hepatitis, blood eosinophilia, and other organ involvement due to hypereosinophilia.30 Eosinophils accompanied by other inflammatory cells are found in the skin and the lymph nodes. Severe hepatitis, in which eosinophilic infiltration or granulomas as well as hepatocyte necrosis and cholestasis are striking features, may result in liver failure accounting for the high mortality rate of 10%. The treatment is based on high-dose corticosteroids. Drugs known to cause DRESS are anticonvulsants, sulfa drugs, antimicrobial agents, anticancer drugs, nonsteroidal anti-inflammatory drugs and anti-diabetic agents.
Tissue eosinophilia is a typical feature of AD. The numbers of eosinophils in the skin are usually modest (2.8 cells/mm2 [range 0 to 90.3]) and correlate with disease severity, as well as the degree of spongiosis in acute exacerbations and marked epidermal hyperplasia in chronic stages.31 Besides eosinophils, eosinophil-derived products such as ECP, EDN (also abbreviated as EDX), and MBP are present in increased amounts in the blood and the skin of AD patients. The measurement of ECP in serum is frequently used as a tool for monitoring AD activity and response to therapy.32 Immunostaining with antibodies to MBP and ECP has demonstrated that eosinophil granule proteins are not only present inside eosinophils but also in the extracellular spaces, suggesting eosinophil degranulation. In biopsies obtained from chronic AD lesions, intact eosinophils are located predominantly within the perivascular mononuclear cell infiltrate. In contrast, in the upper dermis extensive extracellular MBP deposition are observed in the near absence of intact eosinophils.33 The presence of mostly disrupted eosinophils has been confirmed by electron-microscopy studies, which revealed various degrees of eosinophil degeneration ranging from intact eosinophils with granule abnormalities, to intact eosinophils with abnormal granules and pseudopod-like extensions, to eosinophils with degenerated cell and/or nuclear membranes to free eosinophil granules.34 Improvement of AD upon both systemic and topical therapy is usually associated with a decrease of eosinophils and other inflammatory cells in the skin. However, the administration of an anti-IL-5 antibody showed only moderate effects on clinical symptoms although blood eosinophils were almost completely depleted.35
Bullous pemphigoid (BP) is due to an autoimmune response to structural components of junctional adhesion complexes leading to damage of the dermal-epidermal junction with subepidermal blister formation.36 Autoreactive B and T cell responses against the hemidesmosomal antigens BP180 and BP230 have been identified. IL-5 as well as eotaxin are abundant in blister fluids and the production of IL-5 is associated with blood eosinophilia and significant eosinophil infiltration in the skin of BP patients.37 Eosinophils are thought to be implicated in blister formation by releasing toxic granule proteins (ECP, MBP) and proteolytic enzymes, however, the molecular mechanisms are not well understood. In dermatitis herpetiformis, a specific cutaneous manifestation of gluten-sensitive enteropathy due to anti-tissue transglutaminase antibodies, a neutrophilic infiltrate undermingled with eosinophils is found in the papillary dermis. The expression of eotaxin in lesional skin and increased levels of serum ECP suggest a role for eosinophils in disease pathology.21
In Langerhans cell histiocytosis, among the infiltrate of Langerhans cells, scattered or clusters of eosinophils can be found in the papillary and deeper dermis, respectively.38 Langerhans cells produce a broad spectrum of proinflammatory cytokines, e.g. GM-CSF, and chemokines, and are thus likely to recruit and activate eosinophils directly or via stimulation of other cell types. Predominant T helper 2 type cytokine production by cutaneous T cell lymphoma results in eosinophilia, extracellular granule protein depositions as well as increased IL-5 levels in the skin and/or peripheral blood.39 Currently, it is not known whether the eosinophils modulate the proliferation of the malignant cells.
Eosinophils are relatively rare in the normal lung and so they stand out both in tissue and airway lumen samples when present in increased numbers. A number of lung diseases are associated with blood and tissue eosinophilia (Table 2). The extent to which eosinophils cause tissue damage in these diseases remains controversial, but most evidence points to them as being pro-inflammatory effector cells in non-infectious disorders where they are prominent. The most common association, at least in industrialised countries, is with asthma and related airways diseases. Research into these conditions has resulted in much of our current understanding of the role of eosinophils in lung disease. These findings, as well as a summary of other eosinophil-associated lung conditions, are now discussed in some detail.
There has been active debate about the role of eosinophils in asthma for at least the last four decades. Initially they were regarded as ameliorative cells able to dampen inflammatory responses, but this changed with the work of Gleich and colleagues who demonstrated that eosinophil basic proteins, particularly MBP, were toxic for bronchial epithelial cells and MBP was present in large amounts in the airways of patients who had died from asthma.40 At the same time controlled studies of bronchoscopy in mild asthma demonstrated that a BAL eosinophilia tracked with active disease.41 An assumption was made that the abnormal physiology that defines asthma (airway hyperresponsiveness [AHR]) and variable airflow obstruction, was secondary to the airway eosinophilia. This hypothesis was underpinned by a persuasive paradigm that emerged in the 1990's that asthma was driven by activation in the bronchial mucosa of Th2 lymphocytes which through the generation of IL-4, IL-5 and IL-13 are closely associated with a blood and tissue eosinophilia both in humans and animal models.42–44 However, subsequent studies of induced sputum that allowed a more thorough examination of the relationship between airway inflammation and asthmatic airway dysfunction revealed at best a very weak correlation between the degree of airway eosinophilia and the abnormal physiology. Conditions such as eosinophilic bronchitis (EB), which presents as chronic cough, were identified in which airway eosinophilia occurred in the absence of airway dysfunction and some asthmatics were identified who had airway dysfunction without eosinophilia.45–47 Eosinophils are therefore neither necessary nor sufficient for an asthma like airway dysfunction to be present.
Monoclonal antibodies against IL-5 have provided insight into the potential role of eosinophils in asthma. The drug which has been investigated in greatest detail is mepolizumab.48 The first clinical efficacy study of mepolizumab was in a human allergen challenge model. This demonstrated a marked reduction in blood and sputum eosinophils without any effect on either the early or late response or AHR. Although this was a small study the interpretation of which was open to debate,49 a larger trial of clinical asthma came to the same conclusion that eosinophils were not responsible for either the symptoms or physiological abnormalities which characterise asthma.50 In this double blind placebo controlled study, 362 patients with moderate asthma were given three injections of drug one month apart. There was no difference in symptoms or lung function between the two groups. There was about a 50% reduction in severe exacerbations (SE) in the 750 mg group, but the study was not powered to look at exacerbations and this did not quite reach significance p<0.061). Of note, evidence of eosinophilic disease was not an entry criteria for the study and sputum analysis was only undertaken in 37 patients. Another caveat to the conclusion that eosinophils are not causal in asthma pathophysiology is that while mepolizumab was very good at reducing blood and sputum eosinophils it only had a modest (50%) reduction in bronchial wall eosinophils.50 Interestingly, this is similar to the effect of systemic steroids in refractory asthma which have a marked effect on luminal eosinophils, but a much less marked effect on tissue eosinophils (51 and personal observation Andrew Wardlaw). The reasons for this are not clear, but suggest that IL-5 is more important in tissue based eosinophil migration whereas migration through the vascular endothelium into tissue is relatively IL-5 independent with chemotactic stimuli perhaps being more important. This would be consistent with the observation that in contrast to two dimensional Boyden chamber like assays, in a 3-dimensional model of tissue based trafficking, migration in response to growth factors was more robust than migration in response to eotaxin.52
Do these clinical trials mean that eosinophils are not acting as effector cells in asthma? Two issues need to be considered. First, in the above studies inclusion was not restricted to patients with eosinophilic disease. In patients with hypereosinophilic disease, many of whom had respiratory pathology, mepolizumab was highly effective in allowing a reduction in the dose of glucocorticoids required to control disease activity.53 Second, it depends what is meant by asthma. Clarifying this question requires a nuanced understanding of the pathophysiology of asthma and related airways diseases. Asthma was originally defined as marked variability in airflow obstruction over short (minutes) periods of time either spontaneously or in response to treatment and this correlates very closely with the presence of AHR. Asthma symptoms of wheeze, chest tightness and shortness of breath are closely related to this phenotype. However, over the last few decades definitions of asthma have become more descriptive and attempt to encompass the complete physiology seen in asthma and other airway diseases.54 With the new insights gained by very targeted treatments such as mepolizumab there is a strong case to be made for returning to the original definition.55 It is helpful in this regard to deconstruct airway disease into its component pathophysiological abnormalities, a process that is aided by an A to E classification system.56 In this scheme A stands for the Asthma/AHR phenotype, B for Bronchitis, C for Cough, D for Damage (fixed airflow obstruction, bronchiectasis, emphysema) and E for Extrapulmonary factors such as adherence, co-morbidity and triggers. Eosinophils are found in the bronchitis phenotype and are most closely associated with the clinical phenotype of SE although they are also associated with cough particularly in conditions such as EB. As noted above, the majority of people dying of asthma (the end result of untreated SE), have marked eosinophilic inflammation.57, 58 Eosinophils were the best predictor of SE in a steroid reduction study and approaches to management targeting the airway eosinophilia resulted in a marked reduction in SE.59, 60 It therefore follows that the patients who are most likely to respond to anti-eosinophilic therapy are those with marked eosinophilic airway inflammation who suffer from SE. This was confirmed in a study of twelve months treatment with mepolizumab in patients with refractory eosinophilic asthma with SE as the primary outcome measure where a significant 40% reduction in SE was observed.61 Predictably there was no effect on lung function, AHR or day to day asthma symptoms although there was an improvement in quality of life reflecting the impact of SE on morbidity. Interestingly, there was no effect on exhaled nitric oxide, dissociating this biomarker from eosinophilic inflammation and clinical improvement. These findings were echoed in a study published at the same time of patients with marked eosinophilic airway disease (several did not have AHR), using a steroid reduction design in which mepolizumab was found to be highly effective at reducing exacerbations. A marked and significant reduction in steroid dose was possible in the active compared to the placebo group.62 These studies represent direct evidence that eosinophils are causal in the pathogenesis of asthma associated SE. An important outcome of these findings is that eosinophilic airway disease (which will respond to anti-eosinophilic therapy), is a distinct albeit overlapping phenotype from asthma as defined by Hargreave and Nair.62 Studies of anti-eosinophil agents therefore need to have inclusion criteria and outcome measures relevant to the eosinophilic Bronchitis phenotype rather than the Asthma/AHR phenotype (variable airflow obstruction, AHR and symptoms). These patients are clinically recognisable in an airways disease clinic and can also be identified as an eosinophil inflammation predominant cluster in an objective multi-dimensional analysis of asthma phenotype.63 These studies also give some insight into the pathogenesis of asthma SE.64 As noted above, the major effect of mepolizumab was to reduce the luminal eosinophilia with a modest effect on tissue eosinophils. It suggests therefore that SE are principally a luminal event with obstruction caused by blockage of bronchi with mucus and cell debris rather than smooth muscle mediated bronchoconstriction. This would be consistent with the pathology of asthma mortality where mucus impaction is often the primary pathological cause of death. It would also explain why SE are often relatively bronchodilator resistant. Focusing on luminal events in relation to SE would also be consistent with the well-established importance of viral infections in triggering SE, presumably through an interaction with the epithelium in the context of eosinophilic inflammation.65
One of the more common causes of lung eosinophilia is fungal colonization. The most florid expression of this is allergic bronchopulmonary aspergillosis (ABPA), the primary diagnostic criteria of which are asthma, proximal bronchiectasis, a positive skin prick test and positive specific IgE and IgG to Aspergillus fumigatus (Af) and a high total IgE.66 A blood eosinophilia and positive sputum culture for Af are secondary criteria. Classically patients present with exacerbations of their asthma characterised by fleeting lung shadows, but this presentation is now unusual possibly because of the increased use of potent high dose inhaled steroids. A marked significant blood and tissue eosinophilia help guide diagnosis. A number of other molds can cause an ABPA-like picture most of which are other Aspergillus or Penicillium species and IgE sensitisation to a range of fungi is common in more severe asthma.67, 68 Two studies have shown that treatment with anti-fungals is beneficial in ABPA although both were small and the benefits modest.69, 70 Relatively few patients with asthma and a positive specific IgE to Af fulfill all the criteria for ABPA although whether Af plays a significant part in their asthma in these circumstances is not clear. Interestingly, patients with severe asthma and fungal sensitisation had a significant improvement in quality of life after treatment with itraconazole although this class of drugs increases endogenous steroid levels which is a confounding factor.71
Eosinophilic pneumonia is an uncommon condition characterised by a marked peripheral blood and tissue/BAL eosinophilia and pneumonic lung shadowing. Patients may present acutely with breathlessness, hypoxia, general malaise and sometimes fever and can be very unwell. They respond dramatically to high dose systemic steroids.72 Occasionally, presumably because of rapid trafficking of eosinophils into the lung, the peripheral blood can be in the normal range. In cases such as drug allergy or parasitic infection where there is an identifiable cause recurrence can usually be avoided, but many patients with idiopathic disease often develop chronic eosinophilic pneumonia with recurrent relapse requiring long term oral steroids. Relapse of eosinophilic pneumonia is often of slow onset and associated with airflow obstruction in the absence of wheeze or bronchodilator responsiveness suggestive of small airways disease. Relapses invariably respond well to high dose oral steroids.
Churg-Strauss syndrome (CSS) is a rare condition in which patients have asthma (which is often severe), a marked peripheral blood eosinophilia and evidence of a multi-system vasculitic disorder.72, 73 Upper airway symptoms are common and mononeuritis multiplex, which is often slow to respond to treatment, is a characteristic feature. The cause is unknown and the extent to which eosinophils are directly responsible for the tissue damage is unknown (trials of mepolizumab in this condition have not yet been reported). It is interesting however, that neural damage is such a feature considering the neurotoxic properties of EDN and the neurotrophic properties of eosinophils.74, 75 Treatment of the acute phase consists of potent immunosuppressants including high dose systemic steroids, cyclophosphamide and azathioprine although in the longer term low dose oral steroids are often sufficient to maintain remission. There is an association between treatment with leukotriene receptor antagonists and the onset of CSS but this is generally considered to be coincidental although a causal relationship has not been ruled out. 76
Tobacco smoking associated COPD is often a disease that is contrasted with asthma with a more neutrophilic and CD8+ T cell-associated pathology. However, just as some asthma is non-eosinophilic quite a lot of COPD is characterised by eosinophilic airway inflammation particularly during exacerbations.77 These patients are often more steroid responsive than their non-eosinophilic counterparts.78
A number of helminthic parasites have a larval stage that passes through the lung and causes respiratory symptoms.79, 80 The exact pattern of illness varies with the parasite with various acronyms (Table 2). Generally the condition looks like a combination of asthma and eosinophilic pneumonia with low grade fever, dry cough, chest discomfort, shortness of breath, wheeze and occasionally haemoptysis. The chest X-ray classically shows lung shadowing that can be pneumonic in appearance and often lasting from a few days to weeks. Parasites can sometimes be identified in lung tissue samples. Tropical pulmonary eosinophilia caused by infection with filarial parasites can produce a more chronic illness with lethargy and anorexia in association with asthma like symptoms and occasionally mediastinal lymphadenopathy, cavitation and pleural effusion .
Eosinophils are present throughout the healthy GI tract, except for the esophagus, which typically contains no eosinophils.1 Eosinophil-associated gastrointestinal disorders (EGID) are characterized by a high level of eosinophils within isolated or multiple segments of the GI tract. Over the past decade, there has been a striking increase in the incidence of primary EGID, as well as a robust increase in data linking the development of EGID to atopy. The most common form of EGID is eosinophilic esophagitis (EE), which is characterized by a relatively high level of eosinophils within the esophagus (without an acid-induced etiology).81 Other forms of EGID include: eosinophilic gastritis, eosinophilic enteritis, eosinophilic colitis, and eosinophilic gastroenteritis. These disorders are less frequent than EE, but their pathogenesis and treatment are somewhat similar. Clinically, patients with EGID often have failure to thrive (especially in pediatrics), dysphagia, vomiting, abdominal pain and/or diarrhea.82 Patients with EE often present with symptoms that mimic gastroesophageal reflux disease (GERD). The number of eosinophils per high power field (HPF) required to diagnose EGID has not been uniformly agreed upon, which can make the diagnosis of EGID challenging. For this reason, an experienced pathologist knowledgeable with the number of eosinophils typically found in the GI tract at their medical center is essential for interpreting biopsy specimens in patients with suspected EGID. Agreed upon criteria for the diagnosis of EGID is currently being pursued. The diagnostic criteria for EE, established at the First International Gastrointestinal Eosinophilic Research Symposium, is >15 eosinophils/HPF noted in at least one of four biopsy specimens when GERD is ruled out.81 The quantity and distribution of GI eosinophils in pediatric patients without apparent pathologic disease has been reported,83 though the application of this data to the diagnosis of EGID has not been established. In addition to the elevated eosinophil numbers, the usual morphology of the GI tract is typically disrupted in EGID. Depending on the location of the eosinophil accumulation, additional manifestations may include the presence of eosinophilic microabscesses, disruption of the surface epithelium cryptitis, basilar hypertrophy or lamina propria fibrosis.84 Although the presence of elevated eosinophils and disruption of the typical GI tract morphology are crucial for the diagnosis of EGID, the isolated presence of GI eosinophilia is not sufficient. The differential diagnosis for GI eosinophilia is broad and includes EGID, HES, collagen vascular disease, inflammatory bowel disease, and parasitic or fungal infection; disease differentiation based on primary or secondary causes is useful (Table 3). In order to diagnose EGID, the patient must have a biopsy and clinical presentation consistent with EGID; other causes of GI eosinophilia (e.g. parasitic infection, drug hypersensitivity) must be ruled out. This review will focus on primary EGID, disorders not associated with known causes for the eosinophilic inflammation.
The esophagus normally does not contain eosinophils so the finding of esophageal eosinophils denotes pathology. In addition to EE, many disorders are accompanied by eosinophil infiltration in the esophagus, such as GERD, eosinophilic gastroenteritis, GERD, parasitic and fungal infections, inflammatory bowel disease, HES, esophageal leiomyomatosis, myeloproliferative disorders, carcinomatosis, periarteritis, allergic vasculitis, scleroderma and drug injury.85 EE is classified into primary and secondary with the primary subtype including the atopic, nonatopic and familial variants and the secondary subtype including one composed of systemic eosinophilic disorders (e.g. HES) and the other of non-eosinophilic disorders (Table 3). Primary EE has also been called idiopathic EE or allergic esophagitis. The sibling recurrence risk ratio has been estimated to be over 50-fold86 and the familial form of EE is noted in about 10% of patients.87
The cause of EE is poorly understood, but food allergy has been implicated. In fact, most patients have evidence of food and aeroallergen sensitization as defined by skin prick and/or allergen-specific IgE tests; however, only a minority have a history of food anaphylaxis.88 Evidence suggests that esophageal eosinophilic inflammation is mechanistically linked with pulmonary inflammation based on the finding that delivery of specific allergens or the Th2 cytokine IL-13 to the lungs of mice induces experimental EE.89, 90 Increased eosinophil levels in the esophagus of patients with seasonal allergic rhinitis with hypersensitivity to grass has been published.91 Recent studies have found a strong relationship between atopy and EE.92–94 Indeed, patients with EE commonly report variable seasonal symptoms. In addition to eosinophils, T cells and mast cells are elevated in esophageal mucosal biopsies, suggesting chronic Th2 associated inflammation.95 Exposure to antigen via an epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by only a single respiratory antigen exposure.96 IL-5 is required for this eosinophilic inflammation, suggesting a Th2-dependent mechanism. Notably, overexpression of IL-5 induces EE and neutralization of IL-5 completely blocks allergen or IL-13-induced EE in mice.89, 90, 97
A landmark advance in EE research is the recent genome wide microarray profile analysis of esophageal tissue.98 Investigators compared gene transcript expression in esophageal tissue of patients with EE, chronic esophagitis (typical of GERD), and normal individuals. Notably, dysregulated expression of ~1% of the human genome led to the identification of an EE genetic signature. Interestingly, eotaxin-3 was the most overexpressed gene in EE patients and levels correlated with disease severity; a finding that has now been independently replicated.99 Furthermore, a single nucleotide polymorphism (SNP) in the eotaxin-3 was overrepresented in EE patients compared with control individuals. Interestingly, mice with a genetic ablation of the eotaxin receptor (CCR3) were protected from the development of experimental EE. Notably, eotaxin-3 has been shown to be produced by esophageal epithelial cells, and induced by the Th2 cytokine IL-13, which is also markedly overexpressed in the esophagus of EE patients.100 Taken together, these results strongly implicate eotaxin-3 in the pathogenesis of EE and offer a molecular connection between Th2 inflammation and the development of EE.
A specific food allergen avoidance trial is often indicated for patients with atopic EE, and if unsatisfactory or practically difficult (when patients are sensitized to many allergens), a diet consisting of an elemental (amino acid based) formula is often advocated. Interestingly, it has been shown that an elemental diet has potential to reduce the number of eosinophils in the esophageal biopsies and improve symptoms in patients with primary EE (allergic or non-allergic sub-types).101 Patients on elemental diets frequently require a surgically placed gastrostomy tube in order to achieve adequate caloric support. Glucocorticoids (systemic or topical) have also been used with satisfactory results. Systemic glucocorticoids are used for acute exacerbations, while topical glucocorticoids are used to provide chronic control. A study that followed EE patients for 10 years supports the efficacy of continuing corticosteroids and food elimination therapy for EE.101 When using topical steroids we recommend the use of a metered-dose inhaler without a spacer and having the patient swallow the medicine to promote deposition on the esophageal mucosa. The toxicity associated with inhaled glucocorticoids (e.g. adrenal suppression) is unlikely to be seen with swallowed fluticasone due to first-pass hepatic metabolism following gastrointestinal absorption. However, about 10% of patients treated with topical fluticasone develop esophageal candidiasis. While the metered-dose inhaler is recommended with the topical fluticasone, another study has shown success of using an oral suspension of budesonide in EE patients who were unable to use inhalers.102 In the first placebo controlled double blind trial in EE, swallowed topical fluticasone was demonstrated to be effective in inducing disease remission including reduction in eosinophil, mast cell, and CD8 T cell levels, as well as the degree of epithelial hyperplasia.103 Notably, only half of the patients responded to topical glucocorticoids, and 10% responded to placebo. A recent study also showed the promising effect of anti-human-IL-13 antibody in an animal model of IL-13-induced airway and esophageal eosinophilia. 104 In addition, in two open-label trials, humanized anti-IL-5 monoclonal antibody therapy has been shown to be helpful in small numbers of patients.105, 106 Larger scale trials are currently underway. Finally, even if GERD is not present, neutralization of gastric acidity with proton pump inhibitors may improve symptoms and the degree of esophageal pathology.
In contrast to the esophagus, the stomach and intestine have readily detectable baseline eosinophils under healthy conditions, confounding the diagnosis of EGID involving these tissues. For the purposes of this review, eosinophilic gastritis, enteritis and gastroenteritis are grouped together because they are similar clinically and because there is a lack of information available concerning their pathogenesis; however, it is likely that they are indeed distinct processes in most patients. These diseases are characterized by the selective infiltration of eosinophils in the stomach and/or small intestine with variable involvement of the esophagus and/or large intestine. It is now appreciated that many diseases are accompanied by eosinophilia in the stomach, such as infection (parasitic and bacterial) including Helicobacter pylori, periarteritis, inflammatory bowel disease, allergic vasculitis, HES, myeloproliferative disorders, scleroderma, drug injury and drug hypersensivity.82 Similar to EE, these disorders are classified into primary and secondary subtypes. The primary group includes the atopic, nonatopic and familial variants while the secondary subtype contains two groups, one composed of systemic eosinophilic disorders (e.g. HES) and the other of non-eosinophilic disorders (Table 3). Primary eosinophilic enteritis, gastritis, and gastroenteritis have also been called idiopathic or allergic gastroenteropathy. Primary eosinophilic gastroenteritis involves multiple disease entities subcategorized into different types based on the level of histological involvement: mucosal, muscularis and serosal forms.107 Of note, either layer of the GI tract can be involved; as such, endoscopy and biopsy can be normal in patients with the muscularis and/or serosal subtypes.
While these diseases are idiopathic, an allergic mechanism has been suggested.108 Indeed, elevated total IgE and food-specific IgE has been detected in most patients. On the other hand, focal erosive gastritis, enteritis and occasionally esophagitis with prominent eosinophilia, such as the dietary (food) protein-induced enterocolitis and dietary protein enteropathy are characterized by negative skin tests and absent specific IgE.109 Most patients have positive skin prick tests to a variety of food antigens, but do not have typical anaphylactic reactions, consistent with a delayed-food hypersensitivity.
In clinical studies, increased production of Th2 associated cytokines (e.g. IL-4 and IL-5) by peripheral blood T cells has been reported in patients with eosinophilic gastroenteritis.108 Furthermore, lamina propria T cells derived from the duodenum of patients with EGID preferentially secrete Th2 cytokines (especially IL-13) when stimulated with milk proteins.110 IgA deficiency has also been associated with eosinophilic gastroenteritis; perhaps this could be related to the associated increased rate of atopy or to an occult gastrointestinal infection in these patients. Eosinophilic gastroenteritis and the dietary protein-induced syndromes (enterocolitis, enteropathy and colitis) may represent a continuum of EGID with similar underlying immunopathogenic mechanisms. In addition, eosinophilic gastroenteritis can frequently be associated with protein-losing enteropathy.111
Eliminating the dietary intake of the foods implicated by skin tests (or measurement of allergen-specific IgE levels) has variable effects, but complete resolution is generally achieved with elemental diets.111 Once disease remission has been obtained by dietary modification, the specific food groups are slowly reintroduced (at ~3 week intervals for each food group) and endoscopy is performed every three months, to identify disease status. Drugs such as sodium cromoglycate, montelukast, mycophenolate mofetil (an inosine monophosphate dehydrogenase inhibitor), ketotifen, suplatast tosilate and "alternative Chinese medicines" have been suggested, but are generally not successful. However, a publication reported a successful long-term remission of eosinophilic gastroenteritis following montelukast treatment.112 In our institution, an appropriate therapeutic approach includes a trial of food elimination if sensitization to food is found by skin tests and/or measurement of specific IgE levels. If no sensitization is found or if specific food avoidance is not feasible, elemental formula feedings are initiated.
The management of eosinophilic gastroenteritis, in addition to an amino acid based diet, includes the following: systemic and topical steroids, non-corticosteroid therapy, and management of other EGID complications (such as iron deficiency and anemia).113 Anti-inflammatory drugs (systemic or topical steroids) are the main therapy if diet restriction has failed or is not feasible. There are several forms of topical glucocorticoids designed to deliver drugs to specific segments of the GI tract (e.g. budesonide tablets [Entocort™ EC] designed to deliver drug to the ileum and proximal colon). In severe cases refractory or dependent upon glucocorticoid therapy, intravenous alimentation or immunosuppressive antimetabolite therapy with azathioprine or 6-mercaptopurine are alternatives. Finally, even if GERD is not present, neutralization of gastric acidity with proton pump inhibitors may improve symptoms and the degree of esophageal and gastric pathology.
Eosinophils accumulate in the colon of patients with a variety of disorders, including infection (pin and dog hookworms), eosinophilic gastroenteritis, allergic colitis of infancy, drug reactions, and vasculitis, (e.g. CSS, and inflammatory bowel disease).114 Dietary protein-induced proctocolitis of infancy syndrome (also known as allergic colitis of infancy), is the most common cause of blood in the stools in the first year of life.115 Similar to other EGID, these disorders are classified into primary and secondary (Table 3) with the primary type including the atopic and nonatopic variants composed of systemic eosinophilic disorders (e.g. HES) and the other by non-eosinophilic disorders.
Eosinophilic colitis is usually a non-IgE-associated disease. In fact, some studies point to a T-lymphocyte-mediated process, but the exact immunologic mechanisms responsible have not been identified.116 It has been reported that allergic colitis of infancy might be an early expression of protein-induced enteropathy or protein-induced enterocolitis syndrome. Cow's milk and soy proteins are the most frequently implicated foods in allergic colitis of infancy, but a variety of food proteins can also provoke the disease. Interestingly, this condition may more commonly occur in infants exclusively breast-fed and can even occur in infants fed with protein hydrolysate formulas.
Treatment of eosinophilic colitis varies primarily depending upon the disease subtype. Eosinophilic colitis of infancy is generally a benign disease. Upon removal of the offending protein in the diet, the gross blood in the stools typically resolves within days, but occult blood loss may persist longer. Treatment of eosinophilic colitis in older individuals usually requires medical management since IgE-associated triggers are usually not identified. Drugs such as montelukast, sodium cromoglycate, and histamine receptor antagonists are typically not successful. Anti-inflammatory drugs including aminosalicylates and systemic or topical glucocorticoids appear to be efficacious, but careful clinical trials have not been conducted. There are several forms of topical glucocorticoids designed to deliver drugs to the distal colon and rectum, but eosinophilic colitis usually involves the proximal colon. In severe cases, alternative therapy includes intravenous alimentation or immunosuppressive therapy with azathioprine or 6-mercaptopurine.
Eosinophilic tissue diseases are a heterogeneous group of diseases which include common conditions such as asthma and atopic dermatitis, less common but regularly diagnosed diseases such as EE, as well as rare diseases such as EP and CSS. The eosinophilia in these diseases may be associated with allergy to common aeroallergens, but include rarer causes of eosinophilia such as drug allergy and (in non-industrialised countries) parasitic infection. However, in many patients with eosinophilic tissue disease the cause remains elusive. Eosinophilic tissue disease is almost invariably highly responsive to glucocorticoids which are the mainstay of treatment. True steroid resistance is rare although in refractory diseases where the inflammation is peripheral, systemic as opposed to topical steroids are often required. Apparent steroid resistance in eosinophilic disease should always raise questions about adherence to treatment. Although usually effective, systemic steroid therapy is limited by toxicity, providing the impetus for better anti-eosinophil drugs. Promisingly anti-IL5 strategies appear to be well tolerated and effective and provide strong clues about the role of eosinophils in various tissue diseases. To optimally use these drugs we need to recognise that eosinophilic tissue diseases have distinct features. For example, in the case of the lung, asthmatic patients that may benefit from anti-eosinophil directed therapy have a selective phenotype including marked blood and/or sputum eosinophilia, nasal polyposis, and patterns of recurrent severe steroid responsive exacerbations. Taken together, emerging concepts have been presented which highlight the seriousness of eosinophil-associated tissue diseases, the potential role of eosinophils in these processes, and appropriate approaches to differential diagnosis and therapy.
This work was supported in part by the NIH NIAID, FAAN, Food Allergy Project, CURED Foundation, and Buckeye Foundation (to MER).
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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ENG | Chinese
NOVI SAD (FIBA U19 World Championship) - USA head coach Jerry Wainwright admitted his team had to dig deep to defeat Argentina in the quarter-finals of the FIBA U19 World Championship on Friday.
Twenty-two points in the last five minutes guided the US to a double scalp of South American opponents as they secured a 112-86 victory to reach the semi-finals.
USA, who saw off Brazil 104-65 in the eighth-finals, were made to work slightly harder against Argentina, but tormentor-in-chief Patrick Beverley helped them maintain their 100% record.
Wainwright said: "Having experience playing Argentina last year in the 18-and-unders and then seeing them down in the Global Games, even though we didn't play them, we knew they were a team that was going to be a really hard match-up for us.
"We probably could have played small the whole game and it would have been the same result, but I tried to get our big guys some reps and the way (Argentina plays), it's hard to play (them).
"I was really disappointed in our defense. We fouled way too much. The game was called a way that was very physical and for a minute there we lost our composure, but got it back. I think we finished the game the right way."
Beverley led all scorers with 20 points and six rebounds, although he was ably assisted by Raymar Morgan, who added 16 points and pulled down seven rebounds.
Wainwright added: "Our core guys, the David Lightys the Patrick Beverleys, the Johnny Flynns, the Stephan Currys, the Raymar Morgans, that core of guys have really been good.
"Mike Beasley and Deon Thompson, under tough circumstances guarding smaller guys did a really good job."
Argentina, who had only edged into the last eight on points difference, were shown up here, although the result could have been closer had it not been for the wayward shooting from the arc of Facundo Pinero.
Pinero, who missed a crucial last-minute basket in his side's narrow 79-78 defeat to Australia, netted three of seven (42.8%) three-point efforts to contribute to a poor team record of nine of 27 (33.3%).
And the game's MVP Beverley revealed that Argentina had been a much tougher proposition than the scoreline suggested.
He said: "They came out and didn't hold anything back.
"Everybody in the tournament knows that you lose, you go home. That's the mentality I guess they came out with but we just have to keep our composure, finish plays.
"It was a really aggressive game, neither team wanted to lose and it got really aggressive.
"That's the game of basketball, sometimes you have games like that. But as I said before, we just have to keep our composure and try to come out with a victory."
Argentina end their tournament with a 3-4 record while the USA are now on an impressive 7-0 winning run.

subset: commoncrawl


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AWF's Year End Extravaganza event returns to Penrith PCYC!Exciting live pro-wrestling bouts to round out 2017, featuring an 8 Man Tournament paying respect to the memory of late AWF Referee OJ Fitzpatrick, AWF Dual and Tag Team Title Bouts, plus Women's Wrestling.
Scheduled Card:
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The Shoes Visa Gift Card offers a lesson all men must master: women love shoes, and with good reason. 1) Heels make you look taller and thinner. 2) Heels improve posture (you have to keep your back straight). 3) Shoes are sexy. 4) Men like women's shoes (when they notice them). 5) Shoes can change the look of an outfit so you can get more use from it. 6) Women notice each other's shoes. Gentlemen, don't wait for your lady to leave a message on a blackboard like this one. Act now and give her a Shoes Visa Gift Card for a quick trip to the mall to shop for shoes.
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953 Chestnut Drive, Escondido CA, 92025
Sold Price:
3 beds , 2 Full baths
1,266 sqft
Status: Sold
Listing Provided Courtesy Of: John Hengel Real Estate
Real Living Napolitano Real Estate
(619) 435-0135
Last Updated: 11/21/2017 9:38 PM
Description for 953 Chestnut Drive Escondido, CA 92025
Very nice updated single level with pool in nice cull de sac street, Mature nice neighborhood with lots of trees.
Sold Price:
Sold Date:11/30/2015
San Diego
2 Full
1,266 (approx)
Very nice updated single level with pool in nice cull de sac street, Mature nice neighborhood with lots of trees.
Listing Information
Slab Foundation
Gas Water Heater, Water Meter, Public Water Servic
Sewer Connected, Sewer at Street
Cable TV, Electric service available, Natural Gas, Telephone
School Information
Room Information
Hookups in Garage
Interior Features
Dishwasher, Range/Oven Free Standing, Garbage Disposal, Carbon Monoxide Detector
Carpet Wall to Wall
Central Air, Electric, Ceiling Fan(s)
Gas Heat, Forced Air
Living Room, Gas Starter, Masonry
Alarm -Smoke/Fire,
Window Blinds
Exterior / Lot Features
2 Garage Spaces, 2 Parking Spaces, Driveway, Front Entrance, Storage Room
Stucco, Frame
Deck, Patio
In-ground, Child safety fence, Filtered, Gunite, Permits
Sidewalks, Street Lights, Shed, Curbs Walk
Driving Directions
Off chestnut street.
Financial Considerations
Listing Price History
Escondido Real Estate
Escondido is located in California. Escondido, California 92025 has a population of 151,451.
The median household income in Escondido, California 92025 is $49,409. The median household income for the surrounding county is $63,996 compared to the national median of $53,482. The median age of people living in Escondido 92025 is 32.8 years.
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As Facebook continues to evolve and mature, some of its decisions lead to significant repercussions for organizations building apps linking to the Facebook platform. Many apps use Facebook to ease registration (fine) or as an age-gating mechanism to restrict children under thirteen (not so reliable). And it did not take long, based on the defaults and permissions that Facebook had enabled, for apps to start requesting access to full details of an app user's friends within Facebook. Last week, on April 30th, Facebook started to fully enforce a change to its API that governs the access an app may have to information about the app user's friends. And with that, organizations whose apps try to pull data from a user's Facebook account must now consider updating their privacy policy so that it remains accurate and consider new ways in which to recoup any revenue hit or business model changes from the new API restrictions.
The problem that Facebook confronted was that simply because I might be your friend on Facebook does not necessarily mean that I trust your judgment about which apps I might want to have my data. As with apps that pulled geolocation or other data without any obvious purpose, the default sharing of all your friends' Facebook activity struck some as presumptuous and creepy.
So a year ago, in April 2014, Facebook announced on its developer platform pages that beginning a year later no apps would be able to pull such broad swaths of personal information. Specifically, the current Facebook API gives users more control over the information they share with an app:
- Users of the app are able to accept and to decline specific information permissions, rather than an all or nothing choice.
- Asking for access to a person's friend list now must be presented as a specific item within the permissions requested.
- The friend list that an individual agrees the app may pull is limited to the app user's Facebook friends who have already authorized the app.
- And the default permission setting for an app user has been changed from "basic info" to "public profile."
The practical implication of this last point is that an app user can now control whether the app can collect more than whatever the public profile contains. This means that apps are no longer by default able to pull details such as the user's "likes," checkins, subscriptions, events, and so on.
Furthermore, Facebook has tasked a team to audit during the app submission process those that do request more than public profile, email address, and list of friends before the app will be approved. Apps created before April 30, 2014 (when this was originally announced) have had a year to adjust their data collection, while all apps must now be reviewed under the new criteria.
Finally, as with privacy policies generally, apps that have collected personal data under the former rules may continue to use that information and are not required under the new API to delete that data. However, if a user communicates a request for the app owner to remove the information, the entity controlling the app must honor that request.


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Read what people are saying
about Precision Garage Door in:
Fitchburg, WIPrecision Garage Door of Wisconsin
has received 3 reviews, averaging 5.00 Stars:
Date: 10/06/2017Garage Door Opener Repair
Fitchburg, WI
Repairs were done very professionally and efficiently.Jack Dalhman
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Date: 04/18/2012Broken Garage Door Spring Repair
Fitchburg, WI
Rob was First Rate! He knew his stuff and was quick and through. He was professional and friendly. I will certainly recomend him!!Patrick G
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Date: 08/11/2011Broken Garage Door Spring Repair
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I was thrilled with the work that Rob did, he really did a great job. I was pleased he went over every detail of the repair before he did any work. He was professional and polite.Sarah L.
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Tour Scotland photographs and videos from my tours of Scotland. Photography and videography, both old and new, from beautiful Scotland, Scottish castles, seascapes, rivers, islands, landscapes, standing stones, lochs and glens.
Old Photograph Spylaw Park Colinton Scotland
Old photograph of Spylaw Park in Colinton located South West of the centre of Edinburgh, Scotland. The Park was bought by the City of Edinburgh Council in 1911.
All photographs are copyright of Sandy Stevenson, Tour Scotland, and may not be used without permission.
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On Tuesday 3rd October, Bond of Friendship Lodge No. 48 celebrated its Silver Anniversary when Bro. Michele was Installed into the Chair by W. Bro. Susan. The occasion was attended by MW Bro. Christine Chapman, GM and RW Bro. Brenda…
Sunday 1st October saw the start of a new venture for peripatetic lodge Ambassadors No. 13 when it held an informal meeting and lunch at a new venue in Letchworth, Herts. http://www.hfaf.org/girls-return-to-the-cloisters/
Sussex 17 and Rising Star 38 joined forces to represent HFAF Freemasonry for Women at the Bexhill Open Day on Saturday 30th September. Sussex was represented by Bro. Jan and Bro. Shirley and Rising Star by W. Bro. Janet.


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Making the most of Africa's biowaste
Cassava peel, sugar cane vinasse and overripe bananas - residues such as these may be known as biowaste, but that doesn't mean they're necessarily wasted. An EU-funded project identified sources and current uses of such materials in five African countries and proposed quick, simple ways of processing them into products with higher added value.
Published: 12 October 2016
Discovery in Kenya sheds light on the origins of warfare
A ground-breaking anthropological discovery took place in East Africa, where ERC Advanced grantee Dr Marta Mirazon Lahr and her team have been studying human origins. At the excavation site in Nataruk in northern Kenya, they have stumbled upon a real archaeological rarity - the earliest historical evidence of warfare.
Published: 18 May 2016
People can now access millions of scientific data resources about our planet thanks to the EUROGEOSS project. EUROGEOSS (European approach to the global Earth observation system of systems), backed under the Environment Theme of the EU's Seventh Framework Programme (FP7) to the tune of EUR 6.1 million, has developed an innovative way to search thousands of Earth observation catalogues.
Published: 26 February 2016
Fresh resources from food processing
When oil-seed plants and fish are processed, how can we use the parts not traditionally used in food? How about food ingredients, skincare and pesticides? EU-funded researchers have demonstrated sustainable ways to get the most out of produce. Companies are already building factories and machines to put the results to good use.
Published: 11 February 2016
Monitoring agriculture for sustainability
Producing more food to feed a growing global population will require more intensive and extensive farming over the coming decades. Ensuring this can be achieved in a sustainable way is the goal of EU-funded researchers developing methods and tools to monitor and map agricultural areas and crop production.
Published: 16 October 2015
African network for eye on Earth
Earth monitoring - observing land, security and climate change from space - can help countries protect resources and improve lives. But the technology is no use without human capacity. So that capacity-building in Africa targets the continent's priorities, an EU-funded project brought together African and European specialists to build networks and make key investment decisions.
Published: 4 September 2015
EU-Africa synergies for e-waste recycling
The mix of urbanisation and rising technology use has increased the stream of e-waste in Africa, for which recycling capacity is limited. Waste management infrastructures are few and far between, public awareness of health issues is limited and environmental precautions rare. A team of European and African researchers is working on a solution.
Published: 2 September 2015
A global forum for food and fuel forestry
The Kyoto Protocol was one of the first major international treaties that focused on human caused climate change. Signed in 1997 by 192 countries, it came into effect in 2005 with a set of legal requirements for industrialised nations to reduce their greenhouse gas emissions. One aspect of the Protocol is the Clean Development Mechanism (CDM), which enables developed nations to reach their emissions targets by sponsoring emissions-reducing projects in the CDM countries - namely China, India, Brazil and most of Africa.
Published: 12 May 2014
Micronutrients against malnutrition
In a part of southern Kenya where malnutrition is rife, Stanley is an active three year old boy. Along with hundreds of other Kenyan youngsters, he is part of a research project aimed at fighting child malnutrition in Africa. The findings so far have surprised researchers.
Published: 6 May 2014
Recurring water shortages endanger local ecosystems and threaten agriculture-based communities. As climate change continues, forecasters expect droughts to become more frequent and severe
Published: 19 March 2014


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Men Who Stitch #1: Mark BieraugelFriday, June 7, 2013
I'm really excited to introduce you to stitcher Mark Bieruagel – the first in our month-long series of interviews with Men Who Stitch. His projects are a fascinating combination of vintage and new, and it's a pleasure to share his work with you here!
How long have you been stitching?
Because I admired her as a person I took an embroidery class from the artist and entrepreneur Jenny Hart in 2009. I never expected to like embroidery, but suddenly I had a creative outlet and I was hooked on needlework.
What is your favorite aspect of stitching – collecting materials, planning, starting, finishing, etc?
I have to confess I am a bit of a collector and hoarder, so the hunting and gathering of materials is really fun. But I really do love all of the other aspects of creating an embroidered piece.
What is your favorite project that you have stitched?
Recently I created a piece called "Ejecta" which uses floss in a very interesting way. I stitched multiple versions of the word, in different floss colors, and also had the floss 'explode' out of a circle. I even included DMC glow-in-the-dark floss as one of the many colors of floss.
What kind of reactions do you get when people see you stitching?
People are nice about it, and it is easy to just start talking as you're stitching. I'm less nervous talking to strangers when I'm stitching. One man told me about his family all making big latch hook rugs together. People often tell me they don't have the patience for doing needlework so I always encourage them to try it out.
What would your dream project be?
Oh, to stitch a mile of stitches using every single color of DMC floss. That just appeals to me in so many ways, all the colors, the idea of small stitches adding up to a mile, and just the colors changing over that distance. I swear that I've had that dream idea for a long time before this interview.
How many hours a week do you spend stitching?
On a good week I probably spend between 10-12 hours, or maybe more if you include designing, planning, and thinking about pieces. When working on larger pieces it seems the design and planning stages take longer than the actual stitching.
Do you have any other creative hobbies, drawing, painting, etc.?
I enjoy making handmade cards of animals with laser beams coming out of their eyes. I was inspired by an artist named Nowvember out of Portland. I also draw in my sketchbook to get my embroidery ideas down, and with all that practice my drawing is improving.
Do you stitch from patterns or do you create your own?
Mostly I make my own patterns, as the things I stitch aren't your everyday things. I love vintage embroidery transfers and have collected boxes and boxes of them. I recently stitched a series of anthropomorphic vegetables using my vintage transfers. I also enjoy Sublime Stitching's patterns, especially the artist series and the pre-printed pillow cases.
Do you have any favorite DMC colors? What is your favorite DMC thread?
The wonderful rich red, 321, is a near constant in my life. I find I keep going back to it. For an orchid art show I stitched three California native orchids and their pollinators all in that luscious red floss. My favorite DMC thread is the classic cotton floss. So many colors, so easy to stitch with! But I have to give a shout out to glow-in-the dark floss, and the lustrous precious metals.
Do you ever meet and share your work with other stitchers? What is your favorite way to do that?
I have met some fellow stitches through flickr and Facebook, which is one of my favorite ways to meet people from all around the world. My cat Tinky likes to "help" me stitch, and felt artist Moxie recently posted my photo with Tinky where I'm working on the "Ejecta" piece.
We have a stitching and knitting 'lunch hour' at work where I get a chance to share my projects and hear about other people's work. I also have been in art shows with other embroiderers and during gallery openings is a really fun chance to compare notes and talk about technique and materials. The stitching world is so full of fantastic, creative, and encouraging people!
To find out more about Mark, visit:


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All weddings have very personal elements. After all, a wedding is a celebration of two individuals joining their lives together, so it's about as personal as you can get. But what I love best is when those moments, not just the details, but the moments are captured in the photos. This is definitely the case with Jessica and Justin's nuptials, as I'm sure you'll see!
From the Photographer:
Justin and Jessica have a beautiful balance of romance and goofiness. I think this is a perfect combination. They were SO fun to work with, and where up for anything. They trusted me when I led them under some el tracks, going along with my vision of bringing out the water stains on the wall for a background texture:)
We started out the day with both the Bride and Groom's preparations at the Crowne Plaza in West Town. The hotel has a really pretty corridor where we had their 'First Look'. We hopped in the limo, and it was off to some nearby locations to take some fun, creative portraits. On the way back to Loft on the Lake, we picked up Palmer, the Couple's ADORABLE Pomeranian dog.
It was time for the Ceremony, and guests were treated to a warm, romantic atmosphere at Loft on the Lake. Jessica did a lot of the decor herself, and she knocked it out of the park. Their Ceremony was officiated by a friend, and was full of funny stories, heartfelt vows, and all smiles. I just gotta put this out there: I love doggie ringbearers! Though I don't know if you could find a better behaved little guy than Palmer. He was pretty much sleeping in one of the Groomsmen's arms, just being his adorable little self.
Cocktail hour went underway, and I was able to capture some candid moments of their guests, as well as documenting all the gorgeous details and decor in the reception room. In between courses, we heard amazing speeches…including an extremely memorable one from the Bride's Sister. As a surprise, she had written a song about Jessica and Justin to the tune of Taylor Swift's "Love Story". I think you can see by the photos how much of a hit it was!
One Comment
7:31 pm on April 8th, 2014
Beautiful photos! I'm definitely recommending you to my best friend. Where is that awesome, water-stained wall?


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|Happy Thanksgiving! Our offices will be closed November 23-24, 2017. Any orders placed during this time will be processed on November 27th. Have a safe and happy holiday!
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fixed pressure
I am working on incomressible fluid flow problem with the following specifications. Inlet B.C. :fixed velocity boundary condition at 6 m/s with turbulence intensity of 2% OUTLET B.C : fixed pressure boundary condition at 0 pressure with the same turbulence. Problem: At the outlet there is INFLOW. Any Explanation. Geometry : Like Heat Exchanger Baffles are placed in the flow domain.
Re: fixed pressure
(1). You need to find out the real flow pattern first. (2). The flow pattern is determined by your problem specification, which is a strong function of the problem geometry. (3). It is likely that the outlet is not placed far downstream and there is a flow separation there. (4). So, move the outlet condition further downstream to avoid the complication first. (5). In the pressure-based solver, the solution can also run into reverse flow during iteration. But it should disappear by the time the solution converges, if the exit boundary condition is placed properly further downstream.
Re: fixed pressure
It is best to place the outlet far downstream, but sometimes it is impossible. In that case, you should check the possibility of reverse flow in the real flow system. For special cases, inflow through the boundary, including outlet, is possible correct solution. In that case, outlet is not a real outlet but a mixed inflow/outflow boundary.
Hoping that it might be helpful to you.
Sincerely, Jin Wook LEE
Re: fixed pressure
The real flow pattern is dependent on the specific geometry and sometime reverse flow from outlet is expected for some engineering application, for example, some burner.
You also can check if your boundary is set correctly with the following step:
(1) calculate a short case; (2) calculate a long case; (3) compare the presure and velocity fields between the two cases for some specified cross-sections. If the boundary is right, then the results should be same or very closed.
Re: fixed pressure
for your inlet you need 2 bc other than the turbulence intensity. also as Jin said the reversed flow may be physically realistic in which case your code needs to check whether the boundary is inflow or outflow if it is outflow your one bc is adequate if it is inflow you must then specify another bc(?).another option may be to use nonreflecting bc at the exit which may allow the reversed flow.
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A MAN has been rescued from a 10m trench after sand collapsed on him in Cannington today.
It's understood the man, believed to be in his 40s, was buried by sand to his neck.
Five-fire crews and the men's co-workers kept digging away at the sand until he could be lifted out.
It's understood paramedics called DFES to the scene just before 3.30pm.
It's believed the man was eventually freed just after 4pm.
He has been taken to hospital for treatment.
Originally published as Firies rescue man from 10m trench


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The Niagara Falls, Canada
Niagara Falls Travel Blog› entry 10 of 15 › view all entries
Saturday may 2
This morning was early again, but this time the breakfast was included. The choice was ok, even a machine with liquid dough to make a waffle. It did taste good. But everything was plastic. To us that is very strange and polluting. But ok. It seems normal there.
We wanted to be at the Niagara Falls on time and there were also a lot of things we wanted to see.
Continuing the road we reached the boarder of Canada. It seems that we always choose the wrong row. It took about half an hour to cross the border. But from there we saw the hotel, Skyline Inn. But I saw the other one also, the one we were supposed to stay. Sheraton on the Falls. I picked that one for the nice view.
Of course thirsty again and find a nice place to sit in the mall. It was already late and we were thinking where we would have our dinner. Not very much in the nearby area, so Hard rock café again, but I did have vegetables! (I did hope that was the last one I had to visit). After that we went to the Skylon Tower to see what they have to offer. Tomorrow is Sunday and they have a dinner buffet. Seems nice, so would like to reserve a table for tomorrow. Surprise, it was not possible, yes the sign could say that they serve that, but it is low season, so not available. Of course, than they should have make an note on the sign to tell us.
In the evening we had to take care of the amount off calories we had, so we had to walk. We walked to the table of Rock. This is the place where the Falls start to fall over the cliff. And the waterfall is colored by big spotlights. Very nice to see that, but the pictures are not that clear.


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Letter(s) from Natalia Tyuhtiy to Patrice (Belgium)
Letter 1
At first I want to say thank you for email!
Secondly I want to say I hope so much I will receive an answer from you.
And every time I want to fly through the miles and kilometers only to you.
What do you think , my honey is it possible to unite two lonely hearts Only give me the opportunity to show you that I have strong intentions to win your heart and soul. I really feel that you will be mine and I will be yours.
This feeling full my bady.
But what a pity:there are so many kilometers between us! I really want to see you close with me, feel your breath,and do a lot of crazy things only with you.
But now it is only dream. And it depends on us to make our dream come true.
Today is a good weather,it is shining now and I see you are looking at me from your place, you think about me as I think every moment about you.
I have the one only thought in my head:how can we build our future life together?
Allow me read your thoughts about this. Hope you are too want the same from our relations.
You can ask me anything you want.
Big kisses to you.
P.S. I'd like to come to you a lot!thank you for your proposition!
you are wonderful man and it'll be wonderful if we can meet...we can see each other eyes, hold our hands...kiss each other...and whisper "I need you!"
...Oh!you even can't imagine how strong i'd like to see you!
but I don't know if it's possible... =(
i really would like to meet you, and to come to you!
baby, I don't know if I can come, cause this trip will be too expensive for me!but just know that I really would like to come to you a lot!darling, but maybe you'll help me with money, so then I can come, and be with you?what do you think?
With warm love,
Letter 2
hello my love Patrice!!!
Frankly speaking,I understand that you become very close person for me and I really love you!!!
You is the sense of my life. I miss you when I do not get your letters for a long time. Without your attention I would feel lonely and uncomfortable.
Our communication helps me feel strong and sure of myself.
My only and cherished dream is to be with you.
Do not break my dream,ok?
Patrice,I was in the travel agency, and I was told, that I need international passport, it cost 300$ visa 210$ and both way tickets around 240$
but this is too expensive for me darling...(((
can you please help me with it?
in the travel agency I was told that you can use Western union, or money Gram to send me the money...
will you help me with it???
baby, and as you asked, so I haven't got camera now to make you this photo!
but as soon as i'll have I'll send it to you!!!
I'll wait for your answer!
Letter 3
Good day, my darling Patrice!
How are you? How is your day today?
I hope everything is good in your life.
I am fine, of course, missing you as I always do. But, all in all, life is good.
Thank you very much for your nice words and that you care about me!
You are so kind and sweet man!
Today, I had a quite hard working day, my colleague was sick and I had to work instead of her too. But I'm even not tired, because you are always on my mind, thinking about you, I become inspired again and again. You are in my mind all the time! I did not think that it was possible but it is true.
Your words make me feel so good inside that..... now I cannot find the right words to describe how good you make me feel. I think we are both very lucky,we have the same souls,hopes and hearts. We found each other and we both are ready to be together. I think this is something special.
I'll be the most happy woman in the word,when I'll see you and I'll hear nice and sweet words from you in the real life!
darling, as you asked, so you can send me money by western union or Money Gram:
My adress is
Ukraine,town Popasnoe,(93300)
street Rudneva, 18/3
my full name:
Palagina Olga
Baby, i really would like to meet you a lot!
you can't even imagine how I'm exited about it!
please can you help me as soon as you can!!!
I really would like to be with you!!!
I'll wait for your answer!


text:
Ah, camping… enjoying the great outdoors as it was meant to be enjoyed. Building your tent, hiking through rugged terrain, and building a fire; all great ways to help you get in touch with your inner wild-man. But just because you are living like our early ancestors did, it doesn't mean you have to look like them!
Micro Touch Max is a great camping companion, because it allows you to live like a wild-man, but not look like one. No running water or indoor plumbing? No problem! Micro Touch One is a battery operated grooming tool that requires no water or shaving cream. It's small enough to pack in your bag, and light enough to not break your back as you climb your mountain. Micro Touch Max is powerful enough for even the coarsest of hairs, and even has a light… making outdoor use even easier! A rubber grip makes it perfect for on the go use, and the brightly colored design would make it difficult to lose, even in the great outdoors.
So next time you decide to get in-touch with your inner man, don't forget to bring along man's new best friend… the Micro Touch Max


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Back when Facebook wasn't for business, before Twitter was born, and in the days when we were still throwing our checkbooks at the classified sections of our local newspapers because people actually read them, I started a blog.
It wasn't such a big deal, this little Web log. And the whole idea didn't come to me in an epiphany of forward-thinking genius. Rather, it was just Experiment No. 372 in my ongoing struggle to differentiate myself and my business from the 85 million other licensed real estate agents in my market area.
I had no idea what I was doing. I didn't even know what "it" was. I just knew that I had been hearing stuff -- that my once novel, static website was now as common as the cheap seats at a royal wedding, and that the process of not only achieving success in this business but hanging onto it is just that -- a process.
So I Googled "How to create a Web log." I did this right after I Googled "What...


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Do you know how old Italy really is? Any idea what Italy actually means or who Alessandro Volta is? No? Then you'd better read these 21 fun facts about Italy to get clued up before you go.
Source: italiantrips.com
Source: eatingitalyfoodtours.com
Source: eupedia.com
Source: sciencekidz.co.nz
Source: unesco.org
Source: mymelange.net
Source: lifeinitaly.com
Source: dera.ioe.ac.uk
Source: lifeinitaly.com
Source: literaturepage.com
Source: pastafits.org
Source: knowledge.allianz.com
Source: eupedia.com
Source: mymelange.net
Source: comenius-ourstory.com
Source: lifeinitaly.com
Source: italianwinecentral.com
Source: coffeeresearch.org
Source: roughguides.com
Source: reekoscience.com
Things not to miss in Italy
From the stunning Amalfi coast to the artworks of the Vatican, here are the top things not to miss in Italy.
Explore more of Italy with the Rough Guide to Italy. Book hotels for your trip and don't forget to purchase travel insurance before you go.


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Lyons, IL Bowling
Explore Lyons Bowling
Find Lyons Bowling players, teams, games, leagues, and activity partners. Recruit for your teams, promote your leagues, or just see what's happening in Lyons Bowling... and it's all safe, secure, and easy.
Connect around Lyons Bowling
Post bulletins and create your Bowling profile to connect with other Lyons Bowling players and teams. Use the Bulletin Boards to help you meet new friends, recruit for your team, promote your league, and get your game on!
Organize Lyons Bowling Teams, Leagues, & Events
Manage your Lyons Bowling teams online. Sportsvite makes it a cinch, with team email, rosters, RSVPs and more! Start pickup games, manage team schedules, set invite alerts and reminders... even vote for MVPs!
Lyons Bowling Players Find More Bowling Players Create a Profile
Lyons Bowling Bulletins Find More Bulletins Post a Bulletin
Hit me up... looking for Bowling games not in the past month by Lil
Hit me up... looking for Bowling games not in the past month by Jason
Male in Brookfield is available for a Bowling team not in the past month by Kyle
Lyons Bowling Activity
not in the past month
- Bowling Added to Sports Profile
- Lil in Berwyn, IL has added Bowling to her sports profile
not in the past month
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- Rosa in Berwyn, IL has updated her Bowling profile
not in the past month
- Bowling Added to Sports Profile
- Jason in Brookfield, IL has added Bowling to his sports profile
not in the past month
- Bowling Player Looking for a Team
- Bulletin posted by Kyle in Brookfield, IL.
Male in Brookfield is available for a Bowling team
not in the past month
- Bowling Player Looking for a Game
- Bulletin posted by Kyle in Brookfield, IL.
Male in Brookfield is available for Bowling games
More Lyons Sports
- Team Sports
- Lyons Australian Rules Football
- Lyons Baseball
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- Lyons Ice Hockey
- Lyons Jai-Alai
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- Lyons Rugby
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- Lyons Softball
- Lyons Squash
- Lyons Trangleball
- Lyons Ultimate Frisbee
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- Action Sports
- Lyons BASE Jumping
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- Lyons Canyoning
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- Lyons Inline Skating
- Lyons Motorbike
- Lyons Mountain Biking
- Lyons Roller Derby
- Lyons Skateboarding
- Lyons Skating
- Lyons Sky Diving
- Water Sports
- Lyons Canoeing
- Lyons Diving
- Lyons Dragon Boat Racing
- Lyons Flowboarding
- Lyons Inner Tube Water Polo
- Lyons Kayaking
- Lyons Kiteboarding
- Lyons Outrigger Paddling
- Lyons Rowing
- Lyons Sailing
- Lyons Surfing
- Lyons Swimming
- Lyons Wakeboarding
- Lyons Water Skiing
- Lyons Whitewater Rafting
- Lyons Windsurfing
- Fitness
- Lyons Boxing
- Lyons Cheerleading
- Lyons Climbing
- Lyons Crossfit
- Lyons Cycling
- Lyons Dancing
- Lyons Fitness/Training
- Lyons Gymnastics
- Lyons Marathon
- Lyons Martial Arts
- Lyons Running
- Lyons Scuba
- Lyons Tae Kwon Do
- Lyons Track & Field
- Lyons Triathlon
- Lyons Walking
- Lyons Weightlifting
- Lyons Yoga
- Playground / Gym
- Lyons 3D Dodgeball
- Lyons Capture the Flag
- Lyons Croquet
- Lyons Dodgeball
- Lyons Four Square / Box Ball
- Lyons Frockey
- Lyons Hackeysack
- Lyons Handball
- Lyons Horseshoes
- Lyons Kickball
- Lyons Newcomb
- Lyons Oozball
- Lyons Over the Line
- Lyons Paddle Tennis
- Lyons Paddleball
- Lyons Quidditch
- Lyons Racquetball
- Lyons Rockball
- Lyons Stickball
- Lyons Tetherball
- Lyons Wall Ball
- Lyons Wiffleball
- Grass / Field Sports
- Lyons Beach Tennis
- Lyons Bocce
- Lyons Cornhole
- Lyons Disc Golf
- Lyons Equestrian Sports
- Lyons Golf
- Lyons Petanque
- Lyons Pickleball
- Lyons Polo
- Lyons Tennis
Lyons, IL Bowling on Sportsvite
- Welcome to Sportsvite, your Lyons Bowling community online!
- Take a few minutes to check out Lyons Bowling, including local Lyons Bowling players, Lyons Bowling teams, events, leagues and latest bulletins posted from others in the Lyons area.
- Are you an organizer?
- Manage your own Bowling team, organize Bowling events, or list your Bowling league in the local Lyons leagues directory.
- Setup a free account and be matched up with compatible Lyons players and activities!


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REUNION, Fla. -- Lorena Ochoa hustled around the corner, hoping to jump in a car and catch a flight home to Mexico.
No chance.
There were about 100 people waiting for her in the resort lobby, some seeking pictures and autographs, others hoisting glasses of champagne.
Ochoa wanted to sprint away, but she paused for another few minutes. After all, this was deserving of one more celebration.
Ochoa captured her fourth straight victory in four straight weeks Sunday at the Ginn Open. Her 3-under 69 in the final round helped her beat rookie Yani Tseng by three strokes for her fifth victory in six starts this year.
"I'm very grateful. It's been a blessing, you know," Ochoa said. "But I know that bad times will come. It's just the way life is. I'm just trying to enjoy my moment, and I would like to enjoy it for a long time. So even if it's going to be an up-and-down ride, hopefully I can stay there."
Ochoa trailed early in the final round, but went ahead for good with three straight birdies beginning at No. 8. She finished 19 under and has won five of her six starts by a combined 37 shots this year.
Ochoa won four consecutive scheduled LPGA Tour events for just the fifth time in LPGA history. Mickey Wright did it in 1962 and 1963. Kathy Whitworth (1969) and Annika Sorenstam (2001) also accomplished the feat.
Ochoa will give her colleagues a chance to take the spotlight next week in South Florida. She will sit out the Stanford Invitation Pro-Am, and then try to make it five straight in two weeks in Tulsa, Okla.
"She's proven that she's our top player," fellow golfer Paula Creamer said. "She's set that mark pretty high."
Ochoa talked all week about how tiring it was to play four straight events, especially since last week's victory came in her native country and was filled with visits from friends and family members, plus countless media and sponsorship requests.
But even with a little less energy, she was better than everyone else at the Ginn.
"She's really No. 1," said Tseng, who finished 16 under and five shots ahead of third-place Teresa Lu and Suzann Pettersen.
Ochoa was up a stroke to begin the final round, but Tseng pulled ahead with a birdie-birdie start. Ochoa had several chances to move back in front, but she just missed birdie putts on Nos. 5, 6 and 7. She finally grabbed the lead with a 12-foot birdie putt on No. 8, then followed with two more on the next two holes.
The 19-year-old Tseng couldn't keep pace on the back nine, bogeying three of the final six holes and allowing Ochoa to cruise to her latest win. Tseng, who now has two second-place finishes and six top-25 showings in as many starts this year, said she got distracted by thoughts of winning.
"A little bit," she said. "Maybe not just a little bit, more than that."
Ochoa tapped in for par on No. 18, then raised both arms in celebration. She congratulated Tseng and told her they were going to see each other on many Sundays.
Ochoa won a car and $390,000, raising her 2008 earnings to $1,440,500. She also took home another trophy. She grabbed the giant, shell-shaped glass bowl with one hand and held up four fingers with the other.
"The biggest thing is her confidence," Creamer said. "She goes out there and knows she can do it and knows how to win."
It was Ochoa's 10th win in her last 15 tournaments, dating to last year. She won eight times in 2007 and has been even better to start '08.
She opened with an 11-stroke victory in Singapore, defended her Safeway International title with a seven-stroke romp, won the season's first major by five shots and then went wire-to-wire last week in Mexico and won by 11.
Although she worked all offseason on her short game -- she got up-and-down from every bunker at the Ginn and finished 12 under on the par 5s -- she credits her recent success on her mental toughness.
"Even if you don't have your best swing or your best rhythm or you're not feeling the best in your life, you have to be able to manage the score and put yourself in a good position," she said.
She's in position to make it five in a row.
But first, she's ready for a break.
After that final toast in the lobby, Ochoa flew home and had a big lunch planned for Monday with her mom, her brothers, her sister and some in-laws.
She's not sure what's on the menu, but given she just made the record book, she has an idea.
"My mom knows which one is my favorite plate, so hopefully we'll have that," Ochoa said.
The Associated Press contributed to this report.


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Established in 1975, Poor Cow Leather has provided exceptional customer service, high quality products and reasonable prices in leather goods and accessories. In 2015, Poor Cow Leather went under new management, and the principles stated previously have never been more true.
Poor Cow Leather is located in Olean NY, a little bustling town in scenic western New York. Motorcycle season is big here, and PCL provides the area's largest selection of motorcycle gear. Now we can share our large selection of motorcycle boots, leather jackets, leather accessories, clothing, and much more with the rest of the world.
Meet the Team!
Matt LeBlanc, owner


text:
I literally look forward to the Olympics every two years (including the Winter ones), there is something so remarkable about athletes, truly a breed on their own. Anticipating the coming London Olympics, American Vogue's June issue celebrates Team USA, with a "golden" cover and a fashion spread featuring some of the Country's favorite contenders accompanied by stunning Karlie Kloss.
Check it out;
Just in time for the weekend, my Vogue just arrived, I'll be indulging in it's pages under the sun!


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Macweld is a family run business that is committed to producing high quality repairs for our customers on time and at a fair price.
We have qualified engineers on our staff that are certified in all types of welding, From TIG welding right through to onsite structural steel jobs.
Our Mag wheel repair department specializes in the repair of curb damage, cracks, and dents on all types of wheels. We also have a fully equipped paint shop at our disposal that can paint your wheels any color you wish.
When repairing cracks and damage to wheels we use the TIG welding process with special welding rods that are imported from Europe. These rods are specially made to match the composition of the wheels so our repairs are stronger and less likely to crack again.
We pride ourselves in having an extremely short turnaround and providing our customers with wheels that are not only running true again but also looking as good if not better than the original wheel.
We can give price estimates over the phone and can confidently say that we have some of the best prices in town. We also have qualified engineers working on you wheels with 15 plus years experience in the wheel repair industry.
Our guys have dealt with almost every different type of repair you could imagine over the years so if it can be safely repaired then we can do it.
Get your curbed dented or cracked wheels repaired today. Phone MacWeld on 09 294 6676


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London, United Kingdom (PressExposure) July 08, 2009 -- Just one of the ways the Konig Swiss® Humidifiers leads the market is that itâs decorative. No longer will your humidifier be the eyesore of your office or home. At first glance it looks like a piece of Art just hanging on the wall, discrete and stylish. The Humidifiers also have interchangeable panels, and so whatever the style of your room â we have a panel to fit. It can hang comfortably in your Dining Room, your Office or even your Childâs Bedroom. Itâs this kind of thinking that has won 2 Gold Medals from Genève for âOutstanding, Innovative designâ.
There are 7 Decorative panels that range from a standard white version, suitable for any standard wall in the home or the Office, to a waterfall view for those who want to look at something thatâs a little scenic. Also available is a more colourful scene that would look at home in any Childâs Bedroom.
But that isnât all. What good is putting all that work into the design if the humidifiers itself doesnât compliment it? Well the Konig Swiss® Humidifiers was designed for both easy to look at, and easy to use. It doesnât plug into the corner of the room like other, traditional Humidifiers, itâs controlled Non-Electrically by the hydro-pneumatic valve system that regulates and monitors the complete humidification process automatically.
Itâs also incredibly simple to use, just fill the water globe on top of the Humidifier and it takes care of the rest. The wood panel mantel where the water globe sits is made of Beech Wood thatâs hand chosen from the trees of Switzerland and adds a piece of fine furniture style to the humidifiers. That means no unwelcome mist and definitely no noise. In fact itâs so quiet you wonât even know itâs there.
âOur Non- Electric humidifiers embrace the total Green movement providing our dealers with a true green product to offer their customers as an alternative to costly electric versions, and providing a pleasant décor style to match their roomâs décor.â Richard Jarvis, C.E.O Konig Swiss® Inc.
Lisa, CEO of lmk interiors adds âThat is the most beautiful household product I have seen in quite some time!â
Designed and manufactured in Switzerland the Konig Swiss® Humidifiers are stylish and very Eco-Friendly. Itâs Carbon Free and a non-pollutant system so you can rest assured that not only are you enjoying the air around you; youâre also helping not to pollute the air everywhere.
König Swiss makes non-electric, environmentally friendly humidifiers with patented Swiss quality. Available in Switzerland since 1998, König Swiss humidifiers have been sold throughout Europe since 2002, including Germany, Austria, France and Latvia. More information can be found by visiting the website. Press Release Distribution By PressReleasePoint
Contact: Charlotte Everiss Virtual Secretary Solutions London, UK 056-014-55447 email@example.com http://www.virtualsecretarysolutions.co.uk


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Pictures of Nicole Richie Leaving Gym
Nicole Richie Runs Out of the Gym in Style
Nicole Richie Runs Out of the Gym in Style
Nicole Richie was decked out in accessories as she left the Tracy Anderson Method in LA yesterday. She chose a similar layered look last week for a trip to the hair salon after returning home from her travels to Paris. Nicole and her husband, Joel Madden, are finally both back in town after parting ways while she attended Fashion Week earlier in the month and he headed out on tour with Good Charlotte. Joel has a few extra days to spend with his family since one of the festivals that his band was scheduled to play in Japan next week was recently canceled due to the earthquake. The group will get together for a performance on The Tonight Show on Wednesday, though he'll be back on the road for a stop in the Philippines on April 6.
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