RR-Lyrae-type pulsations from a 0.26-solar-mass star in a binary system.

RR Lyrae pulsating stars have been extensively used as tracers of old stellar populations for the purpose of determining the ages of galaxies, and as tools to measure distances to nearby galaxies. There was accordingly considerable interest when the RR Lyrae star OGLE-BLG-RRLYR-02792 (referred to here as RRLYR-02792) was found to be a member of an eclipsing binary system, because the mass of the pulsator (hitherto constrained only by models) could be unambiguously determined. Here we report that RRLYR-02792 has a mass of 0.26 solar masses M[symbol see text] and therefore cannot be a classical RR Lyrae star. Using models, we find that its properties are best explained by the evolution of a close binary system that started with M[symbol see text] and 0.8M[symbol see text]stars orbiting each other with an initial period of 2.9 days. Mass exchange over 5.4 billion years produced the observed system, which is now in a very short-lived phase where the physical properties of the pulsator happen to place it in the same instability strip of the Hertzsprung-Russell diagram as that occupied by RR Lyrae stars. We estimate that only 0.2 per cent of RR Lyrae stars may be contaminated by systems similar to this one, which implies that distances measured with RR Lyrae stars should not be significantly affected by these binary interlopers.

Feasibility of abdominal fat quantification on MRI and impact on effectiveness of abdominal compression for radiotherapy motion management.

The impact of fat on abdominal compression effectiveness in abdominal cancers was determined using magnetic resonance imaging (MRI). Visceral and subcutaneous fat were delineated on T2W 3D MRI, and motion change with compression was measured on 2D cine MRI. Results from 16 participants showed no correlation between fat percentage, body mass index (BMI), and motion change. Median BMI was 28.7 (SD, 4.9). Mean motion reduction was 7.8 mm (IQR, 5.0; p = 0.001) with compression. While no direct link was found between fat, BMI, and compression effectiveness, abdominal compression remains crucial for motion management in radiotherapy planning, providing dosimetric benefits.

Evaluation of Prognostic and Predictive Models in the Oncology Clinic.

Predictive and prognostic models hold great potential to support clinical decision making in oncology and could ultimately facilitate a paradigm shift to a more personalised form of treatment. While a large number of models relevant to the field of oncology have been developed, few have been translated into clinical use and assessment of clinical utility is not currently considered a routine part of model development. In this narrative review of the clinical evaluation of prediction models in oncology, we propose a high-level process diagram for the life cycle of a clinical model, encompassing model commissioning, clinical implementation and ongoing quality assurance, which aims to bridge the gap between model development and clinical implementation.

Changes in Magnetic Resonance Imaging Radiomic Features in Response to Androgen Deprivation Therapy in Patients with Intermediate- and High-risk Prostate Cancer.

AIMS: The benefits of neoadjuvant androgen deprivation therapy (nADT) in the management of intermediate- and high-risk prostate cancer patients have been well-established. The aim of this study was to identify radiomic prognostic features derived from routine anatomic magnetic resonance imaging (MRI) sequences that can predict the response of the prostate cancer to nADT. MATERIALS AND METHODS: Patients with intermediate- and high-risk prostate cancer (with one of clinical stage ≥ T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) who received 3 months of ADT prior to radical external beam radiotherapy were enrolled into this study. The relative blood volume and the relative blood flow were used as dynamic MRI kinetic parameters to quantify vascular changes as responses to nADT. For all pre- and post-nADT data sets, a combination of T2-weighted and contrast-enhanced T1-weighted anatomic images were used to define regions of interest (ROI) as the dominant malignant nodules (DMNs) and the benign prostate (the entire prostate with the summed DMNs being subtracted). MRI textural radiomic features associated with prostate cancer response in the literature of energy and homogeneity were selected. Pyradiomics was used to extract textural features of the ROIs. A Wilcoxon signed-rank test was carried out to investigate if there were statistically significant differences in values of radiomic features between: (i) benign prostate ROI and DMN pre-nADT; (ii) pre- and post-nADT of benign prostate ROI; (iii) pre- and post-nADT of DMN. Changes in radiomic features and dynamic MRI kinetic parameters were correlated using the Spearman correlation test. RESULTS: Twenty prostate cancer patients were recruited into the study. The median time between the first baseline scan and the first on-treatment scan was 91.5 days (range 82-105). One patient had no discernible tumour visible, leaving 19 patients with evaluable data for the analysis. Baseline homogeneity and energy values differed significantly between benign and malignant tissue (P < 0.01). In response to nADT, homogeneity and energy showed reciprocal changes, significantly increased in benign prostate while decreasing in the DMN. The reduction in tumour homogeneity and energy feature values showed a positive association with the decline in tumour blood flow and tumour blood volume induced by androgen deprivation as derived from dynamic MRI parameters. CONCLUSION: Energy and homogeneity radiomic features derived from MRI of benign and malignant prostate showed significant reciprocal changes in response to nADT. This study confirms the potential of these radiomic features to act as surrogate markers of tumour androgen sensitivity due to their strong association with ADT-induced physiological effects in prostate tumours.

Inter- and intra-fractional stability of rectal gas in pelvic cancer patients during MRIgRT.

PURPOSE: Due to the electron return effect (ERE) during magnetic resonance imaging guided radiotherapy (MRIgRT), rectal gas during pelvic treatments can result in hot spots of over-dosage in the rectal wall. Determining the clinical impact of this effect on rectal toxicity requires estimation of the amount and mobility (and stability) of rectal gas during treatment. We therefore investigated the amount of rectal gas and local inter- and intra-fractional changes of rectal gas in pelvic cancer patients. METHODS: To estimate the volume of gas present at treatment planning, the rectal gas contents in the planning computed tomography (CT) scans of 124 bladder, 70 cervical and 2180 prostate cancer patients were calculated. To estimate inter- and intra-fractional variations in rectal gas, 174 and 131 T2-w MRIs for six cervical and eleven bladder cancer patients were used. These scans were acquired during four scan-sessions (~20-25 min each) at various time-points. Additionally, 258 T2-w MRIs of the first five prostate cancer patients treated using MRIgRT at our center, acquired during each fraction, were analyzed. Rectums were delineated on all scans. The area of gas within the rectum delineations was identified on each MRI slice using thresholding techniques. The area of gas on each slice of the rectum was used to calculate the inter- and intra-fractional group mean, systematic and random variations along the length of the rectum. The cumulative dose perturbation as a result of the gas was estimated. Two approaches were explored: accounting or not accounting for the gas at the start of the scan-session. RESULTS: Intra-fractional variations in rectal gas are small compared to the absolute volume of rectal gas detected for all patient groups. That is, rectal gas is likely to remain stable for periods of 20-25 min. Larger volumes of gas and larger variations in gas volume were observed in bladder cancer patients compared with cervical and prostate cancer patients. For all patients, local cumulative dose perturbations per beam over an entire treatment in the order of 60 % were estimated when gas had not been accounted for in the daily adaption. The calculated dose perturbation over the whole treatment was dramatically reduced in all patients when accounting for the gas in the daily set-up image. CONCLUSION: Rectal gas in pelvic cancer patients is likely to remain stable over the course of an MRIgRT fraction, and also likely to reappear in the same location in multiple fractions, and can therefore result in clinically relevant over-dosage in the rectal wall. The over-dosage is reduced when accounting for gas in the daily adaption.

Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces.

Immunohistochemical analysis of challenge sites such as skin and the peritoneal cavity has identified neutrophils as virtually the sole cellular participants in acute bacterial inflammation, peak influx occurring 24-48 h in advance of mononuclear cell populations associated with adaptive immunity. This study challenges the general applicability of this paradigm. We demonstrate here that the earliest detectable cellular response after inhalation of Moraxella catarrhalis organisms is the recruitment of putative class II major histocompatibility complex-bearing dendritic cell (DC) precursors into the airway epithelium, the initial wave arriving in advance of the neutrophil influx. Unlike the neutrophils which rapidly transit into the airway lumen, the DC precursors remain within the epithelium during the acute inflammatory response where they differentiate, and develop the dendriform morphology typical of resident DC found in the normal epithelium. During the ensuing 48-h period, these cells then migrate to the regional lymph nodes. No comparable DC response was observed after epidermal or intraperitoneal challenge, and it may be that mucosal surfaces are unique in their requirement for rapid DC responses during acute inflammation. We hypothesize that the role of the DC influx during acute inflammation may be surveillance for opportunistic viruses, and that this covert protective mechanism is operative at a restricted number of mucosal tissue sites.

Development of the airway intraepithelial dendritic cell network in the rat from class II major histocompatibility (Ia)-negative precursors: differential regulation of Ia expression at different levels of the respiratory tract.

The relative inefficiency of respiratory mucosal immune function during infancy is generally attributed to the immaturity of the neonatal T cell system. However, immune competence in the adult lung has recently been shown to be closely linked to the functional capacity of local networks of intraepithelial dendritic cells (DC). This study examines the density and distribution of these DC throughout the neonatal respiratory tract in rats, focusing particularly on microenvironmental regulation of their class II major histocompatibility complex (MHC) (Ia) expression. In animals housed under dust-controlled conditions, airway epithelial and alveolar Ia+ DC detectable by immunostaining with the monoclonal antibody (mAb) Ox6 are usually not seen until day 2-3 after birth, and adult-equivalent staining patterns are not observed until after weaning. In contrast, the mAb Ox62 detects large numbers of DC in fetal, infant, and adult rat airway epithelium. Costaining of these Ox62+ DC with Ox6 is rare in the neonate and increases progressively throughout infancy, and by weaning Ia+ DC comprised, on average, 65% of the overall intraepithelial DC population. In infant rats, Ia+ DC are observed first at the base of the nasal turbinates, sites of maximum exposure to inhaled particulates, suggesting that their maturation is driven in part by inflammatory stimuli. Consistent with this suggestion, densitometric analysis of Ia staining intensity of individual DC demonstrates that by 2-3 d after birth, Ia expression by nasal epithelial DC was comparable with that of Iahigh epidermal Langerhans cells in adjacent facial skin, at a time when expression by tracheal epithelial DC was 7-10-fold lower. Additionally, the rate of postnatal appearance of Iahigh DC in the airway epithelium was increased by administration of interferon gamma, and decreased by exposure of infant rats to aerosolized steroid. These findings collectively suggest that Ia expression by neonatal respiratory tract DC is locally controlled and can be upregulated by mediators that are produced within the lung and airway epithelium in response to inhalation of proinflammatory stimuli. It was also noted that Ialow neonatal airway DC expressed adult equivalent levels of class I MHC, which suggests differences in capacity to prime for CD8(+)-dependent versus CD4(+)-dependent immunity to inhaled pathogens, during the early postnatal period.

Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli.

A key rate-limiting step in the adaptive immune response at peripheral challenge sites is the transmission of antigen signals to T cells in regional lymph nodes. Recent evidence suggests that specialized dendritic cells (DC) fulfill this surveillance function in the resting state, but their relatively slow turnover in most peripheral tissues brings into question their effectiveness in signaling the arrival of highly pathogenic sources of antigen which require immediate mobilization of the full range of host defenses for maintenance of homeostasis. However, the present report demonstrates that recruitment of a wave of DC into the respiratory tract mucosa is a universal feature of the acute cellular response to local challenge with bacterial, viral, and soluble protein antigens. Consistent with this finding, we also demonstrate that freshly isolated respiratory mucosal DC respond in vitro to a variety of CC chemokines as well as complementary cleavage products and N-formyl-methionyl-leucine-phenylalanine. This suggests that rapid amplification of specific antigen surveillance at peripheral challenge sites is an integral feature of the innate immune response at mucosal surfaces, and serves as an "early warning system" to alert the adaptive immune system to incoming pathogens.

Cardiovascular mortality and morbidity following radical radiotherapy for lung cancer: Is cardiovascular death under-reported?

BACKGROUND: Lung cancer is the most common malignancy worldwide. Radical radiotherapy is an essential treatment in the management of early and locally advanced lung cancer. Cardiac events are known to occur following radical radiotherapy for lung cancer. This study examines the burden of cardiac events post radiotherapy, and estimates the accuracy of death certification in patients who received radical radiotherapy for lung cancer. METHODS: We conducted a retrospective observational cohort study for all patients receiving radical radiotherapy for non-small cell lung cancer (NSCLC) at a large cancer centre between 01/01/2010 to 31/12/2016. Baseline cardiovascular disease and cancer status and treatment data were collected, along with hospital admission data and documented cause of death from the national registry for a median follow-up period of 34 months. RESULTS: Of 1224 patients included in the analysis, 378 (30.9%) patients had cardiovascular disease at baseline, including 140 (11.4%) with prior myocardial infarction. In the 846 patients without known cardiovascular disease, 451 (53.3%) had a QRISK2 predicted 10-year cardiovascular risk >20% over 10 years. During follow-up, 215 hospitalisations occurred (Incidence rate 6.2 per hundred patient years) which were classified as primarily cardiac, and 622 patients died (18 per 100 patient-years). However, death certificates stated a primary cardiac cause of death in only 33 cases (5.3% of deaths). Notably, 29% of patients dying out of hospital and certified as cancer death did not have documented cancer relapse prior to death, and 61% had no community palliative care input prior to death, implying these events may have been sudden and unexpected. CONCLUSION: There is a high prevalence of baseline cardiovascular disease in people undergoing radiotherapy for NSCLC, accompanied by significant rates of post-radiotherapy cardiovascular hospitalisation. However, only a small proportion of deaths are attributed to cardiovascular disease, together with the large amount of sudden deaths observed, this suggests that cardiovascular death is greatly under-reported in official statistics.

Experimental verification the electron return effect around spherical air cavities for the MR-Linac using Monte Carlo calculation.

PURPOSE: Dose deposition around unplanned air cavities during magnetic resonance-guided radiotherapy (MRgRT) is influenced by the electron return effect (ERE). This is clinically relevant for gas forming close to or inside organs at risk (OARs) that lie in the path of a single beam, for example, intestinal track during pelvic treatment. This work aims to verify Monte Carlo calculations that predict the dosimetric effects of ERE around air cavities. For this, we use GafChromic EBT3 film inside poly-methyl methacrylate (PMMA) -air phantoms. METHOD: Four PMMA phantoms were produced. Three of the phantoms contained centrally located spherical air cavities (0.5, 3.5, 7.5 cm diameter), and one phantom contained no air. The phantoms were split to sandwich GafChromic EBT3 film in the center. The phantoms were irradiated on an Elekta Unity system using a single 10 × 10 cm2 7-MV photon beam under the influence of a 1.5-T transverse magnetic field. The measurements were replicated using the Elekta Monaco treatment planning system (TPS). Gamma analysis with pass criteria 3%/3 mm was used to compare the measured and calculated dose distributions. We also consider 3%/2 mm, 2%/3 mm, and 2%/2 mm pass criteria for interest. RESULTS: The gamma analysis showed that >95% of the points agreed between the TPS-calculated and measured dose distributions, using 3%/3 mm criteria. The phantom containing the largest air cavity had the lowest agreement, with most of the disagreeing points lying inside the air cavity (dose to air region). CONCLUSIONS: The dose effects due to ERE around spherical air cavities are being calculated in the TPS with sufficient accuracy for clinical use.

The Challenges of Using MRI During Radiotherapy.

In this article we aim to introduce the main considerations in integrating magnetic resonance imaging (MRI) into the radiotherapy workflow. We will cover the use of MRI for improved delineation, considerations regarding MRI-only workflows, and the potential of functional imaging techniques. The challenges of implementing each of these will be discussed to ensure safe usage in radiotherapy.

Benefit of using motion compensated reconstructions for reducing inter-observer and intra-observer contouring variation for organs at risk in lung cancer patients.

BACKGROUND AND PURPOSE: In lung cancer patients, accuracy in contouring is hampered by image artefacts introduced by respiratory motion. With the widespread introduction of 4DCT there is additional uncertainty caused by the use of different reconstruction techniques which will influence contour definition. This work aims to assess both inter- and intra-observer contour variation on average and motion compensated (mid-position) reconstructions. MATERIAL AND METHODS: Eight early stage non-small cell lung cancer patients that received 4DCT were selected and these scans were reconstructed as average and motion compensated datasets. 5 observers contoured the organs at risk (trachea, oesophagus, proximal bronchial tree, heart and brachial plexus) for each patient and each reconstruction. Contours were compared against a STAPLE volume with distance to agreement metrics. Intra-observer variation was assessed by redelineation after 4 months. RESULTS: The inter-observer variation was significantly smaller using the motion compensated datasets for the trachea (p = 0.006) and proximal bronchial tree (p = 0.004). For intra-observer variation, a reduction in contour variation was seen across all organs at risk in using motion compensated reconstructions. CONCLUSIONS: This work shows that there is benefit in using motion compensated reconstructions for reducing both inter-observer and intra-observer contouring variations for organs at risk in lung cancer patients.

The Potential Value of MRI in External-Beam Radiotherapy for Cervical Cancer.

The reference standard treatment for cervical cancer is concurrent chemoradiotherapy followed by magnetic resonance imaging (MRI)-guided brachytherapy. Improvements in brachytherapy have increased local control rates, but late toxicity remains high with rates of 11% grade ≥3. The primary clinical target volume (CTV) for external-beam radiotherapy includes the cervix and uterus, which can show significant inter-fraction motion. This means that generous margins are required to cover the primary CTV, increasing the radiation dose to organs at risk and, therefore, toxicity. A number of image-guided radiotherapy techniques (IGRT) have been developed, but motion can be random and difficult to predict prior to treatment. In light of the development of integrated MRI linear accelerators, this review discusses the potential value of MRI in external-beam radiotherapy. Current solutions for managing pelvic organ motion are reviewed, including the potential for online adaptive radiotherapy. The impacts of the use of MRI in tumour delineation and in the delivery of stereotactic ablative body radiotherapy (SABR) are highlighted. The potential role and challenges of using multi parametric MRI to guide radiotherapy are also discussed.

Functional studies on dendritic cells in the respiratory tract and related mucosal tissues.

Recent reports indicate that mucosal tissues contain dendritic cell (DC) populations that exhibit phenotypic features distinct from those at more studied sites such as skin. In particular, mucosal DC populations display very rapid baseline turnover rates, which increase in response to local inflammatory stimuli. This property is likely to be central to the role of mucosal DC in surveillance of these front-line tissues for incoming microbial pathogens. As we discuss, it may also indirectly account for the "Th2 default," which is the recognized hallmark of mucosal immune system in the steady state.

Mechanisms of ozone-induced inhibitory effect of bronchoalveolar lavage fluid on alveolar macrophage-mediated immunosuppressive activity in rats.

Resident alveolar macrophages (AM) play an important immunomodulatory role via suppression of lymphocyte proliferation, and nitric oxide (NO) plays a crucial role in this immunosuppression of AM. Our previous report suggested that during ozone (O3)-induced lung inflammation, bronchoalveolar lavage fluid (BALF) inhibited AM-mediated immunosuppression and concanavalin A (Con A)-induced proliferation of lymph node cells (LNC) [E. Koike et al. (1998) Toxicol. Sci. 41, 217-223]. In these studies, we investigated the mechanisms of the inhibition of BALF from O3-exposed rats (O3-BALF). We investigated whether BALF might affect (1) the interferon-gamma (IFN-gamma) production by Con A-stimulated LNC and IFN-gamma-induced NO production by AM, and (2) the interleukin (IL)-2 production by Con A-stimulated LNC and IL-2-induced LNC proliferation. These results demonstrated that O3-BALF inhibited IFN-gamma production by Con A-stimulated LNC, IFN-gamma-induced NO production by AM, and IL-2-induced LNC proliferation. In addition, the major inhibitory factor against AM-mediated immunosuppression in O3-BALF may be a protein of greater than 10 kDa.

Production of multilamellar, small unilamellar and reverse-phase liposomes containing house dust mite allergens. Potential adjuvants in the immunotherapy of allergic disease.

The capacity of multilamellar (MLV), small unilamellar (SUV) and reverse-phase vesicle (REV) liposomes to incorporate house dust mite allergens has been studied. All three liposome preparations entrapped mite proteins with efficiencies of 36% (SUV), 29% (MLV) and 14% (REV). MLV incorporated the complete range of proteins contained in mite extracts with apparent molecular weights ranging from 14,000 to greater than 67,000 as judged by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, several proteins with apparent molecular weights (MW) of 16,000, 36,000 and 43,000 were excluded from the REV and SUV. Immunoblotting analysis using a serum pool prepared from mite allergic individuals showed that whereas the whole spectrum of allergens was incorporated into the MLV, a MW 43,000 allergen was excluded from the REV and SUV. The exclusion of these mite components is probably a function of the relatively prolonged exposure of the original extract to organic solvent in the preparation of the REV and SUV liposomes.

Influence of parainfluenza-1 respiratory tract viral infection on endothelin receptor-effector systems in mouse and rat tracheal smooth muscle.

1. In this study we have compared the effects of parainfluenza-1 respiratory tract viral infection on the density and function of ETA and ETB receptors in rat and mouse tracheal airway smooth muscle. 2. The bronchoconstrictor effect of inhaled methacholine was significantly enhanced in virus-infected rats, at both 4 and 12 days post-inoculation. That is, the concentration of methacholine causing an increase in resistance of 100% (PC100 methacholine) was significantly lower in virus-infected animals at both 4 and 12 days post-inoculation (n = 6-8; P < 0.05). 3. Total specific binding of [125I]-endothelin-1 and the relative proportions of ETA and ETB binding sites for [125I]-endothelin-1 were assessed in tracheal airway smooth muscle in parainfluenza-1-infected rats and mice at days 2, 4 and 12 post-inoculation using the ligands BQ-123 (1 microM; ETA receptor-selective) and sarafotoxin S6c (100 nM; ETB receptor-selective). Total specific binding in mice was significantly reduced at day 2 post-inoculation (n = 5; P < 0.05) but not at days 4 and 12 post-inoculation (n = 5). In control mice, the proportions of ETA and ETB binding sites were 53%:47% at day 2 and 43%:57% at day 4 and these were significantly altered by parainfluenza-1 infection such that, the ratios were 81%:19% at day 2 and 89%:11% at day 4 (P < 0.05). By day 12 post-inoculation, the proportion of ETA and ETB binding sites in tracheal smooth muscle from mice infected with parainfluenza-1 was not significantly different from control. In rat tracheal airway smooth muscle, neither total specific binding nor the ETA and ETB binding site ratio (64%:36%) were significantly altered in virus-inoculated rats at days 2, 4 or 12 post-inoculation (n = 5). 4. Parainfluenza-1 infection in mice had no effect on the sensitivity or maximal contractile effect of endothelin-1 in tracheal smooth muscle at days 2, 4 or 12 post-inoculation (n = 4). In contrast, contraction in response to the ETB receptor-selective agonist sarafotoxin S6c was attenuated by 39% at day 2 and by 93% at day 4 post-inoculation (P < 0.05). However, by day 12 post-inoculation, contractions to sarafotoxin S6c were not significantly different between control and virus-infected mice. In parainfluenza-1-infected rats, there were small but significant reductions in the sensitivity to carbachol, endothelin-1 and sarafotoxin S6c whilst the maximal responses to the highest concentrations of these agonists were not significantly altered by virus infection (n = 8). 5. BQ-123 (3 microM) had no significant effect on cumulative concentration-effect curves to endothelin-1 in tracheal preparations from control mice (n = 4) or parainfluenza-1-infected rats (n = 8). In contrast, in tissues taken from virus-infected mice at day 4 post-inoculation, BQ-123 caused a marked 9.6 fold rightward shift in the concentration-effect curve to endothelin-1 (n = 4). 6. In summary, we have demonstrated that parainfluenza-1 infection in mice transiently reduced the density of tracheal airway smooth muscle ETB receptors and this was reflected in reduced responsiveness to the ETB receptor-selective agonist sarafotoxin S6c. In contrast, whilst parainfluenza-1 infection in rats was associated with the pathological features and bronchial hyperresponsiveness common to respiratory tract viral infection, there was no selective down-regulation of ETB receptor expression or functional activity. The reasons for these species differences are not clear, but may relate to differences in the airway inflammatory response to parainfluenza-1 virus.

Endogenous function and biological significance of aeroallergens: an update.

Significant advances have been made in delineating the structure and function of the clinically important aeroallergens. Most have now been characterized at the molecular level, and their endogenous function determined. In the period of review, however, several novel allergens have been identified. They include the house dust mite lipophorins and gelsolins, and the birch isoflavone reductase. In addition, the functions of previously described allergens have now been established or inferred on the basis of homology studies. For example, cat Fel d 1 and the grass pollen group 1 allergens possess proteolytic activity and the thaumatin-like plant and pollen allergens possess endo-beta1,3-glucanase activity. Similarly, the lipocalin allergens may possess endonuclease activity, and the mite group 2 allergens may bind cholesterol. The three-dimensional structure of the horse dander lipocalin Equ c 1 and the honey bee Api m 2 allergens have also been determined during the review period. Finally, in this period, a variety of novel or improved immunotherapeutic allergen reagents designed to redirect the host immune response from a T-helper-2 to a T-helper-1 cell phenotype have been described, in particular, allergen and immunostimulatory CpG motif conjugates.