Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

Phase Change-Induced Magnetic Switching through Metal-Insulator Transition in VO2/TbFeCo Films.

The ability to manipulate spins in magnetic materials is essential in designing spintronics devices. One method for magnetic switching is through strain. In VO2 on TiO2 thin films, while VO2 remains rutile across the metal-insulator transition, the in-plane lattice area expands going from a low-temperature insulating phase to a high-temperature conducting phase. In a VO2/TbFeCo bilayer, the expansion of the VO2 lattice area exerts tension on the amorphous TbFeCo layer. Through the strain effect, magnetic properties, including the magnetic anisotropy and magnetization, of TbFeCo can be changed. In this work, the changes in magnetic properties of TbFeCo on VO2/TiO2(011) are demonstrated using anomalous Hall effect measurements. Across the metal-insulator transition, TbFeCo loses perpendicular magnetic anisotropy, and the magnetization in TbFeCo turns from out-of-plane to in-plane. Using atomistic simulations, we confirm these tunable magnetic properties originating from the metal-insulator transition of VO2. This study provides the groundwork for controlling magnetic properties through a phase transition.

Measurement of the Dzyaloshinskii-Moriya Interaction in Mn4N Films That Host Skyrmions.

Mn4N thin film is one of the potential magnetic mediums for spintronic devices due to its ferrimagnetism with low magnetization, large perpendicular magnetic anisotropy (PMA), thermal stability, and large domain wall velocity. Recent experiments confirmed the existence of tunable magnetic skyrmions in MgO/Mn4N/CuxPt1-x(x = 0, 0.5, 0.9, 0.95), and density functional theory (DFT) calculation provided a large theoretical value of the interfacial Dzyaloshinskii-Moriya interaction (iDMI) of Mn4N/Pt, which is consistent with the predicted chemical trend of the DMI in transition metal/Pt films. So far, the measured DMI has not been reported in Mn4N, which is needed in order to support the predicted large DMI value. This paper reports the average DMI of MgO/Mn4N(17 nm)/CuxPt1-x(3 nm) extracted from the anomalous Hall effect with various tilted angles, which is based on magnetic droplet theory with DMI effects. The DMI decreases from 0.267 mJ/m2 to 0.011 mJ/m2 with non-linear tendencies as Cu concentration in the CuxPt1-x capping layer increases from 0 to 1, demonstrating the control of the DMI through the CuxPt1-x capping layer. Furthermore, a solid solution model is developed based on an X-ray photoelectron spectroscopy (XPS) compositional depth profile to analyze the possible effects on the DMI from the mixing layers at the surface of Mn4N. After taking into account the mixing layers, the large DMI in Mn4N film with Pt capping is consistent with the predicted DMI.

Provision of High Protein Foods Slows the Age-Related Decline in Nutritional Status in Aged Care Residents: A Cluster-Randomised Controlled Trial.

OBJECTIVES: Malnutrition, particularly protein insufficiency, is common in institutionalised older adults and increases morbidity, mortality, and costs. We aimed to determine whether 12 months supplementation using high-protein foods (milk, cheese, yoghurt) prevents malnutrition in older adults. DESIGN: Cluster randomised control study. SETTING: Sixty Australian aged care facilities. PARTICIPANTS: Older adults living in aged care homes (n=654, mean age 86.7±7.2 years, 72% females). Intervention Facilities randomly allocated to a high-protein (n=30 intervention) or regular (n=30 controls) menu. MEASUREMENTS: Nutritional status assessed using the Mini Nutrition Assessment (MNA) tool and fasting morning blood samples (n=302) assayed for haemoglobin (Hb) and albumin. Food intake was monitored 3-monthly using visual plate waste assessment. Measurements at baseline and month 12 were analysed using random effects model accounting for clustering (facility), repeated measure and confounders. RESULTS: Addition of 11g of protein as 1.5 servings of high-protein foods daily preserved nutritional status that deteriorated in controls [MNA screen (-0.68, 95%CI: -1.03, -0.32, p<0.001) and total (-0.90, 95%CI: -1.45, -0.35, p=0.001) scores], resulting in group differences in MNA screen (0.62, 95%CI: 0.17, 1.06, p=0.007) and total (0.81, 95%CI: 0.11, 1.51, p=0.023) scores and group difference in Hb (3.60g/L, 95%CI: 0.18, 7.03, p=0.039), the net result of preservation with intervention (0.19g/L, 95%CI: -2.04, 2.42, p=0.896) and a decline in controls (-3.41g/L, 95%CI: -6.01, -0.82, p=0.010). No group differences were observed for serum albumin. CONCLUSION: Consumption of high-protein foods is a pragmatic approach to maintaining nutritional status in older adults in aged-care.

Ultrafast switching in synthetic antiferromagnet with bilayer rare-earth transition-metal ferrimagnets.

In spintronics, it is important to be able to manipulate magnetization rapidly and reliably. Several methods can control magnetization, such as by applying current pulses or magnetic fields. An applied current can reverse magnetization with nanosecond speed through the spin torque effect. For faster switching, subpicosecond switching with femtoseconds laser pulse has been achieved in amorphous rare-earth transition-metal ferrimagnets. In this study, we employed atomistic simulations to investigate ultrafast switching in a synthetic antiferromagnet with bilayer amorphous FeGd ferrimagnets. Using a two-temperature model, we demonstrated ultrafast switching in this synthetic antiferromagnet without external magnetic fields. Furthermore, we showed that if we initially stabilize a skyrmion in this heterostructure, the ultrafast laser can switch the skyrmion state using the same mechanism. Furthermore, this bilayer design allows the control of each ferrimagnetic layer individually and opens the possibility for a magnetic tunnel junction.

Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial.

OBJECTIVE: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day. DESIGN: Two year cluster randomised controlled trial. SETTING: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents. PARTICIPANTS: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years). INTERVENTION: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight). MAIN OUTCOME MEASURES: Group differences in incidence of fractures, falls, and all cause mortality. RESULTS: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08). CONCLUSIONS: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000228785.

Alcohol Consumption and Depression Among University Students and Their Perception of Alcohol Use.

OBJECTIVES: To investigate the association between alcohol use and depression among university students in Hong Kong, their stress-coping methods, and their knowledge and perception of the effects of alcohol on health. METHODS: 345 full-time undergraduate students from The University of Hong Kong were invited to complete a questionnaire to assess their alcohol consumption (Alcohol Use Disorders Identification Test, CAGE questionnaire), depressive symptoms (Patient Health Questionnaire-9), and stress-coping methods (Coping Orientation to Problems Experienced Inventory), as well as knowledge and perception of alcohol consumption on health. Multiple linear regression was used to determine significant variables associated with depressive symptoms. Multinominal logistic regression was used to determine the effect of such variables on depressive symptom caseness and AUDIT drinking risk groups. RESULTS: 43.2% of respondents were moderate- to high-risk drinkers, but only 23.2% were self-reported as moderate- to high-level drinkers. 57.9% of respondents had mild to severe depressive symptoms. Probable depression was more likely to occur in female students, those with higher general stress, those who do not use social support for stress-coping, and those who smoke. High-risk drinkers were more likely to occur in older students, smokers, those with higher household income, and those with higher general stress levels. Students with higher levels of depressive symptoms and higher risk of alcohol consumption were more likely to use avoidance for stress-coping. 89.5% of students considered alcohol consumption moderately to very harmful to health, but students demonstrated only moderate knowledge levels of alcohol consumption on health. CONCLUSION: Alcohol consumption and depressive symptoms are prevalent among university students in Hong Kong. The use of avoidance for stress-coping is common in those with higher levels of depressive symptoms and higher-risk drinkers. Students tend to avoid seeking help for depressive symptoms and potentially take up drinking as a coping strategy. Context-specific approaches should be used when providing counselling services for student wellbeing in university settings. Further education of university students on knowledge and perception of alcohol consumption on health should be provided.

Tuning interfacial Dzyaloshinskii-Moriya interactions in thin amorphous ferrimagnetic alloys.

Skyrmions can be stabilized in magnetic systems with broken inversion symmetry and chiral interactions, such as Dzyaloshinskii-Moriya interactions (DMI). Further, compensation of magnetic moments in ferrimagnetic materials can significantly reduce magnetic dipolar interactions, which tend to favor large skyrmions. Tuning DMI is essential to control skyrmion properties, with symmetry breaking at interfaces offering the greatest flexibility. However, in contrast to the ferromagnet case, few studies have investigated interfacial DMI in ferrimagnets. Here we present a systematic study of DMI in ferrimagnetic CoGd films by Brillouin light scattering. We demonstrate the ability to control DMI by the CoGd cap layer composition, the stack symmetry and the ferrimagnetic layer thickness. The DMI thickness dependence confirms its interfacial nature. In addition, magnetic force microscopy reveals the ability to tune DMI in a range that stabilizes sub-100 nm skyrmions at room temperature in zero field. Our work opens new paths for controlling interfacial DMI in ferrimagnets to nucleate and manipulate skyrmions.

Publisher Correction: High Entropy Alloys Mined From Binary Phase Diagrams.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High Entropy Alloys Mined From Binary Phase Diagrams.

High entropy alloys (HEA) are a new type of high-performance structural material. Their vast degrees of compositional freedom provide for extensive opportunities to design alloys with tailored properties. However, compositional complexities present challenges for alloy design. Current approaches have shown limited reliability in accounting for the compositional regions of single solid solution and composite phases. For the first time, a phenomenological method analysing binary phase diagrams to predict HEA phases is presented. The hypothesis is that the HEA structural stability is encoded within the phase diagrams. Accordingly, we introduce several phase-diagram inspired parameters and employ machine learning (ML) to classify 600+ reported HEAs based on these parameters. Compared to other large database statistical prediction models, this model gives more detailed and accurate phase predictions. Both the overall HEA prediction and specifically single-phase HEA prediction rate are above 80%. To validate our method, we demonstrated its capability in predicting HEA solid solution phases with or without intermetallics in 42 randomly selected complex compositions, with a success rate of 81%. The presented search approach with high predictive capability can be exploited to interact with and complement other computation-intense methods such as CALPHAD in providing an accelerated and precise HEA design.

Enhanced Figure of Merit in Bismuth-Antimony Fine-Grained Alloys at Cryogenic Temperatures.

Thermoelectric (TE) materials research plays a vital role in heat-to-electrical energy conversion and refrigeration applications. Bismuth-antimony (Bi-Sb) alloy is a promising material for thermoelectric cooling. Herein, a high figure of merit, ZT, near 0.6 at cryogenic temperatures (100-150 K) has been achieved in melt-spun n-type Bi85Sb15 bulk samples consisting of micron-size grains. The achieved ZT is nearly 50% higher than polycrystalline averaged single crystal ZT of ~0.4, and it is also significantly higher than ZT of less than ~0.3 measured below 150 K in Bi-Te alloys commonly used for cryogenic cooling applications. The improved thermoelectric properties can be attributed to the fine-grained microstructure achieved from rapid solidification, which not only significantly reduced the thermal conductivity but also mitigated a segregation effect. A record low thermal conductivity of ~1.5 W m-1 K-1 near 100 K was measured using the hot disk method. The thermoelectric properties for this intriguing semimetal-semiconductor alloy system were analyzed within a two-band effective mass model. The study revealed a gradual narrowing of the band gap at increasing temperature in Bi-Sb alloy for the first time. Magneto-thermoelectric effects of this Bi-Sb alloy further improved the TE properties, leading to ZT of about 0.7. The magneto-TE effect was further demonstrated in a combined NdFeB/BiSb/NdFeB system. The compactness of the BiSb-magnet system with high ZT enables the utilization of magneto-TE effect in thermoelectric cooling applications.

Mental Health Literacy in Cancer Outpatients in Singapore.

OBJECTIVE: We aimed to evaluate the prevalence of depressive and anxiety symptoms and mental health literacy (MHL) in outpatients with or without cancer in Singapore. METHODS: Oncology outpatients and outpatients without cancer (controls) were assessed for severity of anxiety and depressive symptoms (using the Hospital Anxiety and Depression Scale) and MHL regarding major depressive disorder and generalised anxiety disorder in terms of diagnosis, aetiology, treatment, and attitudes toward mental health services. RESULTS: A total of 89 oncology outpatients and 61 controls were recruited. Those with primary and secondary education had significantly lower MHL scores than those with university education (p = 0.001). Oncology outpatients and controls were comparable in terms of anxiety (13.5% vs 9.8%, p = 0.5), depression (2.2% vs 1.6%, p > 0.99), and total MHL score (7.94 vs 9.13, p = 0.102). CONCLUSIONS: MHL is comparable between oncology outpatients and controls and is positively associated with education level.

The Gap Rock Lighthouse: construction and typhoon damage.

This paper focuses on the Gap Rock lighthouse, a legendary maritime infrastructure built 130 years ago in the Chinese territory and an early example of joint venture among the Qing Dynasty, the British Empire and the Hong Kong Colonial Government over a course of two decades. Based on 4 years of cross-territorial archival and field research as well as in-depth interviews with descendants of two key stakeholders, the origin of this lasting legacy on the sea is traced, followed by a detailed account of its challenging processes of planning, design and construction, and of the considerable damage to the compound by a severe typhoon in 1893. A qualitative analysis of the key contributing factors of the damage was conducted by taking into consideration the Island's unique topography and the historical records of territorial weather reports. A re-construction of the typhoon impact on the Lighthouse is presented to explain the possible mistakes in its siting and design that eventually caused the severe damage. This serves as a reminder of the significance of a thorough geographical investigation for any infrastructure for all construction professionals in the face of climatic change. This article is part of the theme issue 'Environmental loading of heritage structures'.

Robust Formation of Ultrasmall Room-Temperature Neél Skyrmions in Amorphous Ferrimagnets from Atomistic Simulations.

Neél skyrmions originate from interfacial Dzyaloshinskii Moriya interaction (DMI). Recent studies have explored using thin-film ferromagnets and ferrimagnets to host Neél skyrmions for spintronic applications. However, it is unclear if ultrasmall (10 nm or less) skyrmions can ever be stabilized at room temperature for practical use in high density parallel racetrack memories. While thicker films can improve stability, DMI decays rapidly away from the interface. As such, spins far away from the interface would experience near-zero DMI, raising question on whether or not unrealistically large DMI is needed to stabilize skyrmions, and whether skyrmions will also collapse away from the interface. To address these questions, we have employed atomistic stochastic Landau-Lifshitz-Gilbert simulations to investigate skyrmions in amorphous ferrimagnetic GdCo. It is revealed that a significant reduction in DMI below that of Pt is sufficient to stabilize ultrasmall skyrmions even in films as thick as 15 nm. Moreover, skyrmions are found to retain a uniform columnar shape across the film thickness due to the long ferrimagnetic exchange length despite the decaying DMI. Our results show that increasing thickness and reducing DMI in GdCo can further reduce the size of skyrmions at room temperature, which is crucial to improve the density and energy efficiency in skyrmion based devices.

Audit of Mental Capacity Assessment by Primary Care Physicians Versus Consultation-liaison Psychiatrists.

OBJECTIVE: To review the mental capacity assessment of in-patients referred to consultation-liaison psychiatrists and to compare the assessment first made by primary care physicians. METHODS: Medical records of in-patients who were referred to consultation-liaison psychiatrists for mental capacity assessment between May and October 2015 were retrospectively reviewed. Assessment was first made by a primary care physician; complex cases were referred to a consultation-liaison psychiatrist. Audit of each case note was conducted independently by at least two of the authors. RESULTS: Medical records of 37 female and 26 male in-patients aged 24 to 91 (mean, 68.2) years were audited. Only 33.3% of these patients had no psychiatric diagnosis. Overall, assessments by primary care physicians were suboptimal. Assessments by consultation-liaison psychiatrists were more detailed, with documentation of mental capacity (93.7%) and psychiatric diagnosis (88.9%). Nonetheless, patient wishes and beliefs were poorly documented (19.0%), as were whether the patient had a lasting power of attorney or a court-appointed deputy (6.3%) and whether the patient had made advance care planning (0%). CONCLUSION: Overall, mental capacity assessment was inadequately performed by primary care physicians and consultation-liaison psychiatrists. More work needs to be done to engage, educate, and empower all stakeholders involved.

Semi-metals as potential thermoelectric materials.

The best thermoelectric materials are believed to be heavily doped semiconductors. The presence of a band gap is assumed to be essential to achieve large thermoelectric power factor and figure of merit. In this work, we propose semi-metals with large asymmetry between conduction and valence bands as an alternative class of thermoelectric materials. To illustrate the idea, we study semi-metallic HgTe in details experimentally and theoretically. We employ ab initio calculations with hybrid exchange-correlation functional to accurately describe the electronic band structure in conjunction with the Boltzmann Transport theory to investigate the electronic transport properties. We calculate the lattice thermal conductivity using first principles calculations and evaluate the overall figure of merit. To validate our theoretical approach, we prepare semi-metallic HgTe samples and characterize their transport properties. Our first-principles calculations agree well with the experimental data. We show that intrinsic HgTe, a semimetal with large disparity in its electron and hole masses, has a high thermoelectric power factor that is comparable to the best known thermoelectric materials. Finally, we propose other possible materials with similar band structures as potential candidates for thermoelectric applications.

Molecular basis for the production of cyclic peptides by plant asparaginyl endopeptidases.

Asparaginyl endopeptidases (AEPs) are proteases that have crucial roles in plant defense and seed storage protein maturation. Select plant AEPs, however, do not function as proteases but as transpeptidases (ligases) catalyzing the intra-molecular ligation of peptide termini, which leads to peptide cyclization. These ligase-type AEPs have potential biotechnological applications ranging from in vitro peptide engineering to plant molecular farming, but the structural features enabling these enzymes to catalyze peptide ligation/cyclization rather than proteolysis are currently unknown. Here, we compare the sequences, structures, and functions of diverse plant AEPs by combining molecular modeling, sequence space analysis, and functional testing in planta. We find that changes within the substrate-binding pocket and an adjacent loop, here named the "marker of ligase activity", together play a key role for AEP ligase efficiency. Identification of these structural determinants may facilitate the discovery of more ligase-type AEPs and the engineering of AEPs with tailored catalytic properties.

Thickness dependence of ferrimagnetic compensation in amorphous rare-earth transition-metal thin films.

Magnetic compensation in ferrimagnets plays an important role in spintronic and magnetic recording devices. Experimental results have demonstrated a thickness dependence of the compensation temperature ( T comp ) in amorphous TbFeCo thin films. It was speculated that this thickness dependence originated from a variation in the short-range order. In this work, we have investigated the depth-resolved compositional and magnetization profiles using polarized neutron reflectometry. We find that although the composition is uniform across the film thickness, near the substrate interface, the magnetization exhibits a different temperature dependence from that of the rest of the sample. Monte Carlo simulations show that it is this difference in interfacial magnetization that causes the aforementioned thickness dependence of the compensation. These results demonstrate the critical role of the substrate interface in determining the magnetic properties of amorphous ferrimagnetic thin films for spintronic applications.

Tribes and tribulations: interdisciplinary eHealth in providing services for people with a traumatic brain injury (TBI).

BACKGROUND: eHealth has potential for supporting interdisciplinary care in contemporary traumatic brain injury (TBI) rehabilitation practice, yet little is known about whether this potential is being realised, or what needs to be done to further support its implementation. The purpose of this study was to explore health professionals' experiences of, and attitudes towards eHealth technologies to support interdisciplinary practice within rehabilitation for people after TBI. METHODS: A qualitative study using narrative analysis was conducted. One individual interview and three focus groups were conducted with health professionals (n = 17) working in TBI rehabilitation in public and private healthcare settings across regional and metropolitan New South Wales, Australia. RESULTS: Narrative analysis revealed that participants held largely favourable views about eHealth and its potential to support interdisciplinary practice in TBI rehabilitation. However, participants encountered various issues related to (a) the design of, and access to electronic medical records, (b) technology, (c) eHealth implementation, and (d) information and communication technology processes that disconnected them from the work they needed to accomplish. In response, health professionals attempted to make the most of unsatisfactory eHealth systems and processes, but were still mostly unsuccessful in optimising the quality, efficiency, and client-centredness of their work. CONCLUSIONS: Attention to sources of disconnection experienced by health professionals, specifically design of, and access to electronic health records, eHealth resourcing, and policies and procedures related to eHealth and interdisciplinary practice are required if the potential of eHealth for supporting interdisciplinary practice is to be realised.

Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge.

RATIONALE: Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. OBJECTIVE: To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. METHODS: We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 µg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. RESULTS: Immunotherapy-treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase tryptase levels (P = 0.06). CONCLUSIONS: Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.