Can regulatory T cells improve outcomes of sensitised patients after HLA-Ab incompatible renal transplantation: study protocol for the Phase IIa GAMECHANgER-1 trial.

BACKGROUND: Kidney transplantation is the gold-standard treatment for patients with kidney failure. However, one-third of patients awaiting a kidney transplant are highly sensitized to human leukocyte antigens (HLA), resulting in an increased waiting time for a suitable kidney, more acute and chronic rejection, and a shorter graft survival compared to non-highly sensitised patients. Current standard immunosuppression protocols do not adequately suppress memory responses, and so alternative strategies are needed. Autologous polyclonally expanded regulatory T cells (Tregs) have been demonstrated to be safe in transplant settings and could be a potential alternative to modulate memory immune alloresponses. METHODS: The aim of this trial is to determine whether adoptive transfer of autologous Tregs into HLA sensitised patients can suppress memory T and B cell responses against specific HLA antigens. This is a two-part, multi-centre, prospective clinical trial, comprising an observational phase (Part 1) aiming to identify patients with unregulated cellular memory responses to HLA (Pure HLA Proteins) followed by an interventional phase (Part 2). The first 9 patients identified as being eligible in Part 1 will undergo baseline immune monitoring for 2 months to inform statistical analysis of the primary endpoint. Part 2 is an adaptive, open labelled trial based on Simon's two-stage design, with 21 patients receiving Good Manufacturing Practice (GMP)-grade polyclonally expanded Tregs to a dose of 5-10 × 106 cells/kg body weight. The primary EP is suppression of in vitro memory responses for 2 months post-infusion. 12 patients will receive treatment in stage 1 of Part 2, and 9 patients will receive treatment in stage 2 of Part 2 if ≥ 50% patients pass the primary EP in stage 1. DISCUSSION: This is a prospective study aiming to identify patients with unregulated cellular memory responses to Pure HLA Proteins and determine baseline variation in these patterns of response. Part 2 will be an adaptive phase IIa clinical trial with 21 patients receiving a single infusion of GMP-grade polyclonally expanded Tregs in two stages. It remains to be demonstrated that modulating memory alloresponses clinically using Treg therapy is achievable. TRIAL REGISTRATION: EudraCT Number: 2021-001,664-23. REC Number: 21/SC/0253. Trial registration number ISRCTN14582152.

Environmental peanut exposure increases the risk of peanut sensitization in high-risk children.

BACKGROUND: High household peanut consumption is associated with the development of peanut allergy, especially when peanut allergic cases are compared against atopic controls; thus, environmental peanut exposure (EPE) may be a risk factor for peanut sensitization and allergy. In this study, we explored the relationship between EPE and school-age peanut sensitization in a population-based cohort. METHODS: Maternal bed dust was collected postnatally, and EPE was quantified using a polyclonal peanut ELISA. Peanut sensitization was assessed by specific IgE to peanut extract and sIgE to peanut protein component allergens Ara h 1, 2 or 3 ≥ 0.35kU/L (primary peanut sensitization). Initial nested case-control analysis was performed comparing peanut-sensitized cases against high-risk controls (matched for parental atopy) (n = 411) using a conditional regression analysis. This was followed by whole cohort analysis (n = 1878) comparing EPE against peanut sIgE sensitization at ages 4 and 8 years using generalized estimating equations and against primary peanut sensitization at age 8 years using a logistic regression model. Finally, a subgroup analysis was performed comparing the impact of EPE in peanut-sensitized vs egg-sensitized, peanut-tolerant individuals using logistic regression analysis. Levels of EPE were compared between groups using the Mann-Whitney U test. RESULTS: In the nested case-control analysis, a higher level of EPE around birth was associated with peanut-specific IgE sensitization at age 4 years (OR=1.41, 95% CI:1.05-1.90) and primary peanut sensitization at age 8 years (OR=2.11, 95% CI:1.38-3.22) compared against high-risk controls. When the whole BAMSE cohort was assessed, EPE was no longer associated with peanut sensitization; however, on subgroup analysis, EPE was associated with primary peanut sensitization when compared against egg-sensitized peanut-tolerant controls with an adjusted odds ratio of 1.44 per unit EPE (95% CI:1.06-1.94). There was no significant interaction between EPE and FLG loss-of-function mutations, egg sensitization at age 4 years, infantile eczema or parental atopy on peanut sensitization. CONCLUSIONS: Higher levels of environmental exposure to peanut in the first few months of life appear to increase the probability of developing school-age peanut sensitization in atopic children (based on egg sensitization and parental atopy).

A prediction model for the response to oral labetalol for the treatment of antenatal hypertension.

This prospective observational study aimed to identify at presentation the maternal hemodynamic and demographic variables associated with a therapeutic response to oral labetalol and to use these variables to develop a prediction model to anticipate the response to labetalol monotherapy in women with hypertension. It was set at a maternity unit in a UK teaching hospital. Maternal demographic data from 50 pregnant women, presenting with hypertension between January and August 2013, was collected and blood pressure measured with a device validated for pregnancy and pre-eclampsia. Maternal haemodynamics were assessed with a bioreactance monitor. Participants were commenced on oral labetalol, and reviewed until delivery and discharge home. Logistic regression analysis was performed to assess the prediction of response to labetalol according to the maternal demographic and hemodynamic variables. Main outcome measures were the response to labetalol monotherapy up to delivery and discharge home, defined as sustained blood pressure control <140/90, and the rates of severe hypertension. Thirty-seven women (74%) had their blood pressure well controlled with labetalol monotherapy, 13 (26%) failed to achieve control with labetalol alone, of whom 9 developed severe hypertension. Multivariate logistic regression showed that heart rate, ethnicity and stroke volume index were independent predictors of the response to labetalol. The predictive accuracy of the model was 96% (95% confidence interval (CI) 86-99%). Maternal demographics and haemodynamics are potent predictors for the response to labetalol, and these parameters may guide therapy to enable effective blood pressure control and a lowering of severe hypertension rates.

OPTIMUM: a protocol for a multicentre randomised controlled trial comparing Out Patient Talc slurry via Indwelling pleural catheter for Malignant pleural effusion vs Usual inpatient Management.

INTRODUCTION: The development of malignant pleural effusion (MPE) results in disabling breathlessness, pain and reduced physical capability with treatment a palliative strategy. Ambulatory management of MPE has the potential to improve quality of life (QoL). The OPTIMUM trial is designed to determine whether full outpatient management of MPE with an indwelling pleural catheter (IPC) and pleurodesis improves QoL compared with traditional inpatient care with a chest drain and talc pleurodesis. OPTIMUM is currently open for any centres interested in collaborating in this study. METHODS AND ANALYSIS: OPTIMUM is a multicentre non-blinded randomised controlled trial. Patients with a diagnosis of MPE will be identified and screened for eligibility. Consenting participants will be randomised 1:1 either to an outpatient ambulatory pathway using IPCs and talc pleurodesis or standard inpatient treatment with chest drain and talc pleurodesis as per British Thoracic Society guidelines. The primary outcome measure is global health-related QoL at 30 days measured using the EORTC QLQ-C30 questionnaire. Secondary outcome measures include breathlessness and pain measured using a 100 mm Visual Analogue Scale and health-related QoL at 60 and 90 days. A sample size of 142 patients is needed to demonstrate a clinically significant difference of 8 points in global health status at 30 days, for an 80% power and a 5% significance level. ETHICS AND DISSEMINATION: The study has been approved by the NRES Committee South East Coast-Brighton and Sussex (reference 15/LO/1018). The trial results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: UKCRN19615 and ISRCTN15503522; Pre-results.

Medium-term cost-effectiveness of an automated non-invasive ventilation outpatient set-up versus a standard fixed level non-invasive ventilation inpatient set-up in obese patients with chronic respiratory failure: a protocol description.

INTRODUCTION: Obesity is an escalating issue, with an accompanying increase in referrals of patients with obesity-related respiratory failure. Currently, these patients are electively admitted to hospital for initiation of non-invasive ventilation (NIV), but it is unknown whether outpatient initiation is as effective as inpatient set-up. We hypothesise that outpatient set-up using an autotitrating NIV device will be more cost-effective than a nurse-led inpatient titration and set-up. METHODS AND ANALYSIS: We will undertake a multinational, multicentre randomised controlled trial. Participants will be randomised to receive the usual inpatient set-up, which will include nurse-led initiation of NIV or outpatient set-up with an automated NIV device. They will be stratified according to the trial site, gender and previous use of NIV or continuous positive airway pressure. Assuming a 10% dropout rate, a total sample of 82 patients will be required. Cost-effectiveness will be evaluated using standard treatment costs and health service utilisation as well as health-related quality of life measures (severe respiratory insufficiency (SRI) and EuroQol-5 dimensions (EQ-5D)). A change in the SRI questionnaire will be based on the analysis of covariance adjusting for the baseline measurements between the two arms of patients. ETHICS AND DISSEMINATION: This study has been approved by the Westminster National Research Ethics Committee (11/LO/0414) and is the trial registered on the UKCRN portfolio. The trial is planned to start in January 2015 with publication of the trial results in 2017. TRIAL REGISTRATION NUMBER: ISRCTN 51420481.

Diagnostic accuracy of saline infusion sonography in the evaluation of uterine cavity abnormalities prior to assisted reproductive techniques: a systematic review and meta-analyses.

BACKGROUND: The diagnostic accuracy of a 2-D transvaginal scan, which is commonly employed to evaluate the regularity and shape of the uterine cavity in subfertile women, is relatively poor compared with other diagnostic modalities like saline infusion sonography (SIS) or hysteroscopy. SIS is a minimally invasive, cost-effective and acceptable diagnostic modality. Therefore the aim of this systematic review was to assess the diagnostic accuracy of SIS in the evaluation of the uterine cavity in subfertile women. METHODS: A systematic review was conducted of diagnostic studies that compared SIS with hysteroscopy. Twenty relevant studies (including 1645 procedures) were identified and a subsequent meta-analysis was performed. Electronic databases were searched for relevant studies and references of relevant studies were cross checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was examined, studies were plotted in an ROC area and data were pooled. The main outcome measure was the diagnostic accuracy of saline infusion sonography. The pooled sensitivity, specificity, likelihood ratios and the post-test probabilities of saline infusion sonography on the prediction of uterine cavity abnormalities were calculated. RESULTS: The pooled sensitivity of SIS in the detection of all intrauterine abnormalities was 0.88 (95% confidence interval (CI): 0.85-0.90). The pooled specificity was 0.94 (95% CI 0.93-0.96). The positive and negative likelihood ratios were 20.93 (95% CI: 9.06-48.34) and 0.15 (95% CI: 0.10-0.22), respectively. SIS had good accuracy in the detection of all intrauterine abnormalities (area under the summary receiver operating curve (sROC) = 0.97 ± 0.01). SIS also had a high pooled sensitivity and specificity in the detection of congenital uterine anomalies, 0.85 (95% CI: 0.79-0.90) and 1.00 (95% CI 0.99-1.00), respectively. However the limitations of the review include the heterogeneity amongst the included studies. CONCLUSIONS: SIS is a highly sensitive investigative modality and comparable to the gold standard tool, hysteroscopy in the detection of intrauterine abnormalities in subfertile women. SIS is a highly sensitive and specific test in the diagnosis of uterine polyps, submucous myomas, uterine anomalies and intrauterine adhesions and can be used as a screening tool for subfertile patients prior to IVF treatment.

A cohort study to identify simple clinical tests for chronic respiratory failure in obese patients with sleep-disordered breathing.

BACKGROUND: Chronic respiratory failure complicating sleep-disordered breathing in obese patients has important adverse clinical implications in terms of morbidity, mortality and healthcare utilisation. Screening strategies are essential to identify obese patients with chronic respiratory failure. METHOD: Prospective data were collected from patients with obesity-related sleep-disordered breathing admitted for respiratory assessment at a UK national sleep and ventilation centre. Hypercapnia was defined as an arterial partial pressure of carbon dioxide of >6kPa. RESULTS: 245 obese patients (56±13 years) with a body mass index of 48±12 kg/m(2), forced vital capacity (FVC) of 2.1±1.1 L, daytime oximetry (SpO2) of 91±6% and abnormal overnight oximetry were included in the analysis. Receiver operator curve analysis for the whole group showed that an FVC ≤3 L had a sensitivity of 90% and a specificity of 41% in predicting hypercapnia, and an SpO2 ≤95% had a sensitivity of 83% and a specificity of 63% in predicting hypercapnia. Gender differences were observed and receiver operator curve analysis demonstrated 'cut-offs' for (1) SpO2 of ≤95% for men and ≤93% for women and (2) FVC of ≤3.5 L for men and ≤2.3 L for women, in predicting hypercapnia. CONCLUSIONS: The measurement of FVC and clinic SpO2 in obese patients with abnormal overnight limited respiratory studies predicted hypercapnia. This may have clinical utility in stratifying patients attending sleep clinics.

Characterizing motor and non-motor aspects of early-morning off periods in Parkinson's disease: an international multicenter study.

INTRODUCTION: The characteristic off periods that develop over time in subjects with Parkinson's disease (PD) on chronic levodopa therapy are usually considered to be motor complications but more recently the important contribution of non-motor off and non-motor fluctuations has also been acknowledged. Early-morning off (EMO) periods in PD patients are known to be a cause of significant disability, in addition to having a negative impact on quality of life. Yet EMOs are poorly defined, particularly in relation to non-motor symptoms (NMS). METHODS: This European, multicentre, observational study was undertaken to characterize the range and patterns of NMS that occur during EMO periods in a consecutive series of PD patients. RESULTS: The results demonstrate that EMO periods are common and occur in 59.7% of subjects across all disease stages in line with other reports. However, importantly, in 88.0% of those, EMOs were found to be associated with NMS. The predominant NMS associated with EMO were urinary urgency, anxiety, dribbling of saliva, pain, low mood, limb paresthesia and dizziness. The patterns of dopaminergic treatment being taken by patients in this study suggested that a prolonged-release or continuous drug delivery strategy can alleviate some NMS associated with EMO. CONCLUSIONS: In light of these findings it is suggested that greater awareness, recognition and appropriate treatment of EMO and NMS could improve the overall 24-h management of PD. An EMO-specific scale/questionnaire which captures both motor and NMS associated with EMO over the off time period is warranted.

A UK survey of rehabilitation following critical illness: implementation of NICE Clinical Guidance 83 (CG83) following hospital discharge.

OBJECTIVE: To determine the implementation of National Institute for Health and Care Excellence guidance (NICE CG83) for posthospital discharge critical illness follow-up and rehabilitation programmes. DESIGN: Closed-question postal survey. SETTING: Adult intensive care units (ICUs) across the UK, identified from national databases of organisations. Specialist-only and private ICUs were not included. PARTICIPANTS: Senior respiratory critical care physiotherapy clinicians. RESULTS: A representative sample of 182 surveys was returned from the 240 distributed (75.8% (95% CI 70.4 to 81.2)). Only 48 organisations (27.3% (95% CI 20.7 to 33.9)) offered a follow-up service 2-3 months following hospital discharge, the majority (n=39, 84.8%) in clinic format. 12 organisations reported posthospital discharge rehabilitation programmes (6.8% (95% CI 3.1 to 10.5)), albeit only 10 of these operated on a regular basis. Lack of funding was reported as the most frequent (n=149/164, 90%) and main barrier (n=99/156, 63.5%) to providing services. Insufficient resources (n=71/164, 43.3%) and lack of priority by the clinical management team (n=66/164, 40.2%) were also highly cited barriers to service delivery. CONCLUSIONS: NICE CG83 has been successful in profiling the importance of rehabilitation for survivors of critical illness. However, 4 years following publication of CG83 there has been limited development of this clinical service across the UK. Strategies to support delivery of such quality improvement programmes are urgently required to enhance patient care.

Effect of postoperative physical training on activity after curative surgery for non-small cell lung cancer: a multicentre randomised controlled trial.

OBJECTIVE: To evaluate the effect of a combined hospital plus home exercise programme following curative surgery for non-small cell lung cancer (NSCLC). DESIGN: Randomised controlled trial. SETTING: Teaching hospital. PARTICIPANTS: One hundred and thirty-one subjects with NSCLC admitted for curative surgery. INTERVENTIONS: Participants were randomised to usual care or a hospital plus home exercise programme. OUTCOMES: The primary outcome was the between-group difference in physical activity 4 weeks after surgery. Secondary outcomes were the difference in quadriceps strength, exercise tolerance and quality of life [Short Form-36 (SF-36) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-LC13] from pre-operatively (baseline) to 4 weeks after surgery. RESULTS: The participants (n=131) had a mean age of 68 [standard deviation (SD) 11] years and mean forced expiratory volume in 1 second of 2.4 (SD 1.1)l. There were no significant differences in physical activity between the groups 4 weeks after surgery [mean difference adjusted for baseline 12minutes/day, 95% confidence interval (CI) -20.2 to 44.1]. In addition, there were no significant differences in total SF-36 or EORTC QLQ-LC13 scores from baseline to 4 weeks after surgery. Both groups had recovered their pre-operative walking distance 4 weeks after surgery, and there were no differences between the groups (mean difference in Incremental Shuttle Walk Test from baseline to 4 weeks after surgery (-26m, 95% CI -94.2 to 42.3). CONCLUSIONS: A hospital plus home exercise programme showed little benefit in unselected patients with NSCLC following surgery. Regardless of group allocation, the patients had recovered their pre-operative exercise tolerance levels by 4 weeks after surgery.

Diagnostic accuracy of noninvasive markers of liver fibrosis in patients with psoriasis taking methotrexate: a systematic review and meta-analysis.

People with psoriasis taking methotrexate may be at increased risk of developing liver fibrosis compared with the general population. Noninvasive methods of detecting fibrosis have been widely adopted but their clinical utility is uncertain. To evaluate the diagnostic accuracy of noninvasive methods to detect fibrosis compared with liver biopsy (reference standard) in people with psoriasis taking methotrexate. A systematic search using Ovid/Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library and Clinical Trials Register was performed. Diagnostic cohorts or case-control studies of adults taking or being considered for methotrexate therapy were considered. Study quality was evaluated using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2). Pooled data analysis was performed using RevMan 5.1. Bayesian meta-analysis was conducted using Markov chain Monte Carlo simulation. Seventeen studies were included. Sensitivity and specificity were 38% and 83% for standard liver function tests (LFTs), 74% and 77% for procollagen-3 N-terminal peptide (P3NP), 60% and 80% for Fibroscan(®) (Echosens, France, www.echosens.com), and 55% and 49% for ultrasound. Confidence in these results is limited owing to low-quality data; old, small studies displayed significant selection bias and significant variation in the prevalence of fibrosis. No studies were identified evaluating recently developed markers. The clinical utility of LFTs, P3NP and liver ultrasound is poor. Therefore if these tests are used in isolation, a significant proportion of patients with liver fibrosis may remain unidentified. Larger prospective studies are required in this population to validate newer non-invasive methods.

A comparison of the accuracy of film-screen mammography, full-field digital mammography, and digital breast tomosynthesis.

AIM: To measure the change in diagnostic accuracy of conventional film-screen mammography and full-field digital mammography (FFDM) with the addition of digital breast tomosynthesis (DBT) in women recalled for assessment following routine screening. MATERIALS AND METHODS: Ethics approval for the study was granted. Women recalled for assessment following routine screening with screen-film mammography were invited to participate. Participants underwent bilateral, two-view FFDM and two-view DBT. Readers scored each lesion separately for probability of malignancy on screen-film mammography, FFDM, and then DBT. The scores were compared with the presence or absence of malignancy based on the final histopathology outcome. RESULTS: Seven hundred and thirty-eight women participated (93.2% recruitment rate). Following assessment 204 (26.8%) were diagnosed as malignant (147 invasive and 57 in-situ tumours), 286 (37.68%) as benign, and 269 (35.4%) as normal. The diagnostic accuracy was evaluated by using receiving operating characteristic (ROC) and measurement of area under the curve (AUC). The AUC values demonstrated a significant (p = 0.0001) improvement in the diagnostic accuracy with the addition of DBT combined with FFDM and film-screen mammography (AUC = 0.9671) when compared to FFDM plus film-screen mammography (AUC = 0.8949) and film-screen mammography alone (AUC = 0.7882). The effect was significantly greater for soft-tissue lesions [AUC was 0.9905 with the addition of DBT and AUC was 0.9201 for FFDM with film-screen mammography combined (p = 0.0001)] compared to microcalcification [with the addition of DBT (AUC = 0.7920) and for FFDM with film-screen mammography combined (AUC = 0.7843; p = 0.3182)]. CONCLUSION: The addition of DBT increases the accuracy of mammography compared to FFDM and film-screen mammography combined and film-screen mammography alone in the assessment of screen-detected soft-tissue mammographic abnormalities.

Acceleration of cortical thinning in familial Alzheimer's disease.

BACKGROUND: MRI in presymptomatic autosomal dominant Alzheimer's disease mutation carriers (MC) provides an opportunity to detect changes that pre-date symptoms or clinical diagnosis. We used automated cortical thickness (CTh) measurement to compare the grey matter of such a group with cognitively normal controls. METHODS: 9 presymptomatic mutation carriers (4 PSEN1, 5 APP) and 25 healthy, age and sex-matched controls underwent longitudinal volumetric MRI brain imaging. CTh measurement was performed across the whole brain using a validated, automated technique. Four regions of interest (ROI) (entorhinal cortex (ERC), parahippocampal gyrus (PHG), posterior cingulate cortex and precuneus) and two control regions (paracentral and pericalcarine) were selected on the basis of imaging data in existing Alzheimer's disease (AD) literature. Linear mixed models were used to describe normal ageing in controls and the extent to which mean CTh in cases differed from controls according to time since clinical diagnosis, adjusting for normal ageing. RESULTS: An accelerating decline in CTh was observed across all ROI in the MC group. No such decline was demonstrated in the control regions for the MC group. Relative to controls, and adjusting for normal ageing, there was evidence (p=0.05, one-sided test) of lower CTh in the posterior cingulate up to 1.8 years prior to diagnosis and in the precuneus up to 4.1 years prior to diagnosis in the MC group. DISCUSSION: Automated CTh analysis is a relatively practical, rapid and effective technique for assessing subtle structural change in AD. There is evidence that cortical thickness is reduced in mutation carriers a number of years prior to clinical diagnosis.

Patterns of cortical thinning in the language variants of frontotemporal lobar degeneration.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous neurodegenerative disorder. Two subtypes commonly present with a language disorder: semantic dementia (SemD) and progressive nonfluent aphasia (PNFA). METHODS: Patients meeting consensus criteria for PNFA and SemD who had volumetric MRI of sufficient quality to allow cortical thickness analysis were recruited from a tertiary referral clinic: 44 (11 pathologically confirmed) patients with SemD and 32 (4 pathologically confirmed) patients with PNFA and 29 age-matched and gender-matched healthy controls were recruited. Cortical thickness analysis was performed using the Freesurfer software tools. RESULTS: Patients with SemD had significant cortical thinning in the left temporal lobe, particularly temporal pole, entorhinal cortex, and parahippocampal, fusiform, and inferior temporal gyri. A similar but less extensive pattern of loss was seen in the right temporal lobe and (with increasing severity) also in left orbitofrontal, inferior frontal, insular, and cingulate cortices. Patients with PNFA had involvement particularly of the left superior temporal lobe, inferior frontal lobe, and insula, and (with increasing severity) other areas in the left frontal, lateral temporal, and anterior parietal lobes. Similar patterns were seen in the pathologically confirmed cases. Patterns of cortical thinning differed between groups: SemD had significantly more cortical thinning in the temporal lobes bilaterally while PNFA had significantly more thinning in the frontal and parietal lobes. CONCLUSIONS: The language variants of frontotemporal lobar degeneration have distinctive and significantly different patterns of cortical thinning. Increasing disease severity is associated with spread of cortical thinning and the pattern of spread is consistent with progression of clinical deficits.

Improving energy resolution of EELS spectra: an alternative to the monochromator solution.

In this paper, we propose a numerical method which can routinely improve the energy resolution down to 0.2-0.3eV of electron energy-loss spectra acquired in a transmission electron microscope. The method involves measurement of the point-spread function (PSF) corresponding to the spectrometer aberration and to the incident energy spread, and then an inversion of this PSF so as to restore the spectrum. The chosen algorithm is based on an iterative calculation of the maximum likelihood solution known to be very robust against small errors in the PSF used. Restorations have been performed on diamond and graphite C-K edges acquired with an initial energy resolution of around 1eV. After reconstruction, the sharp core exciton lines become clearly visible for both compounds and the final energy resolution is estimated to be about 200-300meV. In the case of graphite, restorations involving both energy resolution and angular resolution have been successfully conducted. Finally, restorations of Fe L(2,3) and O-K edges measured for various iron oxides will be shown.