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Purpose: To investigate compositional changes of knee cartilage at the site of newly appearing cartilage lesions and the surrounding cartilage 1-4 years prior to lesion onset using quantitative T2-measurements.Methods: Fifty-seven cartilage plates with newly appearing cartilage lesions from 45 knees (cases) and 52 plates from 26 control knees from the Osteoarthritis Initiative (OAI) cohort (controls) were evaluated. Using MRI T2-mapping, composition of local (the site of future lesions) and surrounding cartilage (remainder of the cartilage plate) was assessed 1-4 years prior to lesion onset. Analogous cartilage ROIs in control plates without cartilage lesions were assessed over 1-4 years. Mixed models were used to compare T2-means and change rates between local and surrounding cartilage within cases and controls, and to compare change rates in local and surrounding cartilage between cases and controls, adjusting for covariates.Results: Four years prior to lesion onset, we found that local cartilage ROIs had higher T2-values compared to the surrounding cartilage. No such differences were found in control plates. In cases mean local T2-values were persistantly elevated compared to the surrounding cartilage prior to lesion onset reaching significance 1 year prior (+2.94 ms, p = 0.012). T2-values of the surrounding cartilage were also persistantly higher in cases compared to controls, reaching significance 2 years prior to lesion onset (+3.61 ms, p = 0.003).Conclusion: The findings of our study support the concept of compositional cartilage changes as a mechanism for cartilage degradation and that both diffuse and focal changes of cartilage composition within a cartilage plate precede the development of cartilage lesions. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the change in cartilage T2 values and structural degeneration in knee joints over 72 months in women of African American (AA) vs Caucasian American (CA) ethnicity.Methods: Knee 3T magnetic resonance imaging (MRIs) from baseline, 24, 48 and 72 months visits of 100 AA and 100 CA women from the Osteoarthritis Initiative (OAI) were assessed for cartilage T2 values and whole-organ magnetic resonance imaging (WORMS) score. Subjects were pair-matched by age, body mass index (BMI), Kellgren-Lawrence (KL) score, clinical site and subcohort within the OAI. We compared the rate of change in whole knee cartilage T2 values and WORMS cartilage, bone marrow edema pattern (BMEP) and meniscus scores between the two ethnic groups using mixed random effects models.Results: At 24 and 48 months 60 subjects and at 72 months 45 subjects per group were available for analysis resulting in 38 complete pairs with data of all time points. Compared to CA, cartilage T2 values in AA increased at a significantly faster rate at baseline (AA: 0.45 ms/y, CA: 0.35 ms/y, P = 0.029) and averaged over 6 years (AA: 0.36 ms/y, CA: 0.27 ms/y, P = 0.039) with changes in both groups reaching a plateau by 48 months. Cartilage, meniscus and BMEP scores tended to increase in both groups during follow up, but rates of change did not differ by ethnicity.Conclusion: Cartilage T2 values increased faster over 72 months in AA than CA, however changes in WORMS cartilage, meniscus and BMEP scores did not differ. T2 values may be able to distinguish ethnicity-related differences of cartilage degeneration at an early stage before differences in structural joint degeneration appear. [ABSTRACT FROM AUTHOR]

Objective: To determine if cartilage T1ρ and T2 relaxation time measures after ACL injury and prior to reconstruction (baseline) are associated with patient-reported outcomes at baseline, 6-months, and 1-year after surgery.Design: Fifty-four ACL-injured participants were scanned in both knees at baseline using 3T MR T1ρ and T2 mapping. Participants also completed Knee-injury and Osteoarthritis Outcome Score (KOOS) and Marx activity level questionnaires at baseline, 6-months, and 1-year after reconstruction. The difference between cartilage T1ρ or T2 of the injured and contralateral knee (side-to-side difference, SSD) was calculated to account for physiological variations among patients. Linear regression models were built to evaluate the association between the baseline SSD T1ρ or T2 and KOOS or Marx at all time points.Results: Higher baseline SSD T1ρ posterolateral tibia (pLT) was associated with worse KOOS in all subscales except symptoms at baseline, worse KOOS pain at 6-months, and worse KOOS in all subscales except sports function at 1-year. Higher baseline SSD T2 femoral trochlea (TrF) was associated with worse KOOS activities of daily living (ADL) at 1-year. Higher baseline SSD T1ρ pLT was associated with lower Marx activity level at 1-year. More severe cartilage lesions, as assessed by Whole-Organ MRI Scoring (WORMS), was significantly associated with worse KOOS pain at 6-months and 1-year.Conclusion: T1ρ and T2 of cartilage after ACL injury were associated with KOOS after injury and both KOOS and Marx after reconstruction. Such associations may help clinicians stratify outcomes post-injury, and thus, improve patient management. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this retrospective cross-sectional study was to investigate the association between cartilage lesions assessed with 3T-MRI and remodeling of the subchondral bone detected by (99m)Tc-DPD-SPECT/CT.Design: (99m)Tc-DPD-SPECT/CT and MRI of 27 knees of 25 patients with chronic knee pain and risk factors for osteoarthritis (OA) were evaluated by one nuclear physician and one radiologist. Six regions of the knee (in total 162 regions in 27 knees) were assessed according to structural joint lesions graded with a modified Whole Organ MR imaging score (WORMS) and according to subchondral (99m)Tc-DPD-SPECT uptake. Relationships between regional WORMS scores and uptake were quantified using general estimating equations. In a secondary analysis the uptake sum with the WORMS sum per joint was compared using Spearman correlations.Results: Elevated subchondral uptake was significantly associated with the grade of cartilage lesions (P < 0.0001). Mean uptake was significantly higher subjacent to full thickness cartilage lesions compared to partial thickness lesions (P < 0.0001). A similar association was observed between bone marrow edema pattern (BMEP) and cartilage lesions. The sum of uptakes per joint was positively correlated to the WORMS sum (rs = 0.42) and to the sum of cartilage lesions per joint (rs = 0.50).Conclusion: Both functional and structural changes of the subchondral bone in terms of scintigraphic osseous activity and the presence and degree of BMEP were significantly associated with cartilage lesions in patients with OA of the knee. This association was pronounced with full thickness lesions, indicating a possible protective effect of the cartilage layer for the subjacent bone. [ABSTRACT FROM AUTHOR]

Objective: To determine whether knee cartilage composition differs between African-American and Caucasian-American women at risk for Osteoarthritis (OA) using in vivo 3 T MRI T2 relaxation time measurements.Methods: Right knee MRI studies of 200 subjects (100 African-American women, and 100 closely matched Caucasian-American women) were selected from the Osteoarthritis Initiative (OAI). Knee cartilage was segmented in the patellar (PAT), medial and lateral femoral (MF/LF), and medial and lateral tibial compartments (MT/LT)). Mean T2 relaxation time values per compartment and per whole joint cartilage were generated and analyzed spatially via laminar and grey-level co-occurrence matrix (GLCM) texture methods. Presence and severity of cartilage lesions per compartment were graded using a modified WORMS grading. Statistical analysis employed paired t- and McNemar testing.Results: While African-American women and Caucasian-Americans had similar WORMS cartilage lesion scores (P = 0.970), African-Americans showed significantly lower mean T2 values (∼1 ms difference; ∼0.5SD) than Caucasian-Americans in the whole knee cartilage (P < 0.001), and in the subcompartments (LF: P = 0.001, MF: P < 0.001, LT: P = 0.019, MT: P = 0.001) and particularly in the superficial cartilage layer (whole cartilage: P < 0.001, LF: P < 0.001, MF: P < 0.001, LT: P = 0.003, MT: P < 0.001). T2 texture parameters were also significantly lower in the whole joint cartilage of African-Americans than in Caucasian-Americans (variance: P = 0.001; contrast: P = 0.018). In analyses limited to matched pairs with no cartilage lesions in a given compartment, T2 values remained significantly lower in African-Americans.Conclusion: Using T2 relaxation time as a biomarker for the cartilage collagen network, our findings suggest racial differences in the biochemical knee cartilage composition between African-American and Caucasian-American women. [ABSTRACT FROM AUTHOR]

Abstract: In many high income countries men who have sex with men (MSM) and injecting drug users (IDUs) are the two groups with the highest HIV prevalence. Yet these two groups are not mutually exclusive, and those MSM who are also IDUs (MSM–IDUs) may be particularly vulnerable to HIV infection. This may be particularly relevant to the IDU population in countries, like the UK, with a much lower HIV prevalence amongst IDUs than MSM, as the MSM–IDUs could provide a route of HIV infection into the IDU population. In this research two alternative modelling approaches that describe the transmission dynamics of HIV within the IDU, MSM, and heterosexual populations are proposed. These models are constructed with two aims. The first is to investigate the possible impact of interventions that target HIV transmission in the MSM and IDU populations, and the second aim is to investigate the impact of the model structure on the model results. An examination of the assortativity of mixing between risk groups is also undertaken. The models are parameterised for England and Wales. While the MSM–IDU population is small, targeting MSM–IDUs was the most efficient intervention strategy in terms of cases averted per 100 individuals targeted with the intervention. Sensitivity analysis showed that variations in the assumed assortativity of mixing between the population groups in both models have a large impact on model results. This means that to generate quantitatively robust estimates for the impact of different intervention strategies it will be necessary to obtain estimates for assortativity values through empirical work. [Copyright &y& Elsevier]

Abstract: The aim of this paper is to show in explicit detail that, due to the effects of waning and boosting of immunity, an increasing force of infection does not necessarily lead to an increase in the incidence of disease. Under certain conditions, a decrease of the force of infection may in fact lead to an increase of the incidence of disease. Thus we confirm and reinforce the conclusions from , concerning pertussis. We do so, however, in the context of Campylobacter infections in humans deriving from animal reservoirs. For such an externally ‘driven’ epidemic we can ignore the transmission feedback cycle and treat the force of infection as a parameter. As this parameter is, to a certain extent, under public health control, our findings constitute an important warning: reducing exposure may not necessarily lead to a reduction in the occurrence of clinical illness. In a second part of the paper we relate the model parameters to the available data concerning campylobacteriosis. [Copyright &y& Elsevier]

Abstract: The solar EUV irradiance is of key importance for space weather. Most of the time, however, surrogate quantities such as EUV indices have to be used by lack of continuous and spectrally resolved measurements of the irradiance. The ability of such proxies to reproduce the irradiance from different solar atmospheric layers is usually investigated by comparing patterns of temporal correlations. We consider instead a statistical approach. The TIMED/SEE experiment, which has been continuously operating since February 2002, allows for the first time to compare in a statistical manner the EUV spectral irradiance to five EUV proxies: the sunspot number, the f10.7, Ca K, and Mg II indices, and the He I equivalent width. Using multivariate statistical methods, we represent in a single graph the measure of relatedness between these indices and various strong spectral lines. The ability of each index to reproduce the EUV irradiance is discussed; it is shown why so few lines can be effectively reconstructed from them. All indices exhibit comparable performance, apart from the sunspot number, which is the least appropriate. No single index can satisfactorily describe both the level of variability on time scales beyond 27 days, and relative changes of irradiance on shorter time scales. [Copyright &y& Elsevier]

Summary: Multi-resistant bacteria are an increasing challenge for infection control in hospitals and the proportion of patients newly colonized with multi-resistant bacteria during their hospital stay can be used to assess the effectiveness of infection control measures. Current laboratory methods for estimating this require expensive additional tests. We propose an alternative statistical method to estimate the proportion of cases resulting from transmission in a hospital from the distribution of time intervals between subsequent cases. A prerequisite for the application of this method is the existence of records from regular screening of the patients during their hospital stay, usually performed in intensive care units (ICUs). We describe the method and present an example of its application using records of two multi-resistant pathogens collected in an ICU over a three-year period. The estimated proportion of cases resulting from transmission was 0.73 (95% CI: 0.56–0.90) for meticillin-resistant Staphylococcus aureus and 0.45 (95% CI 0.15–0.75) for imipenem-resistant Pseudomonas aeruginosa. The method proposed here can be used for retrospective evaluation of clinical records in order to evaluate the effectiveness of infection control measures in low endemicity settings. [Copyright &y& Elsevier]

Abstract: We use recent solar extreme ultraviolet (EUV) irradiance data from the Solar EUV Experiment aboard the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite to investigate the possibility to retrieve the whole solar EUV irradiance from a minimum number of measurements. Computing a differential emission measure for the whole Sun from the irradiances of 5 lines and using a sixth line to model optically thick emission, we are able to reproduce with a good agreement the variability of the whole solar EUV irradiance. [Copyright &y& Elsevier]

Introduction: Disadvantages of arthroscopically guided surgical techniques for treatment of osteochondral lesions (OCL) of the ankle joint are disruption of viable articular cartilage and insufficient addressing of the subchondral bone. For certain lesion locations, like the posteromedial talus, feasibility is often compromised. The INNOMOTION robotic assistance device proved its value for precise musculoskeletal interventions, such as facet joint and sacroiliac joint infiltrations. We present our first experience with CT-guided robotically-assisted retrograde drilling of osteochondral lesions of the ankle joint and evaluate its feasibility, precision and potential use as a routine operative treatment. Methods: 8 patients diagnosed with OCL of the talus (4) and the distal tibia (4) were included. MRI revealed an intact cartilaginous cover in all cases. Surgery was performed with the INNOMOTION robotic assistance device (Innomedic, Herxheim, Germany) mounted on the table of a CT scanner. The robot-device was referenced to the coordinate system of the CT-scanner. Drill trajectory and depth were planned within acquired CT images. A guiding sleeve for the Kirschner-Wire (K-Wire) was attached to the holding device on the application module and positioned automatically according to the planned trajectory. A 2.5mm K-Wire was advanced through the guiding-sleeve up to the calculated drilling depth. A cannulated drill was placed over the wire and advanced into the lesion. The lesion was curetted and filled with DBM-paste and patient spongiosa. CT-control scans were performed to determine the position of the instruments and to document the exact localization of the deposit. Results: Technically successful CT-guided robot-assisted retrograde drilling was performed in all cases without intra- and postoperative complications. No intervention abort or conversion to arthroscopically guided technique or arthrotomy was necessary. CT-control scans confirmed exact initial placement of the guiding wire within the centre of the OCL, precise drill bit positioning and successful retrograde filling of the bored cavity. Discussion: The first clinical cases demonstrated CT-guided robot-assisted intervention to be a feasible and safe method for retrograde drilling of OCL of the ankle. Precise assistance by the INNOMOTION-robot combined with the superior ability of the CT to visualize skeletal anatomy greatly improves the accuracy of drilling with exact and reliable addressing of OCL without damage to overlying cartilage. Further studies need to evaluate the outcome of this new operative technique and to compare it to conventional retrograde drilling. [Copyright &y& Elsevier]

Purpose: We hypothesized that bone SPECT combined with multiplanar reconstructed CT can identify and target the pain-inducing focus in the foot and can be used to successfully guide anaesthetic infiltrations. Therefore we prospectively investigated feasibility and predictive value of bone SPECT/CT for image guided diagnostic infiltrations in patients with chronic foot pain. Methods: All patients received a standardized bone SPECT/CT of both feet. The scintigraphically most active structures were subsequently infiltrated with local anaesthetics under CT-guidance. The pre- and post-infiltration pain intensity was measured using the visual analogue scale (VAS). Then, we assessed (i) the agreement on pain originating structures determined by standard clinical assessment versus SPECT/CT and (ii) the predictive value of SPECT-CT in groups with and without agreement. Results: 27 of 30 participants reported a pain reduction on VAS of 50% or more, resulting in a response rate of 90%. When assessing the agreement on pain initiating structures determined by standard clinical assessment versus SPECT/CT, we found a disagreement in 16 of 30 (53%) cases. Particularly, disagreement appeared in all 9 participants with symptoms located in the mid-foot (100%). In participants with hind-foot pathology, disagreement was found in 7 of 21 cases (33%). Conclusion: The present study shows the feasibility of 99mTc-DPD-SPECT/CT guided infiltration of osseous structures of patients with chronic foot pain. 99mTc-DPD-SPECT/CT had a higher predictive value on the clinical outcome than the clinical assessment. In the clinical setting 99mTc-DPD-SPECT/CT might overrule the clinical assessment in case of disagreement on the target lesion. [ABSTRACT FROM AUTHOR]

Aim: To assess cartilage quality using delayed gadolinium-enhanced magnetic resonance imaging after repair of osteochondral lesions of the talus using autologous matrix-induced chondrogenesis (AMIC). Materials and methods: A three-dimensional (3D) spoiled gradient-echo (SGE) sequence at 3 T was used to obtain quantitative T1 relaxation times before and after Gd-DTPA2 (Magnevist, 0.2 mM/kg bod weight) administration to assess 23 cases of AMIC-aided repair of osteochondral lesions of the talus. Delta relaxation rates (ΔR1) for reference cartilage (RC) and repair tissue (RT), and the relative delta relaxation rate (rΔR1) were calculated. The morphological appearance of the cartilage RT was graded on sagittal dual-echo steady-state (DESS) views according to the “magnetic resonance observation of cartilage repair tissue” (MOCART) protocol. The study was approved by the institutional review board and written consent from each patient was obtained. Results: The AMIC cases had a mean T1 relaxation time of 1.194 s (SD 0.207 s) in RC and 1.470 s (SD 0.384 s) in RT before contrast medium administration. The contrast-enhanced T1 relaxation time decreased to 0.480 s (SD 0.114 s) in RC and 0.411 s (SD 0.096 s) in RT. There was a significant difference (p > 0.05) between the ΔR1 in RC (1.372 × 10−3/s, range 0.526–3.201 × 10−3/s, SD 0.666 × 10−3/s) and RT (1.856 × 10−3/s, range 0.93–3.336 × 10−3/s, SD 0.609 × 10−3/s). The mean rΔR1 was 1.49, SD 0.45). The mean MOCART score at follow-up was 62.6 points (range 30–95, SD 15.3). Conclusion: The results of the present study suggest that repair cartilage resulting from AMIC-aided repair of osteochondral lesions of the talus has a significantly lower glycosaminoglycan (GAG) content than normal hyaline cartilage, but can be regarded as having hyaline-like properties. [ABSTRACT FROM AUTHOR]

Background: One-lung ventilation (OLV) induces a pro-inflammatory response including cytokine release and leucocyte recruitment in the ventilated lung. Whether volatile or i.v. anaesthetics differentially modulate the alveolar inflammatory response to OLV is unclear.Methods: Thirty patients, ASA II or III, undergoing open thoracic surgery were randomized to receive either propofol 4 mg kg(-1) h(-1) (n = 15) or 1 MAC desflurane in air (n = 15) during thoracic surgery. Analgesia was provided by i.v. infusion of remifentanil (0.25 microg kg(-1) min(-1)) in both groups. The patients were mechanically ventilated according to a standard protocol during two-lung ventilation and OLV. Fibre optic bronchoalveolar lavage (BAL) of the ventilated lung was performed before and after OLV and 2 h postoperatively. Alveolar cells, protein, tumour necrosis factor alpha (TNFalpha), interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM), IL10, and polymorphonuclear (PMN) elastase were determined in the BAL fluid. Data were analysed by parametric or non-parametric tests, as indicated.Results: In both groups, an increase in pro-inflammatory markers was found after OLV and 2 h postoperatively; however, the fraction of alveolar granulocytes (median 63.7 vs 31.1%, P < 0.05) was significantly higher in the propofol group compared with the desflurane group. The time courses of alveolar elastase, IL-8, and IL-10 differed between groups, and alveolar TNFalpha (7.4 vs 3.1 pg ml(-1), P < 0.05) and sICAM-1 (52.3 vs 26.3 ng ml(-1), P < 0.05) were significantly higher in the propofol group.Conclusions: These data indicate that pro-inflammatory reactions during OLV were influenced by the type of general anaesthesia. Different patterns of alveolar cytokines may be a result of increased granulocyte recruitment during propofol anaesthesia. [ABSTRACT FROM AUTHOR]

Abstract: Technetium and rhenium tricarbonyl complexes with derivatized cyclopentadienyl ligands were prepared starting from pertechnetate and an appropriate ferrocene ligand. Furthermore, the complexes (M(CO)3cp-COOC5H9N-R, M=Tc, Re; R=Me, isopropyl) could be obtained starting from the precursor complexes [99mTc(CO)3(H2O)3]+ and [Re(CO)3Br3]2−. Their chemical identity was confirmed by chromatographic methods and electron spray mass spectrometry. The biodistribution of the 99mTc complexes (cytectrene I and cytectrene II) in Wistar rats was studied. Both compounds show high uptake in the brain and fast blood clearance. The pattern of regional distribution in the brain demonstrated in autoradiographic studies indicates binding to the 5-HT1A and α1 adrenergic receptors. [Copyright &y& Elsevier]

The evaluation of measles vaccination programmes has been problematic because the change in actual numbers of infections and susceptibles over time cannot be directly observed. In this paper, we present a method for estimating the time series of number of susceptibles and infections, as well as the critical vaccination coverage in a vaccinated population. The proposed method is applied to data on measles outbreaks in The Netherlands. We show that the results are self-consistent and in line with available independent estimates. A potential application of the proposed method lies in detecting the loss of herd immunity and assessing the risk of major outbreaks in vaccinated populations. [Copyright &y& Elsevier]

This paper reports the synthesis, biological evaluation, in vitro and ex vivo autoradiography of the first Tc-99m ligand with subnanomolar affinity for the 5-HT1A receptor and a remarkably high affinity for the alpha1-adrenergic receptor. The neutral “3+1” mixed-ligand complex combines 4-(6-mercaptohexyl)-1-(2-methoxyphenyl)piperazine as monodentate and 3-(N-methyl)azapentane-1,5-dithiol as tridentate unit with oxotechnetium(V). The analogous rhenium complex was synthesized for complete structural characterization and used in receptor binding assays. In competition experiments both complexes display subnanomolar affinity for the 5-HT1A receptor (IC500.24 nM for Re, 0.13 nM for Tc) but also very high affinities for the alpha1-adrenergic receptor (IC50 0.05 nM for Re, 0.03 nM for Tc). Biodistribution studies show a brain uptake in rat of 0.22% ID five minutes post injection. In vitro autoradiographic studies in rat brain and postmortem human brain indicate accumulation of the Tc-99m complex in brain areas which are rich in 5-HT1A receptors or in alpha1-adrenergic receptors. This in vitro enrichment can be blocked respectively by the 5-HT1A receptor agonist 8-OH-DPAT or by prazosin hydrochloride, an alpha1-adrenergic receptor antagonist. Ex vivo autoradiographic studies in rats show a slight accumulation of the Tc-99m complex in 5-HT1A receptor-rich areas of the brain, which could not be blocked, as well as in regions rich in alpha1-adrenergic receptors, which could be blocked by prazosin hydrochloride. [Copyright &y& Elsevier]

At the 10th Thermospheric Ionospheric GEospheric Research (TIGER/COSPAR) symposium held in Moscow in 2014 the achievements from the start of TIGER in 1998 were summarized. During that period, great progress was made in measuring, understanding, and modeling the highly variable UV-Soft X-ray (XUV) solar spectral irradiance (SSI), and its effects on the upper atmosphere. However, after more than 50 years of work the radiometric accuracy of SSI observation is still an issue and requires further improvement. Based on the extreme ultraviolet (EUV) data from the SOLAR/SolACES, and SDO/EVE instruments, we present a combined data set for the spectral range from 16.5 to 105.5 nm covering a period of 3.5 years from 2011 through mid of 2014. This data set is used in ionospheric modeling of the global Total Electron Content (TEC), and in validating EUV SSI modeling. For further investigations the period of 3.5 years is being extended to about 12 years by including data from SOHO/SEM and TIMED/SEE instruments. Similarly, UV data are used in modeling activities. After summarizing the results, concepts are proposed for future real-time SSI measurements with in-flight calibration as experienced with the ISS SOLAR payload, for the development of a space weather camera for observing and investigating space weather phenomena in real-time, and for providing data sets for SSI and climate modeling. Other planned topics are the investigation of the relationship between solar EUV/UV and visible/near-infrared emissions, the impact of X-rays on the upper atmosphere, the development of solar EUV/UV indices for different applications, and establishing a shared TIGER data system for EUV/UV SSI data distribution and real-time streaming, also taking into account the achievements of the FP7 SOLID (First European SOLar Irradiance Data Exploitation) project. For further progress it is imperative that coordinating activities in this special field of solar–terrestrial relations and solar physics is emphasized. [ABSTRACT FROM AUTHOR]

Abstract: LYRA is the solar UV radiometer that will embark in 2006 onboard Proba2, a technologically oriented ESA micro-mission. LYRA is designed and manufactured by a Belgian–Swiss–German consortium (ROB, PMOD/WRC, IMOMEC, CSL, MPS and BISA) with additional international collaborations. It will monitor the solar irradiance in four UV passbands. They have been chosen for their relevance to Solar Physics, Aeronomy and Space Weather: (1) the 115–125nm Lyman-α channel, (2) the 200–220nm Herzberg continuum range, (3) the Aluminium filter channel (17–70nm) including He II at 30.4nm and (4) the Zirconium filter channel (1–20nm). The radiometric calibration will be traceable to synchrotron source standards (PTB and NIST). The stability will be monitored by onboard calibration sources (LEDs), which allow to distinguish between potential degradations of the detectors and filters. Additionally, a redundancy strategy maximizes the accuracy and the stability of the measurements. LYRA will benefit from wide bandgap detectors based on diamond: it will be the first space assessment of a pioneering UV detectors program. Diamond sensors make the instruments radiation-hard and solar-blind: their high bandgap energy makes them insensitive to visible light and, therefore, make dispensable visible light blocking filters, which seriously attenuate the desired ultraviolet signal. Their elimination augments the effective area and hence the signal-to-noise, therefore increasing the precision and the cadence. The SWAP EUV imaging telescope will operate next to LYRA on Proba2. Together, they will establish a high performance solar monitor for operational space weather nowcasting and research. LYRA demonstrates technologies important for future missions such as the ESA Solar Orbiter. [Copyright &y& Elsevier]