Higher order aberrations in keratoconus .

INTRODUCTION: Keratoconus is a progressive disorder of the cornea that causes thinning (Sedaghat et al. in Sci Rep 11(1):11971, 2021), ectasia, and irregular astigmatism, resulting in poor visual acuity that cannot be corrected with standard sphero-cylindrical spectacle lenses. One feature distinguishing keratoconic corneas is ocular aberrations, manifesting up to five or six times the amount of higher-order aberrations than a normal, healthy eye. These aberrations can cause visual disturbances even at the very early stages of the disease. METHODS: In the past, a diagnosis was derived from clinical symptoms, but technological advances have revealed multiple pre-clinical features, allowing for the differentiation between keratoconic and normal eyes at a much earlier stage. These include anterior and posterior corneal surface elevations, the corneal pachymetry profile, corneal epithelial patterns, wavefront aberration metrics, and corneal biomechanics (Sedaghat et al. in Sci Rep 11(1):11971, 2021).This review discusses the aberrations associated with keratoconus, how to measure them, and treatment methods to minimize their negative influence. CONCLUSIONS: Early diagnosis can lead to early treatment and may allow for arresting progression, thereby improving the long-term prognosis. With the acceleration of refractive surgery, it is important to identify patients with keratoconus, as they are usually contraindicated for refractive surgery.

Applications of topical immunomodulators enhance clinical signs of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC): a meta-analysis.

PURPOSE: This meta-analysis aimed to review the safety and efficacy of topical cyclosporine A (CsA) and topical tacrolimus in allergic eye disease. METHODS: A systematic search identified thirteen studies and a total of 445 patients for inclusion, making this the largest meta-analysis published on the subject. The current review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Thirteen randomized control trials were included in the meta-analysis. Eleven studies used CsA as the treatment, and two used Tacrolimus. In total, 445 participants were included, of whom 76.6% were male. The mean age of participants across the included studies was 14 years. All studies reported clinical signs as evaluated by an examining clinician. Signs were usually assessed by anatomical region, with the most common regions being the conjunctiva and the cornea, and the most common signs assessed were hyperemia and papillae. Three studies accounted for more than 50% of the meta-analysis's weight. Effect size (d) ranged from - 2.37 to - 0.03, negative values favoring immunomodulators. Fixed Effect Meta-Analysis returned an SMD of - 0.81 (95% CI [- 0.98, - 0.65]). However, there was significant heterogeneity (I2 = 61%, Qw = 30.76) in the outcome measure (P = 0.0021); therefore, a random-effect meta-analysis was also completed in which the pooled SMD was - 0.98 (95% CI [- 1.26, - 0.69], τ2 = 0.16). CONCLUSIONS: This study affirms the current scientific community's stance that immunomodulators effectively treat clinical signs, including blepharitis, conjunctival hyperemia, edema, papillae, and corneal damage in severe ocular allergic disease.

Treatment of Rapid Progression of Myopia: Topical Atropine 0.05% and MF60 Contact Lenses.

This retrospective study evaluates the effectiveness of combining 0.05% atropine with MF60 contact lenses in managing rapid myopia progression in children over one year. The study involved three groups: the treatment group (TG) with 15 children (53% male, average age 12.9 ± 1.04), the MF group (MF) with 12 children (50% male, average age 12.8 ± 0.8) using only MF60 lenses, and the control group (CG) with 14 children (43% male, average age 12.1 ± 0.76). Baseline myopia and axial length (AL) were similar across groups, with the TG, MF, and CG showing -4.02 ± 0.70 D, -4.18 ± 0.89 D, -3.86 ± 0.99 D, and 24.72 ± 0.73 mm, 24.98 ± 0.70 mm, 24.59 ± 1.02 mm, respectively. Prior to the study, all groups exhibited significant myopia and AL progression, with no previous myopia control management. The treatment involved daily 0.05% atropine instillation, the use of MF60 lenses and increased outdoor activity. Biannual cycloplegic refraction and slit lamp evaluations confirmed no adverse reactions. After one year, the TG showed a significant reduction in myopia and AL progression (-0.43 ± 0.46 D, p < 0.01; 0.22 ± 0.23 mm, p < 0.01), whereas the CG showed minimal change (-1.30 ± 0.43 D, p = 0.36; 0.65 ± 0.35 mm, p = 0.533). The MF group also exhibited a notable decrease (-0.74 ± 0.45 D, p < 0.01; 0.36 ± 0.23 mm). Increased outdoor activity during the treatment year did not significantly impact myopia control, suggesting its limited additional effect in this cohort. The study concludes that the combination of 0.05% atropine and peripheral defocus soft contact lenses effectively controls myopia progression in children.

[ARTIFICIAL INTELLIGENCE IN OPHTHALMOLOGY].

INTRODUCTION: Artificial intelligence (AI) was first introduced in 1956, and effectively represents the fourth industrial revolution in human history. Over time, this medium has evolved to be the preferred method of medical imagery interpretation. Today, the implementation of AI in the medical field as a whole, and the ophthalmological field in particular, is diverse and includes diagnose, follow-up and monitoring of the progression of ocular diseases. For example, AI algorithms can identify ectasia, and pre-clinical signs of keratoconus, using images and information computed from various corneal maps. Machine learning (ML) is a specific technique for implementing AI. It is defined as a series of automated methods that identify patterns and templates in data and leverage these to perform predictions on new data. This technology was first applied in the 1980s. Deep learning is an advanced form of ML inspired by and designed to imitate the human brain process, constructed of layers, each responsible for identifying patterns, thereby successfully modeling complex scenarios. The significant advantage of ML in medicine is in its' ability to monitor and follow patients with efficiency at a low cost. Deep learning is utilized to monitor ocular diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, cataract, and retinopathy of prematurity. These conditions, as well as others, require frequent follow-up in order to track changes over time. Though computer technology is important for identifying and grading various ocular diseases, it still necessitates additional clinical validation and does not entirely replace human diagnostic skill.

Infrared Nanoimaging of Hydrogenated Perovskite Nickelate Memristive Devices.

Solid-state devices made from correlated oxides, such as perovskite nickelates, are promising for neuromorphic computing by mimicking biological synaptic function. However, comprehending dopant action at the nanoscale poses a formidable challenge to understanding the elementary mechanisms involved. Here, we perform operando infrared nanoimaging of hydrogen-doped correlated perovskite, neodymium nickel oxide (H-NdNiO3, H-NNO), devices and reveal how an applied field perturbs dopant distribution at the nanoscale. This perturbation leads to stripe phases of varying conductivity perpendicular to the applied field, which define the macroscale electrical characteristics of the devices. Hyperspectral nano-FTIR imaging in conjunction with density functional theory calculations unveils a real-space map of multiple vibrational states of H-NNO associated with OH stretching modes and their dependence on the dopant concentration. Moreover, the localization of excess charges induces an out-of-plane lattice expansion in NNO which was confirmed by in situ X-ray diffraction and creates a strain that acts as a barrier against further diffusion. Our results and the techniques presented here hold great potential for the rapidly growing field of memristors and neuromorphic devices wherein nanoscale ion motion is fundamentally responsible for function.

Peripheral defocus as it relates to myopia progression: A mini-review.

Myopia is the most common refractive error in the world and has reached a pandemic level. The potential complications of progressive myopia have inspired researchers to attempt to understand the sources of myopia and axial elongation and to develop modalities to arrest progression. Considerable attention has been given over the past few years to the myopia risk factor known as hyperopic peripheral blur, which is the focus of this review. It will discuss the primary theories believed to be the cause of myopia and the parameters considered to contribute to and influence the effect of peripheral blur, such as the surface retinal area of blur or the depth of blur. The multitude of optical devices designed to provide peripheral myopic defocus will be mentioned, including bifocal and progressive addition ophthalmic lenses, peripheral defocus single-vision ophthalmic lenses, orthokeratology lenses, and bifocal or multifocal center distance soft lenses, as well as their effectivity as discussed in the literature to date.

Effective Decrease in Myopia Progression With Two Mechanisms of Management.

PURPOSE: To ascertain the effectiveness of 0.01% atropine treatment to inhibit myopia progression and the possible additive potency with peripheral defocus contact lenses over 3 years and the rebound effect 1 year after cessation of treatment. METHODS: This prospective study included 127 children aged 8 to 5 years, divided into three treatment groups: 0.01% atropine and single-vision spectacles (At+SV, n = 36), 0.01% atropine and peripheral defocus contact lens (At+PDCL, n = 30), and 0.01% atropine and dual-focus contact lens (At+DF, n = 25). A control group was prescribed single-vision spectacles (n = 36). Cycloplegic spherical equivalence refraction was measured every 6 months during 3 years of treatment and 1 year after cessation. RESULTS: Myopia progression decreased over 3 years of treatment, more during the second and third years than the first year, to a statistically significant degree in the atropine groups (P < .01): in the first, second, and third years, respectively, -0.42 ± 0.34, -0.19 ± 0.18, -0.22 ± 0.19 diopters (D) in the At+SV group, -0.26 ± 0.21, -0.14 ± 0.37, and -0.15 ± 0.31 D in the At+PDCL group, and -0.22 ± 0.15, -0.15 ± 0.22, and -0.11 ± 0.14 D in the At+DF group. Myopia progressed 1 year after cessation of treatment: -0.29 ± 0.28 D in the At+SV group, -0.13 ± 0.28 D in the At+PDCL group, and -0.09 ± 0.18 D in the At+DF group. After 3 years, there was no statistically significant difference in myopia progression between the At+SV and At+PDCL or At+DF groups (P < .05). CONCLUSIONS: Low-dose atropine has been substantiated in this cohort as an effective treatment to decelerate myopia progression over 3 years, more effective in the second and third years of treatment. The combination treatment did not exhibit a statistically significant advantage over monotherapy in this cohort. The At+DF group exhibited a statistically lower rebound effect than the At+SV group. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Wang-Landau sampling of lattice multiblock copolymers.

Synthetic multiblock copolymers are an interesting class of polymeric chains and have emerged as promising materials to mimic the function of complex biomolecules. In this work, we use Wang-Landau sampling to study sequences of multiblock (AnBn)m copolymers on the simple cubic lattice, where n represents the block length and m represents the number of blocks. We first compare to the thermodynamic and structural properties of four sequences previously studied in the continuum [W. Wang et al., J. Chem. Phys. 141, 244907 (2014)] to observe the differences that arise during the collapse process. We then focus on the structural transitions that occur at temperatures below the coil-to-globule transition in the lattice. Moreover, by studying additional sequences, we detail the relationship between the block length, number of blocks, and, thus, overall polymer length with respect to said structural transitions. Finally, we observe how the formation and shape of a ground state core of the more strongly interacting monomer type affect the procession of structural changes that occurs as temperature increases.

Peripheral Defocus and Myopia Management: A Mini-Review.

Myopia is the most common refractive error in the world, and its' prevalence continually increases. The potential pathological and visual complications of progressive myopia have inspired researchers to study the sources of myopia, axial elongation, and explore modalities to arrest progression. Considerable attention has been given over the past few years to the myopia risk factor known as hyperopic peripheral blur, the focus of this review. The primary theories currently believed to be the cause of myopia, the parameters considered to contribute and influence the effect of peripheral blur, such as the surface retinal area or depth of blur will be discussed. The currently available optical devices designed to provide peripheral myopic defocus will be discussed, including bifocal and progressive addition ophthalmic lenses, peripheral defocus single vision ophthalmic lenses, orthokeratology lenses, and bifocal or multifocal center distance soft lenses, as well as their effectivity as mentioned in the literature to date.

Low-Concentration Atropine Monotherapy vs. Combined with MiSight 1 Day Contact Lenses for Myopia Management.

Objectives: To assess the decrease in myopia progression and rebound effect using topical low-dose atropine compared to a combined treatment with contact lenses for myopic control. Methods: This retrospective review study included 85 children aged 10.34 ± 2.27 (range 6 to 15.5) who were followed over three years. All had a minimum myopia increase of 1.00 D the year prior to treatment. The children were divided into two treatment groups and a control group. One treatment group included 29 children with an average prescription of 4.81 ± 2.12 D (sphere equivalent (SE) range of 1.25−10.87 D), treated with 0.01% atropine for two years (A0.01%). The second group included 26 children with an average prescription of 4.14 ± 1.35 D (SE range of 1.625−6.00 D), treated with MiSight 1 day dual focus contact lenses (DFCL) and 0.01% atropine (A0.01% + DFCL) for two years. The control group included 30 children wearing single-vision spectacles (SV), averaging −5.06 ± 1.77 D (SE) range 2.37−8.87 D). Results: There was an increase in the SE myopia progression in the SV group of 1.19 ± 0.43 D, 1.25 ± 0.52 D, and 1.13 ± 0.36 D in the first, second, and third years, respectively. Myopia progression in the A0.01% group was 0.44 ± 0.21 D (p < 0.01) and 0.51 ± 0.39 D (p < 0.01) in the first and second years, respectively. In the A0.01% + DFCL group, myopia progression was 0.35 ± 0.26 D and 0.44 ± 0.40 D in the first and second years, respectively (p < 0.01). Half a year after the cessation of the atropine treatment, myopia progression (rebound effect) was measured at −0.241 ± 0.35 D and −0.178 ± 0.34 D in the A0.01% and A0.01% + DFCL groups, respectively. Conclusions: Monotherapy low-dose atropine, combined with peripheral blur contact lenses, was clinically effective in decreasing myopia progression. A low rebound effect was found after the therapy cessation. In this retrospective study, combination therapy did not present an advantage over monotherapy.

[CONTACT LENS COMPLICATIONS].

INTRODUCTION: This article will review the complications of contact lenses (CL) according to the literature over the past few years including mechanical, inflammatory, allergic, toxic, metabolic, and infectious complications. There are CL complications that are not sight-threatening and there are severe complications that do threaten the sight. In general, any complication from CL that involves the cornea may endorse irreversible damage to sight. Most of the complications that involve the cornea are complications due to infectious backgrounds and are the most severe amongst CL wearers. The more continuous the CL wear is, the greater the danger to develop a complication. In the past it was assumed that switching from hydrogel CL to silicone hydrogel CL would reduce the incidence of CL complications, but this was not the case. From the point of view of wearing habits, the use of reusable CL (weekly or monthly) produced from more advanced raw materials did not reduce the percentage of complications. The complication may be due to incorrect CL compliance, incorrect use of the disinfecting solutions, incorrect compliance and cleaning of the CL. CL wearers aged between 15 to 19 years are the largest risk group to develop complications. Amongst younger aged wearers there is more precision due to parent supervision. The purchase of CL on-line has increased the percentage of complications because the patient purchasing the CL on-line does not attribute importance to the periodic examination by the professional eye therapist.

Correlation of hypoxia PET tracer uptake with hypoxic radioresistance in cancer cells: PET biomarkers of resistance to stereotactic radiation therapy?

PURPOSE: The pO2 threshold of an ideal PET hypoxia tracer for radiotherapy planning in cancer would match those observed in clinically and biologically relevant processes such as radioresistance and HIF1α expression. To identify such tracers, we directly compared uptake in vitro of hypoxia PET tracers ([18F]FMISO, [64Cu]CuATSM, and analogues [64Cu]CuATS, [64Cu]CuATSE, [64Cu]CuCTS, [64Cu]CuDTS, [64Cu]CuDTSE, [64Cu]CuDTSM) with levels of radioresistance and HIF1α expression in cultured cancer cells under identical hypoxic conditions ranging from extreme hypoxia to normoxia. Pimonidazole uptake was also compared as a marker of hypoxia. METHODS: A custom-built hypoxia apparatus enabled all experiments to be performed under identical hypoxic conditions with constant measurement of pO2 in media using an OxyLab pO2™ probe. HCT116 human colonic carcinoma and MCF-7 human Caucasian breast adenocarcinoma cells were irradiated using a cobalt teletherapy unit. Clonogenic assays were used to assess survival. HIF1α expression was determined by western blotting, tracer uptake by gamma counting and pimonidazole binding by flow cytometry. RESULTS: Radioresistance, pimonidazole binding and HIF1α expression increased gradually as pO2 decreased between 25 mmHg and 0 mmHg. In contrast, all the PET hypoxia tracers showed a sharp increase in uptake only when pO2 levels fell below 1 mmHg. Above this threshold, tracer uptake was not elevated above that in normoxic cells. CONCLUSION: This study highlights an important mismatch in pO2 thresholds between these PET tracers and other markers of hypoxia: tracer uptake only occurred at oxygen levels that were well below levels that induced radioresistance, pimonidazole uptake and HIF1α expression. Although their pO2 thresholds do not match the threshold for resistance to conventionally fractionated radiotherapy (pO2 2.5-10 mmHg), their specificity for extreme hypoxia (pO2 ≪ 1 mmHg) suggests these PET tracers may be of particular use to predict outcomes in stereotactic radiation therapy where these maximally resistant cells play a key role in determining the biological effect.

A Novel and Automated Approach to Classify Radiation Induced Lung Tissue Damage on CT Scans.

Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as 'acceptable', 'minor disagreement' or 'major disagreement'. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.

Quantitative Analysis of Radiation-Associated Parenchymal Lung Change.

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible.

Thermodynamics of hydrophobic-polar model proteins on the face-centered cubic lattice.

The HP model, a coarse-grained protein representation with only hydrophobic (H) and polar (P) amino acids, has already been extensively studied on the simple cubic (SC) lattice. However, this geometry severely restricts possible bond angles, and a simple improvement is to instead use the face-centered cubic (fcc) lattice. In this paper, the density of states and ground state energies are calculated for several benchmark HP sequences on the fcc lattice using the replica-exchange Wang-Landau algorithm and a powerful set of Monte Carlo trial moves. Results from the fcc lattice proteins are directly compared with those obtained from a previous lattice protein folding study with a similar methodology on the SC lattice. A thermodynamic analysis shows comparable folding behavior between the two lattice geometries, but with a greater rate of hydrophobic-core formation persisting into lower temperatures on the fcc lattice.

Effects of lattice constraints in coarse-grained protein models.

We compare and contrast folding behavior in several coarse-grained protein models, both on- and off-lattice, in an attempt to uncover the effect of lattice constraints in these kinds of models. Using modern, extended ensemble Monte Carlo methods-Wang-Landau sampling, multicanonical sampling, replica-exchange Wang-Landau sampling, and replica-exchange multicanonical sampling, we investigate the thermodynamic and structural behavior of the protein Crambin within the context of the hydrophobic-polar, hydrophobic-"neutral"-polar (H0P), and semi-flexible H0P model frameworks. We uncover the folding process in all cases; all models undergo, at least, the two major structural transitions observed in nature-the coil-globule collapse and the folding transition. As the complexity of the model increases, these two major transitions begin to split into multi-step processes, wherein the lattice coarse-graining has a significant impact on the details of these processes. The results show that the level of structural coarse-graining is coupled to the level of interaction coarse-graining.

A systematic review on endovascular repair of isolated common iliac artery aneurysms and suggestions regarding diameter thresholds for intervention.

OBJECTIVE: Our aim was to systematically review results of endovascular aneurysm repair for isolated common iliac artery aneurysms (CIAA) regarding outcomes and to determine if changes should be made to current diameter threshold recommendations for intervention. METHODS: A comprehensive systematic review was performed according to the PRISMA guidelines. PubMed, Scopus, and the Cochrane Central databases were searched. RESULTS: Twenty-one studies were deemed eligible and provided data for 879 patients and 981 isolated CIAA treated with endovascular repair. The majority of the patients (90.8%) were males. The weighted mean age of the patients was 71.7 years (range, 37-91 years). The weighted mean diameter for the CIAA was 41. mm 1 (range, 15-110 mm) and for ruptured aneurysms 58.4 mm. The overall technical success rate was 97.6%. The perioperative mortality rate was 0.7%. Secondary patency rates were reported in only four studies and varied between 96.7% and 100%. The overall morbidity rate was 14%, ranging from 0% to 25%. Most of the studies did not report long-term or adequate follow-up data. Rupture of an isolated CIAA at <4 cm diameter was extremely low. CONCLUSIONS: Endovascular treatment of isolated CIAA is feasible and safe with a low mortality and excellent technical success rates. Consideration of increasing the diameter threshold for intervention of CIAA to 4 cm should be considered. Studies with longer follow-up and reliable long-term results are needed.

Ophthalmology practice during the COVID-19 pandemic.

OBJECTIVE: To present an established practice protocol for safe and effective hospital-setting ophthalmic practice during the coronavirus disease 2019 (COVID-19) pandemic. METHODS AND ANALYSIS: Literature was reviewed to identify articles relevant to COVID-19 pandemic and ophthalmology. The following keywords were used: COVID-19, SARS-CoV-2 and telemedicine, combined with eye, ophthalmology, conjunctivitis and tears. Data were extracted from the identified manuscripts and discussed among subspecialists to obtain consensus evidence-based practice. RESULTS: A protocol for ophthalmic practice in the era of COVID-19 pandemic was established. The protocol covered patient screening, clinic flow, required personal protective equipment and modifications of ophthalmic equipment for improved safety. CONCLUSION: Important literature emerged with respect to the practice of ophthalmology in the era of COVID-19. An evidence-based ophthalmic practice protocol was established and should be modified in the future to accommodate new insights on the COVID-19 pandemic.

Investigation of the evolution of radiation-induced lung damage using serial CT imaging and pulmonary function tests.

BACKGROUND AND PURPOSE: Radiation-induced lung damage (RILD) is a common consequence of lung cancer radiotherapy (RT) with unclear evolution over time. We quantify radiological RILD longitudinally and correlate it with dosimetry and respiratory morbidity. MATERIALS AND METHODS: CTs were available pre-RT and at 3, 6, 12 and 24-months post-RT for forty-five subjects enrolled in a phase 1/2 clinical trial of isotoxic, dose-escalated chemoradiotherapy for locally advanced non-small cell lung cancer. Fifteen CT-based measures of parenchymal, pleural and lung volume change, and anatomical distortions, were calculated. Respiratory morbidity was assessed with the Medical Research Council (MRC) dyspnoea score and spirometric pulmonary function tests (PFTs): FVC, FEV1, FEV1/FVC and DLCO. RESULTS: FEV1, FEV1/FVC and MRC scores progressively declined post-RT; FVC decreased by 6-months before partially recovering. Radiologically, an early phase (3-6 months) of acute inflammation was characterised by reversible parenchymal change and non-progressive anatomical distortion. A phase of chronic scarring followed (6-24 months) with irreversible parenchymal change, progressive volume loss and anatomical distortion. Post-RT increase in contralateral lung volume was common. Normal lung volume shrinkage correlated longitudinally with mean lung dose (r = 0.30-0.40, p = 0.01-0.04). Radiological findings allowed separation of patients with predominant acute versus chronic RILD; subjects with predominantly chronic RILD had poorer pre-RT lung function. CONCLUSIONS: CT-based measures enable detailed quantification of the longitudinal evolution of RILD. The majority of patients developed progressive lung damage, even when the early phase was absent or mild. Pre-RT lung function and RT dosimetry may allow to identify subjects at increased risk of RILD.

High-resolution Monte Carlo study of the order-parameter distribution of the three-dimensional Ising model.

We apply extensive Monte Carlo simulations to study the probability distribution P(m) of the order parameter m for the simple cubic Ising model with periodic boundary condition at the transition point. Sampling is performed with the Wolff cluster flipping algorithm, and histogram reweighting together with finite-size scaling analyses are then used to extract a precise functional form for the probability distribution of the magnetization, P(m), in the thermodynamic limit. This form should serve as a benchmark for other models in the three-dimensional Ising universality class.