Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods:Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n ¼ 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and antithyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P ¼ 0.04).Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

One of the most important aspects in the metrology of radiation fields is the problem of the measurement of dose profiles in regions where the dose gradient is large. In such zones, the 'detector size effect' may produce experimental measurements that do not correspond to reality. Mathematically it can be proved, under some general assumptions of spatial linearity, that the disturbance induced in the measurement by the effect of the finite size of the detector is equal to the convolution of the real profile with a representative kernel of the detector. In this work the exact relation between the measured profile and the real profile is shown, through the analytical resolution of the integral equation for a general type of profile fitting function using Gaussian convolution kernels.

Infants and children are a higher risk population for radiation cancer induction compared to adults. Although some values on pediatric patient doses for cardiac procedures have been reported, data to determine reference levels are scarce, especially when compared to those available for adults in diagnostic and therapeutic procedures. The aim of this study is to make a new contribution to the scarce published data in pediatric cardiac procedures and help in the determination of future dose reference levels. This paper presents a set of patient dose values, in terms of air kerma area product (KAP) and entrance surface air kerma (ESAK), measured in a pediatric cardiac catheterization laboratory equipped with a biplane x-ray system with dynamic flat panel detectors. Cardiologists were properly trained in radiation protection. The study includes 137 patients aged between 10 days and 16 years who underwent diagnostic catheterizations or therapeutic procedures. Demographic data and technical details of the procedures were also gathered. The x-ray system was submitted to a quality control programme, including the calibration of the transmission ionization chamber. The age distribution of the patients was 47 for <1 year; 52 for 1-<5 years; 25 for 5-<10 years and 13 for 10-<16 years. Median values of KAP were 1.9, 2.9, 4.5 and 15.4 Gy cm(2) respectively for the four age bands. These KAP values increase by a factor of 8 when moving through the four age bands. The probability of a fatal cancer per fluoroscopically guided cardiac procedure is about 0.07%. Median values of ESAK for the four age bands were 46, 50, 56 and 163 mGy, which lie far below the threshold for deterministic effects on the skin. These dose values are lower than those published in previous papers.

A method to carry out stoichiometric calibrations of CT scanners employed in radiotherapy treatment planning is proposed. The method is based on a simple parametrization of the CT number of a substance, which involves only two variables to describe the substance (electron density and one effective atomic number) and one parameter to describe the beam. The method was tested experimentally on a group of beams. A set of no tissue-like substances of known densities and elemental compositions were employed as calibrators. CT number-to-density curves (RED curves) were calculated with the proposed parametrization and compared to those measured with a commercial density phantom. Differences between the electron densities assigned by the calculated RED curves and the measured ones were in the range 0.009-0.019 (RMS). The proposed method may be employed to carry out accurate stoichiometric calibrations by using only one suitable substance as calibrator, not necessarily tissue-like.

Antral duplication cyst with an antral mucosal lining accounts for 2.2% of all gastric duplications, which represent 4-8% of all alimentary tract duplications. They usually become symptomatic before 2 years of age. We report a 6-year-old child with no previous history of symptoms who was admitted to our hospital because of frequent vomiting and acute abdominal pains for the previous 2 days. Abdominal examination revealed a mass in the epigastric area.

Purpose The aim of this work is to develop a sensitometry model of EBT2 and EBT3 radiochromic films based on the observation that radiation induces growth of two polymer color phases. Methods Previously published data of the active layer absorption spectrum have been used to characterize the contribution to the total absorbance of each polymer color phase. Through a prior proposed external beam therapy absorption spectrum model the total absorbance has been deconvolved into two polymer phase contributions. The integral absorbance in the visible spectrum of each color phase has been calculated and parametrized as an absorbed dose function. A sensitometry model employing linear relationships with the color phase integral absorbances has been investigated. The phase linear coefficient ratio for each color channel is proposed to be a constant. Films belonging to six different production batches, three EBT2 and three EBT3, have been used to verify this model. Results Each polymer color phase integral absorbance in the visible spectrum has been expressed as a simple saturation function of the absorbed dose to the film. The data coming from the six production batches have been fitted to the proposed sensitometry model. This model predicts the measured dose variation in the active layer light attenuation up to fluctuations attributable to uncertainties. Conclusions The calibration curve can be written as a linear combination of simple functions describing the dose dependence of the integral absorbance of each polymer color phase. These functions are characteristics of the active layer material, and not dependent on the model and production batch. According to the proposed model, to calibrate a batch in terms of the active layer light attenuation consists of determining just one linear coefficient.

Contemporary phenotypic trends associated with global change are widely documented, but whether such trends always denote trait optimization under changed conditions remains obscure. Natural selection has shaped the wings of long-distance migratory birds to minimize the costs of transport, and new optimal wing shapes could be promoted by migration patterns altered due to global change. Alternatively, wing shape could vary as a correlated response to selection on other traits favored in a changing environment, eventually moving away from the optimal shape for migration and increasing transport costs. Data from 20 yr of monitoring 2 Common Nightingale (Luscinia megarhynchos) populations breeding in central Spain, where environmental conditions for breeding have deteriorated during recent decades due to increased summer drought, show that birds have reduced wing length relative to body size over the period 1995–2014. However, long-winged nightingales survived their first round-trip migration better, and the shorter the average wing length of individuals, the stronger the survival-associated natural selection favoring longer wings. Maladaptive short wings may have arisen because the mortality costs of migration are outweighed by reproductive benefits accrued by short-winged nightingales in these populations. Assuming that the phenotypic integration of morphological and reproductive adaptations of migratory birds has a genetic basis, we hypothesize that the maladaptive trend towards shorter wings may be a correlated response to selection for moderate breeding investment in drying habitat. Our results provide evidence that contemporary phenotypic change may deviate average trait values from their optima, thereby increasing our understanding of the ecological constraints underpinning adaptation to rapid global change.

Radiochromic film in conjunction with flatbed scanners are frequently employed as dosimeters for advanced techniques in radiotherapy. Their strengths are as follows: light element composition, low energy dependence, near biological tissue equivalence and high spatial resolution. However, they have some weaknesses as well: non-uniformities, read out noise, and scanning artifacts. Several processing protocols have been proposed intending to correct the perturbations these weaknesses produce. The aim of this paper is to present a new processing protocol for radiochromic film dosimetry based on a non-local means denoising algorithm. Three dose distributions of open square fields and a spatial combination of these fields using different angles of incidence and monitor units have been employed to validate the protocol. The dose distributions are traceable to ionization chamber measurements. Additionally, a real dose distribution of a treatment was used to simulate scanning data with noise and scanning lateral artifact, and to study how the protocol behaves under these perturbations. The same measured raw data have been processed by means of an implementation of the multichannel protocol (multigaussian method). It has been found that the proposed protocol reduces dose uncertainty even though it uses fewer scans than the multichannel protocol.