Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.     

Bootstrap Unit‐Root Tests: Comparison and Extensions

Abstract. In this article, we study and compare the properties of several bootstrap unit‐root tests recently proposed in the literature. The tests are Dickey–Fuller (DF) or Augmented DF, based either on residuals from an autoregression and the use of the block bootstrap or on first‐differenced data and the use of the stationary bootstrap or sieve bootstrap. We extend the analysis by interchanging the data transformations (differences vs. residuals), the types of bootstrap and the presence or absence of a correction for autocorrelation in the tests. We show that two sieve bootstrap tests based on residuals remain asymptotically valid. In contrast to the literature which focuses on a comparison of the bootstrap tests with an asymptotic test, we compare the bootstrap tests among themselves using response surfaces for their size and power in a simulation study. This study leads to the following conclusions: (i) augmented DF tests are always preferred to standard DF tests; (ii) the sieve bootstrap performs better than the block bootstrap; (iii) difference‐based tests appear to have slightly better size properties, but residual‐based tests appear more powerful.     

Analytical solutions for one-phase seepage flows impeded by wellbore seals

Steady, one-phase, plane and axisymmetric, Darcian seepage in a homogeneous rock adjacent to a partly isolated wellbore with annular seals is analytically studied. Water flows from an isobaric feeding contour and a fracture, which is kept at the same pressure as the feeding contour, to a wellbore. Partial isolation of the wellbore makes its wall a composition of intermittently arrayed no-flow boundaries, which model the wellbore seals, and isobaric surfaces, which model the annular compartments between the seals and a wellbore tubular on which the seals are mounted. Pressure drops from the aquifer (fracture) to the compartments and further to the borehole that generates a hierarchy of flows mathematically equivalent to the Toth [Freeze, R.A., Cherry, J.A., 1979. Groundwater. Prentice Hall, Englewood Cliffs] hydrogeological patterns of regional, intermediate and local groundwater flows on the scale of catchments. Conformal mappings of complex potential domains onto physical planes, where water seepage takes place, are used to tackle the fragments of the full feeding contour-fracture–sealed wellbore system. Explicit rigorous solutions for the flow characteristics (pressure and stream function) enable calculating optimal wellbore isolation with a criterion of minimal water flow rate from the fracture.     

Personality–relationship transaction in young adulthood.

Personality and social relationships were assessed twice across a 4-year period in a general population sample of 489 German young adults. Two kinds of personality–relationship transaction were observed. First, mean-level change in personality toward maturity (e.g., increase in Conscientiousness and decrease in Neuroticism) was moderated by the transition to partnership but was independent of other developmental transitions. Second, individual differences in personality traits predicted social relationships much better than vice versa. Specifically, once initial correlations were controlled for, Extraversion, Shyness, Neuroticism, self-esteem, and Agreeableness predicted change in various qualities of relationships (especially with friends and colleagues), whereas only quality of relationships with preschool children predicted later Extraversion and Neuroticism. Consequences for the transactional view of personality in young adulthood are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sympathetic response to stimulation of the pontine A5 region in conscious rabbits

OBJECT: This study is a retrospective analysis of clinical data obtained in 28 patients affected by obstructive hydrocephalus who presented with signs of midbrain dysfunction during episodes of shunt malfunction. METHODS: All patients presented with an upward gaze palsy, sometimes associated with other signs of oculomotor dysfunction. In seven cases the ocular signs remained isolated and resolved rapidly after shunt revision. In 21 cases the ocular signs were variably associated with other clinical manifestations such as pyramidal and extrapyramidal deficits, memory disturbances, mutism, or alterations in consciousness. Resolution of these symptoms after shunt revision was usually slow. In four cases a transient paradoxical aggravation was observed at the time of shunt revision. In 11 cases ventriculocistemostomy allowed resolution of the symptoms and withdrawal of the shunt. Simultaneous supratentorial and infratentorial intracranial pressure recordings performed in seven of the patients showed a pressure gradient between the supratentorial and infratentorial compartments, with a higher supratentorial pressure before shunt revision. Inversion of this pressure gradient was observed after shunt revision and resolution of the gradient was observed in one case after third ventriculostomy. In six recent cases, a focal midbrain hyperintensity was evidenced on T2-weighted magnetic resonance imaging sequences at the time of shunt malfunction. This rapidly resolved after the patient underwent third ventriculostomy. CONCLUSIONS: It is probable that in obstructive hydrocephalus, at the time of shunt malfunction, the development of a transtentorial pressure gradient could initially induce a functional impairment of the upper midbrain, inducing upward gaze palsy. The persistence of the gradient could lead to a global dysfunction of the upper midbrain. Third ventriculostomy contributes to equalization of cerebrospinal fluid pressure across the tentorium by restoring free communication between the infratentorial and supratentorial compartments, resulting in resolution of the patient's clinical symptoms.     

Spiral-CT-based assessment of tracheal stenoses using 3-D-skeletonization

PURPOSE: Demonstration of a technique for three-dimensional (3-D) assessment of tracheal-stenoses, regarding site, length and degree, based on spiral computed tomography (S-CT). PATIENTS AND METHODS: S-CT scanning and automated segmentation of the laryngo-tracheal tract (LTT) was followed by the extraction of the LTT medial axis using a skeletonization algorithm. Orthogonal to the medial axis the LTT 3-D cross-sectional profile was computed and presented as line charts, where degree and length was obtained. Values for both parameters were compared between 36 patients and 18 normal controls separately. Accuracy and precision was derived from 17 phantom studies. RESULTS: Average degree and length of tracheal stenoses was found to be 60.5% and 4.32 cm in patients compared with minor caliber changes of 8.8% and 2.31 cm in normal controls (p < 0.0001). For the phantoms an excellent correlation between the true and computed 3-D cross-sectional profile was found (p < 0.005) and an accuracy for length and degree measurements of 2.14 mm and 2.53% respectively could be determined. The corresponding figures for the precision were found to be 0.92 mm and 2.56%. CONCLUSION: LTT 3-D cross-sectional profiles permit objective, accurate and precise assessment of LTT caliber changes. Minor LTT caliber changes can be observed even in normals and, in case of an otherwise normal S-CT study, can be regarded as artifacts.