The Global Stratotype Section and Point (GSSP) of the Serravallian Stage (Middle Miocene)

The Global Stratotype Section and Point (GSSP) for the Base of the Serravallian Stage (Middle Miocene) is defined in the Ras il Pellegrin section located in the coastal cliffs along the Fomm Ir-Rih Bay on the west coast of Malta (35°54'50"N, 14°20'10"E). The GSSP is at the base of the Blue Clay Formation (i.e., top of the transitional bed of the uppermost Globigerina Limestone). This boundary between the Langhian and Serravallian stages coincides with the end of the major Mi-3b global cooling step in the oxygen isotopes and reflects a major increase in Antarctic ice volume, marking the end of the Middle Miocene climate transition and the Earth's transformation into an "Icehouse" climate state. The associated major glacio-eustatic sea-level drop corresponds with sequence boundary Ser1 of Hardenbol et al. (1998) and supposedly with the TB2.5 sequence boundary of Haq et al (1987). This event is slightly older than the last common and/or continuous occurrence of the calcareous nannofossil Sphenolithus heteromorphus, previously considered as guiding criterion for the boundary, and is projected to fall within the younger half of Chron C5ACn. The GSSP level is in full agreement with the definitions of the Langhian and Serravallian in their respective historical stratotype sections in northern Italy and has an astronomical age of 13.82 Ma

Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo

The secreted MIA protein is strongly expressed by advanced primary and metastatic melanomas but not in normal melanocytes. Previous studies have shown that MIA serum levels correlate with clinical tumour progression in melanoma patients. To provide direct evidence that MIA plays a role in metastasis of malignant melanomas, A-mel 3 hamster melanoma cells were transfected with sense- and antisense rhMIA cDNA and analysed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MIA in A-mel 3 cells significantly increased their metastatic potential without affecting primary tumour growth, cell proliferation or apoptosis rate in hamsters, compared with control or antisense transfected cells. Additionally, MIA overexpressing transfectants showed a higher rate of both tumour cell invasion and extravasation. Cells transfected with MIA antisense generally exerted an opposite response. The above changes in function attributed to the expression of MIA may underlie the contribution of MIA to the malignant phenotype. © 2000 Cancer Research Campaig

Maximal regularity for non-autonomous equations with measurable dependence on time

In this paper we study maximal $L^p$-regularity for evolution equations with time-dependent operators $A$. We merely assume a measurable dependence on time. In the first part of the paper we present a new sufficient condition for the $L^p$-boundedness of a class of vector-valued singular integrals which does not rely on H\"ormander conditions in the time variable. This is then used to develop an abstract operator-theoretic approach to maximal regularity. The results are applied to the case of $m$-th order elliptic operators $A$ with time and space-dependent coefficients. Here the highest order coefficients are assumed to be measurable in time and continuous in the space variables. This results in an $L^p(L^q)$-theory for such equations for $p,q\in (1, \infty)$. In the final section we extend a well-posedness result for quasilinear equations to the time-dependent setting. Here we give an example of a nonlinear parabolic PDE to which the result can be applied.Comment: Application to a quasilinear equation added. Accepted for publication in Potential Analysi

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types

Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway

BACKGROUND: Acute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints. METHODS: 57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit. RESULTS: The children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups. CONCLUSION: Children hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis