62 research outputs found
Fast-growing pancreatic neuroendocrine carcinoma in a patient with multiple endocrine neoplasia type 1: a case report
<p>Abstract</p> <p>Introduction</p> <p>Predictive genetic screening and regular screening programs in patients with multiple endocrine neoplasia type 1 are intended to detect and treat malignant tumors at the earliest stage possible. Malignant neuroendocrine pancreatic tumors are the most frequent cause of death in these patients. However, the extent and intervals of screening in patients with multiple endocrine neoplasia type 1 are controversial as neuroendocrine tumors are usually slow growing. Here we report the case of a patient who developed a fast-growing neuroendocrine carcinoma within 15 months of a laparoscopic distal pancreatic resection.</p> <p>Case presentation</p> <p>We followed a group of 45 patients with multiple endocrine neoplasia type 1 by an annual screening program in the Department of Visceral, Thoracic, and Vascular Surgery at the University Hospital Marburg in cooperation with the Department of Radiology and the Division of Endocrinology. A man with multiple endocrine neoplasia type 1 who was diagnosed with a recurrent primary hyperparathyroidism underwent a distal pancreatic resection for a non-functional neuroendocrine tumor. In the context of our regular screening program, a large non-functional neuroendocrine tumor was diagnosed in the pancreatic head 15 months after the first pancreatic surgery. Therefore, we performed an enucleation and regional lymph node resection. At histology, the diagnosis of a neuroendocrine carcinoma with one lymph node metastasis was established. There was no evidence of recurrence 9 months after re-operation.</p> <p>Conclusion</p> <p>Fast-growing neuroendocrine tumors are rare in patients with multiple endocrine neoplasia type 1. The intervals, both postoperative and in newly diagnosed pancreatic lesions, in patients with multiple endocrine neoplasia type 1 should be reduced to 6 months to establish the early diagnosis of rapidly progressive disease in a small subset of patients.</p
The Rapidly Flaring Afterglow of the Very Bright and Energetic GRB 070125
We report on multiwavelength observations, ranging from X-ray to radio wave bands, of the IPN-localized gamma-ray burst GRB 070125. Spectroscopic observations reveal the presence of absorption lines due to O I, Si II, and C IV, implying a likely redshift of z = 1.547. The well-sampled light curves, in particular from 0.5 to 4 days after the burst, suggest a jet break at 3.7 days, corresponding to a jet opening angle of ~7.0°, and implying an intrinsic GRB energy in the 1-10,000 keV band of around Eγ = (6.3–6.9) × 1051 ergs (based on the fluences measured by the gamma-ray detectors of the IPN). GRB 070125 is among the brightest afterglows observed to date. The SED implies a host extinction of AV \u3c 0.9 mag . Two rebrightening episodes are observed, one with excellent time coverage, showing an increase in flux of 56% in ~8000 s. The evolution of the afterglow light curve is achromatic at all times. Late-time observations of the afterglow do not show evidence for emission from an underlying host galaxy or supernova. Any host galaxy would be subluminous, consistent with current GRB host galaxy samples. Evidence for strong Mg II absorption features is not found, which is perhaps surprising in view of the relatively high redshift of this burst and the high likelihood for such features along GRB-selected lines of sight
The Rapidly Flaring Afterglow of the Very Bright and Energetic GRB 070125
We report on multi-wavelength observations, ranging from the X-ray to radio
wave bands, of the IPN-localized gamma-ray burst GRB 070125. Spectroscopic
observations reveal the presence of absorption lines due to O I, Si II, and C
IV, implying a likely redshift of z = 1.547. The well-sampled light curves, in
particular from 0.5 to 4 days after the burst, suggest a jet break at 3.7 days,
corresponding to a jet opening angle of ~7.0 degrees, and implying an intrinsic
GRB energy in the 1 - 10,000 keV band of around E = (6.3 - 6.9)x 10^(51) erg
(based on the fluences measured by the gamma-ray detectors of the IPN network).
GRB 070125 is among the brightest afterglows observed to date. The spectral
energy distribution implies a host extinction of Av < 0.9 mag. Two
rebrightening episodes are observed, one with excellent time coverage, showing
an increase in flux of 56% in ~8000 seconds. The evolution of the afterglow
light curve is achromatic at all times. Late-time observations of the afterglow
do not show evidence for emission from an underlying host galaxy or supernova.
Any host galaxy would be subluminous, consistent with current GRB host-galaxy
samples. Evidence for strong Mg II absorption features is not found, which is
perhaps surprising in view of the relatively high redshift of this burst and
the high likelihood for such features along GRB-selected lines of sight.Comment: 50 pages, 9 figures, 5 tables Accepted to the Astrophysical Journa
GRB 090417B and its Host Galaxy: A Step Towards an Understanding of Optically-Dark Gamma-Ray Bursts
GRB 090417B was an unusually long burst with a T_90 duration of at least 2130
s and a multi-peaked light curve at energies of 15-150 keV. It was optically
dark and has been associated with a bright star-forming galaxy at a redshift of
0.345 that is broadly similar to the Milky Way. This is one of the few cases
where a host galaxy has been clearly identified for a dark gamma-ray burst and
thus an ideal candidate for studying the origin of dark bursts. We find that
the dark nature of GRB 090417B cannot be explained by high redshift, incomplete
observations, or unusual physics in the production of the afterglow. Assuming
the standard relativistic fireball model for the afterglow we find that the
optical flux is at least 2.5 mag fainter than predicted by the X-ray flux. The
Swift/XRT X -ray data are consistent with the afterglow being obscured by a
dense, localized sheet of dust approximately 30-80 pc from the burst along the
line of sight. Our results suggest that this dust sheet imparts an extinction
of A_V >~ 12 mag, which is sufficient to explain the missing optical flux. GRB
090417B is an example of a gamma-ray burst that is dark due to the localized
dust structure in its host galaxy.Comment: Accepted for publication in Ap
Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations
Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin
The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)
Pediatric tumors of the central nervous system are the most common cause of
cancer-related death in children. The five-year survival rate for high-grade
gliomas in children is less than 20\%. Due to their rarity, the diagnosis of
these entities is often delayed, their treatment is mainly based on historic
treatment concepts, and clinical trials require multi-institutional
collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a
landmark community benchmark event with a successful history of 12 years of
resource creation for the segmentation and analysis of adult glioma. Here we
present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which
represents the first BraTS challenge focused on pediatric brain tumors with
data acquired across multiple international consortia dedicated to pediatric
neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on
benchmarking the development of volumentric segmentation algorithms for
pediatric brain glioma through standardized quantitative performance evaluation
metrics utilized across the BraTS 2023 cluster of challenges. Models gaining
knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training
data will be evaluated on separate validation and unseen test mpMRI dataof
high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023
challenge brings together clinicians and AI/imaging scientists to lead to
faster development of automated segmentation techniques that could benefit
clinical trials, and ultimately the care of children with brain tumors
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe
A call for standardised age-disaggregated health data.
The 2030 Sustainable Development Goals agenda calls for health data to be disaggregated by age. However, age groupings used to record and report health data vary greatly, hindering the harmonisation, comparability, and usefulness of these data, within and across countries. This variability has become especially evident during the COVID-19 pandemic, when there was an urgent need for rapid cross-country analyses of epidemiological patterns by age to direct public health action, but such analyses were limited by the lack of standard age categories. In this Personal View, we propose a recommended set of age groupings to address this issue. These groupings are informed by age-specific patterns of morbidity, mortality, and health risks, and by opportunities for prevention and disease intervention. We recommend age groupings of 5 years for all health data, except for those younger than 5 years, during which time there are rapid biological and physiological changes that justify a finer disaggregation. Although the focus of this Personal View is on the standardisation of the analysis and display of age groups, we also outline the challenges faced in collecting data on exact age, especially for health facilities and surveillance data. The proposed age disaggregation should facilitate targeted, age-specific policies and actions for health care and disease management
THE NEEDLE in the 100 deg<sup>2</sup> HAYSTACK: UNCOVERING AFTERGLOWS of FERMI GRB<inf>s</inf> with the PALOMAR TRANSIENT FACTORY
The Fermi Gamma-ray Space Telescope has greatly expanded the number and energy window of observations of gamma-ray bursts (GRBs). However, the coarse localizations of tens to a hundred square degrees provided by the Fermi GRB Monitor instrument have posed a formidable obstacle to locating the bursts' host galaxies, measuring their redshifts, and tracking their panchromatic afterglows. We have built a target-of-opportunity mode for the intermediate Palomar Transient Factory in order to perform targeted searches for Fermi afterglows. Here, we present the results of one year of this program: 8 afterglow discoveries out of 35 searches. Two of the bursts with detected afterglows (GRBs 130702A and 140606B) were at low redshift (z = 0.145 and 0.384, respectively) and had spectroscopically confirmed broad-line Type Ic supernovae. We present our broadband follow-up including spectroscopy as well as X-ray, UV, optical, millimeter, and radio observations. We study possible selection effects in the context of the total Fermi and Swift GRB samples. We identify one new outlier on the Amati relation. We find that two bursts are consistent with a mildly relativistic shock breaking out from the progenitor star rather than the ultra-relativistic internal shock mechanism that powers standard cosmological bursts. Finally, in the context of the Zwicky Transient Facility, we discuss how we will continue to expand this effort to find optical counterparts of binary neutron star mergers that may soon be detected by Advanced LIGO and Virgo. © 2015. The American Astronomical Society. All rights reserved
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population
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