Identifying early symptoms associated with a diagnosis of childhood, adolescent and young adult cancers: a population-based nested case-control study

Background: Childhood, teenage and young adult (CTYA, 0–24 years) cancers are rare and diverse, making timely diagnosis challenging. We aim to explore symptoms and symptom combinations associated with a subsequent cancer diagnosis and to establish their timeframe. Methods: Using the QResearch Database, we carried out a matched nested case-control study. Associations between pre-specified symptoms encountered in primary care and a subsequent diagnosis of any cancer were explored using conditional logistic regression. Median diagnostic intervals were used to split symptoms into “late” and “early” timeframes to identify relevant early symptoms. Results: 3186 cases and 50,576 controls were identified from a cohort of 3,424,771 CTYA. We identified 12 novel associations, of which hemiparesis [OR 90.9 (95%CI 24.7-335.1), PPV = 1.6%], testicular swelling [OR 186.7 (95%CI 86.1-404.8), PPV = 2.4%] and organomegaly [OR 221.6 (95%CI 28.3-1735.9), PPV = 5.4%] had significant positive predictive values (PPV). Limb pain, a known marker of serious illness in children, was a recurrent early symptom across cancer subtypes. Similar clinical presentations were observed across childhood and TYA cancers. Discussion: Using the largest cohort to date, we provide novel information on the time-varying predictive utility of symptoms in the diagnosis of CTYA cancers. Our findings will help to raise clinical and public awareness of symptoms, stratify those at higher-risk and ultimately aid earlier diagnosis

Employing paramagnetic shift for responsive MRI probes

Paramagnetic metal ions with anisotropic magnetic susceptibilities can shift the proton NMR signals of chelating ligands beyond the diamagnetic range of endogenous proton resonances. Such large shifts, along with enhanced longitudinal relaxation rates, allow paramagnetic complexes to be exploited as molecular imaging probes for MRI. Paramagnetically-shifted imaging probes are detected directly against zero background, as opposed to the indirect induced relaxation enhancement of surrounding water molecules, and are reviewed herein. The development of ‘smart’ probes that are sensitive to their surrounding environment is also being developed, and some of the challenges faced for in vivo imaging are discussed, including issues of sensitivity and dose, biodistribution and clearance. Several examples of lanthanide complexes have been investigated, and more recently certain paramagnetic transition metal complexes are being considered as potential imaging agents

Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis

Background: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. Aims: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. Methods: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. Results: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin’s lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin’s lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). Conclusion: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease

High-amplitude, long-term X-ray variability in the solar-type star HD 81809: the beginning of an X-ray activity cycle?

We present the initial results from our XMM program aimed at searching for X-ray activity cycles in solar-type stars. HD 81809 is a G2-type star (somewhat more evolved than the Sun, and with a less massive companion) with a pronounced 8.2 yr chromospheric cycle, as evident from from the Mt. Wilson program data. We present here the results from the initial 2.5 years of XMM observations, showing that large amplitude (a factor of approx. 10) modulation is present in the X-ray luminosity, with a clearly defined maximum in mid 2002 and a steady decrease since then. The maximum of the chromospheric cycle took place in 2001; if the observed X-ray variability is the initial part of an X-ray cycle, this could imply a phase shift between chromospheric and coronal activity, although the current descent into chromospheric cycle minimum is well reflected into the star's X-ray luminosity. The observations presented here provide clear evidence for the presence of large amplitude X-ray variability coherent with the activity cycle in the chromosphere in a star other than the Sun.Comment: Accepted for publication in A&

A 1.3 cm wavelength radio flare from a deeply embedded source in the Orion BN/KL region

Aims: Our aim was to measure and characterize the short-wavelength radio emission from young stellar objects (YSOs) in the Orion Nebula Cluster and the BN/KL star-forming region. Methods: We used the NRAO Very Large Array at a wavelength of 1.3 cm and we studied archival X-ray, infrared, and radio data. Results: During our observation, a strong outburst (flux increasing >10 fold) occurred in one of the 16 sources detected at a wavelength of 1.3cm, while the others remained (nearly) constant. This source does not have an infrared counterpart, but has subsequently been observed to flare in X-rays. Curiously, a very weak variable double radio source was found at other epochs near this position, one of whose components is coincident with it. A very high extinction derived from modeling the X-ray emission and the absence of an infrared counterpart both suggest that this source is very deeply embedded.Comment: 7 pages, 5 figures, accepted for publication in A&

The Evidence Base for Interventions Delivered to Children in Primary Care: An Overview of Cochrane Systematic Reviews

Background: As a first step in developing a framework to evaluate and improve the quality of care of children in primary care there is a need to identify the evidence base underpinning interventions relevant to child health. Our objective was to identify all Cochrane systematic reviews relevant to the management of childhood conditions in primary care and to assess the extent to which Cochrane reviews reflect the burden of childhood illness presenting in primary care.Methodology/Principal Findings: We used the Cochrane Child Health Field register of child-relevant systematic reviews to complete an overview of Cochrane reviews related to the management of children in primary care. We compared the proportion of systematic reviews with the proportion of consultations in Australia, US, Dutch and UK general practice in children. We identified 396 relevant systematic reviews; 385 included primary studies on children while 251 undertook a meta-analysis. Most reviews (n=218, 55%) focused on chronic conditions and over half (n=216, 57%) evaluated drug interventions. Since 2000, the percentage of pediatric primary care relevant reviews only increased by 2% (7% to 9%) compared to 18% (10% to 28%) in all child relevant reviews. Almost a quarter of reviews (n=78, 23%) were published on asthma treatments which only account for 3-5% of consultations. Conversely, 15-23% of consultations are due to skin conditions yet they represent only 7% (n=23) of reviews.Conclusions/Significance: Although Cochrane systematic reviews focus on clinical trials and do not provide a comprehensive picture of the evidence base underpinning the management of children in primary care, the mismatch between the focus of the published research and the focus of clinical activity is striking. Clinical trials are an important component of the evidence based and the lack of trial evidence to demonstrate intervention effectiveness in substantial areas of primary care for children should be addressed.</p

Chandra Orion Ultradeep Project: Observations and Source Lists

We present a description of the data reduction methods and the derived catalog of more than 1600 X-ray point sources from the exceptionally deep January 2003 Chandra X-ray Observatory observation of the Orion Nebula Cluster and embedded populations around OMC-1. The observation was obtained with Chandra's Advanced CCD Imaging Spectrometer (ACIS) and has been nicknamed the Chandra Orion Ultradeep Project (COUP). With an 838 ks exposure made over a continuous period of 13.2 days, the COUP observation provides the most uniform and comprehensive dataset on the X-ray emission of normal stars ever obtained in the history of X-ray astronomy.Comment: 52 pages, 11 figures, 12 tables. Accepted for publication in ApJS, special issue dedicated to Chandra Orion Ultradeep Project. A version with high quality figures can be found at http://www.astro.psu.edu/users/gkosta/COUP_Methodology.pd

An X-ray survey of low-mass stars in Trumpler 16 with Chandra

We identify and characterize low-mass stars in the ~3 Myr old Trumpler 16 (Tr16) region by means of a deep Chandra X-ray observation, and study their optical and near-IR properties. We compare X-ray activity of Tr16 stars with known characteristics of Orion and Cygnus OB2 stars. We analyzed a 88.4 ksec Chandra ACIS-I observation pointed at the center of Tr16. Because of diffuse X-ray emission, source detection was performed using the PWDetect code for two different energy ranges: 0.5-8.0 keV and 0.9-8.0 keV. Results were merged into a single final list. We positionally correlate X-ray sources with optical and 2MASS catalogues. Source events were extracted with the IDL-based routine ACIS-Extract. X-ray variability was characterized using the Kolmogorov-Smirnov test and spectra were fitted by using XSPEC. X-ray spectra of early-type, massive stars were analyzed individually. Our list of X-ray sources consists of 1035 entries, 660 of which have near-IR counterparts and are probably associated with Tr16 members. From near-IR color-color and color-magnitudes diagrams we compute individual masses of stars and their Av values. About 15% of the near-IR counterparts show disk-induced excesses. X-ray variability is found in 77 sources. X-ray emission from OB stars appear softer than the low-mass stars. The Tr16 region has a very rich population of low-mass X-ray emitting stars. An important fraction of its circumstellar disks survive the intense radiation field of its massive stars. Stars with masses 1.5-2.5 Mo display X-ray activity similar to that of stars in Cyg OB2 but much less intense than observed for Orion Nebula Cluster members.Comment: 19 pages, 3 ellectronic tables and 19 figures. Accepted for publication at the A&