The advent of effective adjuvant therapies for patients with resected melanoma has highlighted the need to stratify patients based on risk of relapse given the cost and toxicities associated with ...treatment. Here we assessed circulating tumor DNA (ctDNA) to predict and monitor relapse in resected stage III melanoma.
Somatic mutations were identified in 99/133 (74%) patients through tumor tissue sequencing. Personalized droplet digital PCR (ddPCR) assays were used to detect known mutations in 315 prospectively collected plasma samples from mutation-positive patients. External validation was performed in a prospective independent cohort (n=29).
ctDNA was detected in 37 of 99 (37%) individuals. In 81 patients who did not receive adjuvant therapy, 90% of patients with ctDNA detected at baseline and 100% of patients with ctDNA detected at the postoperative timepoint relapsed at a median follow up of 20months. ctDNA detection predicted patients at high risk of relapse at baseline relapse-free survival (RFS) hazard ratio (HR) 2.9; 95% confidence interval (CI) 1.5–5.6; P=0.002 and postoperatively (HR 10; 95% CI 4.3–24; P<0.001). ctDNA detection at baseline HR 2.9; 95% CI 1.3–5.7; P=0.003 and postoperatively (HR 11; 95% CI 4.3–27; P<0.001 was also associated with inferior distant metastasis-free survival (DMFS). These findings were validated in the independent cohort. ctDNA detection remained an independent predictor of RFS and DMFS in multivariate analyses after adjustment for disease stage and BRAF mutation status.
Baseline and postoperative ctDNA detection in two independent prospective cohorts identified stage III melanoma patients at highest risk of relapse and has potential to inform adjuvant therapy decisions.
The 1.28 GHz MeerKAT Galactic Center Mosaic Heywood, I.; Rammala, I.; Camilo, F. ...
Astrophysical journal/The Astrophysical journal,
02/2022, Letnik:
925, Številka:
2
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Abstract
The inner ∼200 pc region of the Galaxy contains a 4 million M
⊙
supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic-ray energy densities ...that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation-driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total-intensity and spectral-index mosaics of the region from 20 pointings (144 hr on-target in total), covering 6.5 square degrees with an angular resolution of 4″ at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT’s high sensitivity, exceptional
u
,
v
-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new nonthermal filament complexes, and enhanced views of the Radio Arc bubble, Sagittarius A, and Sagittarius B regions. This project is a South African Radio Astronomy Observatory public legacy survey, and the image products are made available with this article.
The 1.28 GHz MeerKAT DEEP2 Image Cotton, W. D.; Matthews, A. M.; Abbott, T. D. ...
Astrophysical journal/The Astrophysical journal,
01/2020, Letnik:
888, Številka:
2
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We present the confusion-limited 1.28 GHz MeerKAT DEEP2 image covering one primary-beam area with θ = 7 6 FWHM resolution and rms noise. Its J2000 center position = 04h 13m 26 4, δ = −80° 00′ 00″ was ...selected to minimize artifacts caused by bright sources. We introduce the new 64-element MeerKAT array and describe commissioning observations to measure the primary-beam attenuation pattern, estimate telescope pointing errors, and pinpoint (u, v) coordinate errors caused by offsets in frequency or time. We constructed a 1.4 GHz differential source count by combining a power-law count fit to the DEEP2 confusion P(D) distribution from 0.25 to 10 Jy with counts of individual DEEP2 sources between 10 Jy and 2.5 mJy. Most sources fainter than S ∼ 100 Jy are distant star-forming galaxies (SFGs) obeying the far-IR/radio correlation, and sources stronger than 0.25 Jy account for ∼93% of the radio background produced by SFGs. For the first time, the DEEP2 source count has reached the depth needed to reveal the majority of the star formation history of the universe. A pure luminosity evolution of the 1.4 GHz local luminosity function consistent with the Madau & Dickinson model for the evolution of SFGs based on UV and infrared data underpredicts our 1.4 GHz source count in the range .
The construction of the seven-dish Karoo Array Telescope (KAT-7) array in the Karoo region of the Northern Cape in South Africa was intended primarily as an engineering prototype for technologies and ...techniques applicable to the MeerKAT telescope. This paper looks at the main engineering and scientific highlights from this effort, and discusses their applicability to both MeerKAT and other next-generation radio telescopes. In particular, we found that the composite dish surface works well, but it becomes complicated to fabricate for a dish lacking circular symmetry; the Stirling cycle cryogenic system with ion pump to achieve vacuum works but demands much higher maintenance than an equivalent Gifford–McMahon cycle system; the ROACH (Reconfigurable Open Architecture Computing Hardware)-based correlator with SPEAD (Streaming Protocol for Exchanging Astronomical Data) protocol data transfer works very well and KATCP (Karoo Array Telescope Control Protocol) control protocol has proven very flexible and convenient. KAT-7 has also been used for scientific observations where it has a niche in mapping low surface-brightness continuum sources, some extended H i
haloes and OH masers in star-forming regions. It can also be used to monitor continuum source variability, observe pulsars, and make Very Long Baseline Interferometry observations.
Highlights • HR-HPV urine test shows high sensitivity (90%) for CIN2+ detection in pilot study. • CIN2+ detection is similar in urine, physician- and self-collected genital samples. • HR-HPV ...detection is similar in first void and initial stream urine collected later. • Unfractionated and pellet urine fractions have similar HR-HPV detection. • Women prefer urine collection versus self-collection for HR-HPV testing.
Precision medicine is rapidly evolving within the field of oncology and has brought many new concepts and terminologies that are often poorly defined when first introduced, which may subsequently ...lead to miscommunication within the oncology community. The European Society for Medical Oncology (ESMO) recognises these challenges and is committed to support the adoption of precision medicine in oncology. To add clarity to the language used by oncologists and basic scientists within the context of precision medicine, the ESMO Translational Research and Personalised Medicine Working Group has developed a standardised glossary of relevant terms.
Relevant terms for inclusion in the glossary were identified via an ESMO member survey conducted in Autumn 2016, and by the ESMO Translational Research and Personalised Medicine Working Group members. Each term was defined by experts in the field, discussed and, if necessary, modified by the Working Group before reaching consensus approval. A literature search was carried out to determine which of the terms, ‘precision medicine’ and ‘personalised medicine’, is most appropriate to describe this field.
A total of 43 terms are included in the glossary, grouped into five main themes—(i) mechanisms of decision, (ii) characteristics of molecular alterations, (iii) tumour characteristics, (iv) clinical trials and statistics and (v) new research tools. The glossary classes ‘precision medicine’ or ‘personalised medicine’ as technically interchangeable but the term ‘precision medicine’ is favoured as it more accurately reflects the highly precise nature of new technologies that permit base pair resolution dissection of cancer genomes and is less likely to be misinterpreted.
The ESMO Precision Medicine Glossary provides a resource to facilitate consistent communication in this field by clarifying and raising awareness of the language employed in cancer research and oncology practice. The glossary will be a dynamic entity, undergoing expansion and refinement over the coming years.
Invasive alien species (IAS) pose a key threat to biodiversity, the economy and human well-being, and continue to increase in abundance and impact worldwide. Legislation and policy currently dominate ...the global agenda for IAS, although translation to localised success may be limited. This calls for a wider range of responses to transform IAS management. An under-appreciated strategy to achieve success may come from bottom-up, experimental innovations (so-called “seeds”), which offer alternative visions of what may be possible for IAS management in the future. We present an application of a participatory process that builds on such innovations to create alternative visions of the future, with actionable pathways to guide change. Through a series of workshops with practitioners and academics, we used this process to explore alternative positive futures for IAS management in South Africa. We then identified a set of domains of change, that could enable these visions to be actioned by appropriate stakeholders. The domains of change highlight the social–ecological nature of the IAS sector, with interconnected actions needed in financial, cultural, social, technological and governance spheres. Key domains identified were the need to shift mindsets and values of society regarding IAS, as well as the need for appropriate and functional financing. This participatory futuring process offers a way to interrogate and scale bottom-up innovations, thereby creating optimism and allowing stakeholders to engage constructively with the future. This represents an important step in fostering the potential of bottom-up innovations to transform IAS management.
Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, ...management of TB infection (TBI) and implementation of TPT.
A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.
Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.
This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.
Vera Rubin ridge (VRR) is an erosion-resistant feature on the northwestern slope of Mount Sharp in Gale crater, Mars, and orbital visible/short-wave infrared measurements indicate it contains ...red-colored hematite. The Mars Science Laboratory Curiosity rover performed an extensive campaign on VRR to study its mineralogy, geochemistry, and sedimentology to determine the depositional and diagenetic history of the ridge and constrain the processes by which the hematite could have formed. X-ray diffraction (XRD) data from the CheMin instrument of four samples drilled on and below VRR demonstrate differences in iron, phyllosilicate, and sulfate mineralogy and hematite grain size. Hematite is common across the ridge, and its detection in a gray-colored outcrop suggested localized regions with coarse-grained hematite, which commonly forms from warm fluids. Broad XRD peaks for hematite in one sample below VRR and the abundance of FeOT in the amorphous component suggest the presence of nano-crystalline hematite and amorphous Fe oxides/oxyhydroxides. Well-crystalline akaganeite and jarosite are present in two samples drilled from VRR, indicating at least limited alteration by acid-saline fluids. Collapsed nontronite is present below VRR, but samples from VRR contain phyllosilicate with d(001) = 9.6 Å, possibly from ferripyrophyllite or an acid-altered smectite. The most likely cementing agents creating the ridge are hematite and opaline silica. We hypothesize late diagenesis can explain much of the mineralogical variation on the ridge, where multiple fluid episodes with variable pH, salinity, and temperature altered the rocks, causing the precipitation and crystallization of phases that are not otherwise in equilibrium.
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