FoundationOne®CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the ...approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology to examine 324 cancer genes in solid tumors. F1CDx reports known and likely pathogenic short variants (SVs), copy number alterations (CNAs), and select rearrangements, as well as complex biomarkers including tumor mutational burden (TMB) and microsatellite instability (MSI), in addition to genomic loss of heterozygosity (gLOH) in ovarian cancer. CGP services can reduce the complexity of biomarker testing, enabling precision medicine to improve treatment decision-making and outcomes for cancer patients, but only if test results are reliable, accurate, and validated clinically and analytically to the highest standard available. The analyses presented herein demonstrate the extensive analytical and clinical validation supporting the F1CDx initial and subsequent FDA approvals to ensure high sensitivity, specificity, and reliability of the data reported. The analytical validation included several in-depth evaluations of F1CDx assay performance including limit of detection (LoD), limit of blank (LoB), precision, and orthogonal concordance for SVs (including base substitutions SUBs and insertions/deletions INDELs), CNAs (including amplifications and homozygous deletions), genomic rearrangements, and select complex biomarkers. The assay validation of >30,000 test results comprises a considerable and increasing body of evidence that supports the clinical utility of F1CDx to match patients with solid tumors to targeted therapies or immunotherapies based on their tumor's genomic alterations and biomarkers. F1CDx meets the clinical needs of providers and patients to receive guideline-based biomarker testing, helping them keep pace with a rapidly evolving field of medicine.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and ...dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described.
To develop an instrument based on ISTAART-AA MBI criteria.
Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults.
We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician.
The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.
General relativity
predicts that short-orbital-period binaries emit considerable amounts of gravitational radiation. The upcoming Laser Interferometer Space Antenna
(LISA) is expected to detect tens ...of thousands of such systems
but few have been identified
, of which only one
is eclipsing-the double-white-dwarf binary SDSS J065133.338+284423.37, which has an orbital period of 12.75 minutes. Here we report the discovery of an eclipsing double-white-dwarf binary system, ZTF J153932.16+502738.8, with an orbital period of 6.91 minutes. This system has an orbit so compact that the entire binary could fit within the diameter of the planet Saturn. The system exhibits a deep eclipse, and a double-lined spectroscopic nature. We see rapid orbital decay, consistent with that expected from general relativity. ZTF J153932.16+502738.8 is a strong source of gravitational radiation close to the peak of LISA's sensitivity, and we expect it to be detected within the first week of LISA observations, once LISA launches in approximately 2034.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In more academic terms, an active focus of malaria transmission is a geographical area that supports malaria transmission, where the local Anopheles population sustains the basic reproductive rate ...(R0; average number of secondary infections arising in a susceptible population as a result of a single individual with malaria over the course of their malaria infection) at a level above 1 16.\n The most inclusive approach to clear infections in humans, including those that are present at densities below the detection limit of rapid diagnostic tests or microscopy 55 is to give mass drug administration (MDA) where a full therapeutic dose of drugs are administered to a population without prior screening. Because all age groups contribute to malaria transmission 57, VIMT may need to be administered to all age groups to see an impact.
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Hospital-acquired infections with Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) infections, are a major cause of illness and death and impose serious economic costs on ...patients and hospitals. However, the recent magnitude and trend of these infections have not been reported. We used national hospitalization and resistance data to estimate the annual number of hospitalizations and deaths associated with S. aureus and MRSA from 1999 through 2005. During this period, the estimated number of S. aureus-related hospitalizations increased 62%, from 294,570 to 477,927, and the estimated number of MRSA-related hospitalizations more than doubled, from 127,036 to 278,203. Our findings suggest that S. aureus and MRSA should be considered a national priority for disease control.
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Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at ...different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR).
Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty.
An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission.
The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.
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Hugh Sturrock and colleagues discuss the role of active case detection in low malaria transmission settings. They argue that the evidence for its effectiveness is sparse and that targeted mass drug ...administration should be evaluated as an alternative or addition to active case detection. Please see later in the article for the Editors' Summary
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Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and ...scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various "Ross-Macdonald" mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955-1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention.
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In a randomized trial involving more than 2000 patients, transcatheter aortic-valve replacement was noninferior to surgical replacement in the primary end point of death from any cause or disabling ...stroke at 2 years.
Transcatheter aortic-valve replacement (TAVR) is a new therapy for patients with severe aortic stenosis who are not candidates for surgery
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Recently, increased operator experience and enhanced transcatheter valve systems have led to a worldwide trend to use TAVR in patients who are at low or intermediate risk.
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This trend has been evaluated in small . . .
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