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Tackle these vocabulary basics in a short practice test: synonyms and antonyms. Synonyms are words that have a similar meaning, and antonyms are words with opposite meanings. Students in first and second grade will think deeply about word meaning as they search for the matching synonym or antonym in each row of this memorizing and writing worksheet.
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Defense lawyers say FTX founder Sam Bankman-Fried can't adequately prepare for trial in six weeks while in jail without proper access to computers, necessary medications to help him concentrate, and a better diet than bread, water and peanut butter
August 22
A rapid sputum-based test can accurately identify the presence of white blood cells by tracking their protein signatures.
Researchers have developed a new rapid sputum-based test that can identify the presence of a key driver of severe asthma, white blood cells. A simple, rapid testing device has the potential to detect key drivers of respiratory diseases, including asthma, and would Improve accessibility and efficiency in identifying patients with asthma.
The full experimental study is published in Angewandte Chemie International Edition.1
In this study, researchers aimed to develop a new sputum-based lateral flow device (LFD), similar to that of a rapid COVID-19 test, that can quickly and accurately identify eosinophils in complex biological samples, such as sputum, by tracking their protein signatures.
“This is what our collaboration set out to achieve,” said John Brennan, PhD, director of McMaster University’s Biointerfaces Institute and senior study author, in a statement.2 “This test and others like it can have the kind of lasting, meaningful impact that will Improve or even save many lives.”
White blood cells, otherwise known as eosinophils, are known to play a role in many airways diseases, including chronic cough, chronic obstructive pulmonary disease (COPD), and certain forms of vasculitis and bronchiectasis. Measurements of eosinophil peroxidase (EPX) are the most abundant and specific of eosinophil cationic proteins and a reliable identifier of eosinophil number and activity.
The researchers developed a protein-targeting element known as a DNAzyme and modified it into the rapid test. Although DNAzymes have primarily been used for detecting metals or bacterial targets, the researchers believed the new platform could be adapted to identify any material of biological origin by detecting its protein signature.
A modified version of the test acted as a bridging strand to allow capture of complimentary DNA (cDNA) modified gold nanoparticles (GNPs) onto a DNA-modified test line to identify measurements of EPX.
Thirty-eight sputum samples from patients or healthy donors were obtained using saline-induction or spontaneous expectorant. Healthy donors included nonsmokers with no known respiratory disease, infection, or symptoms who had not received any vaccination in the prior 8 weeks.
To compare the rapid test results to gold standard sputum cytometry results, the sputum plugs were collected and processed to created 2 sputum samples. One of the samples was centrifuged to remove cellular debris and the other for use with the LFD.
The DNAzyme-based LFD and fluorescence assay for detection of EPX showed good resistance to mammalian nucleases and high sensitivity and selectivity against other eosinophil proteins, including eosinophil cationic protein and eosinophil-derived neurotoxin, and neutrophil proteins, including myeloperoxidase. Furthermore, these assays were validated with patient sputum levels, reaching 100% clinical sensitivity and 96% specificity within 45 minutes.
However, the researchers acknowledge that further work needs to be done to evaluate the rapid test in a clinical setting.
Parameswaran Nair, MD, PhD
“A rapid test to detect eosinophilia would help clinicians make decisions about using drugs, such as steroids or new biologics for patients with severe asthma, and other lung diseases associated with eosinophilia, such as severe cough, and COPD,” said Parameswaran Nair, MD, PhD, professor of medicine at McMaster University and co-author of the study, in a statement.2 “It would also help to limit the unnecessary use of antibiotics.”
References
1. Ali MM, Mukherjee M, Radford K, et al. A rapid sputum‐based lateral flow assay for airway eosinophilia using an RNA‐cleaving DNAzyme selected for Eosinophil peroxidase. Angew Chem Int Ed Engl. Published online July 21, 2023. doi:10.1002/anie.202307451
2. While resolving a key asthma challenge, Hamilton researchers also create a new method to detect proteins in body fluids and other materials. News release. EurekAlert! August 1, 2023. Accessed August 23, 2023. https://www.eurekalert.org/news-releases/997344
Rapid tests are often referred to as point-of-care tests because rather than sending a blood trial to a laboratory, the test can be conducted and the result read in a doctor’s office or a community setting, without specialised laboratory equipment.
Most point-of-care tests require a tiny trial of blood (the fingertip is pricked with a lancet). Other tests require oral fluid (an absorbent pad is swabbed around the outer gums, adjacent to the teeth). They are called ‘rapid’ tests because the result can usually be given within a few minutes.
Most rapid tests detect HIV antibodies. They are not part of HIV itself, but are produced by the human body in response to HIV infection. In the weeks after exposure to HIV, the immune system recognises some components of the virus and begins to generate HIV antibodies in order to damage, neutralise or kill it (this period is known as ‘seroconversion’). These antibodies persist for life.
In contrast, the recommended laboratory tests also detect p24 antigen, a protein contained in HIV's viral core that can be detected sooner than antibodies. Most rapid tests, with the exception of the Determine HIV Early Detect and Determine HIV-1/2 cannot detect p24 antigen.
The accuracy of point-of-care tests is not always equal to those of laboratory tests, especially in relation to exact infection. This is for two main reasons:
As a result, the window period of commonly used rapid tests such as the Determine HIV Early Detect and the INSTI HIV-1/HIV-2 Antibody Test may be one to two weeks longer than for fourth-generation laboratory tests. Other rapid tests, based on older technology, may have longer window periods than this.
Rapid tests can be performed by staff with limited laboratory training. However, memorizing the test result relies on subjective interpretation, and when the result is borderline, experienced staff deliver more consistently accurate results. In a setting with low prevalence of HIV, staff may not see enough true positive samples to gain experience in interpreting test results.
It is good practice for test results to be re-read by a second member of staff, within the time frame specified on the test packaging. Organisations using point-of-care tests must maintain strong links with a pathology laboratory that provides support with clinical governance and quality assurance.
When used in a population with a low prevalence of HIV, false positive results can be a problem. The tests always produce a small number of false positive results, but in a setting where very few people have HIV, the majority of apparent positive results will in fact be incorrect. However, as the proportion of people with HIV being tested increases, the true positives start to outnumber false positives. This means it is more appropriate to use point-of-care tests in high-prevalence populations, such as with gay and bisexual men, than in the general population.
All HIV tests need to have reactive results (a preliminary positive result) confirmed with further tests. Most providers tell people who are testing that a negative result is definitive, but that a reactive result simply indicates the need for further laboratory testing.
A wide range of point-of-care tests have been manufactured in many countries, but only a few of them have been subject to rigorous, independent evaluations, and even fewer are marketed in the UK. Research on HIV tests is only occasionally published in medical journals. Informally, laboratory professionals may have insights into which tests perform best.
It is important to verify that any test used is CE marked. This should mean that the test conforms to European health and safety legislation, although it does not necessarily mean that test performance has been independently evaluated.
There are variations in accuracy from one test to another, with some older tests that are not usually marketed in the UK having a sub-optimal sensitivity and specificity. However, evaluations by the World Health Organization of several rapid diagnostic tests that either have CE marks or are approved by the US Food and Drug Administration (FDA), indicate that most are extremely accurate. The key measures of accuracy are sensitivity (the percentage of results that are correctly positive when HIV is actually present) and specificity (the percentage of results that are correctly negative when HIV is not present).
Of note, in the World Health Organization data below, most tests were performed with samples of plasma or serum. However, the tests are less sensitive when testing whole blood sampled from a finger prick. There is one test (the OraQuick Advance Rapid HIV-1/2) which can also test oral fluid samples in addition to blood.
Also, the figures on sensitivity are based on samples from people who had chronic (not recent) HIV infection, but the tests are less accurate in cases of exact infection, especially those which only detect immunoglobulin G (IgG) antibodies.
Test |
Detects |
Sensitivity |
Specificity |
---|---|---|---|
OraQuick HIV-1/2 Rapid HIV-1/2 (OraSure) |
IgG |
99.1% |
100% |
HIV 1/2 STAT-PAK (Chembio) |
IgG |
99.5% |
100% |
Determine HIV Early Detect (Abbott) | IgG + IgM + p24 | 100% | 99.4% |
Determine HIV-1/2 (Abbott) |
IgG + IgM + p24 |
100% |
98.9% |
Uni-Gold HIV (Trinity) |
IgG + IgM |
99.8% |
99.9% |
INSTI HIV-1/HIV-2 Antibody Test (bioLytical) |
IgG + IgM |
100% |
99.7% |
SD BIOLINE HIV-1/2 3.0 (Standard Diagnostics) |
IgG + IgM |
99.8% |
99.8% |
DPP® HIV 1/2 Assay (Chembio) |
IgG |
99.9% |
99.9% |
There is one rapid, point-of-care test that looks for both antibodies and p24 antigen, in a similar way to antibody/antigen laboratory tests. The Determine HIV-1/2 Ag/Ab Combo was originally introduced in 2009, with an updated version that is now called the Determine HIV Early Detect launched in Europe in 2015 (the older version is still marketed in the United States and in some parts of the world).
The promise of having a ‘fourth-generation’ point of care test that detects p24 antigen is that the window period should be shortened. However, several studies found that although the older version of this test performed well in respect of established HIV infection, its ability to detect exact HIV infection did not match that of laboratory antibody/antigen tests. The test was quite insensitive to p24 antigen, making it only marginally better than antibody-only tests in detecting acute (recent) infection.
"All HIV tests need to have reactive results (a preliminary positive result) confirmed with further tests."
The handful of studies published so far on the newer version suggests it has better performance in acute infection, although it still does not match that of antibody/antigen laboratory tests. The Determine HIV Early Detect’s sensitivity during acute infection has been variously estimated to be 28% (in three African countries), 54% (France), 65% (the Netherlands) and 88% (UK).
An analysis pooled the results of 18 separate studies in which a point-of-care test (including Determine, OraQuick, UniGold and INSTI) was compared with a more sensitive laboratory test. Compared with fourth-generation laboratory tests, the estimated sensitivity of the point-of-care tests was 94.5% (95% confidence interval 87.4-97.7) and specificity was 99.6% (99.4-99.7). Compared with RNA (viral load) tests, the estimated sensitivity was 93.7% (95% confidence interval 88.7-96.5) and specificity 98.1% (95% CI: 97.9-98.2).
Sensitivity was higher in nine studies conducted in African countries than in the nine studies conducted in the United States and other wealthy countries. This is likely to be due to different populations coming forward for screening. Whereas 4.7% of those testing positive in African studies had acute (recent) HIV infection, this figure rose to 13.6% in the high-income countries.
A study in five African countries found that the performance of point-of-care tests was sub-optimal. Samples from some countries were more likely to have false positive results than others, suggesting that tests need to be locally validated and that some tests may be more accurate in relation to some HIV subtypes than others. The researchers found a high number of false positive results, whereas false negative results were relatively rare. The specificities of the First Response HIV Card Test 1–2.0, INSTI HIV-1/HIV-2 Antibody Test, Determine HIV-1/2 and Genie Fast HIV 1/2 were all between 90 and 95%. The findings confirm that the diagnosis of HIV should not be based on results from a single HIV rapid diagnostic test. A combination of HIV tests, and more specifically an algorithm (sequence) of two or three different tests, is required to make an HIV-positive diagnosis. This is recommended in testing guidelines.
All HIV tests need to have reactive (preliminary positive) results confirmed with confirmatory tests. A particular challenge healthcare workers have with rapid tests is how to communicate a reactive result to the person testing (who may be present while the result is being read) and explain that supplementary tests are needed. These problems are less frequently faced with laboratory testing – a large enough blood trial was taken to allow for it to be tested several times and for uncertainties in the diagnosis to be resolved.
The window period refers to the time after infection and before seroconversion, during which markers of infection (p24 antigen and antibodies) are still absent or too scarce to be detectable. Tests cannot reliably detect HIV infection until after the window period has passed. All tests have a window period, which varies from test to test.
Delaney and colleagues estimated window periods for a handful of rapid tests in a 2017 study. However, all these estimates were based on testing blood plasma. In practice, tests are usually done on fingerprick blood (obtained by pricking the finger with a lancet) and the window period is likely to be several days longer.
The fourth-generation Determine HIV-1/2 Ag/Ab Combo was estimated to have a median window period of 19 days (interquartile range 15 to 25 days). This indicates that half of all infections would be detected between 15 and 25 days after exposure. Ninety-nine per cent of HIV-infected individuals would be detectable within 43 days of exposure.
The third-generation INSTI HIV-1/HIV-2 test was estimated to have a median window period of 26 days (interquartile range 22 to 31 days). This indicates that half of all infections would be detected between 22 and 31 days after exposure. Ninety-nine per cent of HIV-infected individuals would be detectable within 50 days of exposure.
Several second-generation tests, such as OraQuick Advance Rapid HIV 1/2, Clearview HIV 1/2 STAT-PACK and SURE CHECK HIV 1/2 were evaluated. The median window period was 31 days (interquartile range 26 to 37 days). This indicates that half of all infections would be detected between 26 and 37 days after exposure. Ninety-nine per cent of HIV-infected individuals would be detectable within 57 days of exposure.
UK guidelines take a cautious approach, describing the window period for all rapid, point-of-care tests as 90 days.
If you are testing with a rapid, point-of-care test and you are concerned that you may have been exposed to HIV during the test’s window period, you could also be tested with a fourth-generation laboratory test. This requires a blood sample, taken through a needle from a vein in the arm, which is tested in a laboratory using a more sensitive test. The results should be available after a few days.
Performance of rapid tests is poorer in a number of situations. Results may not be accurate.
There are three possible test results:
1) Negative (may also be described as ‘non-reactive’). The test did not find any evidence of HIV infection. You probably don’t have HIV (so long as you aren’t testing in one of the situations described in the last section).
2) Reactive (often incorrectly described as ‘positive’ by manufacturers). The test assay has reacted to a substance in your blood. This does not necessarily mean that you are HIV positive. It means you need to take more tests to confirm the result. These extra tests are best done at a healthcare facility where they have access to the most accurate HIV testing technologies.
3) ‘Indeterminate’, ‘equivocal’ or ‘invalid’. The test result is unclear. Another test needs to be done.
The questions that follow are designed to make prospective students aware of the mathematics background required for those intending to take one of the SFU Calculus courses: MATH 150, 151, 154 or 157. The genuine test will cover the same concepts as this practice test does, but the questions will be different. For more information about the expectations, read Calculus Readiness Test Assessment Topics.
If you do not achieve a passing score on the genuine test, we recommend that you enroll in Math 100 course, Precalculus.
Treat the Practice Calculus Readiness Test as a learning experience: if your answer to a question is incorrect, make sure that you understand the concept the question is related to before attempting the genuine test.
You should be aware of the following conditions when you attempt this practice test:
The questions that follow are designed to make prospective students aware of the mathematics background required for those intending to take courses that are designated as Quantitative/Analytical (Q courses). The genuine test will cover the same concepts as this practice test does, but the questions will be different. For more information about the expectations, read Q Assessment Topics.
If you do not achieve a passing score on the genuine test, you will be required to enroll in and pass the course FAN X99: Foundations of Analytical and Quantitative Reasoning prior to taking any Q courses at SFU.
You should be aware of the following conditions when you attempt this practice test:
What does a scale measure? What are the different units of measurement? Which animal weighs less than a pound? Use this review worksheet to get your second graders thinking about length, weight, and volume. This worksheet may look like a measurement practice test, but it’s also a great way to start a conversation about important math concepts.
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