Practical 1: Paper Review Flashcards
What are impact factors?
Impact factors are used to measure the importance of a journal by calculating the number of times selected articles are cited within the last few years.
The higher the impact factor, the more highly ranked the journal
Define impact factor
It is the average number of citations per paper published in that journal during the two preceding years
How is impact factor calculated?
A = the number of times articles published in 2022 and 2023 were cited by indexed journals during 2024
B = the total number of “citable items” published by that journal in 2022 and 2023
=> 2024IF = A/B
Explain in your own words how impact factor is calculated
The number of times articles ppublished in a specific journal have been cited in the past two years divided by the overall number of articles published in that journal in the past two years
What is a review article
An attempt to sum up the current thinking on topic
They are usually written by an expert in the field
They contain information such as:
- main people working in the field
- recent advances and discoveries
- significant gaps in the field
- current debates
- ideas of where the research may go next
What are the six steps to submitting a paper?
Drafted by a corresponding author
Approved by the other authors
Submitted electronically (including references, images, supplemental data etc)
Review by scientist in the field (peer reviewed)
Accepted/accepted with changes/rejected
Correct and resubmission
What are the different organisational components of a paper?
IMRAD (introduction, materials, results and discussion)
Also; title, abstract, authors, acknowledgements, declarations, references
Tables, figures, legends, online supplemental material (usually gross data, genes etc)
What is an introduction to a paper
A background to the work and the rationale for the study
What is the materials/methods of a paper?
A description of the work undertook - should be in sufficient detail to repeat experiment
What is the results of a paper?
Report of the data generated, graphs etc
What is the discussion of a paper?
What are the significance of the results
What is their context with the wider literature
What is a p-value?
A measure of how likely the result you obtained is by random chance
p=1 would be random chance
p=0.00001 would be very unlikely to be random chance
What is usually our p-value cut off?
p<0.05 for p-value results
This means we can be 95% sure that the results are real
What are three characteristics of a good paper?
They should progress logically
They should not be cluttered with acronyms and jargon
They should be clear about methods employed
What are four characteristics of good study design?
High number of subjects or high numbers of replicated experiments
Correct controls (positive and negative)
Double-blind, placebo controlled drug tests
Correct randomisation
What are five signs of a bad paper
Information delivery failure - incomprehensible, badly written, needlessly complicated
A lack of evidence for the hypothesis. Was the theory tested using only one kind of approach or was it repeated too few times?
Novelty - a paer must present something new and timely
Ease of replicatoin - sufficient detail presented such that others could reproduce the experiments
Outrageous hypotheses - making too much of these results
What two drugs did our paper look at?
Basiliximab
Alemtuzumab
What is Basiliximab, how does it work?
It is a monoclonal antibody which binds and blocks the interleukin-2 receptor located on the surface of activated T lymphocytes
It prevents binding of IL-2 to the IL-2-R of CD4 T cells (which normally supports the development and homeostasis of regulatory T cells)
What is Alemtuzumab, how does it work?
Alemtuzumab is a depleting agent i.e. it kills cells
It binds to CD-52 on CD4 T-cells -> it kills T cells (lyses lymphocytes)
Binding to CD-52 on CD4 T cells brings about complement activation result in cell lysis - preventing rejection but has bad renal side effects
How was rejection monitored in the patients in our paper?
Flow cytometric measurement of de novo HLA class I and II donor-specific antibodies at 4 months and 1 year post transplant
Serum creatinine levels, creatinine clearance from 24hour urine and kidney biopsies for C4d at 4months and 1 year post trasnplant
How are DSAs measured using flow cytometry?
EDTA treated serum sample
Looking for IgG antibodies against HLA class I and II using LABScreen single antigen beads
Explain how microbeads are used to measue anti-HLA antibodies using flow cytometry
Microbeads are coated with 100 purified HLA class I or II antigens and preoptimised reagents to detect HLA antibodies in human serum
A negative control serum is used to establish the background value for each bead in a test batch
Test serum is incubated with the coated LABScreen beads
If any HLA natibodies are present in the test serum they will bind to the antigens on the beads
The antibodies are then labelled with PE-conjugated goat anti-human igG (fluorescentl labelled AHG)
The LABScan flow analyser simultaneously detects the fluorescent emission of PE and a specific dye signature from each bead -> allows us to simultaneously identify what HLA antigen has bound (which bead) and if DSA is present (antibody binding)
What are DSAa?
Donor specific antibodies
Anti HLA antibodies formed against MHC I or II
How do we know if the anti-HLA antibodies present are against MHC I or II?
We can only find out by separatin the lymphocytes of a blood sample into T lymphs (MHCI) and B lymphs (MHCI and II)
If binding only occurs with B lymphs then we know its only anti-HLA antibodies agains MHC II
If binding occurs in T lymphs only we know its only anti-HLA antibodies against mHC I
If binding occurs in both we know there is definitely anti-HLA against MHC I but cannot confirm anti-MHC class II
What do we use anti-C4d as an indicator of rejection in tissues?
C4d is a deposited product of complement
C4d is very stable and is therefore a good IHC target
What is the prozone effect?
This is interference caused by very high levels of antibodies
So positive the sample is negative upon addition of AHG
- so much binding occurs that there is no room form cross binding for agglutination etc
What is an induction therapy?
An immunosuprresive therapy administered at time of transplant to reduce rejection
What were the concluions of the paper?
Basilizimab treated patients did not produce DSAs after 1 year of treatment, while 20% of Alemtuzumab patients did
There was no difference between kidney function results or C4d deposition
What is PRA?
Pannel reactive antibody
It is expressed as a % of population against which the recipient has DSA against
e.g. 20% PRA means the recipient produces antibodies against 20% of the population
What is KDPI
Kidney donor profile index
a numerical measure that combines ten donor factors, including clinical parameters and demographics, to summarize into a single number the quality of deceased donor kidneys relative to other recovered kidneys
A measure of how a kidney will function post transplant
What does a KDPI of 20 mean?
It means the kidney will function better than 80% of transplanted kidneys
You want a lot KDPI
What does a KDPI of 20 mean?
It means the kidney will function better than 80% of transplanted kidneys
You want a lot KDPI
