sentence
stringlengths 2
660
| label
stringclasses 6
values |
---|---|
1) Abstract: | Structure |
- It is always important to also having focus on more rare etiologies of IE. | Other |
In the abstract it is stated that the mortality rate is high. | Recap |
This is suggested to be modified to: Initial descriptions of collections of IE cases with A. urinae demonstrated a high morbidity and mortality rate, whereas a recent Swedish epidemiological study could not retrieve this. | Todo |
2) Introduction: | Structure |
- Dukes criteria should be mentioned.
| Todo |
- There is not a species named Streptococcus viridans.
| Weakness |
- Recent diagnostic improvements should be included, especially MALDI-TOF mass spectrometry.
| Todo |
- a gram-positive, catalase-negative | Other |
3) Case description: | Structure |
- Specific description of PM electrode findings should be given.
| Todo |
- A more detailed disease timespan is desirable.
| Todo |
- Microbiological data are very scarce. | Weakness |
Blood-culture system and number of positive bottles should be given. | Todo |
Likewise identification criteria and susceptibility methods and results, including MIC values of relevant antibiotics should be given.
| Todo |
- A thorough microbiological examination of the manuscript seems indicated
| Todo |
- Aerococcus urinae should only be fully written the first time | Todo |
4) Discussion | Structure |
- 16S is slang: it should be partial 16S rRNA gene sequencing analysis | Todo |
Reviewer response for version 1 | Structure |
Concerning a case report of awake craniotomy in patient with cyanotic congenital heart disease (CHD). | Recap |
The authors describe an unusual case of a rather complicated and rare pathology that needs an emergency surgical intervention during a night. | Recap |
I have no specific scientific remarks concerning the content nor the design, but I think that for several reasons this case should be known by large anaesthesia community. | Other |
First, the number of patients with CHD that can be scheduled for surgery is growing so our responsibility is to know how they should be handled, why spontaneous ventilation is preferable than mechanical, for which kind of complications we should be prepared etc. | Other |
Second, we can always discuss which drugs should be used in a case of awake craniotomy, is dexmedetomidine better than other drugs? | Other |
Personal experience and a local policy should be respected in such case. | Other |
What is notable is that the authors were capable to establish, in this short time and during a night, an interdisciplinary consensus involving all disciplines, which was probably crucial to handle this case in this remarkable way. | Strength |
Reviewer response for version 1 | Structure |
This paper describes the protocol for a clinical trial releasing Wolbachia bacterium infected male and female Aedes aegypti mosquitoes in Medellín and Bello, Colombia, with the primary endpoint objective of demonstrating reduction of human dengue infections in the population living in the treated areas. | Recap |
Wolbachia infected female release over time results in replacement of the uninfected Aedes aegypti population with Wolbachia infected mosquitoes that have reduced ability to transmit arboviruses. | Other |
The study design has two components, an interrupted time series (ITS) approach using passive arboviral disease surveillance data from Bello and a large area of Medellín, and a prospective case-control in a smaller area of northeast Medellin using arbovirus laboratory test negative acute febrile illness controls in 6 early release and late release zones. | Recap |
The studies begin approximately one year after mosquito releases (in 2018 for the early release zone and 2019 for the releases outside the case-control area) to allow for mosquito population replacement. | Recap |
This study employs a novel Aedes aegypti vector control approach to address the major and growing tropical public health problem of Aedes transmitted arboviruses including dengue, Zika, and chikungunya viruses. | Recap |
The authors point out that such studies are badly needed as conventional Aedes aegypti vector control approaches have failed or been shown to be non-sustainable, and the only currently licensed dengue vaccine is partially effective and requires a laboratory test prior to immunization. | Recap |
This study protocol builds on laboratory and fieldwork in Australia and elsewhere, and is well designed and well written with considerable detail (design, statistical power and analysis, laboratory testing, data management, etc) to address the question of human arboviral disease impact of Wolbachia replacement in a highly endemic tropical urban setting in Latin America. | Strength |
The protocol is intentionally “pragmatic” to roll out the intervention at large scale under operational conditions in a timely and cost effective manner acceptable to the study community. | Recap |
The authors thus effectively answer potential criticisms of the study design not being a cluster randomized clinical trial as recommended by the WHO Vector Control Advisory Group. | Strength |
The case control study design also importantly accounts for the extent of replacement with Wolbachia infected mosquitoes in the treated area and human mobility out of the treatment area with a calculated Wolbachia exposure index calculated for each acute febrile illness patient. | Strength |
The test negative case control study design obviates the need for expensive clinical cohort follow up to monitor disease incidence and treated and untreated areas. | Strength |
The authors correctly point out that the risk estimate from the test negative case control approach is likely to be unbiased and can be used to calculate efficacy confidence limits. | Strength |
The ITS approach is a less rigorous experimental design in that the vast majority of passively reported cases are not virologically confirmed, and surveillance may not be always be done in a consistent manner, but is another practical approach using available data from the Ministry of Health that allows for monitoring of reductions in arboviral case reports over a long time period (5 years) after the Wolbachia replacement treatment during which arbovirus outbreak cycles would be expected to occur. | Other |
The discussion appropriately comments on the potential generalizability of the findings to other settings and that cost effectiveness analysis of this approach is underway. | Strength |
The following are suggestions to clarify aspects of the protocol: | Structure |
Background: | Structure |
- While Medellín is clearly highly endemic for dengue, including the historical annual average incidence of dengue would be of interest, as the case-control study will be just be done over a one year time period. | Todo |
Dengue transmission dropped to unusually low levels throughout most of South America after the Zika epidemic, and is on the increase in the region as of mid-2019. | Other |
Methods: | Structure |
- The entomologic details regarding the mosquito releases and strain(s) of Wolbachia could be expanded upon. | Todo |
What is being done differently in 2018 and 2019 compared to the 2017 releases that achieved temporary high Wolbachia prevalence?
| Todo |
- More details on the Wolbachia sampling and monitoring strategy would be helpful. | Todo |
What is the extent of the monitoring area? | Todo |
All comuna outside the case-control area? | Todo |
Checking BG traps once a week does not ensure that the mosquito specimens will be identified correctly because of damage from the trap fans to captured mosquitoes. | Weakness |
Many samples will be lost because of loss of power, ants, etc. | Other |
BG traps should be checked daily.
| Other |
- For the ITS component and the secondary endpoint of severe dengue incidence, how does the Ministry of Health define severe dengue, and has severe dengue been consistently defined over time?
| Todo |
- Regarding the case control study participant recruitment, what is the possibility that patients with acute febrile illness in the study areas will seek care in clinics outside the network?
| Todo |
- With regard to the laboratory testing algorithm to exclude potential dengue serologic positives from being control patients, the authors could more explicitly state that PanBio IgG ELISA test is designed with cutoffs to only detect high IgG titers consistent with acute secondary infections, and not past infections. | Todo |
Excluding all patients with IgG antibody due to past dengue infection in this setting would eliminate a large percentage of the potential control patients.
| Weakness |
- Consider observing changes in the vector-bacteria-virus interaction through time. | Todo |
Coevolution is likely. | Other |
Whether virus blocking ability changes over time (e.g., lowered bacteria concentration in the mosquito cells) is not clear. | Weakness |
Reviewer response for version 1 | Structure |
The paper describes protocols for assessing the efficacy of Wolbachia releases on reducing dengue incidence based on data from release trials conducted in municipalities in Columbia. | Recap |
The Wolbachia has been released into 6 adjacent zones covering a sub-area, where 3 of the zones have early releases and the other 3 have later releases – the zones which receive late releases are regarded as non-intervention arms for the purposes of the trial analysis. | Recap |
It is always difficult to measure the efficacy of vector control interventions using randomized trials because of community level effects such as herd immunity, so that the intervention has impacts on both treatments and controls, and the estimated effect of the intervention is diluted – an effect known as contamination. | Other |
In the case of Wolbachia releases, the effect is particularly difficult to quantify because the Wolbachia may spread to mosquito populations in the control arms, or Wolbachia may only have an intermediate (and variable) prevalence in the intervention arms. | Other |
The trial described in this paper has additional complications which the authors describe in the manuscript, including the non-random allocation of intervention clusters and the small size of the study area with intervention arms adjacent to control arms and no buffer between them. | Recap |
The authors explain that these limitations mean that a pragmatic approach to analysis of Wolbachia efficacy is required. | Recap |
I think the paper would benefit from a more rigorous quantitative protocol for how intervention efficacy can be quantified in the presence of contamination (see Silkey et al . | Todo |
2016, Trials 1 ). | Other |
The power calculation that the authors provide doesn’t explore impacts of contamination, or impacts of incomplete spread of Wolbachia in the intervention arm. | Weakness |
In addition the issue of herd immunity should be pointed out in the paper. | Todo |
It seems that given the configuration of the release zones, an effective Wolbachia intervention could greatly interrupt dengue transmission in the non-intervention (later release zones) as well, thus making efficacy very difficult to evaluate. | Weakness |
I find the Wolbachia Exposure Index proposed for individual participants (to account for their movements outside/into release zones) to be problematic. | Weakness |
Aedes aegypti have a very heterogeneous local distribution, and I don’t think variations in exposure can be calculated using travel histories – these estimates are likely to be misleading at best. | Weakness |
Regarding the interrupted time series approach, I think a more detailed and formal mathematical description of the method is needed, detailing the sampling distribution of the infection data with respect to the location of Wolbachia interventions, and the statistical model for handling spatiotemporal autocorrelation. | Todo |
It does not seem straightforward to distinguish the effect of Wolbachia from non-related fluctuations in disease incidence caused by environmental factors. | Weakness |
More explanation of how this will be achieved is required. | Todo |
Please put a scale on the map in Figure 1. | Todo |
Reviewer response for version 1 | Structure |
In this article, the authors Perraudeau, Risso, Street, Purdom and Dudoit present a nice workflow for normalization, dimensionality reduction, clustering, and lineage inference of single-cell RNA-seq data (scRNA-seq) using R packages from the open-source Bioconductor project. | Strength |
I enthusiastically agree with the authors on an “increasing need for workflows that integrate these tools to yield a seamless scRNA-seq data analysis pipeline” and this workflow is a great step in the right direction. | Strength |
However, I have some constructive suggestions that will better integrate other previously developed work and improve this workflow. | Other |
- In this workflow, the authors start with a count table. | Recap |
However, the majority of researchers will start with raw reads (e.g. a FASTQ file). | Other |
It would be great if the author discussed current best practices for the quantification step of scRNA-seq data. | Todo |
Alternatively, the authors could point to other references that have already been developed.
| Todo |
- I would like to see the authors take advantage of the rich functionality and data exploration tools for cell- and gene-specific quality control (QC) introduced in low-level analysis workflows such as the one from Lun et al. (2016) 1 . | Todo |
Also, in this workflow, the authors create multiple SummarizedExperiment objects (e.g. one with only the top 1000 highly variable genes (HVGs), one with all genes, etc). | Recap |
This doesn’t seem efficient, especially with large single cell data sets such as the 1.3 million cells from embryonic mouse brains. | Weakness |
I think both of these concerns can now be addressed with efforts such as the recently developed SingleCellExperiment Bioconductor object ( https://github.com/drisso/SingleCellExperiment ). | Other |
For example, the authors could add a “USE” column in the gene- or cell-specific meta table to represent whether or not a particular gene in a particular cell met the filtering criteria applied. | Todo |
The authors could store W in the reduceDim assay of the SingleCellExperiment object.
| Todo |
- In ZINB-WaVE, the authors specify the number of dimensions for the low-dimensional space (K) to be K=50. | Recap |
Could the authors add more details for the reader explaining why they picked K=50 and describe situations in which a user would want to specify a higher or lower K? | Todo |
In particular, it would be useful to discuss computational time in terms of number of genes and cells. | Todo |
Also, it would be useful to note that if you only wanted to use ZINB-WaVE to remove known covariates for normalization, you can use K=0. | Todo |
Minor comments: | Structure |
- When selecting the top 1000 HVGs, why do the authors not take into account the overall mean-variance relationship and only select genes based on the variance?
| Todo |