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"Kramer, C."
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Modeling influenza seasonality in the tropics and subtropics
Climate drivers such as humidity and temperature may play a key role in influenza seasonal transmission dynamics. Such a relationship has been well defined for temperate regions. However, to date no models capable of capturing the diverse seasonal pattern in tropical and subtropical climates exist. In addition, multiple influenza viruses could cocirculate and shape epidemic dynamics. Here we construct seven mechanistic epidemic models to test the effect of two major climate drivers (humidity and temperature) and multi-strain co-circulation on influenza transmission in Hong Kong, an influenza epidemic center located in the subtropics. Based on model fit to long-term influenza surveillance data from 1998 to 2018, we found that a simple model incorporating the effect of both humidity and temperature best recreated the influenza epidemic patterns observed in Hong Kong. The model quantifies a bimodal effect of absolute humidity on influenza transmission where both low and very high humidity levels facilitate transmission quadratically; the model also quantifies the monotonic but nonlinear relationship with temperature. In addition, model results suggest that, at the population level, a shorter immunity period can approximate the co-circulation of influenza virus (sub)types. The basic reproductive number R 0 estimated by the best-fit model is also consistent with laboratory influenza survival and transmission studies under various combinations of humidity and temperature levels. Overall, our study has developed a simple mechanistic model capable of quantifying the impact of climate drivers on influenza transmission in (sub)tropical regions. This model can be applied to improve influenza forecasting in the (sub)tropics in the future.
Journal Article
The prognostic value of tumour–stroma ratio in primary breast cancer with special attention to triple-negative tumours: a review
PurposeThere is a strong need to improve the prognostication of breast cancer patients in order to prevent over- and undertreatment, especially when considering adjuvant chemotherapy. Tumour stroma characteristics might be valuable in predicting disease progression.MethodsStudies regarding the prognostic value of tumour–stroma ratio (TSR) in breast cancer are evaluated.ResultsA high stromal content is related to a relatively poor prognosis. The most pronounced prognostic effect of this parameter seems to be observed in the triple-negative breast cancer (TNBC) subtype.ConclusionsTSR assessment might represent a simple, fast and reproducible prognostic factor at no extra costs, and could possibly be incorporated into routine pathological diagnostics. Despite these advantages, a robust clinical validation of this parameter has yet to be established in prospective studies.
Journal Article
Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X
Females have a greater immunological advantage than men, yet they are more prone to autoimmune disorders. The basis for this sex bias lies in the X chromosome, which contains many immunity-related genes. Femalemammals use X chromosome inactivation (XCI) to generate a transcriptionally silent inactive X chromosome (Xi) enriched with heterochromatic modifications and XIST/Xist RNA, which equalizes gene expression between the sexes. Here, we examine the maintenance of XCI in lymphocytes from females in mice and humans. Strikingly, we find that mature naïve T and B cells have dispersed patterns of XIST/Xist RNA, and they lack the typical heterochromatic modifications of the Xi. In vitro activation of lymphocytes triggers the return of XIST/Xist RNA transcripts and some chromatin marks (H3K27me3, ubiquitin-H2A) to the Xi. Single-cell RNA FISH analysis of female T cells revealed that the X-linked immunity genes CD40LG and CXCR3 are biallelically expressed in some cells. Using knockout and knockdown approaches, we find that Xist RNA-binding proteins, YY1 and hnRNPU, are critical for recruitment of XIST/Xist RNA back to the Xi. Furthermore, we examined B cells from patients with systemic lupus erythematosus, an autoimmune disorder with a strong female bias, and observed different XIST RNA localization patterns, evidence of biallelic expression of immunity-related genes, and increased transcription of these genes. We propose that the Xi in female lymphocytes is predisposed to become partially reactivated and to overexpress immunity-related genes, providing the first mechanistic evidence to our knowledge for the enhanced immunity of females and their increased susceptibility for autoimmunity.
Journal Article
Development and validation of influenza forecasting for 64 temperate and tropical countries
Accurate forecasts of influenza incidence can be used to inform medical and public health decision-making and response efforts. However, forecasting systems are uncommon in most countries, with a few notable exceptions. Here we use publicly available data from the World Health Organization to generate retrospective forecasts of influenza peak timing and peak intensity for 64 countries, including 18 tropical and subtropical countries. We find that accurate and well-calibrated forecasts can be generated for countries in temperate regions, with peak timing and intensity accuracy exceeding 50% at four and two weeks prior to the predicted epidemic peak, respectively. Forecasts are significantly less accurate in the tropics and subtropics for both peak timing and intensity. This work indicates that, in temperate regions around the world, forecasts can be generated with sufficient lead time to prepare for upcoming outbreak peak incidence.
Journal Article
Carbon criminals, climate crimes
Carbon Criminals, Climate Crimes analyzes the looming threats posed by climate change from a criminological perspective. It advances the field of green criminology through a examination of the criminal nature of catastrophic environmental harms resulting from the release of greenhouse gases. The book describes and explains what corporations in the fossil fuel industry, the U.S. government, and the international political community did, or failed to do, in relation to global warming. Carbon Criminals, Climate Crimes integrates research and theory from a wide variety of disciplines, to analyze four specific state-corporate climate crimes: continued extraction of fossil fuels and rising carbon emissions; political omission (failure) related to the mitigation of these emissions; socially organized climate change denial; and climate crimes of empire, which include militaristic forms of adaptation to climate disruption. The final chapter reviews policies that could mitigate greenhouse gas emissions, adapt to a warming world, and achieve climate justice.
eBook
Probiotics, Nutrition, and the Small Intestine
Purpose of Review
Probiotics are promising remedial treatments for symptoms of small intestine (SI) diseases and promoters of overall good health. Probiotics play an important role in supporting a healthy SI microbiome (eubiosis), and in preventing establishment of unhealthy microbiota. SI eubiosis promotes optimal nutrient uptake, and optimal nutritional status maintains a healthy SI, reducing the likelihood of SI diseases. It is important to understand the advantages and limitations of probiotic therapies.
Recent Findings
Microbial dysbiosis decreases the capacity of the small bowel to utilize and absorb dietary compounds. In some studies, probiotic supplements containing lactic acid bacteria and
Bifidobacterium
have been demonstrated effective in supporting beneficial microbes in the SI while improving barrier integrity and reducing nutrient malabsorption and SI disease-related pathology.
Summary
Strain-specific probiotic therapy may be a natural and effective approach to restoring SI barrier integrity and eubiosis, resulting in improved nutrient absorption and better health, including reducing the incidence of and severity of SI diseases.
Journal Article
Characterizing the interactions between influenza and respiratory syncytial viruses and their implications for epidemic control
Pathogen-pathogen interactions represent a critical but little-understood feature of infectious disease dynamics. In particular, experimental evidence suggests that influenza virus and respiratory syncytial virus (RSV) compete with each other, such that infection with one confers temporary protection against the other. However, such interactions are challenging to study using common epidemiologic methods. Here, we use a mathematical modeling approach, in conjunction with detailed surveillance data from Hong Kong and Canada, to infer the strength and duration of the interaction between influenza and RSV. Based on our estimates, we further utilize our model to evaluate the potential conflicting effects of live attenuated influenza vaccines (LAIV) on RSV burden. We find evidence of a moderate to strong, negative, bidirectional interaction, such that infection with either virus yields 40-100% protection against infection with the other for one to five months. Assuming that LAIV reduces RSV susceptibility in a similar manner, we predict that the impact of such a vaccine at the population level would likely depend greatly on underlying viral circulation patterns. More broadly, we highlight the utility of mathematical models as a tool to characterize pathogen-pathogen interactions.
Influenza viruses and respiratory syncytial viruses may interfere with one another. Here, authors fit mathematical models of virus transmission, and find evidence of a bidirectional, moderate to strong, long-lasting interaction effect.
Journal Article
Forecasting influenza in Europe using a metapopulation model incorporating cross-border commuting and air travel
Past work has shown that models incorporating human travel can improve the quality of influenza forecasts. Here, we develop and validate a metapopulation model of twelve European countries, in which international translocation of virus is driven by observed commuting and air travel flows, and use this model to generate influenza forecasts in conjunction with incidence data from the World Health Organization. We find that, although the metapopulation model fits the data well, it offers no improvement over isolated models in forecast quality. We discuss several potential reasons for these results. In particular, we note the need for data that are more comparable from country to country, and offer suggestions as to how surveillance systems might be improved to achieve this goal.
Journal Article
Video Feedback in Education and Training: Putting Learning in the Picture
This meta-analysis demonstrates that the video feedback method has a statistically significant effect on the interaction skills of professionals in a range of contact professions. The aggregate effect, calculated on the basis of 217 experimental comparisons from 33 experimental studies involving a total of 1,058 people, was 0.40 standard deviation (SE=0.07). The effects of training were greater for programs working with a standard observation form of target skills that were central to the program. Results were more positive for outcome measures that measured positive skills rather than negative ones. In addition, molar outcome measures, which were obtained by means of an assessment scale, showed larger effects than micromeasures, which were scored using event sampling. Finally, recommendations are made for video feedback design and for future research.
Journal Article