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A classic example of microbiome function is its role in nutrient assimilation in both plants and animals, but other less obvious roles are becoming more apparent, particularly in terms of driving infectious and non-infectious disease outcomes and influencing host behaviour. However, numerous biotic and abiotic factors influence the composition of these communities, and host microbiomes can be susceptible to environmental change. How microbial communities will be altered by, and mitigate, the rapid environmental change we can expect in the next few decades remain to be seen. That said, given the enormous range of functional diversity conferred by microbes, there is currently something of a revolution in microbial bioengineering and biotechnology in order to address real-world problems including human and wildlife disease and crop and biofuel production. All of these concepts are explored in further detail throughout the book.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.
Target-based approaches for human African trypanosomiasis (HAT) and related parasites can be a valuable route for drug discovery for these diseases. However, care needs to be taken in selection of both the actual drug target and the chemical matter that is developed. In this article, potential criteria to aid target selection are described. Then the physiochemical properties of typical oral drugs are discussed and compared to those of known anti-parasitics.
Evidence has grown supporting the role for short sleep duration as an independent risk factor for weight gain and obesity. The purpose of the present study was to examine the relationship between sleep duration and dietary quality in European adolescents. The sample consisted of 1522 adolescents (aged 12·5–17·5 years) participating in the European multi-centre cross-sectional ‘Healthy Lifestyle in Europe by Nutrition in Adolescence’ study. Sleep duration was estimated by a self-reported questionnaire. Dietary intake was assessed by two 24 h recalls. The Diet Quality Index for Adolescents with Meal index (DQI-AM) was used to calculate overall dietary quality, considering the components dietary equilibrium, dietary diversity, dietary quality and a meal index. An average sleep duration of ≥ 9 h was classified as optimal, between 8 and 9 h as borderline insufficient and < 8 h as insufficient. Sleep duration and the DQI-AM score were positively associated (β = 0·027, r 0·130, P< 0·001). Adolescents with insufficient (62·05 (sd 14·18)) and borderline insufficient sleep (64·25 (sd 12·87)) scored lower on the DQI-AM than adolescents with an optimal sleep duration (64·57 (sd 12·39)) (P< 0·001; P= 0·018). The present study demonstrated in European adolescents that short sleep duration was associated with a lower dietary quality. This supports the hypothesis that the health consequences of insufficient sleep may be mediated by the relationship of insufficient sleep to poor dietary quality.
The present study aimed to evaluate the relationship between the consumption of selected food groups and insulin resistance, with an emphasis on sugar-sweetened beverages (SSB).
The present research is a large multicentre European study in adolescents, the HELENA-CSS (Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study).
Homeostasis model assessment–insulin resistance index (HOMA-IR) was calculated. Several anthropometric and lifestyle characteristics were recorded. Dietary assessment was conducted by using a short FFQ.
The participants were a subset of the original sample (n 546) with complete data on glucose, insulin and FFQ. All participants were recruited at schools.
Median (25th, 75th percentile) HOMA-IR was 0·62 (0·44, 0·87). Mean HOMA-IR was significantly higher among adolescents consuming brown bread ≤1 time/week than among those consuming 2–6 times/week (P = 0·011). Mean values of HOMA-IR were also higher in adolescents consuming SSB >5 times/week compared with those consuming less frequently, although a statistically significant difference was detected between those consuming SSB 5–6 times/week and 2–4 times/week (P = 0·049). Multiple linear regression analysis showed that only the frequency of SSB consumption was significantly associated with HOMA-IR after controlling for potential confounders. In particular, it was found that HOMA-IR levels were higher among adolescents consuming SSB 5–6 times/week and ≥1 time/d compared with those consuming ≤1 time/week by 0·281 and 0·191 units, respectively (P = 0·009 and 0·046, respectively).
The present study revealed that daily consumption of SSB was related with increased HOMA-IR in adolescents.
More than 50% of the global population already lives in urban settlements and urban areas are projected to absorb almost all the global population growth to 2050, amounting to some additional three billion people. Over the next decades the increase in rural population in many developing countries will be overshadowed by population flows to cities. Rural populations globally are expected to peak at a level of 3.5 billion people by around 2020 and decline thereafter, albeit with heterogeneous regional trends. This adds urgency in addressing rural energy access, but our common future will be predominantly urban. Most of urban growth will continue to occur in small-to medium-sized urban centers. Growth in these smaller cities poses serious policy challenges, especially in the developing world. In small cities, data and information to guide policy are largely absent, local resources to tackle development challenges are limited, and governance and institutional capacities are weak, requiring serious efforts in capacity building, novel applications of remote sensing, information, and decision support techniques, and new institutional partnerships. While ‘megacities’ with more than 10 million inhabitants have distinctive challenges, their contribution to global urban growth will remain comparatively small.
Energy-wise, the world is already predominantly urban. This assessment estimates that between 60–80% of final energy use globally is urban, with a central estimate of 75%. Applying national energy (or GHG inventory) reporting formats to the urban scale and to urban administrative boundaries is often referred to as a ‘production’ accounting approach and underlies the above GEA estimate.
In neonatal intensive care units (NICUs), monitoring hospital-acquired bloodstream infection (BSI) is critical to alert clinicians to variations in the incidence of infection between units and over time. We demonstrate a toolkit of monitoring techniques that account for case mix and could be implemented using routinely available clinical data. This toolkit could enable quality of care comparisons between hospitals to facilitate the sharing of improved practices.
Prospective study over 4 years.
Setting and Patients.
Babies admitted to 2 tertiary London NICUs.
We derived expected numbers of BSI episodes using a Poisson regression risk model adjusting for variations in birth weight, transfers to the NICU from other hospitals, postnatal age, and days spent at each National Health Service level of care. We compared observed and expected numbers of BSI episodes using 2 monitoring techniques: standardized infection ratios (SIRs) and the sequential probability ratio test (SPRT).
Using the SIR method, observed BSI incidence increased over expected incidence in 2002 at both NICUs, but this increase did not reach statistical significance at the 1% level. Using the SPRT method, neither unit showed a clinically important increase or decrease, defined as a 30% deviation from expected incidence.
Risk-adjusted BSI monitoring can be performed using routine hospital data. NICUs could use SIRs for an annual look back at infection incidence and SPRTs for prospective, quarterly monitoring. The SIR and the SPRT methods have different strengths, and both could help clinicians improve infection control and patient care in NICUs.
Dietary fatty acids (FA) play a role in several (patho)physiological processes at any age, and different FA have different effects on lipid status and health outcome. The present study aims to describe the FA intake and its main food sources in a population of healthy European adolescents and to assess the variation in intake as a function of non-dietary factors. FA intake was assessed with 24 h recall interviews in 1804 adolescents aged 12·5–17·5 years. Usual intakes were calculated using the multiple source method. Multilevel analyses, adjusting for study centre, were used to investigate the influence of non-dietary factors. The mean total fat intake was 33·3 (sd 1·2) % of total energy intake (%E). The mean SFA intake was 13·8 (sd 1·2) %E, with 99·8 % of the population exceeding the recommendations. SFA was mainly delivered by meat and cake, pies and biscuits. In most adolescents, the PUFA intake was too low, and 35·5 % of the population did not achieve the minimum recommended intake for α-linolenic acid (ALA). The main determinants of FA intake in the present study population were age and sex, as well as physical activity in the male subgroup. No contributions of body composition, socio-economic status or sexual maturation to the variance in FA intake were observed. In conclusion, the most important public health concerns regarding FA intake in this adolescent population were the low intake of ALA and the high intake of SFA, mainly seen in the younger-aged boys. In this group the major contributor to SFA was meat.
To describe breakfast habits at food group level in European adolescents and to investigate the associations between these habits and sociodemographic factors.
Secondary schools from nine European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Breakfast habits were assessed twice using a computer-based 24 h dietary recall. Adolescents who consumed breakfast on at least one recall day were classified as ‘breakfast consumers’ and adolescents who did not have anything for breakfast on either of the two recall days were considered ‘breakfast skippers’. A ‘breakfast quality index’ to describe breakfast quality was created based on the consumption or non-consumption of cereals/cereal products, dairy products and fruits/vegetables. The sociodemographic factors studied were sex, age, region of Europe, maternal and paternal education, family structure and family affluence.
Adolescents (n 2672, 53 % girls) aged 12–17 years.
The majority of the adolescents reported a breakfast that scored poorly on the breakfast quality index. Older adolescents, adolescents from the southern part of Europe and adolescents from families with low socio-economic status were more likely to consume a low-quality breakfast.
The study highlights the need to promote the consumption of a high-quality breakfast among adolescents, particularly in older adolescents, adolescents from southern Europe and adolescents from families with low socio-economic status, in order to improve public health.