Network Analysis of Host-Virus Communities in Bats and Rodents Reveals Determinants of Cross-Species Transmission

Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence

Manipulating vector transmission reveals local processes in bacterial communities of batss

Infectious diseases result from multiple interactions among microbes and hosts, but community ecology approaches are rarely applied. Manipulation of vector populations provides a unique opportunity to test the importance of vectors in infection cycles while also observing changes in pathogen community diversity and species interactions. Yet for many vector-borne infections in wildlife, a biological vector has not been experimentally verified and few manipulative studies have been performed. Using a captive colony of fruit bats in Ghana, we observed changes in the community of Bartonella bacteria over time after the decline and subsequent reintroduction of bat flies. With reduced transmission, community changes were attributed to ecological drift and potential selection through interspecies competition mediated by host immunity. This work demonstrated that forces maintaining diversity in communities of free-living macroorganisms act in similar ways in communities of symbiotic microorganisms, both within and among hosts. Additionally, this study is the first to experimentally test the role of bat flies as vectors of Bartonella species

A holistic review of the medical school admission process: examining correlates of academic underperformance

Background: Despite medical school admission committees’ best efforts, a handful of seemingly capable students invariably struggle during their first year of study. Yet, even as entrance criteria continue to broaden beyond cognitive qualifications, attention inevitably reverts back to such factors when seeking to understand these phenomena. Using a host of applicant, admission, and post-admission variables, the purpose of this inductive study, then, was to identify a constellation of student characteristics that, taken collectively, would be predictive of students at-risk of underperforming during the first year of medical school. In it, we hypothesize that a wider range of factors than previously recognized could conceivably play roles in understanding why students experience academic problems early in the medical educational continuum. Methods: The study sample consisted of the five most recent matriculant cohorts from a large, southeastern medical school (n=537). Independent variables reflected: 1) the personal demographics of applicants (e.g., age, gender); 2) academic criteria (e.g., undergraduate grade point averages [GPA], medical college admission test); 3) selection processes (e.g., entrance track, interview scores, committee votes); and 4) other indicators of personality and professionalism (e.g., Mayer-Salovey-Caruso Emotional Intelligence Test™ emotional intelligence scores, NEO PI-R™ personality profiles, and appearances before the Professional Code Committee [PCC]). The dependent variable, first-year underperformance, was defined as ANY action (repeat, conditionally advance, or dismiss) by the college's Student Progress and Promotions Committee (SPPC) in response to predefined academic criteria. This study protocol was approved by the local medical institutional review board (IRB). Results: Of the 537 students comprising the study sample, 61 (11.4%) met the specified criterion for academic underperformance. Significantly increased academic risks were identified among students who 1) had lower mean undergraduate science GPAs (OR=0.24, p=0.001); 2) entered medical school via an accelerated BS/MD track (OR=16.15, p=0.002); 3) were 31 years of age or older (OR=14.76, p=0.005); and 4) were non-unanimous admission committee admits (OR=0.53, p=0.042). Two dimensions of the NEO PI-R™ personality inventory, openness (+) and conscientiousness (−), were modestly but significantly correlated with academic underperformance. Only for the latter, however, were mean scores found to differ significantly between academic performers and underperformers. Finally, appearing before the college's PCC (OR=4.21, p=0.056) fell just short of statistical significance. Conclusions: Our review of various correlates across the matriculation process highlights the heterogeneity of factors underlying students’ underperformance during the first year of medical school and challenges medical educators to understand the complexity of predicting who, among admitted matriculants, may be at future academic risk

Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator.

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems

Minimizing the threat of pandemic emergence from avian influenza in poultry systems

BACKGROUND: Live-animal markets are a culturally important feature of meat distribution chains in many populations, yet they provide an opportunity for the maintenance and transmission of potentially emergent zoonotic pathogens. The ongoing human outbreak of avian H7N9 in China highlights the need for increased surveillance and control in these live-bird markets (LBMs). DISCUSSION: Closure of retail markets in affected areas rapidly decreased human cases to rare, sporadic occurrence, but little attention has been paid thus far to the role of upstream elements of the poultry distribution chain such as wholesale markets. This could partly explain why transmission in poultry populations has not been eliminated more broadly. We present surveillance data from both wholesale live-bird markets (wLBMs) and rLBMs in Shantou, China (from 2004–2006), and call on disease-dynamic theory to illustrate why closing rLBMs has only minor effects on the overall volume of transmission. We show that the length of time birds stay in rLBMs can severely limit transmission there, but that the system-wide effect may be reduced substantially by high levels of transmission upstream of retail markets. SUMMARY: Management plans that minimize transmission throughout the entire poultry supply chain are essential for minimizing exposure to the public. These include reducing stay-time of birds in markets to 1 day, standardizing poultry supply chains to limit transmission in pre-retail settings, and monitoring strains with epidemiological traits that pose a high risk of emergence. These actions will further limit human exposure to extant viruses and reduce the likelihood of the emergence of novel strains by decreasing the overall volume of transmission

Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration

Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty

Environmental Temperature Affects Prevalence of Blood Parasites of Birds on an Elevation Gradient: Implications for Disease in a Warming Climate

Background: The rising global temperature is predicted to expand the distribution of vector-borne diseases both in latitude and altitude. Many host communities could be affected by increased prevalence of disease, heightening the risk of extinction for many already threatened species. To understand how host communities could be affected by changing parasite distributions, we need information on the distribution of parasites in relation to variables like temperature and rainfall that are predicted to be affected by climate change.\ud \ud Methodology/Principal Findings: We determined relations between prevalence of blood parasites, temperature, and seasonal rainfall in a bird community of the Australian Wet Tropics along an elevation gradient. We used PCR screening to investigate the prevalence and lineage diversity of four genera of blood parasites (Plasmodium, Haemoproteus, Leucocytozoon and Trypanosoma) in 403 birds. The overall prevalence of the four genera of blood parasites was 32.3%, with Haemoproteus the predominant genus. A total of 48 unique lineages were detected. Independent of elevation, parasite prevalence was positively and strongly associated with annual temperature. Parasite prevalence was elevated during the dry season.\ud \ud Conclusions/Significance: Low temperatures of the higher elevations can help to reduce both the development of avian haematozoa and the abundance of parasite vectors, and hence parasite prevalence. In contrast, high temperatures of the lowland areas provide an excellent environment for the development and transmission of haematozoa. We showed that rising temperatures are likely to lead to increased prevalence of parasites in birds, and may force shifts of bird distribution to higher elevations. We found that upland tropical areas are currently a low-disease habitat and their conservation should be given high priority in management plans under climate change

The Role of Environmental Transmission in Recurrent Avian Influenza Epidemics

Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2–4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host–pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2–4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish

British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres

\ua9 The Author(s) 2024.An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs

Geographic Variability in Access to Primary Kidney Transplantation in the United States, 1996–2005

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75057/1/j.1600-6143.2007.01785.x.pd