Isoniazid resistance in <i>Mycobacterium tuberculosis</i>

Drug resistant tuberculosis (TB) is increasing worldwide and it is now estimated by the World Health Organisation (WHO) that 7% of TB cases globally are resistant to isoniazid (INH). INH is a key drug for the treatment of TB, alongside rifampicin (RIF). Understanding factors which influence the emergence and propagation of INH resistance and the influence of INH resistance on TB treatment success are vital in improving global TB control efforts. Vietnam is ranked 12th of 22 high burden countries for TB and has a high prevalence of INH resistance (25%) with a relatively modest prevalence of TB resistant to both INH and RIF (multi-drug resistant, MDR TB) (2.7%). The first study in this thesis developed rapid screening tests for both RIF and INH resistance in Mycobacterium tuberculosis isolates which showed high accuracy. The specificity and the sensitivity of the MAS-PCR test for INH resistance compared to the conventional phenotypic DST were 100% [95% CI 92.9-100%] and 90% [95% CI 82.4-95.1 %], respectively. The second study demonstrated that the minimum inhibitory concentration (MIC) for INH is influenced by both the mutation responsible for resistance to INH and the lineage backbone of the M.tuberculosis isolate. A two-way ANOVA of MIC including both strain lineage (p=0.003) and resistance mutation (p<0.001) showed highly significant independent effects of both factors on MIC level. MIC to INH of isolates with a katG315 mutation (2ug/ml) was significantly higher compared to MIC to INH of isolates with an inhA-15 mutation (0.25p.g/ml) and wild-type isolates (0- 0.lug/ml) (p<0.00l). The independent effect of the strain lineage on INH MIC was predicted to correspond to a 2.68-fold (95% Cl 1.52-4.73, p<0.001) increase for Beijing lineage strains and a 1.40-fold (95% Cl 0.72-2.74, p=0.32) increase for EuroAmerican lineage strains in comparison with strains of the Indo-Oceanic lineage. The third study investigated the impact of INH resistance on outcome in patients with HIV-associated TB meningitis (HIV/TBM) and showed that HIV/TBM patients infected with INH resistant M.tuberculosis which remains susceptible to RIF have significantly worse outcomes than patients infected with fully susceptible strains. The adjusted hazard ratio for MDR patients in comparison with fully susceptible or streptomycin (STR)-monoresistant isolates was 5.21 [95% Cl 2.38-11.42], p<0.0001 compared with HR= 1.78 [95% Cl 1.18-2.66], p=0.005 for patients with INH resistant isolates (+/-STR resistance). The final study investigated the distribution of N-acetylator-2 (NAT2) phenotypes for INH metabolism in healthy volunteers from the Vietnamese Kinh population and correlated this with phenotypes using caffeine as a surrogate indicator for INH metabolism. This study showed that characterisation of 3 single nucleotide polymorphisms is sufficient to determine the acetylator status of individuals of Vietnamese Kinh ethnicity and that there is a predominance of fast acetylators (65%) in this popUlation. A simple PCR-RFLP test was developed to enable rapid determination of acetylator status for further studies. Collectively, these results contribute to our understanding of INH resistance in M.tuberculosis and provide molecular tools for further studies of this crucial drug

Examining Twitter Content of State Emergency Management During Hurricane Joaquin

Those tasked with disseminating life-protecting messages during crises have many factors to consider. Social media sites have become an information source for individuals during these times, and more research is needed examining the use of specific message strategies by emergency management agencies that may elicit attention and retransmission. This study examines Twitter content concerning Hurricane Joaquin. Content analysis of tweets from state emergency management accounts was performed to provide an overview of the content and stylistic elements used in tweets associated with the event. The findings are discussed in the context of both past research on the matter and implications for emergency management agencies responding to high-consequence events

Crisis Communication in Context: History and Publication Trends

This study aims to describe the development of crisis communication as a subfield of Communication Studies, through an analysis of data taken from journal publications. By tracing the origins of crisis communication, this study identifies some of the primary forces that have influenced its development. Next, the results of an analysis of crisis communication articles drawn from twelve periodicals over nineteen years within the larger communication discipline are offered. The results suggest that Journal of Applied Communication Research has been the most common outlet for this subdiscipline, human subjects data accounts for less than half of the published research, and that crisis communication articles are often prominently featured in mainstream Communication journals. An authorship analysis suggests leading scholars in the subdiscipline, and potential centers of excellence at Wayne State University, Michigan State, and the University of Central Florida

Responding to Campus Shootings: Two Studies Exploring the Effects of Sex and Placement Strategy on Knowledge Acquisition and Organizational Reputation

Two separate studies used quasi-experimental procedures to examine how college students learn about campus shootings from press releases, television news, or exposure to both. The first study found that women tend to report higher levels of learning than men and that participants generally learn the most when exposed to messages delivered through multiple media. The second study extended the findings to include consideration of the impact of learning on organizational reputation. Taken together, the results of both studies offer further evidence that knowledge acquisition can help mitigate against the formation of negative impressions of an organization in crisis. They also offer that the relationship between learning and attitude formation may be mediated by sex. The results are discussed in terms of message placement strategy and sex differences in mediated learning processes. Implications for the relationship between these learning processes and organizational reputation are addressed

Putting the PASS in Class: Peer Mentors’ Identities in Science Workshops on Campus and Online

In this paper, we analyse the introduction of peer mentors into timetabled classes to understand how in-class mentoring supports students’ learning. The peer mentors in this study are high-achieving students who previously completed the same course and who were hired and trained to facilitate Peer Assisted Study Sessions (PASS). PASS gives students the opportunity to deepen their understanding through revision and active learning and are typically held outside of class time. In contrast, our trial embedded peer mentors into classes for a large (~250 students) first-year workshop-based course. We employed a participatory action research methodology to facilitate the peer mentors’ co-creation of the research process. Data sources include peer mentors’ journal entries, student cohort data, and a focus group with teaching staff. We found that during face-to-face workshops, peer mentors role-modelled ideal student behaviour (e.g., asking questions) rather than acting as additional teachers, and this helped students to better understand how to interact effectively in class. The identity of embedded peer mentors is neither that of teachers nor of students, and it instead spans aspects of both as described using a three-part schema comprising (i) identity, (ii) associated roles, and (iii) associated practices. As we moved classes online mid-semester in response to the COVID-19 pandemic, mentors’ identities remained stable, but mentors adjusted their associated roles and practices, including through the technical aspects of their engagement with students. This study highlights the benefits of embedding mentors in classrooms on campus and online

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Evolutionary Dead End in the Galápagos: Divergence of Sexual Signals in the Rarest of Darwin's Finches

Understanding the mechanisms underlying speciation remains a challenge in evolutionary biology. The adaptive radiation of Darwin's finches is a prime example of species formation, and their study has revealed many important insights into evolutionary processes. Here, we report striking differences in mating signals (songs), morphology and genetics between the two remnant populations of Darwin's mangrove finch Camarhynchus heliobates, one of the rarest species in the world. We also show that territorial males exhibited strong discrimination of sexual signals by locality: in response to foreign songs, males responded weaker than to songs from their own population. Female responses were infrequent and weak but gave approximately similar results. Our findings not only suggest speciation in the mangrove finch, thereby providing strong support for the central role of sexual signals during speciation, but they have also implications for the conservation of this iconic bird. If speciation is complete, the eastern species will face imminent extinction, because it has a population size of only 5–10 individuals

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The hemispheric contrast in cloud microphysical properties constrains aerosol forcing

The change in planetary albedo due to aerosol−cloud interactions during the industrial era is the leading source of uncertainty in inferring Earth’s climate sensitivity to increased greenhouse gases from the historical record. The variable that controls aerosol−cloud interactions in warm clouds is droplet number concentration. Global climate models demonstrate that the present-day hemispheric contrast in cloud droplet number concentration between the pristine Southern Hemisphere and the polluted Northern Hemisphere oceans can be used as a proxy for anthropogenically driven change in cloud droplet number concentration. Remotely sensed estimates constrain this change in droplet number concentration to be between 8 cm−3 and 24 cm−3. By extension, the radiative forcing since 1850 from aerosol−cloud interactions is constrained to be −1.2 W⋅m−2 to −0.6 W⋅m−2. The robustness of this constraint depends upon the assumption that pristine Southern Ocean droplet number concentration is a suitable proxy for preindustrial concentrations. Droplet number concentrations calculated from satellite data over the Southern Ocean are high in austral summer. Near Antarctica, they reach values typical of Northern Hemisphere polluted outflows. These concentrations are found to agree with several in situ datasets. In contrast, climate models show systematic underpredictions of cloud droplet number concentration across the Southern Ocean. Near Antarctica, where precipitation sinks of aerosol are small, the underestimation by climate models is particularly large. This motivates the need for detailed process studies of aerosol production and aerosol−cloud interactions in pristine environments. The hemispheric difference in satellite estimated cloud droplet number concentration implies preindustrial aerosol concentrations were higher than estimated by most models

Social preferences and network structure in a population of reef manta rays

Understanding how individual behavior shapes the structure and ecology ofpopulations is key to species conservation and management. Like manyelasmobranchs, manta rays are highly mobile and wide ranging species threatened byanthropogenic impacts. In shallow-water environments these pelagic rays often formgroups, and perform several apparently socially-mediated behaviors. Group structuresmay result from active choices of individual rays to interact, or passive processes.Social behavior is known to affect spatial ecology in other elasmobranchs, but this isthe first study providing quantitative evidence for structured social relationships inmanta rays. To construct social networks, we collected data from more than 500groups of reef manta rays over five years, in the Raja Ampat Regency of West Papua.We used generalized affiliation indices to isolate social preferences from non-socialassociations, the first study on elasmobranchs to use this method. Longer lastingsocial preferences were detected mostly between female rays. We detectedassortment of social relations by phenotype and variation in social strategies, with theoverall social network divided into two main communities. Overall network structurewas characteristic of a dynamic fission-fusion society, with differentiated relationshipslinked to strong fidelity to cleaning station sites. Our results suggest that fine-scaleconservation measures will be useful in protecting social groups of M. alfredi in theirnatural habitats, and that a more complete understanding of the social nature of mantarays will help predict population response