NORTH CAROLINA - API PROGRAM IN HUMAN RESOURCE DEVELOPMENT

Labor and Human Capital,

Developmental succession of the microbiome of Culex mosquitoes

Background: The native microflora associated with mosquitoes have important roles in mosquito development and vector competence. Sequencing of bacterial V3 region from 16S rRNA genes across the developmental stages of Culex mosquitoes (early and late larval instars, pupae and adults) was used to test the hypothesis that bacteria found in the larval stage of Culex are transstadially transmitted to the adult stage, and to compare the microbiomes of field-collected versus laboratory-reared mosquitoes.Results: Beta diversity analysis revealed that bacterial community structure differed among three life stages (larvae, pupae and adults) of Culex tarsalis. Although only similar to 2 % of the total number of bacterial OTUs were found in all stages, sequences from these OTUs accounted for nearly 82 % of the total bacterial sequences recovered from all stages. Thorsellia (Gammaproteobacteria) was the most abundant bacterial taxon found across all developmental stages of field-collected Culex mosquitoes, but was rare in mosquitoes from laboratory-reared colonies. The proportion of Thorsellia sequences in the microbiomes of mosquito life stages varied ontogenetically with the greatest proportions recovered from the pupae of C. tarsalis and the lowest from newly emerged adults. The microbiome of field-collected late instar larvae was not influenced significantly by differences in the microbiota of the habitat due to habitat age or biopesticide treatments. The microbiome diversity was the greatest in the early instar larvae and the lowest in laboratory-reared mosquitoes.Conclusions: Bacterial communities in early instar C. tarsalis larvae were significantly more diverse when compared to late instar larvae, pupae and newly emerged adults. Some of the bacterial OTUs found in the early instar larvae were also found across developmental stages. Thorsellia dominated the bacterial communities in field-collected immature stages but occurred at much lower relative abundance in adults. Differences in microbiota observed in larval habitats did not influence bacterial community profiles of late instar larvae or adults. However, bacterial communities in laboratory-reared C. tarsalis larvae differed significantly from the field. Determining the role of Thorsellia in mosquitoes and its distribution across different species of mosquitoes warrants further investigation

Development and Preliminary Evaluation of a Telephone-based Mindfulness Training Intervention for Survivors of Critical Illness

Rationale: Persistent symptoms of psychological distress represent an unmet need among intensive care unit (ICU) survivors. Objectives: We aimed to develop and pilot test a simple telephone-based mindfulness training intervention to address this population’s unique needs. Methods: Open trial involving survivors of medical and surgical critical illness and their informal caregivers, using a pretest–posttest design. Measurements and Main Results: We developed a six-session, telephone-delivered, ICU survivor–specific mindfulness intervention based on past focus groups, the medical literature, and the precedent of the most effective components of existing mindfulness programs. A total of 11 survivors of mechanical ventilation were enrolled, together with 2 informal caregivers for exploratory purposes. Three patients dropped out before intervention initiation because of progressive illness or severe social stressors. Of the 10 remaining participants, 8 (80%) completed the program within 7 weeks. Among these eight patients and caregivers who completed all study procedures, six (75%) experienced improvement in symptoms of psychological distress (anxiety, depression, or post-traumatic stress disorder). Changes in distress symptoms were correlated with improvement in mindfulness qualities, adaptive coping, and emotion regulation. Participants reported high satisfaction with the program in postintervention interviews. Conclusions: A new ICU survivor–specific mindfulness training intervention delivered by telephone was acceptable and feasible. Changes in symptoms of distress were correlated with changes in skills that were targeted by the mindfulness program. Controlled trials are needed to further evaluate this promising intervention

Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium

BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity. METHODS: In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50 = 5-11 μM) of rhinovirus-induced type I IFNβ, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti-inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need

GS-TEC::the Gaia Spectrophotometry Transient Events Classifier

We present an algorithm for classifying the nearby transient objects detected by the Gaia satellite. The algorithm will use the low-resolution spectra from the blue and red spectro-photometers on board of the satellite. Taking a Bayesian approach we model the spectra using the newly constructed reference spectral library and literature-driven priors. We find that for magnitudes brighter than 19 in Gaia $G$ magnitude, around 75\% of the transients will be robustly classified. The efficiency of the algorithm for SNe type I is higher than 80\% for magnitudes $G\leq$18, dropping to approximately 60\% at magnitude $G$=19. For SNe type II, the efficiency varies from 75 to 60\% for $G\leq$18, falling to 50\% at $G$=19. The purity of our classifier is around 95\% for SNe type I for all magnitudes. For SNe type II it is over 90\% for objects with $G \leq$19. GS-TEC also estimates the redshifts with errors of $\sigma_z \le$ 0.01 and epochs with uncertainties $\sigma_t \simeq$ 13 and 32 days for type SNe I and SNe II respectively. GS-TEC has been designed to be used on partially calibrated Gaia data. However, the concept could be extended to other kinds of low resolution spectra classification for ongoing surveys.Comment: 17 pages, 14 figures, accepted to be published in Monthly Notices of the Royal Astronomical Society [MNRAS

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study

Background Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. Methods For this multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled feasibility trial, adults with OAC (including Siewert I–II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. Results A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low‐density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0·83 (95 per cent c.i. −1·4 to −0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow‐up. Adverse events were similar between the groups. Quality‐of‐life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non‐randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. Conclusion This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com)

Attitudes Toward Organizational Change among Public Middle Managers

Positive attitudes toward change (PATC) are an important current issue in public organizations facing profound financial and managerial reforms. This study aims to identify social and organizational antecedents of PATC. The investigated population is composed of middle managers working in Swiss public hospitals (N = 720), which are currently being confronted by major reforms. Partial mediation effects of organizational commitment (OC) in the relationships between independent variables and PATC are also controlled. The findings show that perceived social support (work relationships with colleagues and supervisors) as well as perceived organizational support (employee voice and participation, information and communication, work-life balance) are positively and significantly related to PATC. Stress perception is shown to have a negative impact on PATC. This article provides valuable contributions with respect to antecedents of attitudes toward change in a population of public middle managers

Population neuroimaging:generation of a comprehensive data resource within the ALSPAC pregnancy and birth cohort

Neuroimaging offers a valuable insight into human brain development by allowing in vivo assessment of structure, connectivity and function. Multimodal neuroimaging data have been obtained as part of three sub-studies within the Avon Longitudinal Study of Parents and Children, a prospective multigenerational pregnancy and birth cohort based in the United Kingdom. Brain imaging data were acquired when offspring were between 18 and 24 years of age, and included acquisition of structural, functional and magnetization transfer magnetic resonance, diffusion tensor, and magnetoencephalography imaging. This resource provides a unique opportunity to combine neuroimaging data with extensive phenotypic and genotypic measures from participants, their mothers, and fathers