BackgroundThe glasshouse whitefly, Trialeurodes vaporariorum, is a damaging crop pest and an invasive generalist capable of feeding on a broad range of host plants. As such this species has evolved mechanisms to circumvent the wide spectrum of anti-herbivore allelochemicals produced by its host range. T. vaporariorum has also demonstrated a remarkable ability to evolve resistance to many of the synthetic insecticides used for control.ResultsTo gain insight into the molecular mechanisms that underpin the polyphagy of T. vaporariorum and its resistance to natural and synthetic xenobiotics, we sequenced and assembled a reference genome for this species. Curation of genes putatively involved in the detoxification of natural and synthetic xenobiotics revealed a marked reduction in specific gene families between this species and another generalist whitefly, Bemisia tabaci. Transcriptome profiling of T. vaporariorum upon transfer to a range of different host plants revealed profound differences in the transcriptional response to more or less challenging hosts. Large scale changes in gene expression (> 20% of genes) were observed during adaptation to challenging hosts with a range of genes involved in gene regulation, signalling, and detoxification differentially expressed. Remarkably, these changes in gene expression were associated with significant shifts in the tolerance of host-adapted T. vaporariorum lines to natural and synthetic insecticides.ConclusionsOur findings provide further insights into the ability of polyphagous insects to extensively reprogram gene expression during host adaptation and illustrate the potential implications of this on their sensitivity to synthetic insecticides.

Background: The clinical and economic burden of pulmonary arterial hypertension (PAH) is poorly understood outside the United States. This retrospective database study describes the characteristics of patients with PAH in England, including their healthcare resource utilisation (HCRU) and associated costs. Methods: Data from 1 April 2012 to 31 March 2018 were obtained from the National Health Service (NHS) Digital Hospital Episode Statistics database, which provides full coverage of patient events occurring in NHS England hospitals. An adult patient cohort was defined using an algorithm incorporating pulmonary hypertension (PH) diagnosis codes, PAH-associated procedures, PH specialist centre visits and PAH-specific medications. HCRU included inpatient admissions, outpatient visits and Accident and Emergency (A&E) attendances. Associated costs, calculated using national tariffs inflation-adjusted to 2017, did not include PAH-specific drugs on the High Cost Drugs list. Results: The analysis cohort included 2527 patients (68.4% female; 63.6% aged ⩾50 years). Mean annual HCRU rates ranged from 2.9 to 3.2 for admissions (21–25% of patients had ⩾5 admissions), 9.4–10.3 for outpatient visits and 0.8–0.9 for A&E attendances. Costs from 2013 to 2017 totalled £43.2M (£33.9M admissions, £8.3M outpatient visits and £0.9M A&E attendances). From 2013 to 2017, mean cost per patient decreased 13% (from £4400 to £3833) for admissions and 13% (from £1031 to £896) for outpatient visits, but increased 52% (from £81 to £123) for A&E attendances. Conclusion: PAH incurs a heavy economic burden on a per-patient basis, highlighting the need for improved treatment strategies able to reduce disease progression and hospitalisations. The reviews of this paper are available via the supplemental material section.

have completed treatment with 78% success rate, 39 % cured rate and 4.3% loss to follow up. Of the 44% cases still in care, none was lost-to-follow-up however, 5.6% failed treatment and diagnosed Pre-Extensive-Drug Resistant-TB. Conclusions: Undoubtedly, this study underscored a successful implementation of the decentralized model of care. It documented a treatment success rate (78%) with minimal Loss-to-follow-up. However, it showed Pre-XDR/XDR-TB as an emerging concern that must be tackled by National Tuberculosis Program to achieve TB control target.

Objectives: To identify a PAH patient cohort using the Hospital Episode Statistics (HES) administrative database and evaluate hospital healthcare resource utilisation (HRU) and economic burden of illness in England. Methods: An algorithm was developed to identify a PAH cohort. HES data were extracted (01. 04.2012 to 31.03.2018) and patients were identified as those diagnosed (index date) alive on the 1 st of June of each calendar year. The number of events and associated costs were calculated for Accident & Emergency (A&E), inpatient, and outpatient services. Results: Over 5 complete years, 2,527 patients were identified, compared with 2,695 reported in The UK 5 th National Pulmonary Hypertension (PH) Audit. The PAH cohort presented a mean follow-up period of 44.8 months (SD=20.5). Gender (68.4% female) and age distribution aligned well with reported literature and the National PH Audit. The mean age at index was 58.0 years (SD=16.8). In 2017 (1,825 patients), PAH patients had a mean of 0.4 A&E attendances (SD=1.0) with a mean cost of £123.18 (SD=£247.37) per patient. PAH patients had a mean of 1.4 inpatient admissions (SD=4.3) for a mean cost of £3,832.91 (SD=£6,032.14) and a mean length of stay of 3.3 days (SD=7.6). The mean length of hospitalisation was 3.8 days (SD=8.1) for PAH-related events and 2.3 days (SD=6.2) for non-PAH-related events. PAH patients had a mean of 5.0 outpatient visits (SD=7.4) with an associated mean cost of £895.86 (SD=£831.93) per patient. In 2017, the total cost for PAH patients was £8.9m where £7.0m was associated with inpatient admissions. Of the total inpatient admission costs, £5.7m was attributed to PAHrelated admissions. Conclusions: The epidemiological characteristics of the PAH cohort in England were in line with reported literature. In 2017, 64.3% of the total inpatient admission costs were for a PAH-related event. In summary, these results confirm that there is an HRU burden across all services.

adopted for the analysis of association between bevacizumab use and pulmonary embolism. The data mining algorithm used for the analysis were Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). A value of ROR-1.96SE.1, PRR$2 were considered as positive signal. Results: A total of 52,770 reports for Pulmonary embolism have been reported in the FDA database. Amongst which 1,264 reports were associated with bevacizumab. Pulmonary embolism ranked 25 th among 900 bevacizumab associated adverse drug events. The mean age was 61.21 and female to male ratio was 1.01:1. A positive signal was obtained with ROR: 3.40 and PRR: 3.42. 394 death reports and the non-death serious reports included hospitalization, lifethreatening, disability, and other serious events with 53, 36, 4 and 626 reports respectively. Linear regression analysis indicated there was no significant correlation between the PRR and time (R=0.045; p=0.876) and ROR and time (R=0.60; p=0.831). The Log Likelihood ratio for pulmonary embolism with bevacizumab was found to be 548.23 and the reporting ratio was 2.94 (Critical value-5.68). Conclusions: A positive signal was observed for bevacizumab associated pulmonary embolism, although a causal relation cannot be definitively proved. Health care professionals should be cautious about the possibility of serious adverse events associated with bevacizumab and should report to concerned regulatory authorities.