Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial (“real-world”) patients, aged 16–59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18–59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy

Compared to conventional, ecological intensive management promotes beneficial proteolytic soil microbial communities for agro-ecosystem functioning under climate change-induced rain regimes

Projected climate change and rainfall variability will affect soil microbial communities, biogeochemical cycling and agriculture. Nitrogen (N) is the most limiting nutrient in agroecosystems and its cycling and availability is highly dependent on microbial driven processes. In agroecosystems, hydrolysis of organic nitrogen (N) is an important step in controlling soil N availability. We analyzed the effect of management (ecological intensive vs. conventional intensive) on N-cycling processes and involved microbial communities under climate change-induced rain regimes. Terrestrial model ecosystems originating from agroecosystems across Europe were subjected to four different rain regimes for 263 days. Using structural equation modelling we identified direct impacts of rain regimes on N-cycling processes, whereas N-related microbial communities were more resistant. In addition to rain regimes, management indirectly affected N-cycling processes via modifications of N-related microbial community composition. Ecological intensive management promoted a beneficial N-related microbial community composition involved in N-cycling processes under climate change-induced rain regimes. Exploratory analyses identified phosphorus-associated litter properties as possible drivers for the observed management effects on N-related microbial community composition. This work provides novel insights into mechanisms controlling agro-ecosystem functioning under climate change

Reflections on Pandemic (H1N1) 2009 and the International Response

Gabriel Leung and Angus Nicoll provide their reflections on the international response to the 2009 H1N1 influenza pandemic, including what went well and what changes need to be made in anticipation of future flu pandemics

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

Age-related decline in associative learning in healthy Chinese adults

10.1371/journal.pone.0080648PLoS ONE811-POLN

Stereotactic, single-dose irradiation of stage I non-small cell lung cancer and lung metastases

BACKGROUND: We prospectively reviewed response rates, local control, and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors. METHODS: Fifty-eight patients underwent radiosurgery involving single-dose irradiation. With 25 patients, 31 metastases in the lungs were irradiated; with each of 33 patients, stage I non-small cell lung cancer (NSCLC) was subject to irradiation. The standard dose prescribed to the isocenter was 30 Gy with an axial safety margin of 10 mm and a longitudinal safety margin of 15 mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed. RESULTS: The volume of the metastases (CTV) varied from 2.8 to 55.8 cm(3 )(median: 6.0 cm(3)) and the PTV varied from 12.2 to 184.0 cm(3 )(median: 45.0 cm(3)). The metastases ranged from 0.7 to 4.5 cm in largest diameter. The volume of the bronchial carcinomas varied from 4.2 to 125.4 cm(3)(median: 17.5 cm(3)) and the PTV from 15.6 to 387.3 cm(3 )(median: 99.8 cm(3)). The bronchial carcinomas ranged from 1.7 to 10 cm in largest diameter. Follow-up periods varied from 6.8 to 63 months (median: 22 months for metastases and 18 months for NSCLC). Local control was achieved with 94% of NSCLC and 87% of metastases. No serious symptomatic side effects were observed. According to the Kaplan-Meier method the overall survival probability rates of patients with lung metastases were as follows: 1 year: 97%, 2 years: 73%, 3 years: 42%, 4 years: 42%, 5 years: 42% (median survival: 26 months); of those with NSCLC: 1 year: 83%, 2 years: 63%, 3 years: 53%, 4 years: 39%: (median survival: 20.4 months). CONCLUSION: Non-fractionated single-dose irradiation of metastases in the lungs or of small, peripheral bronchial carcinomas is an effective and safe form of local treatment and might become a viable alternative to invasive techniques

A Simple Scoring System to Differentiate between Relapse and Re-Infection in Patients with Recurrent Melioidosis

Melioidosis is a serious infectious disease caused by the Gram-negative bacterium, Burkholderia pseudomallei. This organism is present in the environment in areas where melioidosis is endemic (most notably East Asia and Northern Australia), and infection is acquired following bacterial inoculation or inhalation. Despite prolonged oral eradicative treatment, recurrent melioidosis occurs in approximately 10% of survivors of acute melioidosis. Recurrent melioidosis can be caused by relapse (failure of initial eradicative treatment) or re-infection with a new infection. The aim of this study was to develop a simple scoring system to distinguish between re-infection and relapse, since this has implications for antimicrobial treatment of the recurrent episode, but telling the two apart normally requires bacterial genotyping. A prospective study of melioidosis patients in NE Thailand conducted between 1986 and 2005 identified 141 patients with recurrent melioidosis. Of these, 92 patients had relapse and 49 patients had re-infection as confirmed by genotyping techniques. We found that relapse was associated with previous inadequate treatment and shorter time to clinical features of recurrence, while re-infection was associated with renal insufficiency and presentation during the rainy season. A simple scoring index to help distinguish between relapse and re-infection was developed to provide important bedside information where rapid bacterial genotyping is unavailable. Guidelines are provided on how this scoring system could be implemented

Industrial Structure and Political Outcomes: The Case of the 2016 US Presidential Election

This paper analyzes the US presidential election of 2016, examining the patterns of industrial structure and party competition in both the major party primaries and the general election. It attempts to identify the new, historically specific factors that led to the upheavals, especially the steady growth of a “dual economy” that locks more and more Americans out of the middle class. It draws extensively on a newly assembled, more comprehensive database to identify the specific political forces that coalesced around each candidate, including the various stages of the Trump campaign

Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment - case report

<p>Abstract</p> <p>Background</p> <p>Stereotactic body radiation therapy (SBRT) applied by helical tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously.</p> <p>Case Presentation</p> <p>A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected.</p> <p>Conclusions</p> <p>Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen.</p