Microbial extracellular enzyme activity affects performance in a full-scale modified activated sludge process

The rate-limiting step of wastewater treatment is the breakdown of polymers by extracellular enzyme activity (EEA). The efficacy of EEA on biomass from full scale conventional activated sludge (AS) and modified AS with bench scale and full scale rotating biofilm reactors (RBR) was compared. The maximum amino-peptidase EEA was 394 ± 34 μmolL−1 min−1 for the bench RBR which was 11.7 and 4.5 times greater than maximum α-glucosidase and phosphatase EEA in these reactors. At full scale the RBR gave ~4.6, 13.5 and 6.3 times the EEA for amino-peptidase, α-glucosidase and phosphatase (based on enzyme Vmax) compared to the highest EEA in conventional AS biomass. Controlled overloading of the bench RBRs revealed that EEA increased with OLR up to 190 g tCOD m−2d−1 and further increases in OLR reduced the EEA. Pretreatment of wastewater by EEA in the RBR was linked to better performance of the modified activated sludge process. Maintaining high EEA of biofilms is critical for the design of high OLR wastewater treatment systems

The sigma and f_0(980) from Ke4 + pi-pi scatterings data

We systematically reconsider, within an improved "analytic K-matrix model", the extraction of the sigma = f_0(600) and f_0(980) masses, widths and hadronic couplings using new Ke4 = K-->pi-pi e nu_e data on pi-pi phase shift below 390 MeV and different sets of pi-pi--> pi-pi / K-K scatterings data from 400 MeV to 1.4 GeV. Our results are summarized in Tables 1, 2 and 5. In units of MeV, the complex poles are: M_sigma=452(12) - i 260(15) and M_f=981(34) -i 18(11), which are comparable with some recent high-precision determinations and with PDG values. Besides some other results, we find: |g_{sigma K+K-}|/|g_{sigma pi+pi-}|=0.37(6) which confirms a sizeable g_{sigma K+K-} coupling found earlier, and which disfavours a large pi-pi molecule or four-quark component of the sigma, while its broad pi-pi width (relative to the one of the rho-meson) cannot be explained within a \bar qq scenario. The narrow pi-pi width of the f_0(980) and the large value: |g_{f K+K-}|/|g_{f pi+pi-}|=2.59(1.34), excludes its pure (\bar uu+\bar dd) content. A significant gluonium component eventually mixed with \bar qq appears to be necessary for evading the previous difficulties.Comment: 9 pages, 3 figures, 6 table

A Helminth Immunomodulator Exploits Host Signaling Events to Regulate Cytokine Production in Macrophages

Parasitic worms alter their host's immune system to diminish the inflammatory responses directed against them, using very efficient immunomodulating molecules. We have previously shown that the helminth immunomodulator cystatin (AvCystatin) profoundly reduces the progression of inflammatory diseases via modulation of macrophages. Here we elucidate the signaling events in macrophages triggered by AvCystatin. Labeled AvCystatin was predominantly taken up by macrophages and subsequently induced the phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2 and p38. IL-10 expression induced by AvCystatin in macrophages was tyrosine kinase sensitive and dependent on activation of both MAP kinases, in clear contrast to expression of IL-12/23p40. In addition, phosphorylation of the transcription factors CREB and STAT3 was induced by AvCystatin and regulated by phospho-ERK. Chemical inhibition of phosphoinositide 3-kinase (PI3K) reduced AvCystatin-induced cytokine release; however, AKT, the downstream target of PI3K, was not activated following AvCystatin exposure. To characterize signaling elements involved in alteration of the macrophage phenotype we applied mathematical modeling. Experimental testing of the in silico generated hypotheses identified dual specificity phosphatase (DUSP) 1 and 2, as regulators in AvCystatin triggered macrophages in vitro and in vivo. In particular, DUSP1 was subsequently found to be responsible for regulation of ERK- and p38-phosphorylation and controlled the IL-10 expression in macrophages by AvCystatin. Thus, we show that AvCystatin exploits activation and deactivation pathways of MAP kinases to induce regulatory macrophages. This study provides insights into molecular mechanisms of macrophage manipulation by parasites and highlights the utility of mathematical modeling for the elucidation of regulatory circuits of immune cells

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

The relative burden of community-acquired pneumonia hospitalizations in older adults: a retrospective observational study in the United States

Abstract Background The risk of community-acquired pneumonia (CAP) increases with age and significantly impacts morbidity and mortality in the elderly population. The burden of illness and cost of preventing CAP has not been compared to other serious diseases. Methods This retrospective analysis used claims data from 2014 to 2015 and compared hospitalizations for CAP, myocardial infarction (MI), stroke, and osteoporotic fractures (OF) in adults aged ≥65 years enrolled in a Medicare Advantage insurance plan. Individuals who had not already been hospitalized for one of these conditions and did not have evidence of long-term care were included in the study. Hospitalizations for each condition were described by length of stay, readmissions, mortality, and total costs. Preventive measures included vaccinations for CAP and medications for MI, stroke, and OF. Results A total of 1,949,352 individuals were included in the cohort. In 2015, the rate of CAP-related hospitalizations was the highest at 846.7 per 100,000 person-years compared to 405 for MI, 278.9 for stroke, and 343.9 for OF. Vaccination costs for CAP were $40.2 million including$14.1 million for pneumococcal and $26.1 million for influenza vaccines. The cost of preventive medications for MI and stroke reached over$661 million and OF totaled $169 million. Conclusions Although CAP has a higher burden of hospitalization and total costs than MI, stroke, and OF in the elderly population, prevention efforts were disproportionately smaller for CAP. Prioritization of CAP prevention is needed to substantially reduce the burden of CAP