Extending periodic eddy covariance latent heat fluxes through tree sap-flow measurements to estimate long-term total evaporation in a peat swamp forest

A combination of measurement and modelling was used to find a pragmatic solution to estimate the annual total evaporation from the rare and indigenous Nkazana Peat Swamp Forest (PSF) on the east coast of Southern Africa to improve the water balance estimates within the area. Actual total evaporation (ETa) was measured during three window periods (between 7 and 9 days each) using an eddy covariance (EC) system on a telescopic mast above the forest canopy. Sap flows of an understory tree and an emergent tree were measured using a low-maintenance heat pulse velocity system for an entire hydrological year (October 2009 to September 2010). An empirical model was derived, describing the relationship between ETa from the Nkazana PSF and sap-flow measurements. These overlapped during two of the window periods (R2 = 0.92 and 0.90), providing hourly estimates of ETa from the Nkazana PSF for a year, totalling 1125 mm (while rainfall was 650 mm). In building the empirical model, it was found that to include the understory tree sap flow provided no benefit to the model performance. In addition, the relationship between the emergent tree sap flow with ETa between the two field campaigns was consistent and could be represented by a single empirical model (R2 = 0.90; RMSE = 0.08 mm h−1). During the window periods of EC measurement, no single meteorological variable was found to describe the Nkazana PSF ETa satisfactorily. However, in terms of evaporation models, the hourly FAO Penman–Monteith reference evaporation (ETo) best described ETa during the August 2009 (R2 = 0.75), November 2009 (R2 = 0.85) and March 2010 (R2 = 0.76) field campaigns, compared to the Priestley–Taylor potential evaporation (ETp) model (R2 = 0.54, 0.74 and 0.62 during the respective field campaigns). From the extended record of ETa (derived in this study from sap flow) and ETo, a monthly crop factor (Kc) was derived for the Nkazana PSF, providing a method of estimating long-term swamp forest water-use from meteorological data. The monthly Kc indicated two distinct periods. From February to May, it was between 1.2 and 1.4 compared with June to January, when the crop factor was 0.8 to 1.0. The derived monthly Kc values were verified as accurate (to one significant digit) using historical data measured at the same site, also using EC, from a previous study. The measurements provided insights into the microclimate within a subtropical peat swamp forest and the contrasting sap flow of emergent and understory trees. They showed that expensive, high-maintenance equipment can be used during manageable window periods in conjunction with low-maintenance systems, dedicated to individual trees, to derive a model to estimate long-term ETa over remote heterogeneous forests. In addition, the contrast in annual ETa and rainfall emphasised the reliance of the Nkazana PSF on groundwater

Co-occurrence of diabetes and hopelessness predicts adverse prognosis following percutaneous coronary intervention

We examined the impact of co-occurring diabetes and hopelessness on 3-year prognosis in percutaneous coronary intervention patients. Consecutive patients (n = 534) treated with the paclitaxel-eluting stent completed a set of questionnaires at baseline and were followed up for 3-year adverse clinical events. The incidence of 3-year death/non-fatal myocardial infarction was 3.5% in patients with no risk factors (neither hopelessness nor diabetes), 8.2% in patients with diabetes, 11.2% in patients with high hopelessness, and 15.9% in patients with both factors (p = 0.001). Patients with hopelessness (HR: 3.28; 95% CI: 1.49-7.23) and co-occurring diabetes and hopelessness (HR: 4.89; 95% CI: 1.86-12.85) were at increased risk of 3-year adverse clinical events compared to patients with no risk factors, whereas patients with diabetes were at a clinically relevant but not statistically significant risk (HR: 2.40; 95% CI: 0.82-7.01). These results remained, adjusting for baseline characteristics an

Living alone is a risk factor for mortality in men but not women from the general population: a prospective cohort study

During the past decades a rising trend of living alone can be observed in the population especially in urban areas. Living alone is considered a psychosocial risk factor. We studied the relationship between living alone, cardiovascular risk factors and mortality. We analysed data from the population-based MONICA/KORA cohort study including 3596 men and 3420 women of at least one of three surveys carried out between 1984 and 1995 in the region of Augsburg, Germany. They were between 45 and 74 years old and were followed-up until 31 December 2002. During follow-up 811 men and 388 women died. Cox proportional hazards analysis was used to examine the association between living alone and mortality

Explanations of socioeconomic differences in changes in physical function in older adults: results from the Longitudinal Aging Study Amsterdam

BACKGROUND: This study examines the association between socioeconomic status and changes in physical function in younger- (aged 55–70 years) and older-old (aged 70–85 years) adults and seeks to determine the relative contribution of diseases, behavioral, and psychosocial factors in explaining this association. METHODS: Data were from 2,366 men and women, aged 55–85 years, participating in the Longitudinal Aging Study Amsterdam (LASA). Two indicators of socioeconomic status were used: education and income. Physical function was measured by self-reported physical ability over nine years of follow-up. RESULTS: In older adults, low socioeconomic status was related to a poorer level of physical function during nine years of follow-up. In subjects who were between 55 and 70 years old, there was an additional significant socioeconomic-differential decline in physical function, while socioeconomic differentials did not further widen in subjects 70 years and older. Behavioral factors, mainly BMI and physical activity, largely explained the socioeconomic differences in physical function in the youngest age group, while psychosocial factors reduced socioeconomic status differences most in the oldest age group. CONCLUSION: The findings indicate age-specificity of both the pattern of socioeconomic status differences in function in older persons and the mechanisms underlying these associations

High Effectiveness of Broad Access Direct-Acting Antiviral Therapy for Hepatitis C in an Australian Real-World Cohort: The REACH-C Study

Australia was one of the first countries with unrestricted access to government subsidized direct-acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real-world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow-up. Real-world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH-C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention-to-treat (ITT) and per-protocol (PP) analyses. Within REACH-C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43-0.72), cirrhosis (aOR 0.52, 95% CI 0.41-0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46-0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28-0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow-up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44-2.11; IDU + OAT: aOR 1.39, 95% CI 1.11-1.74; OAT only, aOR 1.36; 95% CI 1.13-1.68) and age (aOR 0.97, 95% CI 0.97-0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow-up presents a real-world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow-up

Diffuse glioma growth: a guerilla war

In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies

Maximizing upgrading and downgrading margins for ordinal regression

In ordinal regression, a score function and threshold values are sought to classify a set of objects into a set of ranked classes. Classifying an individual in a class with higher (respectively lower) rank than its actual rank is called an upgrading (respectively downgrading) error. Since upgrading and downgrading errors may not have the same importance, they should be considered as two different criteria to be taken into account when measuring the quality of a classifier. In Support Vector Machines, margin maximization is used as an effective and computationally tractable surrogate of the minimization of misclassification errors. As an extension, we consider in this paper the maximization of upgrading and downgrading margins as a surrogate of the minimization of upgrading and downgrading errors, and we address the biobjective problem of finding a classifier maximizing simultaneously the two margins. The whole set of Pareto-optimal solutions of such biobjective problem is described as translations of the optimal solutions of a scalar optimization problem. For the most popular case in which the Euclidean norm is considered, the scalar problem has a unique solution, yielding that all the Pareto-optimal solutions of the biobjective problem are translations of each other. Hence, the Pareto-optimal solutions can easily be provided to the analyst, who, after inspection of the misclassification errors caused, should choose in a later stage the most convenient classifier. The consequence of this analysis is that it provides a theoretical foundation for a popular strategy among practitioners, based on the so-called ROC curve, which is shown here to equal the set of Pareto-optimal solutions of maximizing simultaneously the downgrading and upgrading margins

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Development of a transformation system for chlamydia trachomatis: restoration of glycogen biosynthesis by acquisition of a plasmid shuttle vector

Chlamydia trachomatis remains one of the few major human pathogens for which there is no transformation system. C. trachomatis has a unique obligate intracellular developmental cycle. The extracellular infectious elementary body (EB) is an infectious, electron-dense structure that, following host cell infection, differentiates into a non-infectious replicative form known as a reticulate body (RB). Host cells infected by C. trachomatis that are treated with penicillin are not lysed because this antibiotic prevents the maturation of RBs into EBs. Instead the RBs fail to divide although DNA replication continues. We have exploited these observations to develop a transformation protocol based on expression of ?-lactamase that utilizes rescue from the penicillin-induced phenotype. We constructed a vector which carries both the chlamydial endogenous plasmid and an E.coli plasmid origin of replication so that it can shuttle between these two bacterial recipients. The vector, when introduced into C. trachomatis L2 under selection conditions, cures the endogenous chlamydial plasmid. We have shown that foreign promoters operate in vivo in C. trachomatis and that active ?-lactamase and chloramphenicol acetyl transferase are expressed. To demonstrate the technology we have isolated chlamydial transformants that express the green fluorescent protein (GFP). As proof of principle, we have shown that manipulation of chlamydial biochemistry is possible by transformation of a plasmid-free C. trachomatis recipient strain. The acquisition of the plasmid restores the ability of the plasmid-free C. trachomatis to synthesise and accumulate glycogen within inclusions. These findings pave the way for a comprehensive genetic study on chlamydial gene function that has hitherto not been possible. Application of this technology avoids the use of therapeutic antibiotics and therefore the procedures do not require high level containment and will allow the analysis of genome function by complementatio