Common Carp Disrupt Ecosystem Structure and Function Through Middle-out Effects

Middle-out effects or a combination of top-down and bottom-up processes create many theoretical and empirical challenges in the realm of trophic ecology. We propose using specific autecology or species trait (i.e. behavioural) information to help explain and understand trophic dynamics that may involve complicated and nonunidirectional trophic interactions. The common carp (Cyprinus carpio) served as our model species for whole-lake observational and experimental studies; four trophic levels were measured to assess common carp-mediated middle-out effects across multiple lakes. We hypothesised that common carp could influence aquatic ecosystems through multiple pathways (i.e. abiotic and biotic foraging, early life feeding, nutrient). Both studies revealed most trophic levels were affected by common carp, highlighting strong middle-out effects likely caused by common carp foraging activities and abiotic influence (i.e. sediment resuspension). The loss of water transparency, submersed vegetation and a shift in zooplankton dynamics were the strongest effects. Trophic levels furthest from direct pathway effects were also affected (fish life history traits). The present study demonstrates that common carp can exert substantial effects on ecosystem structure and function. Species capable of middle-out effects can greatly modify communities through a variety of available pathways and are not confined to traditional top-down or bottom-up processes

Improving implementation of evidence based practice for people with psychosis through training the wider workforce: Results of the GOALS feasibility randomised controlled trial

BACKGROUND AND OBJECTIVES: There is a pressing need to improve access to evidence-based practice for people with psychosis. The primary aim of this study was to assess clinical feasibility of a manualised, evidence-based CBT intervention (GOALS) targeting a personalised recovery goal, delivered by the frontline workforce, following brief training. Secondly, we aimed to conduct preliminary statistical analyses of key outcomes and costs. METHODS:\ud The GOALS study is a feasibility randomised controlled trial (ISRCTN 73188383). 75 participants with current psychosis were recruited and randomly allocated to receive either treatment as usual alone or with GOALS therapy. RESULTS: Brief training enabled frontline staff to deliver the therapy according to protocol and 74% of therapy participants partially or fully achieved their goals. There were significant improvements with a moderate effect size of 0.56 on goal attainment. However, preliminary statistical analyses found no significant differences between groups on our primary outcome of activity levels or other secondary outcomes Health economic analysis found that point estimates of costs, controlling for baseline costs, implied savings (even including intervention costs), but the difference was not statistically significant. LIMITATIONS: The study was designed as a feasibility RCT, and therefore the results of secondary estimates of efficacy effects should be treated with caution. CONCLUSIONS: This approach holds promise in supporting people with psychosis to reach personal recovery goals, cost effectively

Agricultural intensification and the evolution of host specialism in the enteric pathogen Campylobacter jejuni.

Modern agriculture has dramatically changed the distribution of animal species on Earth. Changes to host ecology have a major impact on the microbiota, potentially increasing the risk of zoonotic pathogens being transmitted to humans, but the impact of intensive livestock production on host-associated bacteria has rarely been studied. Here, we use large isolate collections and comparative genomics techniques, linked to phenotype studies, to understand the timescale and genomic adaptations associated with the proliferation of the most common food-born bacterial pathogen (Campylobacter jejuni) in the most prolific agricultural mammal (cattle). Our findings reveal the emergence of cattle specialist C. jejuni lineages from a background of host generalist strains that coincided with the dramatic rise in cattle numbers in the 20th century. Cattle adaptation was associated with horizontal gene transfer and significant gene gain and loss. This may be related to differences in host diet, anatomy, and physiology, leading to the proliferation of globally disseminated cattle specialists of major public health importance. This work highlights how genomic plasticity can allow important zoonotic pathogens to exploit altered niches in the face of anthropogenic change and provides information for mitigating some of the risks posed by modern agricultural systems

Alteration of Proteins and Pigments Influence the Function of Photosystem I under Iron Deficiency from Chlamydomonas reinhardtii

BACKGROUND: Iron is an essential micronutrient for all organisms because it is a component of enzyme cofactors that catalyze redox reactions in fundamental metabolic processes. Even though iron is abundant on earth, it is often present in the insoluble ferric [Fe (III)] state, leaving many surface environments Fe-limited. The haploid green alga Chlamydomonas reinhardtii is used as a model organism for studying eukaryotic photosynthesis. This study explores structural and functional changes in PSI-LHCI supercomplexes under Fe deficiency as the eukaryotic photosynthetic apparatus adapts to Fe deficiency. RESULTS: 77K emission spectra and sucrose density gradient data show that PSI and LHCI subunits are affected under iron deficiency conditions. The visible circular dichroism (CD) spectra associated with strongly-coupled chlorophyll dimers increases in intensity. The change in CD signals of pigments originates from the modification of interactions between pigment molecules. Evidence from sucrose gradients and non-denaturing (green) gels indicates that PSI-LHCI levels were reduced after cells were grown for 72 h in Fe-deficient medium. Ultrafast fluorescence spectroscopy suggests that red-shifted pigments in the PSI-LHCI antenna were lost during Fe stress. Further, denaturing gel electrophoresis and immunoblot analysis reveals that levels of the PSI subunits PsaC and PsaD decreased, while PsaE was completely absent after Fe stress. The light harvesting complexes were also susceptible to iron deficiency, with Lhca1 and Lhca9 showing the most dramatic decreases. These changes in the number and composition of PSI-LHCI supercomplexes may be caused by reactive oxygen species, which increase under Fe deficiency conditions. CONCLUSIONS: Fe deficiency induces rapid reduction of the levels of photosynthetic pigments due to a decrease in chlorophyll synthesis. Chlorophyll is important not only as a light-harvesting pigment, but also has a structural role, particularly in the pigment-rich LHCI subunits. The reduced level of chlorophyll molecules inhibits the formation of large PSI-LHCI supercomplexes, further decreasing the photosynthetic efficiency

Comparative Genomic Analysis of Clinical Strains of Campylobacter jejuni from South Africa

BACKGROUND: Campylobacter jejuni is a common cause of acute gastroenteritis and is also associated with the post-infectious neuropathies, Guillain-Barré and Miller Fisher syndromes. In the Cape Town area of South Africa, C. jejuni strains with Penner heat-stable (HS) serotype HS:41 have been observed to be overrepresented among cases of Guillain-Barré syndrome. The present study examined the genetic content of a collection of 32 South African C. jejuni strains with different serotypes, including 13 HS:41 strains, that were recovered from patients with enteritis, Guillain-Barré or Miller Fisher syndromes. The sequence-based typing methods, multilocus sequence typing and DNA microarrays, were employed to potentially identify distinguishing features within the genomes of these C. jejuni strains with various disease outcomes. METHODOLOGY/PRINCIPAL FINDINGS: Comparative genomic analyses demonstrated that the HS:41 South African strains were clearly distinct from the other South African strains. Further DNA microarray analysis demonstrated that the HS:41 strains from South African patients with the Guillain-Barré syndrome or enteritis were highly similar in gene content. Interestingly, the South African HS:41 strains were distinct in gene content when compared to HS:41 strains from other geographical locations due to the presence of genomic islands, referred to as Campylobacter jejuni integrated elements (CJIEs). Only the integrated element CJIE1, a Campylobacter Mu-like prophage, was present in the South African HS:41 strains whereas this element was absent in two closely-related HS:41 strains from Mexico. A more distantly-related HS:41 strain from Canada possessed both integrated elements CJIE1 and CJIE2. CONCLUSION/SIGNIFICANCE: These findings demonstrate that CJIEs may contribute to the differentiation of closely-related C. jejuni strains. In addition, the presence of bacteriophage-related genes in CJIE1 may contribute to the genomic diversity of C. jejuni strains. This comparative genomic analysis of C. jejuni provides fundamental information that potentially could lead to improved methods for analyzing the epidemiology of disease outbreaks

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Early mobilisation in mechanically ventilated patients:A systematic integrative review of definitions and activities

From PubMed via Jisc Publications RouterHistory: received 2018-10-23, accepted 2018-12-11Publication status: epublishMechanically ventilated patients often develop muscle weakness post-intensive care admission. Current evidence suggests that early mobilisation of these patients can be an effective intervention in improving their outcomes. However, what constitutes early mobilisation in mechanically ventilated patients (EM-MV) remains unclear. We aimed to systematically explore the definitions and activity types of EM-MV in the literature. Whittemore and Knafl's framework guided this review. CINAHL, MEDLINE, EMBASE, PsycINFO, ASSIA, and Cochrane Library were searched to capture studies from 2000 to 2018, combined with hand search of grey literature and reference lists of included studies. The Critical Appraisal Skills Programme tools were used to assess the methodological quality of included studies. Data extraction and quality assessment of studies were performed independently by each reviewer before coming together in sub-groups for discussion and agreement. An inductive and data-driven thematic analysis was undertaken on verbatim extracts of EM-MV definitions and activities in included studies. Seventy-six studies were included from which four major themes were inferred: (1) , (2) , (3) and (4) . The first theme indicates that EM-MV is either not fully defined in studies or when a definition is provided this is not standardised across studies. The remaining themes reflect the diversity of EM-MV activities which depends on patients' characteristics and ICU settings; the negotiated decision-making process between patients and staff; and their interdependent relationship during the implementation. This review highlights the absence of an agreed definition and on what constitutes early mobilisation in mechanically ventilated patients. To advance research and practice an agreed and shared definition is a pre-requisite