Impact of nitrogen (N) and phosphorus (P) enrichment and skewed N:P stoichiometry on the skeletal formation and microstructure of symbiotic reef corals.

Reported divergent responses of coral growth and skeletal microstructure to the nutrient environment complicate knowledge-based management of water quality in coral reefs. By re-evaluating published results considering the taxonomy of the studied corals and the N:P stoichiometry of their nutrient environment, we could resolve some of the major apparent contradictions. Our analysis suggests that Acroporids behave differently to several other common genera and show distinct responses to specific nutrient treatments. We hypothesised that both the concentrations of dissolved inorganic N and P in the water and their stoichiometry shape skeletal growth and microstructure. We tested this hypothesis by exposing Acropora polystoma fragments to four nutrient treatments for > 10 weeks: high nitrate/high phosphate (HNHP), high nitrate/low phosphate (HNLP), low nitrate/high phosphate (LNHP) and low nitrate/low phosphate (LNLP). HNHP corals retained high zooxanthellae densities and their linear extension and calcification rates were up to ten times higher than in the other treatments. HNLP and LNLP corals bleached through loss of symbionts. The photochemical efficiency (Fv/Fm) of residual symbionts in HNLP corals was significantly reduced, indicating P-starvation. Micro-computed tomography (µCT) of the skeletal microstructure revealed that reduced linear extension in nutrient limited or nutrient starved conditions (HNLP, LNHP, LNLP) was associated with significant thickening of skeletal elements and reduced porosity. These changes can be explained by the strongly reduced linear extension rate in combination with a smaller reduction in the calcification rate. Studies using increased skeletal density as a proxy for past thermal bleaching events should consider that such an increase in density may also be associated with temperature-independent response to the nutrient environment. Furthermore, the taxonomy of corals and seawater N:P stoichiometry should be considered when analysing and managing the impacts of nutrient pollution. Supplementary Information: The online version contains supplementary material available at 10.1007/s00338-022-02223-0.

Erector spinae plane block vs. peri-articular injection for pain control after arthroscopic shoulder surgery: a randomised controlled trial.

Interscalene brachial plexus block is the standard regional analgesic technique for shoulder surgery. Given its adverse effects, alternative techniques have been explored. Reports suggest that the erector spinae plane block may potentially provide effective analgesia following shoulder surgery. However, its analgesic efficacy for shoulder surgery compared with placebo or local anaesthetic infiltration has never been established. We conducted a randomised controlled trial to compare the analgesic efficacy of pre-operative T2 erector spinae plane block with peri-articular infiltration at the end of surgery. Sixty-two patients undergoing arthroscopic shoulder repair were randomly assigned to receive active erector spinae plane block with saline peri-articular injection (n = 31) or active peri-articular injection with saline erector spinae plane block (n = 31) in a blinded double-dummy design. Primary outcome was resting pain score in recovery. Secondary outcomes included pain scores with movement; opioid use; patient satisfaction; adverse effects in hospital; and outcomes at 24 h and 1 month. There was no difference in pain scores in recovery, with a median difference (95%CI) of 0.6 (-1.9-3.1), p = 0.65. Median postoperative oral morphine equivalent utilisation was significantly higher in the erector spinae plane group (21 mg vs. 12 mg; p = 0.028). Itching was observed in 10% of patients who received erector spinae plane block and there was no difference in the incidence of significant nausea and vomiting. Patient satisfaction scores, and pain scores and opioid use at 24 h were similar. At 1 month, six (peri-articular injection) and eight (erector spinae plane block) patients reported persistent pain. Erector spinae plane block was not superior to peri-articular injection for arthroscopic shoulder surgery.

Identification of native endophytic Trichoderma spp. for investigation of in vitro antagonism towards Armillaria mellea using synthetic- and plant-based substrates.

AIMS: To isolate endophytic Trichoderma species and investigate the potential for biological control of the root rot pathogen Armillaria mellea. METHODS AND RESULTS: In all, 40 Trichoderma isolates were obtained from a range of host plants and identities were confirmed by ITS, rpb2 and tef1 sequence. When tested in dual culture assays for antagonism against A. mellea, Trichoderma isolates overgrew the A. mellea colonies within four days and by eight days 38 Trichoderma isolates significantly reduced A. mellea colony size. Armillaria mellea was unable to be recovered from five of eight co-cultivations tested, suggesting Trichoderma had killed the A. mellea in these cases. Pre-colonized hazel disks were used to determine what happens in a more heterogeneous situation with A. mellea and a refined set of eight Trichoderma isolates. Similar to plate-based assays, Trichoderma quickly covered A. mellea stopping any further growth and two Trichoderma isolates were able to eradicate A. mellea. CONCLUSIONS: Of the Trichoderma spp. tested, endophytic isolates of Trichoderma virens and T. hamatum offered the greatest antagonism towards A. mellea. Using pre-colonized hazel disks was of great importance for this work to demonstrate the fungal interactions in plant material. SIGNIFICANCE AND IMPACT OF THE STUDY: Controlling Armillaria root rot is difficult with chemical treatments, thus an environmentally benign and cost-effective alternative is required. This study highlights the prospect of biological control as an effective, environmentally friendly alternative to chemicals.

Plio-Pleistocene climate sensitivity evaluated using high-resolution CO2 records.

Theory and climate modelling suggest that the sensitivity of Earth's climate to changes in radiative forcing could depend on the background climate. However, palaeoclimate data have thus far been insufficient to provide a conclusive test of this prediction. Here we present atmospheric carbon dioxide (CO2) reconstructions based on multi-site boron-isotope records from the late Pliocene epoch (3.3 to 2.3 million years ago). We find that Earth's climate sensitivity to CO2-based radiative forcing (Earth system sensitivity) was half as strong during the warm Pliocene as during the cold late Pleistocene epoch (0.8 to 0.01 million years ago). We attribute this difference to the radiative impacts of continental ice-volume changes (the ice-albedo feedback) during the late Pleistocene, because equilibrium climate sensitivity is identical for the two intervals when we account for such impacts using sea-level reconstructions. We conclude that, on a global scale, no unexpected climate feedbacks operated during the warm Pliocene, and that predictions of equilibrium climate sensitivity (excluding long-term ice-albedo feedbacks) for our Pliocene-like future (with CO2 levels up to maximum Pliocene levels of 450 parts per million) are well described by the currently accepted range of an increase of 1.5 K to 4.5 K per doubling of CO2.

Boron isotope evidence for oceanic carbon dioxide leakage during the last deglaciation.

Atmospheric CO2 fluctuations over glacial-interglacial cycles remain a major challenge to our understanding of the carbon cycle and the climate system. Leading hypotheses put forward to explain glacial-interglacial atmospheric CO2 variations invoke changes in deep-ocean carbon storage, probably modulated by processes in the Southern Ocean, where much of the deep ocean is ventilated. A central aspect of such models is that, during deglaciations, an isolated glacial deep-ocean carbon reservoir is reconnected with the atmosphere, driving the atmospheric CO2 rise observed in ice-core records. However, direct documentation of changes in surface ocean carbon content and the associated transfer of carbon to the atmosphere during deglaciations has been hindered by the lack of proxy reconstructions that unambiguously reflect the oceanic carbonate system. Radiocarbon activity tracks changes in ocean ventilation, but not in ocean carbon content, whereas proxies that record increased deglacial upwelling do not constrain the proportion of upwelled carbon that is degassed relative to that which is taken up by the biological pump. Here we apply the boron isotope pH proxy in planktic foraminifera to two sediment cores from the sub-Antarctic Atlantic and the eastern equatorial Pacific as a more direct tracer of oceanic CO2 outgassing. We show that surface waters at both locations, which partly derive from deep water upwelled in the Southern Ocean, became a significant source of carbon to the atmosphere during the last deglaciation, when the concentration of atmospheric CO2 was increasing. This oceanic CO2 outgassing supports the view that the ventilation of a deep-ocean carbon reservoir in the Southern Ocean had a key role in the deglacial CO2 rise, although our results allow for the possibility that processes operating in other regions may also have been important for the glacial-interglacial ocean-atmosphere exchange of carbon.

An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence.

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.

Sea-level and deep-sea-temperature variability over the past 5.3 million years.

Ice volume (and hence sea level) and deep-sea temperature are key measures of global climate change. Sea level has been documented using several independent methods over the past 0.5 million years (Myr). Older periods, however, lack such independent validation; all existing records are related to deep-sea oxygen isotope (δ(18)O) data that are influenced by processes unrelated to sea level. For deep-sea temperature, only one continuous high-resolution (Mg/Ca-based) record exists, with related sea-level estimates, spanning the past 1.5 Myr. Here we present a novel sea-level reconstruction, with associated estimates of deep-sea temperature, which independently validates the previous 0-1.5 Myr reconstruction and extends it back to 5.3 Myr ago. We find that deep-sea temperature and sea level generally decreased through time, but distinctly out of synchrony, which is remarkable given the importance of ice-albedo feedbacks on the radiative forcing of climate. In particular, we observe a large temporal offset during the onset of Plio-Pleistocene ice ages, between a marked cooling step at 2.73 Myr ago and the first major glaciation at 2.15 Myr ago. Last, we tentatively infer that ice sheets may have grown largest during glacials with more modest reductions in deep-sea temperature.

Efficacy and safety results of patients with HCV genotype 2 or 3 infection treated with ombitasvir/paritaprevir/ritonavir and sofosbuvir with or without ribavirin (QUARTZ II-III).

The efficacy and safety of an investigational combination of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) plus sofosbuvir (SOF) ± ribavirin (RBV) in patients with HCV genotype 2 or 3 infection with or without cirrhosis was evaluated. Patients with HCV genotype 3 infection without cirrhosis were randomized to receive OBV/PTV/r + SOF ± RBV for 12 weeks; OBV/PTV/r + SOF + RBV was administered to genotype 3-infected patients with cirrhosis for 12 weeks and to genotype 2-infected patients without cirrhosis for either 6 or 8 weeks. Efficacy was assessed by sustained virologic response [HCV RNA <25 IU/mL] 12 weeks post-treatment (SVR12). Safety was assessed in all treated patients. In patients with genotype 3 infection with or without cirrhosis treated with 12 weeks of OBV/PTV/r + SOF ± RBV, the overall SVR12 rate was 98% (50/51), with no virologic failures. Patients with genotype 2 infection treated with OBV/PTV/r + SOF + RBV had SVR12 rates of 90% (9/10) and 44% (4/9) following 8- and 6-week treatment durations, respectively; failure to achieve SVR12 for these patients was due to relapse without baseline or treatment-emergent resistance-associated substitutions. Thus, the investigational combination of OBV/PTV/r with SOF ± RBV was well tolerated and achieved high SVR rates with no virologic failures in patients with genotype 3 infection. Combining direct-acting antivirals with complementary mechanisms of action and different viral targets may be an effective treatment strategy that may allow for shorter durations of therapy.

Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C-SCAPE study.

People with hepatitis C virus (HCV) infection other than genotype 1 represent a heterogeneous group. The aim of the phase 2 C-SCAPE study was to evaluate elbasvir/grazoprevir (EBR/GZR), with or without ribavirin (RBV), in participants with HCV genotype 2, 4, 5 or 6 infection. This was a part randomised, open-label, parallel-group study (NCT01932762; PN047-03) of treatment-naive, noncirrhotic participants. Participants with HCV genotype 2 infection received GZR 100 mg + RBV ± EBR 50 mg for 12 weeks and those with genotype 4, 5 or 6 infection were randomized to receive EBR/GZR ± RBV for 12 weeks. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12; HCV RNA <25 IU/mL). Among participants with genotype 2 infection, SVR12 was achieved by 80% (24/30) of those receiving EBR/GZR + RBV and 73% (19/26) of those receiving GZR + RBV. SVR rates were high in participants with HCV genotype 4 infection receiving EBR/GZR with and without RBV (100% [10/10] and 90% [9/10]; respectively). In contrast, the addition of RBV to EBR/GZR appeared to increase SVR12 in participants with genotype 5 infection (EBR/GZR, 25%; EBR/GZR + RBV 100% [4/4]). In participants with genotype 6 infection, SVR12 was 75% (3/4) in both those receiving EBR/GZR and those receiving EBR/GZR + RBV. The safety profile was similar across treatment arms, with adverse events tending to occur more frequently among participants receiving RBV. In conclusion, these data support the inclusion of participants with genotype 4 or 6 infection in the EBR/GZR phase 3 studies. EBR/GZR ± RBV was unsatisfactory for participants with genotype 2 or 5 infection.

Impact of baseline clinical and laboratory features on the risk of thrombosis in children with acute lymphoblastic leukemia: A prospective evaluation.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study. PROCEDURES: Samples collected prior to the start of ALL therapy were evaluated for genetic and acquired PDs (proteins C and S, antithrombin, procoagulant factors VIII (FVIII:C), IX, XI and von Willebrand factor antigen levels, gene polymorphisms of factor V G1691A, prothrombin gene G20210A and methylene tetrahydrofolate reductase C677T, anticardiolipin antibodies, fasting lipoprotein(a), and homocysteine). RESULTS: Of 131 enrolled patients (mean age [range] 6.4 [1-17] years) 70 were male patients and 20 patients (15%) developed sTE. Acquired or inherited PD had no impact on the risk of sTE. Multivariable analyses identified older age (odds ratio [OR] 1.13; 95% confidence interval [CI]: 1.01, 1.26) and non-O blood group (OR 3.64, 95% CI: 1.06, 12.51) as independent predictors for development of sTE. Patients with circulating blasts had higher odds of developing sTE (OR 6.66; 95% CI: 0.82, 53.85). CONCLUSION: Older age, non-O blood group, and presence of circulating blasts, but not PDs, predicted the risk of sTE during ALL therapy. We recommend evaluation of these novel risk factors in the development of ALL-associated TE. If confirmed, these easily accessible variables at diagnosis can help develop a risk-prediction model for ALL-associated TE.

Implementing routine blood-borne virus testing for HCV, HBV and HIV at a London Emergency Department - uncovering the iceberg?

UK guidelines recommend routine HIV testing in high prevalence emergency departments (ED) and targeted testing for HBV and HCV. The 'Going Viral' campaign implemented opt-out blood-borne virus (BBV) testing in adults in a high prevalence ED, to assess seroprevalence, uptake, linkage to care (LTC) rates and staff time taken to achieve LTC. Diagnosis status (new/known/unknown), current engagement in care, and severity of disease was established. LTC was defined as patient informed plus ⩾1 clinic visit. A total of 6211/24 981 ED attendees were tested (uptake 25%); 257 (4.1%) were BBV positive (15 co-infected), 84 (33%) required LTC. 100/147 (68%) HCV positives were viraemic; 44 (30%) required LTC (13 new, 16 disengaged). 26/54 (48%) HBV required LTC (seven new, 11 disengaged). 16/71 (23%) HIV required LTC (10 new, five disengaged). 26/84 (31%) patients requiring LTC had advanced disease (CD4 1, Fibroscan F3/F4 or liver cancer), including five with AIDS-defining conditions and three hepatocellular carcinomas. There were five BBV-related deaths. BBV prevalence was high (4.1%); most were HCV (2.4%). HIV patients were more successfully and quickly LTC than HBV or HCV patients. ED testing was valuable as one-third of those requiring LTC (new, disengaged or unknown status patients) had advanced disease.

Evaluation of PCR primers targeting the groEL gene for the specific detection of Streptococcus agalactiae in the context of aquaculture.

AIMS: The aim of this study was to design a set of primers for specific detection and identification of Streptococcus agalactiae in polymerase chain reaction (PCR) that can detect a diverse range of S. agalactiae isolates from different hosts and that it is capable of discriminating between S. agalactiae and other species that are closely related or potentially present in aquaculture environments, notably Streptococcus iniae. METHODS AND RESULTS: Primers, based on the groEL2 gene of S. agalactiae, were shown to be epidemiologically sensitive to 97 isolates of S. agalactiae, representing 11 clonal complexes derived from piscine, terrestrial and aquatic mammalian host species. The primers were tested with 10 S. iniae isolates and 22 other comparator species with no cross-reaction observed after optimization of reaction conditions. They have a high analytical sensitivity, detecting as few as 10 copies of S. agalactiae genomic DNA per reaction and are capable of detecting the target in DNA extracted from the brains of infected fish. CONCLUSIONS: The primers proved suitable for the sensitive and specific detection of S. agalactiae from dairy-, human- and fish-related origins by PCR. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to the importance of S. agalactiae as a pathogen, many PCR primers have been published for this bacterium, designed largely for its detection in dairy and human samples, but many cross-reacting with S. iniae. The ability to differentiate between S. agalactiae and S. iniae in aquaculture derived samples is important as both infect fish, causing similar disease symptoms and are phenotypically similar, yet control strategies and zoonotic risk are species specific.

Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial.

BACKGROUND: Obesity is strongly associated with prevalence of obstructive sleep apnea (OSA), and weight loss has been shown to reduce disease severity. OBJECTIVE: To investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea-hypopnea index (AHI) after 32 weeks. Liraglutide's weight loss efficacy was also examined. SUBJECTS/METHODS: In this randomized, double-blind trial, non-diabetic participants with obesity who had moderate (AHI 15-29.9 events h(-1)) or severe (AHI ⩾30 events h(-1)) OSA and were unwilling/unable to use continuous positive airway pressure therapy were randomized for 32 weeks to liraglutide 3.0 mg (n=180) or placebo (n=179), both as adjunct to diet (500 kcal day(-1) deficit) and exercise. Baseline characteristics were similar between groups (mean age 48.5 years, males 71.9%, AHI 49.2 events h(-1), severe OSA 67.1%, body weight 117.6 kg, body mass index 39.1 kg m(-2), prediabetes 63.2%, HbA1c 5.7%). RESULTS: After 32 weeks, the mean reduction in AHI was greater with liraglutide than with placebo (-12.2 vs -6.1 events h(-1), estimated treatment difference: -6.1 events h(-1) (95% confidence interval (CI), -11.0 to -1.2), P=0.0150). Liraglutide produced greater mean percentage weight loss compared with placebo (-5.7% vs -1.6%, estimated treatment difference: -4.2% (95% CI, -5.2 to -3.1%), P<0.0001). A statistically significant association between the degree of weight loss and improvement in OSA end points (P<0.01, all) was demonstrated post hoc. Greater reductions in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) were seen with liraglutide versus placebo (both P<0.001). The safety profile of liraglutide 3.0 mg was similar to that seen with doses ⩽1.8 mg. CONCLUSIONS: As an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA. The results confirm that weight loss improves OSA-related parameters.

Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign.

OBJECTIVES: Routine HIV screening is recommended in those UK hospitals and primary care settings where the HIV prevalence is > 0.2%. For hepatitis B virus (HBV) and hepatitis C virus (HCV), however, testing is targeted at at-risk groups. We investigated the prevalence of these blood-borne viruses (BBVs) during a routine testing pilot in UK Emergency Departments (EDs). METHODS: During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in areas of high HIV prevalence offered routine tests for HIV, HBV and HCV to adults having blood taken as part of routine care. Patients who tested positive were linked to care. RESULTS: A total of 7807 patients had blood taken during their ED visit; of these, 2118 (27%) were tested for BBVs (range 9-65%). Seventy-one BBV tests were positive (3.4%) with 32 (45.1%) new diagnoses. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged 25-54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Assuming the cost per diagnosis is £7, the cost per new case detected would be £988 for HCV, £1351 for HBV and £2478 for HIV. CONCLUSIONS: In the first study in the UK to report prospectively on BBV prevalence in the ED, we identified a high number of new viral hepatitis diagnoses, especially hepatitis C, in addition to the HIV diagnoses. Testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.

Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin.

Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.

The good, the bad and the tasty: The many roles of mushrooms.

Fungi are often inconspicuous in nature and this means it is all too easy to overlook their importance. Often referred to as the "Forgotten Kingdom", fungi are key components of life on this planet. The phylum Basidiomycota, considered to contain the most complex and evolutionarily advanced members of this Kingdom, includes some of the most iconic fungal species such as the gilled mushrooms, puffballs and bracket fungi. Basidiomycetes inhabit a wide range of ecological niches, carrying out vital ecosystem roles, particularly in carbon cycling and as symbiotic partners with a range of other organisms. Specifically in the context of human use, the basidiomycetes are a highly valuable food source and are increasingly medicinally important. In this review, seven main categories, or 'roles', for basidiomycetes have been suggested by the authors: as model species, edible species, toxic species, medicinal basidiomycetes, symbionts, decomposers and pathogens, and two species have been chosen as representatives of each category. Although this is in no way an exhaustive discussion of the importance of basidiomycetes, this review aims to give a broad overview of the importance of these organisms, exploring the various ways they can be exploited to the benefit of human society.

The combined effects of maternal depression and excess weight on neonatal outcomes.

OBJECTIVE: Maternal overweight/obesity and depression are among the most prevalent pregnancy complications, and although individually they are associated with poor pregnancy outcomes, their combined effects are unknown. Owing to this, the objective of this study was to determine the prevalences and the individual and combined effects of depression and overweight/obesity on neonatal outcomes. METHODS: A retrospective cohort study of all singleton hospital births at >20 weeks gestation in Ontario, Canada (April 2007 to March 2010) was conducted. The primary outcome measure was a composite neonatal outcome, which included: stillbirth, neonatal death, preterm birth, birth weight <2500 g, <5% or >95%, admission to a neonatal special care unit, or a 5-min Apgar score <7. RESULTS: Among the 70,605 included women, 49.7% had a healthy pre-pregnancy BMI, whereas 50.3% were overweight/obese; depression was reported in 5.0% and 6.2%, respectively. Individually, depression and excess pre-pregnancy weight were associated with an increased risk of adverse neonatal outcomes, but the highest risk was seen when they were both present (16% of non-depressed healthy weight pregnant women, 19% of depressed healthy weight women, 20% of non-depressed overweight/obese women and 24% of depressed overweight/obese women). These higher risks of adverse neonatal outcomes persisted after accounting for potential confounding variables, such as maternal age, education and pre-existing health problems (adjusted odds ratio (OR) 1.22, 95% confidence interval (CI) 1.13-1.33, adjusted OR 1.23, 95% CI 1.18-1.28 and adjusted OR 1.42, 95% CI 1.31-1.54, in the last three groups above, respectively, relative to non-depressed healthy weight women). There was no significant interaction between weight category and depression (P=0.2956). CONCLUSIONS: When dually present, maternal overweight/obesity and depression combined have the greatest impact on the risk of adverse neonatal outcomes. Our findings have important public health implications given the exorbitant proportions of both of these risk factors.

Pregnancy complications associated with the co-prevalence of excess maternal weight and depression.

OBJECTIVES: Obesity and depression have become prevalent pregnancy complications, individually associated with adverse perinatal health outcomes. Despite the co-prevalence of these two risk factors, their combined effects on maternal health are yet to be studied. The objective of this study was to examine the combined associations of overweight/obesity and depression with maternal and delivery complications. METHODS: A retrospective cohort study of women with singleton gestations at >20 weeks, in Ontario, Canada (April 2007 to March 2010), was conducted. Our primary outcomes were a composite of maternal complications (for example, gestational hypertension, pre-eclampsia, preterm premature rupture of membranes and so on), and a composite of delivery complications (for example, caesarean delivery, shoulder dystocia, postpartum haemorrhage and so on). RESULTS: The study population consisted of 70 605 women, of whom 50.3% were overweight/obese. Depression was reported in 5.0% of normal-weight women and 6.2% of overweight/obese women. The proportion of women with maternal complications was the highest among the overweight/obese depressed pregnant women (16% of normal-weight non-depressed, 22% of normal-weight depressed, 22% of overweight/obese non-depressed and 29% of overweight/obese depressed, P<0.001), as was the proportion of women with delivery complications (44%, 49%, 50% and 53%, respectively, P<0.001). Overweight/obese depressed pregnant women also experienced the highest odds of the composite of maternal complications and the composite of delivery complications (adjusted odds ratio (OR): 1.55, 95% confidence interval (CI): 1.35-1.77 and OR: 1.27, 95% CI: 1.13-1.42, respectively) after adjustment for potential confounders. CONCLUSIONS: The combined associations of excess weight and depression with adverse pregnancy outcomes are important to recognize in order to focus counselling and care, both before and during pregnancy.

Systematic analysis of funding awarded for viral hepatitis-related research to institutions in the United Kingdom, 1997-2010.

Viral hepatitis is responsible for great health, social and economic burden both globally and in the UK. This study aimed to assess the research funding awarded to UK institutions for viral hepatitis research and the relationship of funded research to clinical and public health burden of viral hepatitis. Databases and websites were systematically searched for information on infectious disease research studies funded for the period 1997-2010. Studies specifically related to viral hepatitis research were identified and categorized in terms of funding by pathogen, disease and by a research and development value chain describing the type of science. The overall data set included 6165 studies (total investment £2.6 billion) of which £76.9 million (3.0%) was directed towards viral hepatitis across 323 studies (5.2%). By pathogen, there were four studies specifically investigating hepatitis A (£3.8 million), 69 studies for hepatitis B (21.4%) with total investment of £14.7 million (19.1%) and 236 (73.1%) hepatitis C studies (£62.7 million, 81.5%). There were 4 studies investigating hepatitis G, and none specifying hepatitis D or E. By associated area, viral hepatitis and therapeutics research received £17.0 million, vaccinology £3.1 million and diagnostics £2.9 million. Preclinical research received £50.3 million (65.4%) across 173 studies, whilst implementation and operational research received £19.4 million (25.3%) across 128 studies. The UK is engaged in much hepatology research, but there are areas where the burden is great and may require greater focus, such as hepatitis E, development of a vaccine for hepatitis C, and further research into hepatitis-associated cancers. Private sector data, and funding information from other countries, would also be useful in priority setting.