Soil organisms in organic and conventional cropping systems.

Apesar do crescente interesse pela agricultura orgânica, são poucas as informações de pesquisa disponíveis sobre o assunto. Assim, num Argissolo Vermelho-Amarelo distrófico foram comparados os efeitos de sistemas de cultivo orgânico e convencional, para as culturas do tomate (Lycopersicum esculentum) e do milho (Zea mays), sobre a comunidade de organismos do solo e suas atividades. As populações de fungos,bactérias e actinomicetos, determinadas pela contagem de colônias em meio de cultura, foram semelhantes para os dois sistemas de produção. A atividade microbiana, avaliada pela evolução de CO2, manteve-se superior no sistema orgânico, sendo que em determinadas avaliações foi o dobro da evolução verificada no sistema convencional. O número de espécimes de minhoca foi praticamente dez vezes maior no sistema orgânico. Não foi observada diferença na taxa de decomposição de matéria orgânica entre os dois sistemas. De modo geral, o número de indivíduos de microartrópodos foi superior no sistema orgânico do que no sistema convencional, refletindo no maior índice de diversidade de Shannon. As maiores populações de insetos foram as da ordem Collembola, enquanto para os ácaros a maior população foi a da superfamília Oribatuloidea. Indivíduos dos grupos Aranae, Chilopoda, Dyplopoda, Pauropoda, Protura e Symphyla foram ocasionalmente coletados e de forma similar entre os sistemas

Factors associated with depression and anxiety in the adult population of Qatar after the first COVID-19 wave: a cross-sectional study

There is limited data from Arabic-speaking countries on risk factors for depression and anxiety during the COVID-19 pandemic. Country-specific data is necessary given differences in culture, demographics, and COVID-19 infection and mortality rates. The main purpose of the study is to identify the factors associated with symptoms of depression-anxiety in the adult population of Qatar during the first year of the COVID-19 pandemic. We conducted a cross-sectional online survey in Qatar between July and December 2020 after Qatar’s first COVID-19 wave and before the beginning of the second wave. Depression-anxiety was defined as a cut-off of 20 or higher on the Patient Health Questionnaire-Anxiety Depression Scale (PHQ-ADS). Of 1138 participants, 71.0% were female, 69.0% Arabs, 70.0% Non-Qataris, and 77.0% were < 40 years (the median age in Qatar is 32 years). In a fully-adjusted model, six variables were significantly associated with moderate-to-severe levels of depression or anxiety on the PHQ-ADS; Arab ethnicity (OR = 1.67, p = 0.026), never married versus married (OR = 1.69, p = 0.015), prior history of psychiatric disorder versus no history (OR = 1.80, p = 0.009), increased worries due to social media use for COVID-related news/updates (OR = 1.72, p = 0.003), a history of COVID-19 (OR = 1.76, p = 0.039), loneliness (OR = 1.91, p < 0.001), and lower levels of religiosity (OR = 0.96, p = 0.039). These associations also pertained in the reduced model, with the exception of religiosity which was only marginally statistically significant (OR = 0.97, p = 0.055). The potential risk factors identified may assist with anxiety and depression prevention in future COVID-19 waves, and similar national events, and assist with early intervention to treat sufferers

Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open -label phase III study

Background: Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients. Patients and methods: Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response. Results: Patients were randomly assigned to receive durvalumab (n 1⁄4 240), durvalumab plus tremelimumab (n 1⁄4 247), or SoC (n 1⁄4 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72e1.08; P 1⁄4 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85e1.26; P 1⁄4 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9e43.1), 30.4% (24.7e36.3), and 30.5% (24.7 e36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade !3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Conclusion: There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab

Discovery of distinct immune phenotypes using machine learning in pulmonary arterial hypertension

RATIONALE: Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, though it remains unknown if distinct immune phenotypes exist. OBJECTIVE: Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles. METHODS AND RESULTS: In a prospective observational study of Group 1 PAH patients evaluated at Stanford University (discovery cohort, n=281) and University of Sheffield (validation cohort, n=104) between 2008-2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks- cluster 1 (n=58)(TRAIL, CCL5, CCL7, CCL4, MIF), cluster 3 (n=77)(IL-12, IL-17, IL-10, IL-7, VEGF), and cluster 4 (n=37)(IL-8, IL-4, PDGF-β, IL-6, CCL11). Demographics, PAH etiologies, comorbidities, and medications were similar across clusters. Non-invasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%, CI 35.4-64.1%) and favorable for cluster 3 (82.4%, CI 72.0-94.3%)(across-cluster p<0.001). Findings were replicated in the validation cohort, where machine learning classified four immune clusters with comparable proteomic, clinical, and prognostic features. CONCLUSIONS: Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization Group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity

Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis:a randomised controlled pilot and feasibility study

Summary Background Little evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis. Methods We did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197. Findings Of 138 patients referred to the study, 75 were recruited and randomly assigned—26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44·5 weeks (IQR 26–51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (–5·65 [95% CI −10·37 to −0·93]; p=0·019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (–4·52 [95% CI −9·30 to 0·26]; p=0·064) or between the antipsychotics and CBT groups (–1·13 [95% CI −5·81 to 3·55]; p=0·637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in the antipsychotics (3·22 [95% CI 0·58 to 5·87]; p=0·017) or antipsychotics plus CBT (3·99 [95% CI 1·36 to 6·64]; p=0·003) groups. Only one serious adverse event was thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group). Interpretation A head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two is feasible and safe in people with first-episode psychosis

Effect of cylinder deactivation on tribological performance of piston compression ring and connecting rod bearing

Thermo-mixed-hydrodynamics of compression rings and big-end bearings are presented. Frictional losses under normal engine operating conditions for a gasoline engine and those with cylinder deactivation (CDA) are predicted. With CDA, the combustion chamber pressure increases in the active cylinders, whilst some residual pressure remains in the deactivated ones. For the former, the increased in-cylinder temperatures reduce viscous friction, whilst reducing the load carrying capacity, promoting increased boundary interactions. In deactivated cylinders, lower contact temperatures yield increased viscous friction. Overall, a 5% improvement in expended fuel is expected with the application of CDA. However, 10% of these gains are expended due to increased friction. The study demonstrates the need to consider total system effects when introducing new technologies such as CDA

Study Protocol for a Randomised Controlled Trial of CBT vs Antipsychotics vs Both in 14–18-year-olds: Managing Adolescent First Episode Psychosis: a Feasibility Study (MAPS)

Background Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and family intervention (FI). The evidence for APs in treating psychosis is limited in adolescents compared to adults. Nevertheless, it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects, including cardiovascular and metabolic effects, than in adults. CBT and FI can improve outcomes in adults, but there are no studies of psychological interventions (PI) in patients under 18 years old. Given this limited evidence base, NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP. Methods/design The current study aimed to establish the feasibility and acceptability of conducting such a trial by recruiting 14–18-year-olds with a first episode of psychosis into a feasibility prospective randomised open blinded evaluation (PROBE) design, three-arm, randomised controlled trial of APs alone versus PI alone versus a combination of both treatments. We aimed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites. APs were prescribed by participants’ usual psychiatrists. PI comprised standardised cognitive behavioural therapy and family intervention sessions. Discussion This is the first study to compare APs to PI in an adolescent population with FEP. Recruitment finished on 31 October 2018. The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences. Trial registration Current controlled trial with ISRCTN, ISRCTN80567433. Registered on 27 February 2017

Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study

Head and neck squamous cell carcinoma (HNSCC) is among the 10 most common cancers worldwide, with increasing incidence.1 Approximately 10% of patients with HNSCC will be diagnosed with metastatic disease, and even when treated early, around half will have disease recurrence.2,3 The platinum-based doublet chemotherapy with cetuximab regimen has been the most widely-used therapy and considered standard of care (SoC) since it was proven effective in 2007 for recurrent/metastatic (R/M) HNSCC in the first-line setting.3,4 However, patients typically progress even after aggressive first-line therapy, and, until recently, the available options (e.g. cetuximab, methotrexate, and taxanes) have delivered limited survival benefits.3 Durvalumab is an immunotherapeutic agent that blocks the interaction between programmed cell death ligand 1 (PD-L1) and its receptors.5 Durvalumab demonstrated encouraging response rates and duration of response (DoR) with a manageable safety profile in patients with HNSCC.6 Although monotherapy agents that block the programmed cell death protein 1 (PD-1)/PD-L1 axis have shown clinical activity, immunotherapy combinations have the potential to improve upon monotherapy activity.7e9 Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and PD-L1/PD-1 pathways have largely non-redundant roles, suggesting that blockade of both could have additive or synergistic effects.10 Indeed, the combination of durvalumab and tremelimumab, an anti-CTLA-4 monoclonal antibody, was explored based on improved efficacy over monotherapy in other solid tumor types.7 This observation, in addition to the activity demonstrated by durvalumab in earlier R/M HNSCC studies, served as the rationale to evaluate durvalumab and tremelimumab in patients with R/M HNSCC. Several studies, including the EAGLE study, were initiated to evaluate combination immunotherapy regimens in various patient groups.11,12 The EAGLE study was the first phase III study to investigate durvalumab and tremelimumab in patients with R/M HNSCC who had progressed after platinumbased therapy. During the conduct of the EAGLE study, anti-PD-1 monoclonal antibodies were approved for use for R/M HNSCC progression following a platinum-based regimen. Treatment with these immunotherapies resulted in a median overall survival (OS) of 7.5e8.4 months.13,14 These immunotherapies are now recommended for second-line treatment as monotherapies for patients with R/M HNSCC.3,13,14 More recently, immunotherapy alone or in combination with platinum-based chemotherapy has shown improvements in OS in the first-line setting, underscoring the clinical utility of immunotherapy in HNSCC.15 Here, we report the results of the randomized phase III EAGLE trial evaluating durvalumab and durvalumab plus tremelimumab versus SoC therapies in patients with R/M HNSCC who have progressed following a platinumcontaining regimen