To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
To develop a risk score for deep sternal wound infection (DSWI) after isolated coronary artery bypass grafting (CABG).
Multicenter, prospective study.
Tertiary-care referral hospitals.
The study included 7,352 patients from the European multicenter coronary artery bypass grafting (E-CABG) registry.
An additive risk score (the E-CABG DSWI score) was estimated from the derivation data set (66.7% of patients), and its performance was assessed in the validation data set (33.3% of patients).
DSWI occurred in 181 (2.5%) patients and increased 1-year mortality (adjusted hazard ratio, 4.275; 95% confidence interval [CI], 2.804–6.517). Female gender (odds ratio [OR], 1.804; 95% CI, 1.161–2.802), body mass index ≥30 kg/m2 (OR, 1.729; 95% CI, 1.166–2.562), glomerular filtration rate <45 mL/min/1.73 m2 (OR, 2.410; 95% CI, 1.413–4.111), diabetes (OR, 1.741; 95% CI, 1.178–2.573), pulmonary disease (OR, 1.935; 95% CI, 1.178–3.180), atrial fibrillation (OR, 1.854; 95% CI, 1.096–3.138), critical preoperative state (OR, 2.196; 95% CI, 1.209–3.891), and bilateral internal mammary artery grafting (OR, 2.088; 95% CI, 1.422–3.066) were predictors of DSWI (derivation data set). An additive risk score was calculated by assigning 1 point to each of these independent risk factors for DSWI. In the validation data set, the rate of DSWI increased along with the E-CABG DSWI scores (score of 0, 1.0%; score of 1, 1.8%; score of 2, 2.2%; score of 3, 6.9%; score ≥4: 12.1%; P < .0001). Net reclassification improvement, integrated discrimination improvement, and decision curve analysis showed that the E-CABG DSWI score performed better than other risk scores.
DSWI is associated with poor outcome after CABG, and its risk can be stratified using the E-CABG DSWI score.
Drawing on the new institutional theory and the resources based view of the firm (RBV), this study tries to shed light upon the idea that isomorphic organizational changes seek legitimacy over efficiency. Using data from 102 Spanish companies and employing partial least squares, a variance-based structural equation modeling technique, this study concludes that both objectives are achievable simultaneously when firms implement total quality management (TQM) as an integrative stream of both theories. Furthermore, empirical results reveal that: (i) institutional pressures (IP) condition significantly the implementation of TQM, (ii) TQM exerts a double mediating role in the IP-legitimacy and IP-efficiency relationships, and (iii) both efficiency and legitimacy objectives are achieved by means of TQM. However, we observe a dual phenomenon: (i) while we find a significant positive effect of TQM on overall performance (OP) via efficiency and (ii) we failed to find support for the TQM-OP link via legitimacy.
Diaphragm dysfunction following surgery for congenital heart disease is a known complication leading to delays in recovery and increased post-operative morbidity and mortality. We aimed to determine the incidence of and risk factors associated with diaphragm plication in children undergoing cardiac surgery and evaluate timing to repair and effects on hospital cost and length of stay.
We conducted a multi-institutional retrospective observational cohort study. Forty-three hospitals from the Pediatric Health Information System database were included, and a total of 112,110 patients admitted between January 2004 and December 2014 were analysed.
Patients less than 18 years of age who underwent cardiac surgery were included. Risk Adjustment for Congenital Heart Surgery was utilized to determine procedure complexity. The overall incidence of diaphragm dysfunction was 2.2% (n = 2513 out of 112,110). Of these, 24.0% (603 patients) underwent diaphragm plication. Higher complexity cardiac surgery (Risk Adjustment for Congenital Heart Surgery 5–6) and age less than 4 weeks were associated with a higher likelihood of diaphragm plication (p-value < 0.01). Diaphragmatic plication was associated with increased hospital length of stay (p-value < 0.01) and increased medical cost.
Diaphragm plication after surgery for congenital heart disease is associated with longer hospital length of stay and increased cost. There is a strong correlation of prolonged time to plication with increased length of stay and medical cost. The likelihood of plication increases with younger age and higher procedure complexity. Methods to improve early recognition and treatment of diaphragm dysfunction should be developed.
This research attempts to systematically establish shape descriptor states through elliptic Fourier analysis (EFA) using pili (Canarium ovatum Engl.) kernel as a model. Kernel images of 53 pili accessions from the National Plant Genetic Resources Laboratory (NPGRL), University of the Philippines Los Baños were acquired using VideometerLab 3. Shape features, such as roundness, compactness and elongation, were extracted from the images. Shapes outlines were characterized using elliptic Fourier coefficients calculated from SHAPE version 1.3 software. Principal component analysis and cluster analysis were used to elucidate clusters representing the shape descriptor states. The first principal component accounts for the variation in length to width ratio; whereas, the second and third principal components explain the variation in the location of the widest portion and the truncation of the apex and base of the kernel, respectively. Cluster analysis separated the different accessions into six distinct clusters at 0.04 Euclidian distance. Six descriptor states, narrowly elliptic, elliptic, widely elliptic, ovate, obovate and lance-ovate, were characterized from the shape outlines and visualized through R's shape on r package. The discrimination between clusters was validated through MANOVA and LDA with 95% correct classification. The Fourier coefficients were also able to represent the variation observed from the physical properties of shape. The method may be used in establishing shape descriptors of all plant parts of all crop species.
Femoral vein access is the first choice for percutaneous atrial septal defect closure, and when it cannot be used due to anatomic reasons, the alternative sites should be considered, frequently increasing the complexity of the procedure. Here we report the case of a 3-year-old boy, with situs inversus and dextrocardia, electively referred for percutaneous closure of an ostium secundum atrial septal defect. During the procedure, agenesis of the infra-hepatic segment of the inferior caval vein was diagnosed, and no double inferior caval vein or right superior caval vein were identified by ultrasound or angiography. Therefore, we opted to perform the procedure through the left internal jugular vein, with fluoroscopy and transesophageal echocardiographic guidance. Catheters were navigated through a hydrophilic guidewire, and a Stiff guidewire was positioned in the left ventricle for better support. An Amplatzer septa occluder 19 was successfully deployed without major difficulties and the patient was discharged after 24 hours in good clinical condition. Percutaneous atrial septal defect closure through alternative access sites, especially in the presence of situs inversus, may pose significant challenges to the interventional team. In this case, the left internal jugular vein has shown to be a feasible option, allowing the navigation and manipulation of devices without complications. Provided the expertise of the interventional team, and awareness of the risks involved, alternative access sites can be successfully used for paediatric structural interventions.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg−1 day−1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.
Weed management is a major challenge in organic crop production, and organic farms generally harbor larger weed populations and more diverse communities compared with conventional farms. However, little research has been conducted on the effects of different organic management practices on weed communities and crop yields. In 2014 and 2015, we measured weed community structure and soybean [Glycine max (L.) Merr.] yield in a long-term experiment that compared four organic cropping systems that differed in nutrient inputs, tillage, and weed management intensity: (1) high fertility (HF), (2) low fertility (LF), (3) enhanced weed management (EWM), and (4) reduced tillage (RT). In addition, we created weed-free subplots within each system to assess the impact of weeds on soybean yield. Weed density was greater in the LF and RT systems compared with the EWM system, but weed biomass did not differ among systems. Weed species richness was greater in the RT system compared with the EWM system, and weed community composition differed between RT and other systems. Our results show that differences in weed community structure were primarily related to differences in tillage intensity, rather than nutrient inputs. Soybean yield was lower in the EWM system compared with the HF and RT systems. When averaged across all four cropping systems and both years, soybean yield in weed-free subplots was 10% greater than soybean yield in the ambient weed subplots that received standard management practices for the systems in which they were located. Although weed competition limited soybean yield across all systems, the EWM system, which had the lowest weed density, also had the lowest soybean yield. Future research should aim to overcome such trade-offs between weed control and yield potential, while conserving weed species richness and the ecosystem services associated with increased weed diversity.
The savannah enclaves (i.e. patches) in the southern Brazilian Amazonia are among the most threatened and poorly surveyed sites in Amazonia. As part of an extensive mammal survey, we set camera traps in three of these savannah enclaves. We obtained 23 independent records of pampas deer Ozotoceros bezoarticus, a medium sized Neotropical cervid that is strongly associated with open habitats and categorized as Vulnerable on the Brazilian Red List of threatened species. These savannah enclaves with confirmed populations of pampas deer lie outside the species’ previously presumed historical range and are at least 350 km from any known extant population. Together, these savannah enclaves add c. 4,000 km2 to the pampas deer's currently known range. The small pampas deer populations in these enclaves are probably isolated by a matrix of Amazon forest, raising questions about spatial genetic structure and meta-population dynamics, and making them vulnerable to local extinction. We highlight the need for further studies, particularly genetic, to assess the conservation status of these populations, the results of which could potentially inform management decisions in other areas of the heavily fragmented range of this species.
Some authors advocate the use of a dedicated formula to predict the Fontan pressure starting from pre-Fontan catheterisation data. This paper aims at testing the predictive value of the mentioned formula through a retrospective clinical study.
Methods and Results:
Pre-Fontan catheterisation data and Fontan pressure measured at the completion were retrospectively collected. Pre-Fontan data were used to calculate the predicted pressure in the Fontan system. The predicted values were compared to the Fontan pressure measured at the Fontan completion and with the needs for fenestration. One hundred twenty-four Fontan patients were retrospectively enrolled (At Fontan: median age 30.73 [24.70–37.20] months, median weight 12.00 [10.98–14.15] kg). Fontan conduit was fenestrated in 78 patients. A poor correlation (r2 = 0.05128) between the measured and predicted data for non-fenestrated patients was observed. In the case of Fontan-predicted pressure <17.59 mmHg, the formula identified a good short-term clinical outcome with a sensitivity of 92%.
The proposed formula showed a poor capability in estimating the actual pressure into the Fontan system and in identifying patients needing fenestration. As the pressure into the Fontan system is determined by multiple factors, the tested formula could be an additional data in a multi-parametric approach.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
To evaluate the quality and content of free smoking cessation apps and assess their adherence to the US Public Health Service guideline for treating tobacco use and dependence.
In total 180 apps were downloaded from the App Store and Google Play Store in January 2018; the top-ranking 30 apps were retrieved for the search terms: ‘smoking cessation’, ‘quit smoking’, ‘stop smoking’. Technical quality was rated using the Mobile Application Rating Scale (MARS) and by assessing other characteristics, behavioral change strategies and adherence to the 5As.
A total 67 free-to-download apps were identified for full review (n = 40 from the Apple App Store and n = 27 from the Google Play Store). The average MARS score was 16.2/19.0: Engagement (3.3/5.0), Functionality (4.4/5.0), Aesthetics (4.0/5.0), and Information (2.6/5.0). Overall, 43 apps allowed sharing, 12 allowed for an app community, and five required a password. The following features were observed: assessment (n = 51), feedback (n = 38), information/education (n = 45), monitoring (n = 52), and goal setting (n = 23). Significant differences were found among apps adhering to the 5As: Ask (n = 44), Advise (n = 54), Assess (n = 30), Assist (n = 62), and Arrange (n = 0).
Given the growth in smoking cessation apps, future efforts should focus on improving their technical quality and adherence to the 5As.
Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls.
Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry.
Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls.
Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.
Exceptional sub-micrometer details of shell microstructure are preserved in phosphatic micro-steinkerns representing several phyla from shell beds of the Upper Ordovician of the Cincinnati Arch region, USA. These fossils provide the most detailed record of Ordovician mollusk shell microstructures, as well as exceptional details on the earliest cases of undisputed nacre. The trend towards nacre in the Mollusca is one aspect of the surge in escalation between mollusks and their predators during the Great Ordovician Biodiversification Event.
To compare the accuracy of Mini-Mental State Examination (MMSE) and of the Montreal Cognitive Assessment (MoCA) in tracking mild cognitive impairment (MCI) and Alzheimer’s Disease (AD).
A Systematic review of the PubMed, Bireme, Science Direct, Cochrane Library, and PsycInfo databases was conducted. Using inclusion and exclusion criteria and staring with 1,629 articles, 34 articles were selected. The quality of the selected research was evaluated through the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2).
More than 80% of the articles showed MoCA to be superior to MMSE in discriminating between individuals with mild cognitive impairment and no cognitive impairment. The area under the curve varied from 0.71 to 0.99 for MoCA, and 0.43 to 0.94 for MMSE, when evaluating the ability to discriminate MCI in the cognitively healthy elderly individuals, and 0.87 to 0.99 and 0.67 to 0.99, respectively, when evaluating the detection of AD. The AUC mean value for MoCA was significantly larger compared to the MMSE in discriminating MCI from control [0.883 (CI 95% 0.855-0.912) vs MMSE 0.780 (CI 95% 0.740-0.820) p < 0.001].
The screening tool MoCA is superior to MMSE in the identification of MCI, and both tests were found to be accurate in the detection of AD.
The current study aims to evaluate the effects of increasing levels of xylanase enzyme (XYL) on sugarcane silage fermentation, fermentative losses, chemical composition, dry matter (DM), neutral detergent fibre (NDF) degradation and aerobic stability. A completely randomized design trial was performed with five treatments and 50 experimental silos. Treatments were: 0, 100, 200, 300 and 400 mg of XYL per kg of DM. XYL contained 10 000 U/g. There was a quadratic effect of XYL on silage pH and acetic acid concentration: lower pH and higher acetic acid concentrations were found at intermediary levels of the enzyme. XYL decreased lactic acid concentration linearly. Furthermore, the enzyme had a quadratic effect on effluent and total losses, with higher losses at intermediary XYL levels. There was a quadratic effect of XYL on organic matter (OM), non-fibre carbohydrates (NFC) and crude protein (CP) content. In addition, a quadratic effect of XYL was observed on NDF content and degradation. Intermediary levels of XYL showed higher concentration of OM and NFC. The addition of XYL had no effect on silage temperature and pH after aerobic exposure. Thus, intermediate levels of XYL increased acetic acid and decreased silage pH. Besides positive effects on silage composition, intermediary XYL levels decreased NDF degradation.
A systematic method for determining colour descriptor states using image analysis is proposed using pili (Canarium ovatum) as a model. Kernel images of 52 pili accessions from the core collection of the Institute of Crop Science and National Plant Genetic Resources Laboratory, University of the Philippines Los Baños were captured using a calibrated VideometerLab 3 setup. Colour descriptor states were derived from the average International Commission on Illumination lightness (L*), green–red (a*) and blue–yellow (b*) colour component values. Cluster analysis and subsequent colour-parameter averaging per cluster were performed to produce representative colour values of descriptor states. The Euclidian distance (Delta E) of 3.5 was used to cut the cluster into readily distinguishable colour differences resulting to three descriptor states – light brown, brown and dark brown. Continuous colour variation of brown colour was observed indicating a possible quantitative nature of the trait. The use of delta E in elucidating the descriptor lists served as a gauge in successfully identifying distinguishable variations between colours. The method described can be applied to the elucidation of colour descriptor states of all parts of the plant of all crop species.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).