Balancing productivity, profitability, and environmental health is a key challenge for agricultural sustainability. Most crop production systems in the United States are characterized by low species ...and management diversity, high use of fossil energy and agrichemicals, and large negative impacts on the environment. We hypothesized that cropping system diversification would promote ecosystem services that would supplement, and eventually displace, synthetic external inputs used to maintain crop productivity. To test this, we conducted a field study from 2003–2011 in Iowa that included three contrasting systems varying in length of crop sequence and inputs. We compared a conventionally managed 2-yr rotation (maize-soybean) that received fertilizers and herbicides at rates comparable to those used on nearby farms with two more diverse cropping systems: a 3-yr rotation (maize-soybean-small grain + red clover) and a 4-yr rotation (maize-soybean-small grain + alfalfa-alfalfa) managed with lower synthetic N fertilizer and herbicide inputs and periodic applications of cattle manure. Grain yields, mass of harvested products, and profit in the more diverse systems were similar to, or greater than, those in the conventional system, despite reductions of agrichemical inputs. Weeds were suppressed effectively in all systems, but freshwater toxicity of the more diverse systems was two orders of magnitude lower than in the conventional system. Results of our study indicate that more diverse cropping systems can use small amounts of synthetic agrichemical inputs as powerful tools with which to tune, rather than drive, agroecosystem performance, while meeting or exceeding the performance of less diverse systems.
Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and ...substantia nigra, where they play a role in learning and control of motivated actions. However, the pattern of CB1-R expression across different striatal compartments, microcircuits and efferent targets, and the contribution of different CB1-R-expressing neurons to this pattern, are unclear. We use a combination of conventional techniques and novel genetic models to evaluate CB1-R expression in striosome (patch) and matrix compartments of the striatum, and in nigral targets of striatal medium spiny projection neurons (MSNs). CB1-R protein and mRNA follow a descending dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with elevated expression in striosomes relative to the surrounding matrix. The lateral predominance of striosome CB1-Rs contrasts with that of the classical striosomal marker, the mu opioid receptor (MOR), which is expressed most prominently in rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P. This topology of CB1-R expression is maintained downstream in the globus pallidus and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally within the substantia nigra pars reticulata, and colocalize with bundles of ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons in the substantia nigra pars compacta (striosome-dendron bouquets). Within striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice, demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is local MSN collaterals. These data suggest a role for CB1-Rs in caudal dorsolateral striosome collaterals and striosome-dendron bouquet projections to lateral substantia nigra, where they are anatomically poised to mediate presynaptic disinhibition of both striosomal MSNs and midbrain dopamine neurons in response to endocannabinoids and cannabinomimetics.
Summary
Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. This phase Ib study evaluated vantictumab in combination ...with nab-paclitaxel and gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma. Patients received vantictumab at escalating doses in combination with standard dosing of nab-paclitaxel and gemcitabine according to a 3 + 3 design. A total of 31 patients were treated in 5 dosing cohorts. Fragility fractures attributed to vantictumab occurred in 2 patients in Cohort 2 (7 mg/kg every 2 weeks), and this maximum administered dose (MAD) on study was considered unsafe. The dosing schedule was revised to every 4 weeks for Cohorts 3 through 5, with additional bone safety parameters added. Sequential dosing of vantictumab followed by nab-paclitaxel and gemcitabine was also explored. No fragility fractures attributed to vantictumab occurred in these cohorts; pathologic fracture not attributed to vantictumab was documented in 2 patients. The study was ultimately terminated due to concerns around bone-related safety, and thus the maximum tolerated dose (MTD) of the combination was not determined. The MAD of vantictumab according to the revised dosing schedule was 5 mg/kg (
n
= 16).
Objectives
To determine the standardised body mass index (BMIz) trajectory before and after adenotonsillectomy/tonsillectomy between children in different weight classifications in a larger sample ...than has been studied previously, and to identify which patient factors would explain the difference in these outcomes.
Design
We used a retrospective chart review and leveraged data of weight status pre‐ and post‐adenotonsillectomy/tonsillectomy from a cohort of paediatric patients seen between May 2004 and April 2017.
Setting
Data were collected from an electronic medical record at a single Midwest paediatric health system.
Participants
The study population included a convenience sample of 1,751 paediatric patients who underwent adenotonsillectomy or tonsillectomy and had at least two height and weight measurements recorded on the same date both before and after surgery.
Main Outcome Measures
Change in BMIz trajectories before and after surgery.
Results
Of 1751 paediatric patients (ages 3‐11) underwent adenotonsillectomy/tonsillectomy procedures. Age at time of surgery and gender were not significant predictors. Children in different weight classifications demonstrated differences in BMIz trajectory after surgery. Children with overweight/obesity experience a decrease in BMIz, whereas children with underweight or normal weight experience an increase in BMIz.
Conclusions
Improvement in weight status is seen after surgery: increased BMI for those underweight and decreased BMI for those with overweight/obesity. We advocate for behavioural strategies as a first‐line treatment in children with underweight or overweight/obesity, and results suggest that coordinating these efforts alongside adenotonsillectomy/tonsillectomy when indicated for medical reasons may be warranted. However, further research is needed to confirm these findings due to the observational nature of this study.
Given the limited evidence available, the impact of nasogastric (NG) tube placement on swallowing in children is not well understood. When a child needs to be fed enterally, the current standard is ...to initially place an NG tube and leave it in place for the first few months of supplemental or total enteral nutrition. It is important to understand if placement of NG tubes has a negative effect on a patient's swallow.
We retrospectively reviewed the charts of those children who had videofluoroscopic swallow studies (VFSS) to identify all children who had an NG tube in place at the time of swallow study. Age and sex matched children were identified who had undergone VFSS without an NG in place. These charts were reviewed for diagnosis at the time of the VFSS and presence or absence of aspiration or laryngeal penetrations.
Sixty-three children with NG tubes were identified, along with 63 age and sex matched children without NG tubes in place, at the time of VFSS. Ages ranged from 7 days to 13 years. The NG group had a significantly higher proportion demonstrating aspiration (46% vs. 23.8%, p = 0.0089).
This study supports the need for further prospective evaluation of NG tubes and their effect on swallow, as well as more careful consideration of prolonged NG tube placement in patients with feeding problems. Consideration should be given to removal of the NG prior to VFSS to prevent the impact of NG placement on results of the swallow study which could lead to inappropriate modifications to the patient's care plan.
Objective To evaluate brain activation in response to common food and nonfood logos in healthy weight and obese children. Study design Ten healthy weight children (mean body mass index in the 50th ...percentile) and 10 obese children (mean body mass index in the 97.9th percentile) completed self-report measures of self-control. They then underwent functional magnetic resonance imaging while viewing food and nonfood logos. Results Compared with the healthy weight children, obese children showed significantly less brain activation to food logos in the bilateral middle/inferior prefrontal cortex, an area involved in cognitive control. Conclusion When shown food logos, obese children showed significantly less brain activation than the healthy weight children in regions associated with cognitive control. This provides initial neuroimaging evidence that obese children may be more vulnerable to the effects of food advertising.
Rural children are more at risk for childhood obesity but may have difficulty participating in pediatric weight management clinical trials if in-person visits are required. Remote assessment of ...height and weight observed via videoconferencing may provide a solution by improving the accuracy of self-reported data. This study aims to validate a low-cost, scalable video-assisted protocol for remote height and weight measurements in children and caregivers. Families were provided with low-cost digital scales and tape measures and a standardized protocol for remote measurements. Thirty-three caregiver and child (6-11 years old) dyads completed remote (at home) height and weight measurements while being observed by research staff via videoconferencing, as well as in-person measurements with research staff. We compared the overall and absolute mean differences in child and caregiver weight, height, body mass index (BMI), and child BMI adjusted Z-score (BMIaz) between remote and in-person measurements using paired samples t-tests and one sample t-tests, respectively. Bland-Altman plots were used to estimate the limits of agreement (LOA) and assess systematic bias. Simple regression models were used to examine associations between measurement discrepancies and sociodemographic factors and number of days between measurements. Overall mean differences in child and caregiver weight, height, BMI, and child BMIaz were not significantly different between remote and in-person measurements. LOAs were - 2.1 and 1.7 kg for child weight, - 5.2 and 4.0 cm for child height, - 1.5 and 1.7 kg/m
for child BMI, - 0.4 and 0.5 SD for child BMIaz, - 3.0 and 2.8 kg for caregiver weight, - 2.9 and 3.9 cm for caregiver height, and - 2.1 and 1.6 kg/m
for caregiver BMI. Absolute mean differences were significantly different between the two approaches for all measurements. Child and caregiver age were each significantly associated with differences between remote and in-person caregiver height measurements; there were no significant associations with other measurement discrepancies. Remotely observed weight and height measurements using non-research grade equipment may be a feasible and valid approach for pediatric clinical trials in rural communities. However, researchers should carefully evaluate their measurement precision requirements and intervention effect size to determine whether remote height and weight measurements suit their studies.Trial registration: ClinicalTrials.gov NCT04142034 (29/10/2019).
The purpose of this study is to describe and assess a remote height and weight protocol that was developed for an ongoing trial conducted during the SARS COV-2 pandemic.
Thirty-eight rural families ...(children 8.3 ± 0.7 years; 68% female; and caregivers 38.2 ± 6.1 years) were provided detailed instructions on how to measure height and weight. Families obtained measures via remote data collection (caregiver weight, child height and weight) and also by trained staff. Differences between data collection methods were examined.
Per absolute mean difference analyses, slightly larger differences were found for child weight (0.21 ± 0.21 kg), child height (1.53 ± 1.29 cm), and caregiver weight (0.48 ± 0.42 kg) between school and home measurements. Both analyses indicate differences had only minor impact on child BMI percentile (- 0.12, 0.68) and parent BMI (0.05, 0.13). Intraclass coefficients ranged from 0.98 to 1.00 indicating that almost all of the variance was due to between person differences and not measurement differences within a person.
Results suggest that remote height and weight collection is feasible for caregivers and children and that there are minimal differences in the various measurement methods studied here when assessing group differences. These differences did not have clinically meaningful impacts on BMI. This is promising for the use of remote height and weight measurement in clinical trials, especially for hard-to reach-populations.
Clinical. Registered in clinicaltrials.gov ( NCT03304249 ) on 06/10/2017.
There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised.
To ...develop consensus statements for all domains of DAT.
A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed.
A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion.
Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials.
We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers.
The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations has developed comprehensive consensus statements for deferred active treatment for localised prostate cancer covering all domains, aimed at guiding and informing routine clinical practice and research.
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