Purpose
There is growing enthusiasm for robotic-assisted laparoscopic operations across many surgical specialities, including colorectal surgery, often not supported by robust clinical or ...cost-effectiveness data. A proper assessment of this new technology is required, prior to widespread recommendation or implementation.
Methods/design
The ROLARR trial is a pan-world, prospective, randomised, controlled, unblinded, superiority trial of robotic-assisted versus standard laparoscopic surgery for the curative treatment of rectal cancer. It will investigate differences in terms of the rate of conversion to open operation, rate of pathological involvement of circumferential resection margin, 3-year local recurrence, disease-free and overall survival rates and also operative morbidity and mortality, quality of life and cost-effectiveness. The primary outcome measure is the rate of conversion to open operation. For 80% power at the 5% (two-sided) significance level, to identify a relative 50% reduction in open conversion rate (25% to 12.5%), 336 patients will be required. The target recruitment is 400 patients overall to allow loss to follow-up. Patients will be followed up at 30 days and 6 months post-operatively and then annually until 3 years after the last patient has been randomised.
Discussion
In many centres, robotic-assisted surgery is being implemented on the basis of theoretical advantages, which have yet to be confirmed in practice. Robotic surgery is an expensive health care provision and merits robust evaluation. The ROLARR trial is a pragmatic trial aiming to provide a comprehensive evaluation of both robotic-assisted and standard laparoscopic surgery for the curative resection of rectal cancer.
Atomoxetine selectively inhibits the reuptake of norepinephrine. Given the noradrenergic system's role in executive function, pharmacotherapy options that affect norepinephrine are of particular ...clinical interest in Parkinson disease-related executive dysfunction.
The aim of this study was to assess the efficacy and safety of atomoxetine for Parkinson disease-related executive dysfunction.
MEDLINE (1946 to May 2018) and EMBASE (1947 to May 2018) were queried using the search term combination: Parkinson's disease, Parkinson disease, inhibition, impulse behavior, impulse control disorder, executive function, executive dysfunction, cognition, cognitive dysfunction, cognitive defect, response inhibition, strategic planning, strategy, or verbal fluency and atomoxetine hydrochloride or atomoxetine. Studies analyzed for relevance evaluated clinical outcomes of patients treated with atomoxetine for Parkinson disease-related executive dysfunction. Studies appropriate to the objective were evaluated, including 1 open-label flexible dose trial, 2 placebo-controlled longitudinal trials, and 4 placebo-controlled crossover single-dose trials.
In patients with Parkinson disease, treatment with atomoxetine resulted in improvements in several markers of executive dysfunction including impulsivity, risk taking, and global cognition. Study durations ranged from single-dose trials to 10 weeks and used varying doses of atomoxetine. Atomoxetine was well tolerated in most studies with some reports of gastrointestinal adverse effects and insomnia.
Based on the reviewed literature, atomoxetine continues to be a therapy of interest for the treatment of executive dysfunction in patients with Parkinson disease. Larger long-term trials are necessary to further define the role of atomoxetine for patients with Parkinson disease-related executive dysfunction.
Anthropogenic nutrient enrichment is driving global biodiversity decline and modifying ecosystem functions. Theory suggests that plant functional types that fix atmospheric nitrogen have a ...competitive advantage in nitrogen-poor soils, but lose this advantage with increasing nitrogen supply. By contrast, the addition of phosphorus, potassium, and other nutrients may benefit such species in low-nutrient environments by enhancing their nitrogen-fixing capacity. We present a global-scale experiment confirming these predictions for nitrogen-fixing legumes (Fabaceae) across 45 grasslands on six continents. Nitrogen addition reduced legume cover, richness, and biomass, particularly in nitrogen-poor soils, while cover of non-nitrogen-fixing plants increased. The addition of phosphorous, potassium, and other nutrients enhanced legume abundance, but did not mitigate the negative effects of nitrogen addition. Increasing nitrogen supply thus has the potential to decrease the diversity and abundance of grassland legumes worldwide regardless of the availability of other nutrients, with consequences for biodiversity, food webs, ecosystem resilience, and genetic improvement of protein-rich agricultural plant species.
Background
To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for ...patients who underwent primary surgery +/− adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine‐enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after “standard‐of‐care” SOC rehabilitation.
Method
Pilot prospective 8‐week (TEBER) program following 8 weeks of (SOC) rehabilitation.
Results
Twenty‐seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, “range‐of‐liquids” improved by +0.36 95% CI, 0.02–0.70, p = 0.05 and “range‐of‐solids” improved by +0.73 95% CI, 0.12–1.34, p = 0.03. There was a positive trend toward better oral cavity obliteration; residual volume decreased by −1.2 95% CI, −2.45 to 0.053, p = 0.06, and “nutritional‐mode” increased by +0.55 95% CI, −0.15 to 1.24, p = 0.08.
Conclusion
This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.
The Drosophila polyadenosine RNA binding protein Nab2, which is orthologous to a human protein lost in a form of inherited intellectual disability, controls adult locomotion, axon projection, ...dendritic arborization, and memory through a largely undefined set of target RNAs. Here, we show a specific role for Nab2 in regulating splicing of ~150 exons/introns in the head transcriptome and focus on retention of a male-specific exon in the sex determination factor Sex-lethal (Sxl) that is enriched in female neurons. Previous studies have revealed that this splicing event is regulated in females by N6-methyladenosine (m6A) modification by the Mettl3 complex. At a molecular level, Nab2 associates with Sxl pre-mRNA in neurons and limits Sxl m6A methylation at specific sites. In parallel, reducing expression of the Mettl3, Mettl3 complex components, or the m6A reader Ythdc1 rescues mutant phenotypes in Nab2 flies. Overall, these data identify Nab2 as an inhibitor of m6A methylation and imply significant overlap between Nab2 and Mettl3 regulated RNAs in neuronal tissue.
T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL- 17 ...response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6⁺ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6⁺Vδ4⁺ T cells in immunity against S. aureus skin infections.
•Youth who leave home or care without permission are at risk for CSE.•Youth prefer smaller group care settings that are closer to home.•Group care settings should incorporate the attributes preferred ...by youth.•Group home staff must be trained on CSE and minimize stigmatizing youth.
Identifying safe and stable housing is of critical importance for the prevention of commercial sexual exploitation (CSE) among children and youth involved in the child welfare or juvenile justice systems living in out of home care. The current study seeks to explore youth’s experiences, opinions, and perceptions of out of home care, with a focus on group care, in order to identify what types of living situations are preferred and how out of home care can be improved. A convenience sample of 121 girls and young women responded to a survey about out of home care. Just over half were identified as having experienced CSE (60%: n = 73) and all youth were involved in either the juvenile justice or child welfare system. Overall, youth preferred unlocked out of home care options that were closer to home and/or more home-like (e.g., small group homes or foster homes). Youth reported several pros and cons of each out of home care option and offered their opinions on how to improve care. Youth with histories of CSE were more likely to run away from home or care but there were several similarities in running behavior between both groups, highlighting the need for prevention efforts among youth who leave care without permission as well as the importance of identifying stable housing. Grounded in the youth’s voice and perspective, several specific recommendations for improving out of home care options are offered based on the findings.
Host shifts to new plant species can drive speciation for plant-feeding insects, but how commonly do host shifts also drive diversification for the parasites of those same insects? Oak gall wasps ...induce galls on oak trees and shifts to novel tree hosts and new tree organs have been implicated as drivers of oak gall wasp speciation. Gall wasps are themselves attacked by many insect parasites, which must find their hosts on the correct tree species and organ, but also must navigate the morphologically variable galls with which they interact. Thus, we ask whether host shifts to new trees, organs, or gall morphologies correlate with gall parasite diversification. We delimit species and infer phylogenies for two genera of gall kleptoparasites, Synergus and Ceroptres, reared from a variety of North American oak galls. We find that most species were reared from galls induced by just one gall wasp species, and no parasite species was reared from galls of more than four species. Most kleptoparasite divergence events correlate with shifts to non-ancestral galls. These shifts often involved changes in tree habitat, gall location, and gall morphology. Host shifts are thus implicated in driving diversification for both oak gall wasps and their kleptoparasitic associates.
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