Developmental activities of elite junior hockey players: an analysis of early sport specialization.

Early sport specialization is a popular and contentious topic in the scientific literature and popular media. The lure of extrinsic rewards has led to increasing rates of specialization among young athletes, while expert recommendations promote multisport participation. The purpose of this study was to describe and analyze developmental activities of a group of elite junior hockey players in Canada. Within this context, elements of specialization were investigated in accordance with existing theoretical frameworks and long-term athlete development models to enhance the literature. Fifteen participants from the Ontario Hockey League completed quantitative retrospective interviews, detailing past sport and recreational activities. Thirty-one developmental milestones were assessed. Accumulated hours of activity were categorized in accordance with Côté's (1999) Developmental Model of Sports Participation, along with the number and types of sports in which they participated during childhood. Jayanthi et al.'s (2015) continuum was utilized to determine the age at which the athletes became moderately and highly specialized. Accrued hours of deliberate practice reported by participants increased from ages 6 to 16 years, as did competition in organized hockey games. Reported hours of deliberate play peaked at 9 years of age and decreased thereafter. Participants played a combined 16 sports other than hockey, ranging from an average of 2.0 at age 6, to a maximum average of 5.6 at 12 years old, and decreasing each year to 2.3 by age 15. The greatest number of hours in other sports was accumulated at 12 years of age. Using a three-point scale, participants considered themselves "highly specialized" at 14 years old; however, other quantitative indicators suggested this may have occurred at 12 years of age. Relative to previous research on early sport specialization, participants in this study spent more time practicing hockey, while ceasing hockey-specific play and other sports at younger ages. Despite a diverse sport history, hockey competition was initiated earlier than recommended, showing high levels of sport commitment as young as 9 years old. The early specialization path remains a popular trajectory among coaches, parents, and athletes in Canadian ice hockey.

Arbuscular Mycorrhizae Shift Community Composition of N-Cycling Microbes and Suppress Soil N2O Emission.

Mycorrhizae are ubiquitous symbiotic associations between arbuscular mycorrhizal fungi (AMF) and terrestrial plants, in which AMF receive photosynthates from and acquire soil nutrients for their host plants. Plant uptake of soil nitrogen (N) reduces N substrate for microbial processes that generate nitrous oxide (N2O), a potent greenhouse gas. However, the underlying microbial mechanisms remain poorly understood, particularly in agroecosystems with high reactive N inputs. We examined how plant roots and AMF affect N2O emissions, N2O-producing (nirK and nirS) and N2O-consuming (nosZ) microbes under normal and high N inputs in conventional (CONV) and organically managed (OM) soils. Here, we show that high N input increased soil N2O emissions and the ratio of nirK to nirS microbes. Roots and AMF did not affect the (nirK + nirS)/nosZ ratio but significantly reduced N2O emissions and the nirK/nirS ratio. They reduced the nirK/nirS ratio by reducing nirK-Rhodobacterales but increasing nirS-Rhodocyclales in the CONV soil while decreasing nirK-Burkholderiales but increasing nirS-Rhizobiales in the OM soil. Our results indicate that plant roots and AMF reduced N2O emission directly by reducing soil N and indirectly through shifting the community composition of N2O-producing microbes in N-enriched agroecosystems, suggesting that harnessing the rhizosphere microbiome through agricultural management might offer additional potential for N2O emission mitigation.

Genome-wide association study for morphological traits and resistance to Peryonella pinodes in the USDA pea single plant plus collection.

Peas (Pisum sativum) are the second most cultivated pulse crop in the world. They can serve as human food, fodder, and cover crop. The most serious foliar disease of pea cultivars worldwide is Ascochyta blight, which can be caused by several pathogens. Of these, Peyronella pinodes is the most aggressive and prevalent worldwide. Several traits, including resistance to Peyronella pinodes, stem diameter, internode length between nodes 2-3 and 5-6, and area of 7th leaf, were measured in 269 entries of the pea single plant plus collection. The heritability (H2) of the morphological traits was relatively high, while disease resistance had low heritability. Using 53,196 single-nucleotide polymorphism markers to perform a genome-wide association study to identify genomic loci associated with variation in all the traits measured, we identified 27 trait-locus associations, 5 of which were associated with more than 1 trait.

Shifts in the Composition and Activities of Denitrifiers Dominate CO2 Stimulation of N2O Emissions.

Elevated atmospheric CO2 (eCO2) often increases soil N2O emissions, but the underlying mechanisms remain largely unknown. One hypothesis suggests that high N2O emissions may stem from increased denitrification induced by CO2 enhancement of plant carbon (C) allocation belowground. However, direct evidence illustrating linkages among N2O emissions, plant C allocation, and denitrifying microbes under eCO2 is still lacking. We examined the impact of eCO2 on plant C allocation to roots and their associated arbuscular mycorrhizal fungi and its subsequent effects on N2O emissions and denitrifying microbes in the presence of two distinct N sources, ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N). Our results showed that the form of the N inputs dominated the effects of eCO2 on N2O emissions: eCO2 significantly increased N2O emissions with NO3--N inputs but had no effect with NH4+-N inputs. eCO2 increased plant biomass N more with NH4+-N than with NO3--N inputs, likely reducing microbial access to available N under NH4+-N inputs and/or contributing to higher N2O emissions under NO3--N inputs. eCO2 enhanced root and mycorrhizal N uptake and also increased N2O emissions under NO3--N inputs. Further, eCO2 enhancement of N2O emissions under NO3--N inputs concurred with a shift in the soil denitrifier community composition in favor of N2O-producing (nirK- and nirS-type) over N2O-consuming (nosZ-type) denitrifiers. Together, these results indicate that eCO2 stimulated N2O emissions mainly through altering plant N preference in favor of NH4+ over NO3- and thus stimulating soil denitrifiers and their activities. These findings suggest that effective management of N sources may mitigate N2O emissions by negating the eCO2 stimulation of soil denitrifying microbes and their activities.

Near-infrared spectroscopic models for analysis of winter pea (Pisum sativum L.) quality constituents.

BACKGROUND: Winter pea (Pisum sativum L.) grows well in a wide geographic region, both as a forage and cover crop. Understanding the quality constituents of this crop is important for both end uses; however, analysis of quality constituents by conventional wet chemistry methods is laborious, slow and costly. Near infrared reflectance spectroscopy (NIRS) is a precise, accurate, rapid and cheap alternative to using wet chemistry for estimating quality constituents. We developed and validated NIRS calibration models for constituent analysis of this crop. RESULTS: Of the 11 constituent models developed, nine constituents including moisture, dry-matter, total-nitrogen, crude protein, acid detergent fiber, neutral detergent fiber, AD-lignin, cellulose and non-fibrous carbohydrate had low standard errors and a high coefficient of determination (R2 = 0.88-0.98; 1 - VR, which is the coefficient of determination during cross-validation = 0.77-0.92) for both calibration and cross-validation, indicating their potential for quantitative predictability. The calibration models for ash (R2 = 0.65; 1 - VR = 0.46) and hemicellulose (R2 = 0.75; 1 - VR = 0.50) also appeared to be adequate for qualitative screening. Predictions of an independent validation set yielded reliable agreement between the NIRS predicted values and the reference values with low standard error of prediction (SEP), low bias, high coefficient of determination (r2 = 0.82-0.95), high ratios of performance to deviation (RPD = SD/SEP; 2.30-3.85) and high ratios of performance to interquartile distance (RPIQ = IQ/SEP; 2.57-7.59) for all 11 constituents. CONCLUSION: Precise, accurate and rapid analysis of winter pea for major forage and cover crop quality constituents can be performed at a low cost using the NIRS calibration models developed. © 2018 Society of Chemical Industry.

Impact of thrombelastography in paediatric intensive care.

We assessed the clinical impact of thrombelastography (TEG®) results (TEG® 5000, Haemonetics Corporation, Braintree, MA, USA) by measuring their ability to cause changes in a theoretical treatment plan and contribute to the understanding of haemostasis. We prospectively included paediatric intensive care unit (PICU) patients who had standard tests of haemostasis and TEG ordered and had an arterial catheter or extracorporeal access port in situ. Blood for standard tests and TEG was taken simultaneously. Independent of patient care, general patient information and results of standard laboratory tests were presented to five clinicians who were asked to document their theoretical treatment plan. Clinicians were then shown TEG results and asked if they caused a change in their plan, if they confirmed initial standard laboratory test results, if they enabled a better understanding of haemostasis and if they provided additional information. Inter-rater agreement between the clinicians was determined. Forty-two TEG results were obtained from 34 patients. Overall, the inclusion of TEG results led to a change in treatment plan in 97 of 207 occasions (47%), confirmed standard laboratory test results in 177 of 204 occasions (87%), enabled a better understanding of haemostasis in 140 of 204 occasions (69%) and provided additional information in 131 of 204 occasions (64%). Variation existed between clinicians, seemingly due to individual differences, with poor inter-rater agreement. We conclude that TEG results led to changes in treatment plans almost half the time, confirmed findings of standard tests and provided a better understanding of haemostasis, but randomised controlled trials are required to determine the role and influence of TEG results on patient outcome.

Changes in cerebral oxygen saturation and haemoglobin concentration during paediatric cardiac surgery.

Although near-infrared spectroscopy (NIRS) enables bedside assessment of cerebral oxygenation, it provides little information on the cause of deoxygenation. The authors aimed to investigate the changes in cerebral oxygenation and haemoglobin concentration and their associations during paediatric cardiac surgery in order to elucidate the physiology underlying cerebral deoxygenation. An observational retrospective study on 399 patients who underwent paediatric cardiac surgery was conducted. With use of NIRS, cerebral oxygen saturation as expressed by tissue oxygen index (TOI) before and after surgery, concentration changes in oxygenated haemoglobin (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) after surgery were studied as were the associations between these values and clinical variables. TOI decreased after surgery (preoperative versus postoperative value, 66.0% [56.9, 71.3] versus 63.2% [54.3, 69.4], median [25th, 75th percentile], P <0.001) and the decrease was greater in higher category groups in the Risk Adjusted Classification for Congenital Heart Surgery (RACHS-1). [HHb] increased from its baseline (+1.74 µmol/l [-1.57, +5.84], P <0.001) and the increase was greater in higher risk category groups. On the contrary, there was no evidence for a change in [HbO2] (+0.45 µmol/l [-4.76, +5.30], P=0.42). Cerebral oxygen saturation decreased after paediatric cardiac surgery and the decrease was greater in patients of higher risk groups. The increase in [HHb] was considered to play a predominant role in the cerebral deoxygenation noted, in particular in higher RACHS-1 category groups.

Gestational experience alters sex allocation in the subsequent generation.

Empirical tests of adaptive maternal sex allocation hypotheses have presented inconsistent results in mammals. The possibility that mothers are constrained in their ability to adjust sex ratios could explain some of the remaining variation. Maternal effects, the influence of the maternal phenotype or genotype on her developing offspring, may constrain sex allocation through physiological changes in response to the gestational environment. We tested if maternal effects constrain future parental sex allocation through a lowered gestational stress environment in laboratory mice. Females that experienced lowered stress as embryos in utero gave birth to female-biased litters as adults, with no change to litter size. Changes in offspring sex ratio was linked to peri-conceptual glucose, as those females that had increasing blood glucose peri-conceptionally gave birth to litters with a higher male to female sex ratio. There was, however, no effect of the lowered prenatal stress for developing male embryos and their sperm sex ratio when adult. We discuss the implications of maternal effects and maternal stress environment on the lifelong physiology of the offspring, particularly as a constraint on later maternal sex allocation.

The epigenetic regulators CBP and p300 facilitate leukemogenesis and represent therapeutic targets in acute myeloid leukemia.

Growing evidence links abnormal epigenetic control to the development of hematological malignancies. Accordingly, inhibition of epigenetic regulators is emerging as a promising therapeutic strategy. The acetylation status of lysine residues in histone tails is one of a number of epigenetic post-translational modifications that alter DNA-templated processes, such as transcription, to facilitate malignant transformation. Although histone deacetylases are already being clinically targeted, the role of histone lysine acetyltransferases (KAT) in malignancy is less well characterized. We chose to study this question in the context of acute myeloid leukemia (AML), where, using in vitro and in vivo genetic ablation and knockdown experiments in murine models, we demonstrate a role for the epigenetic regulators CBP and p300 in the induction and maintenance of AML. Furthermore, using selective small molecule inhibitors of their lysine acetyltransferase activity, we validate CBP/p300 as therapeutic targets in vitro across a wide range of human AML subtypes. We proceed to show that growth retardation occurs through the induction of transcriptional changes that induce apoptosis and cell-cycle arrest in leukemia cells and finally demonstrate the efficacy of the KAT inhibitors in decreasing clonogenic growth of primary AML patient samples. Taken together, these data suggest that CBP/p300 are promising therapeutic targets across multiple subtypes in AML.

Extracorporeal membrane modality conversions.

We report the case of a patient with cardiovascular and respiratory failure due to severe anaphylaxis requiring multiple extracorporeal membrane oxygenation (ECMO) cannulation strategies to provide adequate oxygen delivery and ventilatory support during a period of rapid physiological change. ECMO provides partial or complete support of oxygenation-ventilation and circulation. The choice of which ECMO modality to use is governed by anatomical (vessel size, cardiovascular anatomy and previous surgeries) and physiological (respiratory and/or cardiac failure) factors. The urgency with which ECMO needs to be implemented (emergency cardiopulmonary resuscitation (eCPR), urgent, elective) and the institutional experience will also influence the type of ECMO provided. Here we describe a 12-year-old schoolgirl who, having been resuscitated with peripheral veno-venous (VV) ECMO for severe hypoxemia due to status asthmaticus in the setting of acute anaphylaxis, required escalation to peripheral veno-arterial (VA) ECMO for precipitous cardiovascular deterioration. Insufficient oxygen delivery for adequate cellular metabolic function and possible cerebral hypoxia due to significant differential hypoxia necessitated ECMO modification. After six days of central (transthoracic) VA ECMO support and 21 days of intensive care unit (ICU) care, she made a complete recovery with no neurological sequelae. The use of ECMO support warrants careful consideration of the interplay of a patient's pathophysiology and extracorporeal circuit dynamics. Particular emphasis should be placed on the potential for mismatch between cardiovascular and respiratory support as well as the need to meet metabolic demands through adequate cerebral, coronary and systemic oxygenation. Cannulation strategies occasionally require alteration to meet and anticipate the patient's evolving needs.

What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort.

OBJECTIVE: To determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA). METHODS: Serial autoantibody profiles, bDMARD treatment sequences and clinical data were collected from patients identified from our database that since 2005 received (i) a first bDMARD (tumour necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. RESULTS: Of over 1000 patients, 454 RA patients received a first TNFi. Infliximab group demonstrated higher ANA seroconversion rates (31.2%) compared with etanercept (11.8%) and adalimumab (16.1%) (p<0.001). Median (range) treatment duration prior to ANA seroconversion was 10.9 (1.3-80.0) months. Positive anti-dsDNA titres of IgG class (median (range) of 77 IU/mL (65-109)) were noted in six (7.2%) patients, within a median (range) of 2.0 (0.8-4.2) years. Three patients developed classifiable lupus. 4 of 74 (5.4%) primary non-responders and 24 of 111 (21.6%) secondary non-responders developed positive ANA antibodies after TNFi initiation (p=0.003). Seven (9.5%) tocilizumab-treated patients changed to positive ANA; five (8.6%) abatacept-treated patients changed to positive ANA status. CONCLUSIONS: This study demonstrates no utility of serial ANA/dsDNA testing that could be used to predict onset of seroconversion and therefore the development of lupus/vasculitis. An association however between seroconversion and the development of a secondary non-response to bDMARD therapy is suggested.

A comparison study of haemolysis production in three contemporary centrifugal pumps.

One challenge in providing extracorporeal circulation is to supply optimal flow while minimising adverse effects, such as haemolysis. To determine if the recent generation constrained vortex pumps with their inherent design improvements would lead to reduced red cell trauma, we undertook a study comparing three devices. Utilizing a simulated short-term ventricular assist circuit primed with whole human blood, we examined changes in plasma free haemoglobin values over a six-day period. The three pumps investigated were the Maquet Rotaflow, the Levitronix PediVAS and the Medos Deltastream DP3.This study demonstrated that all three pumps produced low levels of haemolysis and are suitable for use in a clinical environment. The Levitronix PediVAS was significantly less haemolytic than either the Rotaflow (p<0.05) or the DP3 (p<0.05). There was no significant difference in plasma free haemoglobin between the Rotaflow and the DP3 (p=0.71).

Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia.

Recent evidence suggests that inhibition of bromodomain and extra-terminal (BET) epigenetic readers may have clinical utility against acute myeloid leukemia (AML). Here we validate this hypothesis, demonstrating the efficacy of the BET inhibitor I-BET151 across a variety of AML subtypes driven by disparate mutations. We demonstrate that a common 'core' transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment. This program is enriched for genes that contain 'super-enhancers', recently described regulatory elements postulated to control key oncogenic driver genes. Moreover, our program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response. We focus AML with mutations of the Nucleophosmin gene (NPM1) and show evidence to suggest that wild-type NPM1 has an inhibitory influence on BRD4 that is relieved upon NPM1c mutation and cytosplasmic dislocation. This leads to the upregulation of the core transcriptional program facilitating leukemia development. This program is abrogated by I-BET therapy and by nuclear restoration of NPM1. Finally, we demonstrate the efficacy of I-BET151 in a unique murine model and in primary patient samples of NPM1c AML. Taken together, our data support the use of BET inhibitors in clinical trials in AML.

Examining the relationship between relative age, competition level, and dropout rates in male youth ice-hockey players.

The relative age effect suggests that athletes born in the first two quartiles of a given selection year experience a selection advantage and therefore a greater opportunity for success. We describe two studies examining the relationship between relative age, competition level, and dropout rates of Ontario Minor Hockey Association male ice-hockey players from ages 10 to 15 years (n = 14 325). In Study 1, dropout was highest among players born in quartiles three and four [χ(2) (3) = 16.32, P < 0.05; w = 0.06], while Study 2 found dropped out players to have less movement between competition levels compared to retained players. This study confirms a relationship between relative age and dropout from ice-hockey and adds further depth to our understanding of this persistent phenomenon.

Exercise intervention for a musculoskeletal disorder in an oral health student: a case report.

OBJECTIVES: to describe and evaluate the effect of an exercise self-management programme for an oral health student who was suffering from a musculoskeletal disorder which had developed in the clinical environment during the course of training. DESIGN: Single participant case report. SETTING: The University of Otago Faculty of Dentistry and School of Physiotherapy. METHODS: The participant was a 21-year-old female student, enrolled in the University of Otago Bachelor of Oral Health (BOH) course, who was suffering back and neck pain which had developed during her training. A series of chairside stretches, regular home-based stretches, aerobic conditioning and postural strengthening exercises was prescribed. Pain and function was assessed using standardised questionnaires at the commencement of the exercise programme, and again at 6 weeks and 13 weeks. RESULTS: The participant demonstrated an improvement in her outcome questionnaires exceeding the MCID scores after 13 weeks. CONCLUSIONS: This case report provides a basis for highlighting the importance of measuring and monitoring MSD in a student learning oral health skills; it supports the findings of previous studies showing that an exercise intervention has some benefit for MSD in oral health students.

Palliative care for dementia--time to think again?

It is estimated that there are 35.6 million people with dementia worldwide and this is projected to increase to over 115 million by the year 2050. Dementia is a progressive neurodegenerative disease that significantly reduces survival. End-of-life care received by this group is often poor and does not equate to that offered in other life limiting illnesses. This review highlights results from a large UK study of informal carers of people with dementia to explore what are determinants of care for people with dementia and their family carers. New perspectives as to models of care for end-of-life care for patients with dementia are discussed together with how these may be implemented and delivered within wider community settings and contexts, where many people with dementia may be cared for in the future.

A peer-led decision support intervention improves decision outcomes in black women with breast cancer.

Previous reports suggest that Black breast cancer patients receive less patient-centered cancer care than their White counterparts. Interventions to improve patient-centered care (PCC) in Black breast cancer patients are lacking. Seventy-six women with histologically confirmed breast cancer were recruited from the Washington, DC area. After a baseline telephone interview, women received an in-person decision support educational session led by a trained survivor coach. The coach used a culturally appropriate guidebook and decision-making model-TALK Back!(©) A follow-up assessment assessed participants' acceptability of the intervention and intermediate outcomes. After the intervention, participants reported increased: self-efficacy in communicating with providers (70 %) and self-efficacy in making treatment decisions (70 %). Compared to baseline scores, post-intervention communication with providers significantly increased (p= .000). This is the first outcome report of an intervention to facilitate PCC in Black breast cancer patients. Testing this intervention using RCTs or similar designs will be important next steps.

The AAA+ ATPase RUVBL2 is a critical mediator of MLL-AF9 oncogenesis.

The most frequent chromosomal translocations in pediatric acute myeloid leukemia affect the 11q23 locus and give rise to mixed lineage leukemia (MLL) fusion genes, MLL-AF9 being the most prevalent. The MLL-AF9 fusion gene has been shown to induce leukemia in both mouse and human models. In this study, we demonstrate that leukemogenic activity of MLL-AF9 requires RUVBL2 (RuvB-like 2), an AAA+ ATPase family member that functions in a wide range of cellular processes, including chromatin remodeling and transcriptional regulation. Expression of RUVBL2 was dependent on MLL-AF9, as it increased upon immortalization of human cord blood-derived hematopoietic progenitor cells with the fusion gene and decreased following loss of fusion gene expression in conditionally immortalized mouse cells. Short hairpin RNA-mediated silencing experiments demonstrated that both the immortalized human cells and the MLL-AF9-expressing human leukemia cell line THP-1 required RUVBL2 expression for proliferation and survival. Furthermore, inhibition of RUVBL2 expression in THP-1 cells led to reduced telomerase activity and clonogenic potential. These data were confirmed with a dominant-negative Walker B-mutated RUVBL2 construct. Taken together, these data suggest the possibility of targeting RUVBL2 as a potential therapeutic strategy for MLL-AF9-associated leukemia.

MLL-AF9-mediated immortalization of human hematopoietic cells along different lineages changes during ontogeny.

The MLL-AF9 fusion gene is associated with aggressive leukemias of both the myeloid and lymphoid lineage in infants, whereas in adults, this translocation is mainly associated with acute myeloid leukemia. These observations suggest that differences exist between fetal and adult tissues in terms of the 'cell of origin' from which the leukemia develops. Here we show that depending on extrinsic cues, human neonatal CD34(+) cells are readily immortalized along either the myeloid or lymphoid lineage upon MLL-AF9 expression and give rise to mainly lymphoid leukemia in immunocompromised mice. In contrast, immortalization of adult bone marrow CD34(+) cells is more difficult to achieve and is myeloid-biased, even when MLL-AF9 is expressed in purified hematopoietic stem cells (HSCs). Transcriptome analysis identified enrichment of HSC but not progenitor gene signatures in MLL-AF9-expressing cells. Although not observed in adult cells, neonatal cells expressing MLL-AF9 were enriched for gene signatures associated with poor prognosis, resistance to chemotherapeutic agents and MYC signaling. These results indicate that neonatal cells are inherently more prone to MLL-AF9-mediated immortalization than adult cells and suggest that intrinsic properties of the cell of origin, in addition to extrinsic cues, dictate lineage of the immortalized cell.