Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a ...casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.
Background
Within the same school class, it is usual to find children who differ in age by almost a full calendar year. Although associations between being relatively young and poor academic outcomes ...are well documented, and relatively consistent, the associations between being relatively young and psychosocial outcomes are less clearly documented.
Aims
To review research which presents data relating to associations between a child's relative age and their psychosocial development.
Methods
A systematic review was conducted and reported in accordance with PRISMA guidelines.
Results
Fifty‐nine papers met the inclusion criteria. The outcomes of the narrative synthesis and three meta‐analyses found consistent, but very small, associations with relative age indicating that those who are relatively young are more likely to have more negative behaviour, mental well‐being, and social experiences.
Conclusions
Although being relatively young is associated with more negative psychosocial outcomes, the magnitude of these associations is consistently small. Furthermore, many of the outcome measures used are likely to be the result of multiple influences, not limited to the effects of relative age. Therefore, the findings are reassuring as they suggest that relative age itself is unlikely to substantially increase an individual's risk of poor psychosocial development.
Haptophytes are recognized as seminal players in aquatic ecosystem function. These algae are important in global carbon sequestration, form destructive harmful blooms, and given their rich fatty acid ...content, serve as a highly nutritive food source to a broad range of eco-cohorts. Haptophyte dominance in both fresh and marine waters is supported by the mixotrophic nature of many taxa. Despite their importance the nuclear genome sequence of only one haptophyte, Emiliania huxleyi (Isochrysidales), is available. Here we report the draft genome sequence of Chrysochromulina tobin (Prymnesiales), and transcriptome data collected at seven time points over a 24-hour light/dark cycle. The nuclear genome of C. tobin is small (59 Mb), compact (∼ 40% of the genome is protein coding) and encodes approximately 16,777 genes. Genes important to fatty acid synthesis, modification, and catabolism show distinct patterns of expression when monitored over the circadian photoperiod. The C. tobin genome harbors the first hybrid polyketide synthase/non-ribosomal peptide synthase gene complex reported for an algal species, and encodes potential anti-microbial peptides and proteins involved in multidrug and toxic compound extrusion. A new haptophyte xanthorhodopsin was also identified, together with two "red" RuBisCO activases that are shared across many algal lineages. The Chrysochromulina tobin genome sequence provides new information on the evolutionary history, ecology and economic importance of haptophytes.
The scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with ...functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula.
We reviewed 61 patients (37 male, 24 female; mean age 42 years (SD 19)) who had undergone resection of the scapula. The most common resection was type 2 (n = 34) according to the Tikhoff-Linberg classification, or type S1A (n = 35) on the Enneking classification.
The ten-year disease-specific survival was 76%. High tumour grade (hazard ratio (HR) 4.27; p = 0.016) and a total resection of the scapula (HR 3.84; p = 0.015) were associated with worse survival. The ten-year metastasis-free and local recurrence-free survivals were 82% and 86%, respectively. Total scapular resection (HR 6.29; p = 0.004) was associated with metastatic disease and positive margins were associated with local recurrence (HR 12.86; p = 0.001). At final follow-up, the mean shoulder forward elevation and external rotation were 79° (SD 62°) and 27° (SD 25°), respectively. The most recent functional outcomes evaluated included the mean Musculoskeletal Tumor Society Score (76% (SD 17%)), the American Shoulder and Elbow Score (73% (SD 20%)), and the Simple Shoulder Test (7 (SD 3)). Preservation of the glenoid (p = 0.001) and scapular spine (p < 0.001) improved clinical outcomes; interestingly, preservation of the scapular spine without the glenoid improved outcomes (p < 0.001) compared to preservation of the glenoid alone (p = 0.05).
Resection of the scapula is a major undertaking with an oncological outcome related to tumour grade, and a functional outcome associated with the status of the scapular spine and glenoid. Positive resection margins are associated with local recurrence.
Abstract
Background
Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. ...Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium.
Methods
We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40–74 years; cervical: ages 21–64 years; colorectal: ages 50–75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type.
Results
The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively.
Conclusions
Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings.
Abstract Background Endoprostheses (EPC) are often utilized for reconstruction of the proximal humerus with either hemiarthroplasty (HA) or reverse arthroplasty (RA) constructs. RA constructs have ...improved outcomes in patients with primary lesions, but no studies have compared techniques in metastatic disease. The aim of this study is to compare functional outcomes and complications between HA and RA constructs in patients undergoing endoprosthetic reconstruction for proximal humerus metastases. Methods We retrospectively reviewed our institutional arthroplasty database to identify 66 (56% male; 38 HA and 28 RA) patients with a proximal humerus reconstruction for a non‐primary malignancy. The majority (88%) presented with pathologic fracture, and the most common diagnosis was renal cell carcinoma (48%). Resultss Patients with RA reconstructions had better postoperative forward elevation (74° vs. 32°, p < 0.01) and higher functional outcome scores. HA patients had more complications (odds ratio 13, p < 0.01), with instability being the most common complication. Conclusions Patients with nonprimary malignancies of the proximal humerus had improved functional outcomes and fewer complications after undergoing reconstruction with a reverse EPC compared to a HA EPC. Preference for reverse EPC should be given in patients with good prognosis and ability to complete postoperative rehabilitation.
Introduction
The elbow is a rare location for primary and metastatic tumors in the upper extremity. The goal of reconstruction is to provide painless motion and stability for hand function. Total ...elbow arthroplasty (TEA) is commonly utilized, with either off‐the‐self components, modular segmental endoprosthesis, or allograft‐prosthesis composites (APC). The purpose of this study was to analyze and compare commonly utilized elbow reconstructions and report outcomes of (1) patient function and (2) implant survival and complications.
Methods
We reviewed 33 patients (18 females and 15 males) undergoing elbow arthroplasty for reconstruction of an underlying oncologic process including linked TEA (n = 22, 67%), APC (n = 9, 27%), and endoprosthesis (n = 2, 6%). The most common indication was metastatic disease (n = 17, 52%), with 24 patients (73%) presenting with a pathologic fracture.
Results
Five‐year implant survival was following elbow reconstruction was 88%. The mean most recent Mayo Elbow Performance Score and Musculoskeletal Tumor Society Score were 84 ± 18 and 78 ± 15%. Postoperative complications occurred in 15 elbows (45%), most commonly periprosthetic fracture (n = 5, 15%), leading to reoperation in six elbows (18%).
Conclusion
Although elbow arthroplasty is associated with a high incidence of complications, it provides a stable platform for upper extremity function in patients with oncologic processes of the elbow.
IntroductionInfants born very preterm are at risk of adverse neurodevelopmental outcomes, including cognitive deficits, motor impairments and cerebral palsy. Earlier identification enables targeted ...early interventions to be implemented with the aim of improving outcomes.Methods and analysisProtocol for 6-year follow-up of two cohorts of infants born <31 weeks gestational age (PPREMO: Prediction of Preterm Motor Outcomes; PREBO: Prediction of Preterm Brain Outcomes) and a small term-born reference sample in Brisbane, Australia. Both preterm cohorts underwent very early MRI and concurrent clinical assessment at 32 and 40 weeks postmenstrual age (PMA) and were followed up at 3, 12 and 24 months corrected age (CA). This study will perform MRI and electroencephalography (EEG). Primary outcomes include the Movement Assessment Battery for Children second edition and Full-Scale IQ score from the Wechsler Intelligence Scale for Children fifth edition (WISC-V). Secondary outcomes include the Gross Motor Function Classification System for children with cerebral palsy; executive function (Behavior Rating Inventory of Executive Function second edition, WISC-V Digit Span and Picture Span, Wisconsin Card Sorting Test 64 Card Version); attention (Test of Everyday Attention for Children second edition); language (Clinical Evaluation of Language Fundamentals fifth edition), academic achievement (Woodcock Johnson IV Tests of Achievement); mental health and quality of life (Development and Well-Being Assessment, Autism Spectrum Quotient-10 Items Child version and Child Health Utility-9D).AimsExamine the ability of early neonatal MRI, EEG and concurrent clinical measures at 32 weeks PMA to predict motor, cognitive, language, academic achievement and mental health outcomes at 6 years CA.Determine if early brain abnormalities persist and are evident on brain MRI at 6 years CA and the relationship to EEG and concurrent motor, cognitive, language, academic achievement and mental health outcomes.Ethics and disseminationEthical approval has been obtained from Human Research Ethics Committees at Children’s Health Queensland (HREC/19/QCHQ/49800) and The University of Queensland (2019000426). Study findings will be presented at national and international conferences and published in peer-reviewed journals.Trial registration numberACTRN12619000155190p.Web address of trialhttp://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619000155190p
Background
Primary care providers and health systems have prominent roles in guiding effective cancer screening.
Objective
To characterize variation in screening abnormality rates and timely initial ...follow-up for common cancer screening tests.
Design
Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.
Participants
Adults undergoing mammography with or without digital breast tomosynthesis (
n
= 97,683 ages 40–75 years), fecal occult blood or fecal immunochemical tests (
n
= 759,553 ages 50–75 years), or Papanicolaou with or without human papillomavirus tests (
n
= 167,330 ages 21–65 years).
Intervention
Breast, colorectal, or cervical cancer screening.
Main Measures
Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up.
Key Results
There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7 % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5–10.3 %; colorectal, 3.0–4.8 %; cervical, 6.3–9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2–95.8 %; colorectal, 43.4–52.0 %; cervical, 29.6–61.4 %).
Conclusions
Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.