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To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.
A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.
Navajo Nation, USA.
Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles.
The Navajo Fruit and Vegetable Prescription (FVRx) Programme.
A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.
Introduction: Medical record review (MRR) studies are commonly used in Emergency Medicine (EM) research. It is not always clear how sample size calculations are reported, or the methods by which they were derived. This scoping review sought to examine reporting and justification of MRR sample sizes from the EM literature. Methods: Using Web of Science, we identified the top ten journals, based on impact factor rating in 2018, within the field of Emergency Medicine. Journals were excluded if they were not in English or did not include sufficient articles for analysis. Within each of these ten selected journals, we searched for chart reviews and related terms: "medical record", "outpatient record", "inpatient record", "clinical record", and "nursing note". From this search subset, five articles were randomly selected from each journal. Data about sample size and sample size selection were extracted and analyzed by two reviewers independently for each article. Results: Of the 50 articles randomly selected, 48 articles were retrospective MRRs and two articles were prospective MRRs. 78% (39 articles) chose sample size based on availability, 14% (seven articles) chose sample size based on power calculations, 4% (two articles) chose sample size based on a previous study's methodology, and 4% (two articles) did not give details on sample size selection. Conclusion: While some emergency medicine MRRs based sample size selection on power or previous studies, the vast majority are based on availability with study-specific exclusion/inclusion criteria. This may indicate they are using a smaller sample size than necessary to be sufficiently powered to assess their end goal. More work is required to determine the effect of this on outcomes and interpretability of results, as well as which method is most accurate and efficient.
Nearly half of care home residents with advanced dementia have clinically significant agitation. Little is known about costs associated with these symptoms toward the end of life. We calculated monetary costs associated with agitation from UK National Health Service, personal social services, and societal perspectives.
Prospective cohort study.
Thirteen nursing homes in London and the southeast of England.
Seventy-nine people with advanced dementia (Functional Assessment Staging Tool grade 6e and above) residing in nursing homes, and thirty-five of their informal carers.
Data collected at study entry and monthly for up to 9 months, extrapolated for expression per annum. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Health and social care costs of residing in care homes, and costs of contacts with health and social care services were calculated from national unit costs; for a societal perspective, costs of providing informal care were estimated using the resource utilization in dementia (RUD)-Lite scale.
After adjustment, health and social care costs, and costs of providing informal care varied significantly by level of agitation as death approached, from £23,000 over a 1-year period with no agitation symptoms (CMAI agitation score 0–10) to £45,000 at the most severe level (CMAI agitation score >100). On average, agitation accounted for 30% of health and social care costs. Informal care costs were substantial, constituting 29% of total costs.
With the increasing prevalence of dementia, costs of care will impact on healthcare and social services systems, as well as informal carers. Agitation is a key driver of these costs in people with advanced dementia presenting complex challenges for symptom management, service planners, and providers.
Balloon Eustachian tuboplasty is a surgical management option for Eustachian tube dysfunction; it has shown promising results in studies worldwide, but has had limited uptake in the UK. This study reports long-term outcomes for patients offered balloon Eustachian tuboplasty for chronic dilatory and baro-challenge-induced Eustachian tube dysfunction, and describes practical experience gained from its implementation.
Balloon Eustachian tuboplasty was conducted in 25 patients (36 ears) with Eustachian tube dysfunction over three years. Information on presenting symptoms and signs, audiometric findings, tympanometry, and Eustachian Tube Dysfunction Questionnaire-7 scores were recorded pre- and post-operatively with a minimum follow up of one year.
Sixteen (64 per cent) of the 25 patients demonstrated symptom resolution after balloon Eustachian tuboplasty according to the Eustachian Tube Dysfunction Questionnaire-7. Fourteen (64 per cent) of the 22 patients with a type B or C tympanogram pre-operatively, had a type A trace post-operatively. Fifteen (75 per cent) of 20 patients with pre-operative conductive hearing loss showed improvement post-operatively, and 11 (50 per cent) of 22 patients with pre-operative middle-ear effusion or tympanic membrane retraction showed resolution.
Balloon Eustachian tuboplasty can improve subjective and objective measures of Eustachian tube dysfunction, and provide longer-term resolution.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
In the USA, western Washington (WWA) and the Alaska (AK) Interior are two regions where maritime and continental climates, high latitude and cropping systems necessitate early maturing spring wheat (Triticum aestivum L.). Both regions aim to increase the production of hard spring bread wheat for human consumption to support regional agriculture and food systems. The Nordic region of Europe has a history of breeding for early maturing spring wheat and also experiences long daylengths with mixed maritime and continental climates. Nordic wheat also carries wildtype (wt) NAM-B1, an allele associated with accelerated senescence and increased grain protein and micronutrient content, at a higher frequency than global germplasm. Time to senescence, yield, protein and mineral content were evaluated on 42 accessions of Nordic hard red spring wheat containing wt NAM-B1 over 2 years on experimental stations in WWA and the AK Interior. Significant variation was found by location and accession for time to senescence, suggesting potential parental lines for breeding programmes targeting early maturity. Additionally, multiple regression analysis showed that decreased time to senescence correlated negatively with grain yield and positively with grain protein, iron and zinc content. Breeding for early maturity in these regions will need to account for this potential trade-off in yield. Nordic wt NAM-B1 accessions with early senescence yet with yields similar to regional checks are reported. Collaboration among alternative wheat regions can aid in germplasm exchange and varietal development as shown here for the early maturing trait.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
The hypothalamic–pituitary–adrenal axis (HPAA) plays a critical role in the functioning of all other biological systems. Thus, studying how the environment may influence its ontogeny is paramount to understanding developmental origins of health and disease. The early post-conceptional (EPC) period could be particularly important for the HPAA as the effects of exposures on organisms’ first cells can be transmitted through all cell lineages. We evaluate putative relationships between EPC maternal cortisol levels, a marker of physiologic stress, and their children’s pre-pubertal HPAA activity (n=22 dyads). Maternal first-morning urinary (FMU) cortisol, collected every-other-day during the first 8 weeks post-conception, was associated with children’s FMU cortisol collected daily around the start of the school year, a non-experimental challenge, as well as salivary cortisol responses to an experimental challenge (all Ps<0.05), with some sex-related differences. We investigated whether epigenetic mechanisms statistically mediated these links and, therefore, could provide cues as to possible biological pathways involved. EPC cortisol was associated with >5% change in children’s buccal epithelial cells’ DNA methylation for 867 sites, while children’s HPAA activity was associated with five CpG sites. Yet, no CpG sites were related to both, EPC cortisol and children’s HPAA activity. Thus, these epigenetic modifications did not statistically mediate the observed physiological links. Larger, prospective peri-conceptional cohort studies including frequent bio-specimen collection from mothers and children will be required to replicate our analyses and, if our results are confirmed, identify biological mechanisms mediating the statistical links observed between maternal EPC cortisol and children’s HPAA activity.
Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.
Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30–87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1–2.2; P = 0.02) and between ages 0–4 and 15–39 years among male contacts (OR 2.7, 95% CI 0.83–8.9 and 1.1, 95% CI 0.99–1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
To assess whether pre-operative assessment with a bone conduction hearing device on a softband is an accurate predictor of performance with one of two transcutaneous hearing implants.
Cohort study comparing pre-and post-operative speech audiometry using correlation analysis.
Pre-operative pure tone audiometry and aided half optimum speech recognition thresholds were compared with post-operative aided results for each ear that had undergone implantation. Data were collected prospectively.
Full data were available in 24 ears. In 19 out of 24 ears (79 per cent), the difference between pre- and post-operative speech scores was less than 10 dB, demonstrating a good clinical correlation. The Pearson correlation coefficient was calculated at 0.66 (95 per cent confidence interval = 0.357–0.842), indicating a strong statistical correlation.
Pre-operative softband testing shows good clinical correlation and strong statistical correlation with hearing implant performance. The findings suggest there is value in using the test to predict performance and guide patients’ expectations.