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Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.
While negative affect reliably predicts binge eating, it is unknown how this association may decrease or ‘de-couple’ during treatment for binge eating disorder (BED), whether such change is greater in treatments targeting emotion regulation, or how such change predicts outcome. This study utilized multi-wave ecological momentary assessment (EMA) to assess changes in the momentary association between negative affect and subsequent binge-eating symptoms during Integrative Cognitive Affective Therapy (ICAT-BED) and Cognitive Behavior Therapy Guided Self-Help (CBTgsh). It was predicted that there would be stronger de-coupling effects in ICAT-BED compared to CBTgsh given the focus on emotion regulation skills in ICAT-BED and that greater de-coupling would predict outcomes.
Adults with BED were randomized to ICAT-BED or CBTgsh and completed 1-week EMA protocols and the Eating Disorder Examination (EDE) at pre-treatment, end-of-treatment, and 6-month follow-up (final N = 78). De-coupling was operationalized as a change in momentary associations between negative affect and binge-eating symptoms from pre-treatment to end-of-treatment.
There was a significant de-coupling effect at follow-up but not end-of-treatment, and de-coupling did not differ between ICAT-BED and CBTgsh. Less de-coupling was associated with higher end-of-treatment EDE global scores at end-of-treatment and higher binge frequency at follow-up.
Both ICAT-BED and CBTgsh were associated with de-coupling of momentary negative affect and binge-eating symptoms, which in turn relate to cognitive and behavioral treatment outcomes. Future research is warranted to identify differential mechanisms of change across ICAT-BED and CBTgsh. Results also highlight the importance of developing momentary interventions to more effectively de-couple negative affect and binge eating.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Introduction: The legalization of cannabis for recreational use in 2018 remains a controversial topic. There are multiple perceived benefits of cannabis including pain relief, treatment of epilepsy syndromes, and improving body weight of cancer patients. However, there are also many potential risks. The short-term health consequences include cannabinoid hyperemesis syndrome and cannabis induced psychosis. These conditions directly impact the influx of patients presenting to Emergency Departments (ED). There is currently limited research in the area of cannabis legalization burden. However, the studies performed have shown a significant impact in those states which cannabis is legal. A study completed in Colorado found that hospitalization rates with marijuana related billing codes increased from 274 to 593 per 100 000 hospitalizations after the state legalization of recreational cannabis. This study aims to examine if Canada's hospitals are experiencing the same burden as other jurisdictions. Methods: A descriptive study was preformed via a retrospective chart review of cannabis related visits in tertiary EDs in St. John's, NL, from six months prior to the date of legalization of cannabis for recreational use, to six months after. Hospital ED visit records from both the Health Science Centre and St. Clare's Mercy Hospital were searched using keywords to identify patients who presented with symptoms related to cannabis use. We manually reviewed all visit records that included one or more of these terms to distinguish true positives from false positive cases, unrelated to cannabis use. Results: A total of 287 charts were included in the study; 123 visits were related to cannabis use six months prior to legalization, and 164 six months after legalization. A significant increase in ED visits following the legalization of recreational cannabis was seen (p < .001). There was no significant difference in the age of users between the two groups. Additionally, the number one presenting complaint due to cannabis use was vomiting (47.7%), followed by anxiety (12.2%). Conclusion: Following the implementation of the Cannabis Act in Canada, EDs in St. John's, NL had a statistically significant increase in the number of visits related to cannabis use. It is important to determine such consequences to ensure hospitals and public health agencies are prepared to treat the influx of visits and are better equipped to manage the associated symptoms.
Psychological stress is associated with accelerated cellular aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.
We examined the effect of stress on a DNA methylation age predictor that was shown to correlate strongly with chronological age across human tissues (Horvath 2013). Genome-wide DNA methylation was measured in peripheral blood using the 450K Illumina array in three independent cohorts: the Grady Trauma Project/GTP (N=366); a panic disorder case/control sample recruited at the Max Planck Institute of Psychiatry/MPI-P (N=318); and the Conte Center for the Psychobiology of Early-Life Trauma/Conte (N=42). Age acceleration was calculated by subtracting chronological age from age predicted by DNA methylation. Psychiatric symptomatology and stressors were assessed using standard questionnaires.
DNA methylation age strongly correlated with chronological age in all samples (r=0.9, p=2.5x10<sup>-133</sup>). Cumulative lifetime stress but not childhood or current stress predicted age acceleration in GTP (p=0.012) and MPI-P (p=0.021). Moreover, epigenetic age acceleration predicted depression (GTP: p=0.002; Conte: p=0.014) and panic disorder (p=0.007). In secondary analyses, we examined the effect of lifetime stress on individual CpGs of the DNA methylation age predictor. After correcting for multiple comparisons, we identified in both GTP and MPI-P a stress-regulated CpG near MCAM, a gene implicated in aging-related diseases, including cardiovascular disease and cancers.
Cumulative lifetime stress, but not childhood or current stress, and psychiatric phenotypes are associated with accelerated epigenetic aging. Our findings may explain the accelerated cellular aging and increased disease risk associated with chronic stress and psychiatric disorders.
The increased prevalence of metabolic syndrome in people with severe mental illness (SMI) is well documented. The International Diabetes Federation (IDF) criteria for metabolic syndrome are three or more of the following: waist circumference ( 80 cm (females), (94 cm (males) OR BMI (30, triglycerides >1.7 mmol/l or on treatment, raised blood pressure (systolic >130 mg Hg or diastolic >85 mm Hg, OR on treatment for hypertension), raised fasting blood glucose (.5.6 mmol/l) OR diagnosed type II diabetes) and reduced HDL cholesterol (< 1.03 mmol/l) OR on treatment.
The IMPACT RCT is a Department of Health funded trial of a health promotion intervention (HPI) delivered by care co-ordinators to people with SMI across South London, Kent and Sussex. The intervention is focussed on improving health by addressing modifiable lifestyle factors such as diet, physical activity, obesity, cigarette smoking, alcohol and substance use.
We investigated the prevalence of metabolic syndrome in a sample of 212 patients for whom we had relevant baseline measures.
Data (weight, BMI, waist circumference, blood pressure, fasting HDL cholesterol, triglycerides and glucose levels) were analysed on 212 patients.
45% of the sample met IDF criteria for metabolic syndrome. Mean BMI was 30.6, glucose 6.4 mmol/L, triglycerides 2.0 mmol/L, HDL 1.2 (mmol/L), waist circumference 105.8 cm, and BP 122/82 mm Hg.
Metabolic syndrome was highly prevalent in this sample, significantly increasing the risk of physical morbidity and potentially lowering life expectancy. There is an unmet need for health promotion interventions in order to lower morbidity and mortality risk in these populations.
The Department of Health in the UK wants the National Health Service to make £20 Billion worth of efficiency savings by 2015 to reinvest.
In the UK the General Hospitals use paper records which are then scanned to create electronic records while Psychiatric Hospitals require that information to be typed on to their electronic records and these electronic records are not available to each other.
Therefore liaison psychiatry assessments require a written entry to be made in the Medical notes and a second entry typed on to the psychiatric electronic patient record which requires a full psychiatric history.
This duplication in typing information was consuming a considerable amount of this Teams time and resources which could have instead been spent with patients.
To identify how much time is spent by Staff typing information on to the psychiatric electronic patient records.
We electronically checked for the preceding three months the amount of time spent typing information on to the electronic records after every liaison psychiatry assessment.
We were then able to obtain the average for every week.
On average about 36 to 40 hours were spent every week typing information on to the electronic records.
Liaison Psychiatry should dispense with the requirement for information to be duplicated on to the electronic patient records and should instead scan the written entry made in the Medical notes.
This should lead to a saving of about £50,000, enough to employ an additional member of Staff every week.
Convolutional neural networks are a subclass of deep learning or artificial intelligence that are predominantly used for image analysis and classification. This proof-of-concept study attempts to train a convolutional neural network algorithm that can reliably determine if the middle turbinate is pneumatised (concha bullosa) on coronal sinus computed tomography images.
Consecutive high-resolution computed tomography scans of the paranasal sinuses were retrospectively collected between January 2016 and December 2018 at a tertiary rhinology hospital in Australia. The classification layer of Inception-V3 was retrained in Python using a transfer learning method to interpret the computed tomography images. Segmentation analysis was also performed in an attempt to increase diagnostic accuracy.
The trained convolutional neural network was found to have diagnostic accuracy of 81 per cent (95 per cent confidence interval: 73.0–89.0 per cent) with an area under the curve of 0.93.
A trained convolutional neural network algorithm appears to successfully identify pneumatisation of the middle turbinate with high accuracy. Further studies can be pursued to test its ability in other clinically important anatomical variants in otolaryngology and rhinology.
Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. However, few intervention studies have been conducted in these communities. We present a pragmatic stepped-wedge trial of a novel psychological group intervention intended to improve resilience among older adults in senior housing communities.
A pragmatic modified stepped-wedge trial design.
Five senior housing communities in three states in the US.
Eighty-nine adults over age 60 years residing in independent living sector of senior housing communities.
Raise Your Resilience, a manualized 1-month group intervention that incorporated savoring, gratitude, and engagement in value-based activities, administered by unlicensed residential staff trained by researchers. There was a 1-month control period and a 3-month post-intervention follow-up.
Validated self-report measures of resilience, perceived stress, well-being, and wisdom collected at months 0 (baseline), 1 (pre-intervention), 2 (post-intervention), and 5 (follow-up).
Treatment adherence and satisfaction were high. Compared to the control period, perceived stress and wisdom improved from pre-intervention to post-intervention, while resilience improved from pre-intervention to follow-up. Effect sizes were small in this sample, which had relatively high baseline resilience. Physical and mental well-being did not improve significantly, and no significant moderators of change in resilience were identified.
This study demonstrates feasibility of conducting pragmatic intervention trials in senior housing communities. The intervention resulted in significant improvement in several measures despite ceiling effects. The study included several features that suggest high potential for its implementation and dissemination across similar communities nationally. Future studies are warranted, particularly in samples with lower baseline resilience or in assisted living facilities.
Rules of thumb (RoTs) are proposed as a means of promoting higher levels of Defined Contribution (DC) pension saving and to help stimulate debate about the high and uncertain cost of pension provision, leading to the development of solutions. The Lifetime Pension Contribution (LPC) tells young people what pension contribution is required over a full working life to achieve a decent retirement income, calculated as 23% of average UK earnings. Another RoT is that each 1% of earnings provides a pension of 1.5% of earnings. Other RoTs show how costs vary by retirement age and if the saverʼs retirement planning is on track. The current high cost of pensions is partly due to low interest rates and the inefficiencies of the DC market, with inadequate bulk purchasing power and risk sharing. RoTs might help encourage higher employer contributions, either through automatic enrolment or on a voluntary basis.
Topical nasal decongestants are frequently used as part of the medical management of symptoms related to Eustachian tube dysfunction.
This study aimed to assess the effect of topical xylometazoline hydrochloride sprayed in the anterior part of the nose on Eustachian tube active and passive opening in healthy ears.
Active and passive Eustachian tube function was assessed in healthy subjects before and after intranasal administration of xylometazoline spray, using tympanometry, video otoscopy, sonotubometry, tubo-tympano-aerodynamic-graphy and tubomanometry.
Resting middle-ear pressures were not significantly different following decongestant application. Eustachian tube opening rate was not significantly different following the intervention, as measured by all function tests used. Sonotubometry data showed a significant increase in the duration of Eustachian tube opening following decongestant application.
There remains little or no evidence that topical nasal decongestants improve Eustachian tube function. Sonotubometry findings do suggest that further investigation with an obstructive Eustachian tube dysfunction patient cohort is warranted.
Effective management of uncertainty can lead to better, more informed decisions. However, many decision makers and their advisers do not always face up to uncertainty, in part because there is little constructive guidance or tools available to help. This paper outlines six Uncertainty Principles to manage uncertainty.
Face up to uncertainty
Deconstruct the problem
Don’t be fooled (un/intentional biases)
Models can be helpful, but also dangerous
Think about adaptability and resilience
Bring people with you
These were arrived at following extensive discussions and literature reviews over a 5-year period. While this is an important topic for actuaries, the intended audience is any decision maker or advisor in any sector (public or private).
Deep learning using convolutional neural networks represents a form of artificial intelligence where computers recognise patterns and make predictions based upon provided datasets. This study aimed to determine if a convolutional neural network could be trained to differentiate the location of the anterior ethmoidal artery as either adhered to the skull base or within a bone ‘mesentery’ on sinus computed tomography scans.
Coronal sinus computed tomography scans were reviewed by two otolaryngology residents for anterior ethmoidal artery location and used as data for the Google Inception-V3 convolutional neural network base. The classification layer of Inception-V3 was retrained in Python (programming language software) using a transfer learning method to interpret the computed tomography images.
A total of 675 images from 388 patients were used to train the convolutional neural network. A further 197 unique images were used to test the algorithm; this yielded a total accuracy of 82.7 per cent (95 per cent confidence interval = 77.7–87.8), kappa statistic of 0.62 and area under the curve of 0.86.
Convolutional neural networks demonstrate promise in identifying clinically important structures in functional endoscopic sinus surgery, such as anterior ethmoidal artery location on pre-operative sinus computed tomography.
Propagating inhomogeneous electromagnetic waves called surface plasmon polaritons (SPPs) can be excited by free-space beams on corrugated conducting surfaces at resonance angles determined by corrugation period, permittivity, and optical frequency. SPPs are coupled to and co-propagate with surface charge displacements. Complete electrical isolation of individual conducting corrugations prevents the charge displacement necessary to sustain an SPP, such that excitation resonances of traveling SPPs are absent. However, SPPs can be excited via electric induction if a smooth conducting surface exists below and nearby the isolated conducting corrugations. The dependence of SPP excitation resonances on that separation is experimentally investigated here at long-wave infrared wavelengths. We find that excitation resonances for traveling SPPs broaden and disappear as the dielectric’s physical thickness is increased beyond ~1% of the free-space wavelength. The resonance line width increases with refractive index and optical thickness of the dielectric.
We have detected 27 new supernova remnants (SNRs) using a new data release of the GLEAM survey from the Murchison Widefield Array telescope, including the lowest surface brightness SNR ever detected, G 0.1 – 9.7. Our method uses spectral fitting to the radio continuum to derive spectral indices for 26/27 candidates, and our low-frequency observations probe a steeper spectrum population than previously discovered. None of the candidates have coincident WISE mid-IR emission, further showing that the emission is non-thermal. Using pulsar associations we derive physical properties for six candidate SNRs, finding G 0.1 – 9.7 may be younger than 10 kyr. Sixty per cent of the candidates subtend areas larger than 0.2 deg2 on the sky, compared to < 25% of previously detected SNRs. We also make the first detection of two SNRs in the Galactic longitude range 220°–240°.