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Vitamin D deficiency is associated with an increased risk of falls and fractures. Assuming this association is causal, we aimed to identify the number and proportion of hospitalisations for falls and hip fractures attributable to vitamin D deficiency (25 hydroxy D (25(OH)D) <50 nmol/l) in Australians aged ≥65 years. We used 25(OH)D data from the 2011/12 Australian Health Survey and relative risks from published meta-analyses to calculate population-attributable fractions for falls and hip fracture. We applied these to data published by the Australian Institute of Health and Welfare to calculate the number of events each year attributable to vitamin D deficiency. In men and women combined, 8·3 % of hospitalisations for falls (7991 events) and almost 8 % of hospitalisations for hip fractures (1315 events) were attributable to vitamin D deficiency. These findings suggest that, even in a sunny country such as Australia, vitamin D deficiency contributes to a considerable number of hospitalisations as a consequence of falls and for treatment of hip fracture in older Australians; in countries where the prevalence of vitamin D deficiency is higher, the impact will be even greater. It is important to mitigate vitamin D deficiency, but whether this should occur through supplementation or increased sun exposure needs consideration of the benefits, harms, practicalities and costs of both approaches.
In most of the world Toxoplasma gondii is comprised of archetypal types (types I, II and III); however, South America displays several non-archetypal strains. This study used an experimental mouse model to characterize the immune response and parasite kinetics following infection with different parasite genotypes. An oral inoculation of 50 oocysts per mouse from T. gondii M4 type II (archetypal, avirulent), BrI or BrIII (non-archetypal, virulent and intermediate virulent, respectively) for groups (G)2, G3 and G4, respectively was used. The levels of mRNA expression of cytokines, immune compounds, cell surface markers and receptor adapters [interferon gamma (IFNγ), interleukin (IL)-12, CD8, CD4, CD25, CXCR3 and MyD88] were quantified by SYBR green reverse transcription-quantitative polymerase chain reaction. Lesions were characterized by histology and detection by immunohistochemistry established distribution of parasites. Infection in G2 mice was mild and characterized by an early MyD88-dependent pathway. In G3, there were high levels of expression of pro-inflammatory cytokines IFNγ and IL-12 in the mice showing severe clinical symptoms at 8–11 days post infection (dpi), combined with the upregulation of CD25, abundant tachyzoites and tissue lesions in livers, lungs and intestines. Significant longer expression of IFNγ and IL-12 genes, with other Th1-balanced immune responses, such as increased levels of CXCR3 and MyD88 in G4, resulted in survival of mice and chronic toxoplasmosis, with the occurrence of tissue cysts in brain and lungs, at 14 and 21 dpi. Different immune responses and kinetics of gene expression appear to be elicited by the different strains and non-archetypal parasites demonstrated higher virulence.
Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/l) is recognised as a public health problem globally. The present study details the prevalence and predictors of vitamin D deficiency in a nationally representative sample (n 3250) of Australian Aboriginal and Torres Strait Islander adults aged ≥18 years. We used data from the 2012–2013 Australian Aboriginal and Torres Strait Islander Health Survey (AATSIHS). Serum 25(OH)D concentrations were measured by liquid chromatography-tandem MS. Survey-weighted logistic regression models were used to determine the independent predictors of vitamin D deficiency. Approximately 27 % of adult AATSIHS participants were vitamin D deficient. Vitamin D deficiency was more prevalent in remote areas (39 %) than in non-remote areas (23 %). Independent predictors of vitamin D deficiency included assessment during winter (men, adjusted OR (aOR) 5·7; 95 % CI 2·2, 14·6; women, aOR 2·2; 95 % CI 1·3, 3·8) and spring (men, aOR 3·3; 95 % CI 1·4, 7·5; women, aOR 2·6; 95 % CI 1·5, 4·5) compared with summer, and obesity (men, aOR 2·6; 95 % CI 1·2, 5·4; women, aOR 4·3; 95 % CI 2·8, 6·8) compared with healthy weight. Statistically significant associations were evident for current smokers (men only, aOR 2·0; 95 % CI 1·2, 3·4), remote-dwelling women (aOR 2·0; 95 % CI 1·4, 2·9) and university-educated women (aOR 2·4; 95 % CI 1·2, 4·8). Given the high prevalence of vitamin D deficiency in this population, strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches are needed.
Large prospective observational studies have cast doubt on the common assumption that endovascular thrombectomy (EVT) is superior to intravenous thrombolysis for patients with acute basilar artery occlusion (BAO). The purpose of this study was to retrospectively review our experience for patients with BAO undergoing EVT with modern endovascular devices.
All consecutive patients undergoing EVT with either a second-generation stent retriever or direct aspiration thrombectomy for BAO at our regional stroke center from January 1, 2013 to March 1, 2019 were included. The primary outcome measure was functional outcome at 1 month using the modified Rankin Scale (mRS) score. Multivariable logistic regression was used to assess the association between patient characteristics and dichotomized mRS.
A total of 43 consecutive patients underwent EVT for BAO. The average age was 67 years with 61% male patients. Overall, 37% (16/43) of patients achieved good functional outcome. Successful reperfusion was achieved in 72% (31/43) of cases. The median (interquartile range) stroke onset to treatment time was 420 (270–639) minutes (7 hours) for all patients. The procedure-related complication rate was 9% (4/43). On multivariate analysis, posterior circulation Alberta stroke program early computed tomography score and Basilar Artery on Computed Tomography Angiography score were associated with improved functional outcome.
EVT appears to be safe and feasible in patients with BAO. Our finding that time to treatment and successful reperfusion were not associated with improved outcome is likely due to including patients with established infarcts. Given the variability of collaterals in the posterior circulation, the paradigm of utilizing a tissue window may assist in patient selection for EVT. Magnetic resonance imaging may be a reasonable option to determine the extent of ischemia in certain situations.
Three-dimensional printing is a revolutionary technology that is disrupting the status quo in surgery. It has been rapidly adopted by otolaryngology as a tool in surgical simulation for high-risk, low-frequency procedures. This systematic review comprehensively evaluates the contemporary usage of three-dimensional printed otolaryngology simulators.
A systematic review of the literature was performed with narrative synthesis.
Twenty-two articles were identified for inclusion, describing models that span a range of surgical tasks (temporal bone dissection, airway procedures, functional endoscopic sinus surgery and endoscopic ear surgery). Thirty-six per cent of articles assessed construct validity (objective measures); the other 64 per cent only assessed face and content validity (subjective measures). Most studies demonstrated positive feedback and high confidence in the models’ value as additions to the curriculum.
Whilst further studies supported with objective metrics are merited, the role of three-dimensional printed otolaryngology simulators is poised to expand in surgical training given the enthusiastic reception from trainees and experts alike.
Grains rich in starch constitute the primary source of energy for both pigs and humans, but there is incomplete understanding of physiological mechanisms that determine the extent of digestion of grain starch in monogastric animals including pigs and humans. Slow digestion of starch to produce glucose in the small intestine (SI) leads to undigested starch escaping to the large intestine where it is fermented to produce short-chain fatty acids. Glucose generated from starch provides more energy than short-chain fatty acids for normal metabolism and growth in monogastrics. While incomplete digestion of starch leads to underutilised feed in pigs and economic losses, it is desirable in human nutrition to maintain consistent body weight in adults. Undigested nutrients reaching the ileum may trigger the ileal brake, and fermentation of undigested nutrients or fibre in the large intestine triggers the colonic brake. These intestinal brakes reduce the passage rate in an attempt to maximise nutrient utilisation, and lead to increased satiety that may reduce feed intake. The three physiological mechanisms that control grain digestion and feed intake are: (1) gastric emptying rate; (2) interplay of grain digestion and passage rate in the SI controlling the activation of the ileal brake; and (3) fermentation of undigested nutrients or fibre in the large intestine activating the colonic brake. Fibre plays an important role in influencing these mechanisms and the extent of their effects. In this review, an account of the physiological mechanisms controlling the passage rate, feed intake and enzymatic digestion of grains is presented: (1) to evaluate the merits of recently developed methods of grain/starch digestion for application purposes; and (2) to identify opportunities for future research to advance our understanding of how the combination of controlled grain digestion and fibre content can be manipulated to physiologically influence satiety and food intake.
Vitamin D deficiency is recognised as a public health problem globally, and a high prevalence of deficiency has previously been reported in Australia. This study details the prevalence of vitamin D deficiency in a nationally representative sample of Australian adults aged ≥25 years, using an internationally standardised method to measure serum 25-hydroxyvitamin D (25(OH)D) concentrations and identifies demographic and lifestyle factors associated with vitamin D deficiency. We used data from the 2011–2013 Australian Health Survey (n 5034 with complete information on potential predictors and serum 25(OH)D concentrations). Serum 25(OH)D concentrations were measured by a liquid chromatography-tandem MS that is certified to the reference measurement procedures developed by the National Institute of Standards and Technology, Ghent University and the US Centers for Disease Control and Prevention. Vitamin D deficiency and insufficiency were defined as serum 25(OH)D concentrations <50 nmol/l and 50 to <75 nmol/l, respectively. Overall, 20 % of participants (19 % men; 21 % women) were classified as vitamin D deficient, with a further 43 % classified as insufficient (45 % men; 42 % women). Independent predictors of vitamin D deficiency included being born in a country other than Australia or the main English-speaking countries, residing in southern (higher latitude) states of Australia, being assessed during winter or spring, being obese, smoking (women only), having low physical activity levels and not taking vitamin D or Ca supplements. Given our increasingly indoor lifestyles, there is a need to develop and promote strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches.
Patients with Parkinson’s disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent’s pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2–6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to address specific aspects of the performance of X-ray powder diffraction instruments. This report describes SRM 1879b, the third generation of this powder diffraction SRM. SRM 1879b is intended for use in the preparation of calibration standards for the quantitative analyses of cristobalite by X-ray powder diffraction in accordance with National Institute for Occupational Safety and Health (NIOSH) Analytical Method 7500, or equivalent. A unit of SRM 1879b consists of approximately 5 g of cristobalite powder bottled in an argon atmosphere. It is certified with respect to crystalline phase purity, or amorphous phase content, and lattice parameter. Neutron powder diffraction, both time-of-flight and constant wavelength, was used to certify the phase purity using SRM 676a as an internal standard. A NIST-built diffractometer, incorporating many advanced design features was used for certification measurements for lattice parameters.
Phased Array Feed (PAF) technology is the next major advancement in radio astronomy in terms of combining high sensitivity and large field of view. The Focal L-band Array for the Green Bank Telescope (FLAG) is one of the most sensitive PAFs developed so far. It consists of 19 dual-polarization elements mounted on a prime focus dewar resulting in seven beams on the sky. Its unprecedented system temperature of ~17 K will lead to a 3 fold increase in pulsar survey speeds as compared to contemporary single pixel feeds. Early science observations were conducted in a recently concluded commissioning phase of the FLAG where we clearly demonstrated its science capabilities. We observed a selection of normal and millisecond pulsars and detected giant pulses from PSR B1937+21.
This paper presents latest thinking from the Institute and Faculty of Actuaries’ Model Risk Working Party and follows on from their Phase I work, Model Risk: Daring to Open the Black Box. This is a more practical paper and presents the contributors’ experiences of model risk gained from a wide range of financial and non-financial organisations with suggestions for good practice and proven methods to reduce model risk. After a recap of the Phase I work, examples of model risk communication are given covering communication: to the Board; to the regulator; and to external stakeholders. We present a practical framework for model risk management and quantification with examples of the key actors, processes and cultural challenge. Lessons learned are then presented from other industries that make extensive use of models and include the weather forecasting, software and aerospace industries. Finally, a series of case studies in practical model risk management and mitigation are presented from the contributors’ own experiences covering primarily financial services.
Electronic health records (EHRs) provide great promise for identifying cohorts and enhancing research recruitment. Such approaches are sorely needed, but there are few descriptions in the literature of prevailing practices to guide their use. A multidisciplinary workgroup was formed to examine current practices in the use of EHRs in recruitment and to propose future directions. The group surveyed consortium members regarding current practices. Over 98% of the Clinical and Translational Science Award Consortium responded to the survey. Brokered and self-service data warehouse access are in early or full operation at 94% and 92% of institutions, respectively, whereas, EHR alerts to providers and to research teams are at 45% and 48%, respectively, and use of patient portals for research is at 20%. However, these percentages increase significantly to 88% and above if planning and exploratory work were considered cumulatively. For most approaches, implementation reflected perceived demand. Regulatory and workflow processes were similarly varied, and many respondents described substantive restrictions arising from logistical constraints and limitations on collaboration and data sharing. Survey results reflect wide variation in implementation and approach, and point to strong need for comparative research and development of best practices to protect patients and facilitate interinstitutional collaboration and multisite research.
Body image disturbance (BID) is a core symptom of anorexia nervosa (AN), but as yet distinctive features of BID are unknown. The present study aimed at disentangling perceptual and attitudinal components of BID in AN.
We investigated n = 24 women with AN and n = 24 controls. Based on a three-dimensional (3D) body scan, we created realistic virtual 3D bodies (avatars) for each participant that were varied through a range of ±20% of the participants’ weights. Avatars were presented in a virtual reality mirror scenario. Using different psychophysical tasks, participants identified and adjusted their actual and their desired body weight. To test for general perceptual biases in estimating body weight, a second experiment investigated perception of weight and shape matched avatars with another identity.
Women with AN and controls underestimated their weight, with a trend that women with AN underestimated more. The average desired body of controls had normal weight while the average desired weight of women with AN corresponded to extreme AN (DSM-5). Correlation analyses revealed that desired body weight, but not accuracy of weight estimation, was associated with eating disorder symptoms. In the second experiment, both groups estimated accurately while the most attractive body was similar to Experiment 1.
Our results contradict the widespread assumption that patients with AN overestimate their body weight due to visual distortions. Rather, they illustrate that BID might be driven by distorted attitudes with regard to the desired body. Clinical interventions should aim at helping patients with AN to change their desired weight.
Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.
Far-UV photons (FUV, E < 13.6 eV) from hot massive stars regulate, or at least influence, the heating, ionization, and chemistry of most of the neutral interstellar medium (H i and H2 clouds). Investigating the interaction between FUV radiation and interstellar matter (molecules, atoms and grains) thus plays an important role in astrochemistry.
The Orion Bar, an interface region between the Orion A molecular cloud and the H ii region around the Trapezium cluster, is a textbook example of a strongly illuminated dense PDR (photodissociation region). The Bar is illuminated by a FUV field of a few 104 times the mean interstellar radiation field. Because of its proximity and nearly edge-on orientation, it provides a very good template to investigate the chemical content, structure, and dynamics of a strongly irradiated molecular cloud edge. We have used ALMA to mosaic a small field of the Bar where the critical transition from atomic to molecular gas takes place. These observations provide an unprecedented sharp view of this transition layer (≲ 1″ resolution or ≲ 414 AU). The resulting images (so far in the rotational emission of CO, HCO+, H13CO+, SO+, SO, and reactive ions SH+ and HOC+) show the small-scale structure in gas density and temperature, and the steep abundance gradients. The images reveal a pattern of high-density substructures, photo-ablative gas flows and instabilities at the edge of the molecular cloud. These first ALMA images thus show a more complex morphology than the classical clump/interclump static model of a PDR.
In order to quantify the chemical content in strongly FUV-irradiated gas, we have also used the IRAM-30 m telescope to carry out a complete line-survey of the illuminated edge of the Bar in the millimeter domain. Our observations reveal the presence of complex organic molecules (and precursors) that were not expected in such a harsh environment. In particular, we have reported the first detection of the unstable cis conformer of formic acid (HCOOH) in the ISM. The energy barrier to internal rotation (the conversion from trans to cis) is approximately 4827 cm−1 (≈7000 K). Hence, this detection is surprising. The low inferred trans-to-cis abundance ratio of 2.8±1.0 supports a photoswitching mechanism: a given conformer absorbs a FUV stellar photon that radiatively excites the molecule to electronic states above the interconversion barrier. Subsequent fluorescent decay leaves the molecule in a different conformer form. This mechanism, which we have specifically studied with ab initio quantum calculations, was not considered so far in astrochemistry although it can affect the structure of a variety of molecules in PDRs.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2′-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort.
Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables.
F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4–43.8) compared to controls (45.0 pmol/l, 95% CI 42.9–47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5–39.9) compared to controls (44.9 pmol/l, 95% CI 43.2–46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants).
Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.