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This research communication reports the responses to supplementing dairy cattle with a hydrogenated fat-embedded calcium gluconate feed additive. The role of hindgut health in ruminant performance and wellbeing is an area of growing interest. Various prebiotic compounds have been used to promote lower gut health in various non-ruminant species. Calcium gluconate, a prebiotic compound, has previously been observed to increase milk fat yield when fed to ruminants in a form capable of resisting fermentation in the rumen, though the mechanism(s) behind this response remain unclear. The objective of this study was to compare the responses of lactating cattle to two different supplementation levels of a hydrogenated fat-embedded calcium gluconate (HFCG) product to evaluate a potential linear dose response. Forty-six lactating Holstein dairy cattle were used in a 3 × 3 replicated Latin square design with 28 d periods to evaluate a previously used dose of HFCG (approximately 16 g/d) with both a negative control and a dose of 25 g/d. Supplementation of multiparous animals with 16 g/d HFCG significantly (P < 0.05) increased milk fat yield and content relative to the negative control, and subsequently improved gross feed efficiency (P < 0.05); additionally, the presence of a potential non-linear dose response was observed for these parameters. Responses when supplemented with 25 g/d HFCG did not differ from the negative control. No production responses were observed in primiparous animals. The mode of action of HFCG, in addition to the potential differential response in primiparous animals remains unclear and warrants further investigation.
This chapter discusses the concept, design, implementation challenges and emerging models of successful strategic purchasing (SP) in low- and middle-income countries (L&MICs). The purchasing function is concerned with allocation and use of funds to ensure more value for the existing money by setting the right financial incentives to providers and ensuring that all individuals have access to needed health services. There is a marked difference across countries in terms of how they purchase health care. Passive purchasing implies following a predetermined budget or simply paying bills when presented. In contrast, SP involves a continuous search for the best ways to maximize health system performance by proactively answering questions such as – for whom to buy, what to buy, from whom to buy, how to pay and what impact. There are enablers and choke points for implementation of provider payment systems that need consideration. For L&MICs to do SP effectively, calls for building technical capacity in provider payment, greater policy coherence, institutional relationship between government and purchasers, and a step-by-step approach allowing countries to move towards SP.
Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 hours/day with water-only fasting for the remaining 16 hours. The objective of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome, and CVD risk (secondary outcomes) compared to usual care. The study will be a two-site, two-arm, parallel-group superiority randomized control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class, and healthy eating and physical activity guidelines. Magnetic resonance imaging, blood draws, and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end-point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.
We investigated the efficacy and complication profile of intranasal dexmedetomidine for transthoracic echocardiography sedation in patients with single ventricle physiology and shunt-dependent pulmonary blood flow during the high-risk interstage period.
A single-centre, retrospective review identified interstage infants who received dexmedetomidine for echocardiography sedation. Baseline and procedural vitals were reported. Significant adverse events related to sedation were defined as an escalation in care or need for any additional/increased inotropic support to maintain pre-procedural haemodynamics. Minor adverse events were defined as changes from baseline haemodynamics that resolved without intervention. To assess whether sedation was adequate, echocardiogram reports were reviewed for completeness.
From September to December 2020, five interstage patients (age 29–69 days) were sedated with 3 mcg/kg intranasal dexmedetomidine. The median sedation onset time and duration time was 24 minutes (range 12–43 minutes) and 60 minutes (range 33–60 minutes), respectively. Sedation was deemed adequate in all patients as complete echocardiograms were accomplished without a rescue dose. When compared to baseline, three (60%) patients had a >10% reduction in heart rate, one (20%) patient had a >10% reduction in oxygen saturations, and one (20%) patient had a >30% decrease in blood pressure. Amongst all patients, no significant complications occurred and haemodynamic changes from baseline did not result in need for intervention or interruption of study.
Intranasal dexmedetomidine may be a reasonable option for echocardiography sedation in infants with shunt-dependent single ventricle heart disease, and further investigation is warranted to ensure efficacy and safety in an outpatient setting.
Debris-covered glaciers are an important component of the mountain cryosphere and influence the hydrological contribution of glacierized basins to downstream rivers. This study examines the potential to make estimates of debris thickness, a critical variable to calculate the sub-debris melt, using ground-based thermal infrared radiometry (TIR) images. Over four days in August 2019, a ground-based, time-lapse TIR digital imaging radiometer recorded sequential thermal imagery of a debris-covered region of Peyto Glacier, Canadian Rockies, in conjunction with 44 manual excavations of debris thickness ranging from 10 to 110 cm, and concurrent meteorological observations. Inferring the correlation between measured debris thickness and TIR surface temperature as a base, the effectiveness of linear and exponential regression models for debris thickness estimation from surface temperature was explored. Optimal model performance (R2 of 0.7, RMSE of 10.3 cm) was obtained with a linear model applied to measurements taken on clear nights just before sunrise, but strong model performances were also obtained under complete cloud cover during daytime or nighttime with an exponential model. This work presents insights into the use of surface temperature and TIR observations to estimate debris thickness and gain knowledge of the state of debris-covered glacial ice and its potential hydrological contribution.
Although compelling evidence from observational studies supports a positive association between consumption of cereal fibre and CVD risk reduction, randomised controlled trials (RCT) often target viscous fibre type as the prospective contributor to lipid lowering to reduce CVD risk. The objective of our study is to compare the lipids-lowering effects of viscous dietary fibre to non-viscous, cereal-type fibre in clinical studies. RCT that evaluated the effect of viscous dietary fibre compared with non-viscous, cereal fibre on LDL cholesterol and alternative lipid markers, with a duration of ≥ 3 weeks, in adults with or without hypercholesterolaemia were included. Medline, EMBASE, CINAHL and the Cochrane Central Register were searched through October 19, 2021. Data were extracted and assessed by two independent reviewers. The generic inverse variance method with random effects model was utilised to pool the data which were expressed as mean differences (MD) with 95 % CI. Eighty-nine trials met eligibility criteria (n 4755). MD for the effect of viscous dietary fibre compared with non-viscous cereal fibre were LDL cholesterol (MD = –0·26 mmol/l; 95 % CI: –0·30, −0·22 mmol/l; P < 0·01), non-HDL cholesterol (MD = –0·33 mmol/l; 95 % CI: –0·39, −0·28 mmol/l; P < 0·01) and Apo-B (MD = –0·04 g/l; 95 % CI: –0·06, −0·03 g/l; P < 0·01). Viscous dietary fibre reduces LDL cholesterol and alternative lipid markers relative to the fibre from cereal sources, hence may be a preferred type of fibre-based dietary intervention targeting CVD risk reduction.
This chapter takes stock of the political impact of the Sustainable Development Goals within countries. It explores the various initiatives taken by national governments, sub-national authorities, the corporate sector and civil society, and assesses their strategies and approaches to implement the Sustainable Development Goals in their spheres. The chapter finds that the steering effects of the global goals are so far mainly present in political discourse. While we also witness the emergence of new types of institutions, relationships and partnerships, they apparently reproduce existing structures and priorities of key players, indicating selective goal implementation. What we observe the least are steering effects on the (re-)allocation of resources. Thus, the chapter suggests that the Sustainable Development Goals are not (yet) leading to fundamental change and the voluntary nature of the 2030 Agenda makes it fairly easy for actors to implement the global goals in a way that benefits their self-interests.
The Elicited Imitation Task (EIT) is a popular technique for efficiently measuring global proficiency in multiple languages, and accumulated evidence indicates high reliability and strong relationships with other proficiency measures. Nevertheless, several dimensions of EIT design remain open to investigation, including the assumption that a pause is required in between the aural stimulus and oral response, to ensure processing of the input and prevent so-called parroting. This study investigated the relationship between three poststimulus pause conditions, learners’ proficiency and working memory, and their EIT scores as well as their perceptions of task difficulty, mental effort, focus, and interest. Findings indicated no differences in performances or perceptions between the 0-second pause, 2-second pause, and 5-second pause conditions, and a weak relationship between EIT performance and working memory. Across all conditions, the EIT distinguished consistently among proficiency levels, correlated strongly with a criterion proficiency measure, and produced remarkably reliable scores.
American Indian and Alaska Native peoples (AI/AN) have a disproportionately high rate of obesity, but little is known about the social determinants of obesity among older AI/AN. Thus, our study assessed social determinants of obesity in AI/AN aged ≥ 50 years.
We conducted a cross-sectional analysis using multivariate generalised linear mixed models to identify social determinants associated with the risk of being classified as obese (BMI ≥ 30·0 kg/m2). Analyses were conducted for the total study population and stratified by median county poverty level.
Indian Health Service (IHS) data for AI/AN who used IHS services in FY2013.
Totally, 27 696 AI/AN aged ≥ 50 years without diabetes.
Mean BMI was 29·8 ± 6·6 with 43 % classified as obese. Women were more likely to be obese than men, and younger ages were associated with higher obesity risk. While having Medicaid coverage was associated with lower odds of obesity, private health insurance was associated with higher odds. Living in areas with lower rates of educational attainment and longer drive times to primary care services were associated with higher odds of obesity. Those who lived in a county where a larger percentage of people had low access to a grocery store were significantly less likely to be obese.
Our findings contribute to the understanding of social determinants of obesity among older AI/AN and highlight the need to investigate AI/AN obesity, including longitudinal studies with a life course perspective to further examine social determinants of obesity in older AI/AN.
OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.
The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use.
Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%.
In each survey, 28−47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%−37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%−41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%−40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60).
The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.
This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group.
Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models.
ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= −.061 SD/year, Latinos = −.055,Whites= −.055). ϵ4 association with semantic memory change was strongest in White participants (−.071), intermediate in Latino participants (−.041), and weakest in Black participants (−.022).
Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
In response to the 2014-2016 West Africa Ebola virus disease (EVD) epidemic, the Centers for Disease Control and Prevention (CDC) designated 56 US hospitals as Ebola treatment centers (ETCs) with high-level isolation capabilities. We aimed to determine ongoing sustainability of ETCs and identify how ETC capabilities have impacted hospital, local, and regional COVID-19 readiness and response.
An electronic survey included both qualitative and quantitative questions and was structured into two sections: operational sustainability and role in the COVID-19 response.
Setting and Participants:
The survey was distributed to site representatives from the 56 originally designated ETCs; 37 (66%) responded.
Data were coded and analyzed using descriptive statistics.
Of the 37 responding ETCs, 33 (89%) reported they were still operating while 4 had decommissioned. ETCs that maintain high-level isolation capabilities incurred a mean of $234,367 in expenses per year. All but one ETC reported that existing capabilities (e.g., trained staff, infrastructure) before COVID-19 positively affected their hospital, local, and regional COVID-19 readiness and response (e.g., ETCs trained staff, donated supplies, and shared developed protocols).
Existing high-level isolation capabilities and expertise developed following the 2014-2016 EVD epidemic were leveraged by ETCs to assist hospital-wide readiness for COVID-19 and support response for other local and regional hospitals However, ETCs face continued challenges in sustaining those capabilities for high-consequence infectious diseases.
Mountain glaciers have response times that govern retreat due to anthropogenic climate change. We use geometric attributes to estimate individual response times for 383 glaciers in the Cascade mountain range of Washington State, USA. Approximately 90% of estimated response times are between 10 and 60 years, with many large glaciers on the short end of this distribution. A simple model of glacier dynamics shows that this range of response times entails consequential differences in recent and ongoing glacier changes: glaciers with decadal response times have nearly kept pace with anthropogenic warming, but those with multi-decadal response times are far from equilibrium, and their additional committed retreat stands well beyond natural variability. These differences have implications for changes in glacier runoff. A simple calculation highlights that transient peaks in area-integrated melt, either at the onset of forcing or due to variations in forcing, depend on the glacier's response time and degree of disequilibrium. We conclude that differences in individual response times should be considered when assessing the state of a population of glaciers and modeling their future response. These differences in response can arise simply from a range of different glacier geometries, and the same basic principles can be expected in other regions as well.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.