Large Effect Research Articles

Skin injury: Associations with variables related to perfusion and pressure.

Skin injuries are a major healthcare problem that are not well understood or prevented in the critically ill, suggesting that underappreciated variables are contributing. This pilot study tested the hypothesis that perfusion-related factors contribute to skin injuries diagnosed as hospital-acquired pressure injuries (HAPIs). A total of 533 adult patients were followed over 2574 critical care days (mean age 62.4, standard deviation (SD) 14.3 years, mean body mass index 30.4 (SD 7.4) kg/m2, 36.4% female). This was a secondary analysis of prospective, non-randomised clinical data from an intensive care unit at a large urban teaching hospital. Factors related to perfusion, specifically two or more infusions of vasopressors/inotropes, temporary mechanical circulatory support (MCS), extracorporeal membrane oxygenation, and durable MCS, were analysed to determine whether they were more strongly associated with HAPIs than immobility due to prolonged mechanical ventilation (>72 h) or operating room time (>6 h). Patients diagnosed with a HAPI had a statistically significant higher risk of being exposed to variables related to perfusion and immobility (P < 0.05 for each variable). Perfusion-related variables, except durable MCS, had a larger effect on skin breakdown (number needed to harm (NNH) 4-10) than immobility-associated variables (NNH 12-17). The finding that perfusion-related variables predicted HAPIs may warrant consideration of alternative diagnoses, such as skin failure due to impaired perfusion as a pathophysiological process that occurs concurrently with multisystem organ failure. Differentiation of skin injuries primarily from circulatory malfunction, rather than external pressure, may guide the development of more effective treatment and prevention protocols. This pilot study suggests that the contribution of perfusion to skin injuries should be explored further.

Soil available phosphorus and pH are key factors affecting the site index of Larix kaempferi plantations in China

Assessing the quality of forest sites is crucial for evaluating the potential productivity of forests and formulating effective management strategies. Therefore, it is essential to understand how environmental variables affect the site quality. This study focuses on quantifying the effects of 44 different environmental variables including climate, topography, and soil properties on the site index of Larix kaempferi plantations in three different climate regions in China, utilizing the random forest algorithm. L. kaempferi site index was determined from stem analysis data by felling dominant trees from 51 even-aged stands. The results indicated that the proposed random forest model explained ~59.47% of site index variations. Among many environmental variables, available phosphorus, pH, degree-days above 5°C (DD5), and spring mean maximum temperature (Tmax_MAM) had significant effects on the site index (P &amp;lt; 0.05), and the importance of soil chemical properties generally exhibits relatively larger effects on the site index than climate variables and topography variables. The partial dependence analysis revealed that the L. kaempferi plantations had maximum values at ~30 mg/kg of available phosphorus in the first soil layers, 30 mg/kg of available phosphorus in the second soil layers, 20 mg/kg of available phosphorus in the third soil layers, the DD5 between 2,600and 3,000°C, and Tmax_MAM ~15°C. Our findings attempt to provide a better understanding of the site–growth relationship.

The distribution of beneficial mutational effects between two sister yeast species poorly explains natural outcomes of vineyard adaptation.

Domesticated strains of Saccharomyces cerevisiae have adapted to resist copper and sulfite, two chemical stressors commonly used in winemaking. S. paradoxus has not adapted to these chemicals despite being consistently present in sympatry with S. cerevisiae in vineyards. This contrast could be driven by a number of factors including niche differences or differential access to resistance mutations between species. In this study, we used a comparative mutagenesis approach to test whether S. paradoxus is mutationally constrained with respect to acquiring greater copper and sulfite resistance. For both species, we assayed the rate, effect size, and pleiotropic costs of resistance mutations and sequenced a subset of 150 mutants. We found that the distributions of mutational effects displayed by the two species were similar and poorly explained the natural pattern. We also found that chromosome VIII aneuploidy and loss of function mutations in PMA1 confer copper resistance in both species, whereas loss of function mutations in REG1 were only a viable route to copper resistance in S. cerevisiae. We also observed a de novo duplication of the CUP1 gene in S. paradoxus but not in S. cerevisiae. For sulfite, loss of function mutations in RTS1 and KSP1 confer resistance in both species, but mutations in RTS1 have larger effects in S. paradoxus. Our results show that even when available mutations are largely similar, species can differ in the adaptive paths available to them. They also demonstrate that assays of the distribution of mutational effects may lack predictive insight concerning adaptive outcomes.

Investigating the universality of consonant and vowel co-occurrence restrictions

Certain phonotactic constraints on the co-occurrence of segments appear to be much more common across the world’s languages than others. In many languages, similar consonant co-occurrence is restricted through Obligatory Contour Principle (OCP) effects, while there are some exceptions for identical consonants. In vowels, the opposite pattern appears to hold: many languages have vowel harmony processes, where vowels within a domain are required to share some feature. Languages that encourage similar consonant co-occurrence or restrict similar vowel co-occurrence appear to be exceedingly uncommon. However, evidence of this pattern so far only comes from studies of individual languages or families, or of only consonants or vowels. We investigate patterns of co-occurrence in vowels and consonants in 107 Northern Eurasian languages across 21 families using Bayesian negative binomial regression to explicitly model the effects of aggregate similarity and segment identity on co-occurrence counts (the results of which can be interpreted similarly to observed/expected ratios). We find that the effect of similarity is remarkably consistent across languages: Similar consonant co-occurrence is disfavored, while aggregate similarity has no effect on vowel co-occurrence. Identical segment co-occurrence effects are much more variable across languages, with a tendency towards disfavoring identical consonants, and favoring identical vowels. We also find larger effects in consonants than in vowels, suggesting that consonant co-occurrence is more strongly constrained than vowel co-occurrence. We also find that there is no evidence for or against any correlations between vowel and consonant co-occurrence, suggesting that more data is needed to evaluate this possibility.

Comparative analysis of the duodenojejunal microbiome with the oral and fecal microbiomes reveals its stronger association with obesity and nutrition

ABSTRACT The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While most research focuses on the fecal microbiota due to its easier accessibility, the small intestine, as a major site for nutrient sensing and absorption, warrants further investigation to determine its microbiota composition and functions. Here, we conducted a clinical research project in 30 age- and sex-matched participants with (n = 15) and without (n = 15) obesity. Duodenojejunal fluid was obtained by aspiration during endoscopy. Phenotyping included clinical variables related to metabolic status, lifestyle, and psychosocial factors using validated questionnaires. We performed metagenomic analyses of the oral, duodenojejunal, and fecal microbiome, alongside metabolomic data from duodenojejunal fluid and feces, integrating these data with clinical and lifestyle information. Our results highlight significant associations between duodenojejunal microbiota composition and usual dietary intake, as well as clinical phenotypes, with larger effect sizes than the associations between these variables and fecal microbiota. Notably, we found that the duodenojejunal microbiota of patients with obesity exhibited higher diversity and showed distinct differences in the abundance of several duodenojejunal microbiota species compared with individuals without obesity. Our findings support the relevance of studying the role of the small intestinal microbiota in the pathogenesis of nutrition-related diseases.

8406 A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZP-3813, a Novel Small Peptide Growth Hormone Receptor Antagonist, in Healthy Subjects

Abstract Disclosure: S. Allas: Employee; Self; Amolyt Pharma. Stock Owner; Self; Amolyt Pharma. G. Ravel: Employee; Self; Amolyt Pharma. Stock Owner; Self; Amolyt Pharma. C. Farrell: Employee; Self; ICON plc. S. Fillon: Employee; Self; Amolyt Pharma. O. Taha: Employee; Self; Amolyt Pharma. M.D. Culler: Employee; Self; Amolyt Pharma. Stock Owner; Self; Amolyt Pharma. M. Ovize: Employee; Self; Amolyt Pharma. Stock Owner; Self; Amolyt Pharma. M. Sumeray: Employee; Self; Amolyt Pharma. Stock Owner; Self; Amolyt Pharma. A.J. Van der Lely: Consulting Fee; Self; Amolyt Pharma. Acromegaly is a rare disease typically caused by a benign growth hormone (GH)-secreting pituitary adenoma that stimulates over-production of insulin-like growth factor-1 (IGF1) from the liver. Treatment with somatostatin analog (SSA) monotherapy does not provide optimal control of circulating IGF-1 levels in the majority of patients. AZP-3813, a 16-amino acid, bicyclic GH receptor antagonist (GHRA) binds to the GH receptor and prevents endogenous GH from stimulating the production of IGF-1. The compound is being developed as an add-on therapy for the treatment of acromegaly in patients insufficiently controlled with SSAs. In normal animals, AZP-3813 potently decreases circulating levels of IGF-1 and further suppressive effects are observed when combined with the SSA, octreotide. Randomized double-blind placebo-controlled single and multiple ascending dose studies (SAD and MAD, respectively) are being conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZP-3813 in healthy subjects. Here we report data from all SAD cohorts and the first 3 MAD cohorts. In the SAD study, 5 subjects received a single subcutaneous administration of 3 mg AZP-3813 or placebo (3:2) and 8 subjects received 10, 20, 40, 60, 90, 120 mgAZP-3813 or placebo (6:2). In the MAD study, 8 subjects received 10, 20, 40 mg AZP-3813 or placebo (6/2) QD for 14 consecutive days. In both SAD and MAD studies, treatment was well tolerated in all subjects with no safety concerns. Cmax and AUC increased in a dose-proportional manner. The half-life of AZP-3813 was estimated to be 18-22 hours. In the SAD study, AZP-3813 induced a dose-related decrease in circulating IGF-1 levels at doses of 10 mg and above with a more prolonged reduction up to 72 hours at higher doses. In the MAD study, AZP-3813 induced a gradual and sustained dose-related decrease in circulating IGF-1 levels at 20 and 40 mg/day, with a larger effect after 2 weeks of dosing as compared to single administration at the same dose, consistent with a cumulative effect of repeated administration. Mean placebo-adjusted % change from baseline for the 20 and 40 mg cohorts were 19% and 44%, respectively. This study is ongoing, and updates on additional MAD cohorts will be reported at the meeting. These data clearly demonstrate that AZP-3813, the novel GHRA, substantially decreases circulating IGF-1 levels in healthy individuals, thereby supporting further testing in patients with acromegaly. Presentation: 6/1/2024

5154 Regulation Of T2D Genes In Human Adipocytes

Abstract Disclosure: Q. Zhang: None. Type 2 diabetes (T2D) is a chronic disease that affects 415 million people around the world and was the fourth leading cause of death (2015). Insulin resistance (IR), one of the major pathophysiological mechanisms that characterize T2D, is defined as the state in which cells, tissues, or organisms no longer respond appropriately to endogenous or exogenous insulin. We have generated detailed transcriptomes and chromatin state maps from the isolated adipocytes of insulin sensitive (IS) and insulin resistant (IR) human subjects. Mapping IR/IS differentially enriched H3K27ac peaks onto T2D GWAS SNPs suggested several loci as noncoding regulatory elements (REs) of human IR. We focused on the IRS1 gene, a known T2D related locus that encodes a critical protein in the insulin signaling cascade. We developed a CRISPRi-based assay that enabled us to determine which noncoding regulatory elements are required for normal IRS1 expression in human adipocytes. Our data indicate that many IR/IS differentially regulated H3K27ac peaks are critical regulatory elements for IRS1 transcription, although we did not observe that peaks that were increased in the IS state had a larger effect, as predicted. Overall, we have developed a CRISPRi-based screening system for noncoding elements in human adipocytes, which can be deployed to study many different loci related to metabolic disease. Presentation: 6/2/2024

Giant serous cystadenomas encountered in clinical practice: A case series

Benign serous cystadenomas represent 16% of all ovarian epithelial neoplasms, and account for up to two-thirds of epithelial tumors of the ovary. They are commonly encountered after the 3rd decade of life and in the later decades, due to the slow growth nature over lifetime. These tumors may begin as small unilocular subcentimeter lesions, but may expand to fill the entire abdominal cavity. This may present with mass effect to surrounding tissues and organs, and lead to sequela of compartment syndrome of the peritoneal cavity. We present a case series of surgical evaluation and management of extremely enlarged serous cystadenomas of the ovary (&gt;30 cm) encountered in an atypical age presentation, with the first case involving a 19 year old who had a known 6 cm cyst four years prior, who presented to emergency room (ER) with gastrointestinal (GI) symptoms secondary to the tumors mass effect, imaging demonstrating a massive tumor, subsequently requiring surgical dissection. The second case demonstrates a 25 year old with known cyst (&gt;20 cm) two years prior who presented with even larger effect (close to 40 cm size) and worsening symptoms due to the tumors mass effect requiring removal. In both cases, patients presented to emergency room with acute symptoms, exploratory laparotomy was required for complete evacuation of lesion and for resolution of symptoms.

Quantifying the impact of surgical teams on each stage of the operating room process

IntroductionOperating room (OR) efficiency is a key factor in determining surgical healthcare costs. To enable targeted changes for improving OR efficiency, a comprehensive quantification of the underlying sources of variability contributing to OR efficiency is needed. Previous literature has focused on select stages of the OR process or on aggregate process times influencing efficiency. This study proposes to analyze the OR process in more fine-grained stages to better localize and quantify the impact of important factors.MethodsData spanning from 2019-2023 were obtained from a surgery center at a large academic hospital. Linear mixed models were developed to quantify the sources of variability in the OR process. The primary factors analyzed in this study included the primary surgeon, responsible anesthesia provider, primary circulating nurse, and procedure type. The OR process was segmented into eight stages that quantify eight process times, e.g., procedure duration and procedure start time delay. Model selection was performed to identify the key factors in each stage and to quantify variability.ResultsProcedure type accounted for the most variability in three process times and for 44.2% and 45.5% of variability, respectively, in procedure duration and OR time (defined as the total time the patient spent in the OR). Primary surgeon, however, accounted for the most variability in five of the eight process times and accounted for as much as 21.1% of variability. The primary circulating nurse was also found to be significant for all eight process times.DiscussionThe key findings of this study include the following. (1) It is crucial to segment the OR process into smaller, more homogeneous stages to more accurately assess the underlying sources of variability. (2) Variability in the aggregate quantity of OR time appears to mostly reflect the variability in procedure duration, which is a subinterval of OR time. (3) Primary surgeon has a larger effect on OR efficiency than previously reported in the literature and is an important factor throughout the entire OR process. (4) Primary circulating nurse is significant for all stages of the OR process, albeit their effect is small.

Do home mathematical activities relate to early mathematical skills? A systematic review and meta-analysis.

Children's foundational mathematical skills are critical for future academic attainment. While home mathematical activities (HMAs) have been proposed to support these skills, the extent to which engaging in them supports mathematical skills remains unclear. This preregistered systematic review and multilevel meta-analysis identified 351 effect sizes from 72 samples in 20 countries, exploring the relation between frequency of HMAs and mathematical skills in children aged 7 years and under (Mage = 61 months). A small significant positive relation was found (r = .13), moderated by risk of bias, with larger effects associated with a higher risk of bias. Specific ways the field can move forward are discussed to better understand the role of the home mathematical environment in early mathematics.

Modeled temperature, mortality impact and external benefits of cool roofs and rooftop photovoltaics in London

AbstractPopulation exposure to high temperatures poses health risks and increases mortality. ‘Cool roofs’ (high-albedo roofs) and rooftop photovoltaics (RPV) may reduce temperatures in urban areas. Here, using advanced urban climate modeling, we model impacts of these measures on air temperature and heat-related mortality in London during the record-breaking hot summer of 2018. We estimate changes in mean near-surface air temperature of −0.3 °C in the RPV scenario and −0.8 °C in the cool roof scenario. We find that the heat-related mortality in this period (estimated 655–920) could have been reduced by 96 (12%) by RPV, or 249 (32%) by cool roofs, in scenarios where all roofs have these measures. Monetized using value of statistical life, we estimate benefits for RPV and cool roofs of £237 M and £615 M, respectively. We estimate that up to 20 TWh of electrical energy would be generated in the full RPV scenario. We show that, for conditions such as in London June–August 2018, RPV or cool roofs may reduce near-surface air temperatures and associated heat-related mortality, with cool roofs having a larger effect.

Validating the Motives for Online Gaming Questionnaire (MOGQ) within the WHO and APA gaming disorder symptoms frameworks

The increasing interest in digital games and the reasons behind their popularity worldwide warrants further psychometric investigation of motivation factors for engagement in digital games. The present study aimed to validate the Motives for Online Gaming Questionnaire (MOGQ) in a Swedish sample and compare the associations between the seven motivational factors and gaming disorder symptoms across the American Psychiatric Association and World Health Organization diagnostic frameworks. Furthermore, considering the utility of more concise psychological measures, a 14-item version of the MOGQ was developed (MOGQ-14). A sample of 678 Swedish video game players (68.4% men, 29.7% women, and 1.9% other, Mage = 29.5 years, range 15 to 66) were included in the analyses after participating in an online survey. The analyses revealed that the Swedish version of the MOGQ had good psychometric properties. All MOGQ factors showed good reliability (McDonald’s omega), and all intercorrelations among the MOGQ dimensions were consistent with previous findings. The results showed that, on average, men reported higher gaming motivations concerning competition than women. The relationships between six gaming motivation factors (social, escape, competition, coping, skill development, fantasy) and gaming disorder symptoms were consistent with previous research. Findings indicated that the relationship between motivations (escape and recreation) and gaming disorder symptoms varied across APA and WHO diagnostic frameworks, depending on the motivation scale used (MOGQ or MOGQ-14). Recreation significantly differed in its relationship with symptoms when using MOGQ, and the MOGQ-14 showed larger effect sizes in the WHO framework for escape and recreation motivations.

Gut microbiota dysbiosis in ankylosing spondylitis: a systematic review and meta-analysis

BackgroundAnkylosing spondylitis (AS) is a connective tissue disease that primarily affects spinal joints, peripheral joints, and paravertebral soft tissues, leading to joint stiffness and spinal deformity. Growing evidence has implicated gut microbiota in the regulation of AS, though the underlying mechanisms remain poorly understood.MethodsWe conducted a comprehensive search of PubMed, Embase, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, China Science and Technology Journal Database (VIP), and China National Knowledge Internet (CNKI) databases from the time the databases were created until 30 July 2023. To evaluate changes in α-diversity and the abundance of certain microbiota families in AS, standardized mean difference (SMD) and 95% confidence interval (CI) calculations were made. Meta-analyses were performed using STATA 12.0 and the quality of the literature was assessed by following systematic review guidelines.ResultsThis systematic review and meta-analysis included 47 studies, providing insights into the gut microbiota composition in patients with AS compared to healthy controls (HCs). Our findings indicate a significant reduction in gut microbial diversity in patients with AS, as evidenced by a decrease in both richness and evenness. Specifically, the Shannon index showed a moderate decrease (SMD = -0.27, 95% CI: -0.49, -0.04; P &amp;lt; 0.001), suggesting a less diverse microbial ecosystem in patients with AS. The Chao1 index further confirmed this trend, with a larger effect size (SMD = -0.44, 95% CI: -0.80, -0.07; P &amp;lt; 0.001), indicating a lower species richness. The Simpson index also reflected a significant reduction in evenness (SMD = -0.30, 95% CI: -0.53, -0.06; P &amp;lt; 0.001). Additionally, patients with AS who received anti-rheumatic combination treatment exhibited a more pronounced reduction in α-diversity compared to untreated patients, highlighting the potential impact of this treatment on gut microbiota balance. In terms of specific microbial families, we observed a significant decrease in the abundance of Bifidobacterium (SMD = -0.42, 95% CI: -2.37, 1.52; P &amp;lt; 0.001), which is known for its beneficial effects on gut health. Conversely, an increase in the abundance of Bacteroidetes was noted (SMD = 0.42, 95% CI: -0.93, 1.76; P &amp;lt; 0.001), suggesting a possible shift in the gut microbiota composition that may be associated with AS pathophysiology.ConclusionOur analysis revealed changes in α-diversity and the relative abundance of specific bacteria in AS. This suggests that targeting the gut microbiota could provide new therapeutic opportunities for treating AS.Systematic review registrationhttps://www.crd.york.ac.uk./PROSPERO/, identifier CRD42023450028.

Trends in Chemistry Education Research on Student Transformation in the Philippines: A Meta-analytic Review

Creating innovative methodologies and interventions in chemistry education is essential to promote positive student transformation outcomes. Although chemistry educators are key in utilizing its potential in the classroom, very little is known about its efficacy in teaching and learning. This study aims to determine the current research trends in chemistry education. It examines the effect of chemistry education research findings included in the meta-analysis on using varied teaching methodologies on student transformation outcomes. A systematic review and meta-analysis of a pool of studies related to chemistry instruction in the Philippines and through on site or online browsing were conducted. Results show that the country's pedagogical trend in chemistry education centers mainly on cooperative and inquiry-based learning, which aligns with and supports the framework and goals of 21st-century teaching. Results suggested that chemistry teachers can consider employing one of the various pedagogies and methods that effectively improve students' cognitive and affective outcomes. Heterogeneity test warrants that significant differences exist between the grouped features. The effect size data are directly influenced by the significance of the test derived from each study. Studies with significant results tend to have a larger effect size and significantly affect the study variables.

The impact of air temperature and humidity on Children’s blood pressure mediated by Lipids: A prospective cohort study

ObjectivesFew studies illustrate the mechanism between air temperature and blood pressure (BP) in childhood. This study aims to investigate the associations between air temperature, humidity exposure, and BP trajectories in children and adolescents, and explore the potential mediating roles of lipid profiles in these relationships. MethodsThis prospective cohort study included 5,971 children with 10,800 person-times measurements at baseline from the Chongqing Health Cohort, with evaluations conducted in 2014–2015 (baseline) and follow-ups in 2016 (urban areas) and 2019 (urban and rural areas). Multilevel mixed-effects models were used to analyse the impacts of air temperature and humidity on BP levels and the incidence of elevated BP, while accounting for potential confounders. Mediation analyses were performed to evaluate the mediating effects of lipid profiles, including low-density lipoprotein (LDL), total cholesterol (TC), and specific lipid species. ResultsAfter adjusting for covariates, higher air temperature quartiles were associated with both decreased BP levels and elevated BP risk (RR: 0.83; 95 % CIs: 0.78, 0.89; P = 0.028). Conversely, higher humidity quartiles exhibited a U-shaped relationship with BP levels. Greater variability in air temperature was linked to increase BP levels. The cumulative effects of air temperature exposure on BP were significant from pregnancy to age 10, with females exhibiting larger effects (β:-3.291, 95 % CIs: −4.242,-2.340, P < 0.001). LDL and TC partially mediated the associations between air temperature and BP levels, particularly in males. Specific lipid species, including SM (d21:1), LPC (17:0), and PC (O-36:3), also exhibited significant mediating effects. ConclusionsThis study provides novel insights into the intricate interplay between air temperature, humidity, lipid metabolism, and blood pressure regulation in children. Lower average temperatures and extreme humidity levels were associated with increased risks of elevated BP, potentially mediated by lipid profiles. Early interventions targeting air temperature exposure and lipid metabolism could mitigate hypertension risk, promoting improved cardiovascular outcomes in children.

Transcutaneous vagus nerve stimulation effects on chronic pain: systematic review and meta-analysis.

Chronic pain is one of the major causes of disability with a tremendous impact on an individual's quality of life and on public health. Transcutaneous vagus nerve stimulation (tVNS) is a safe therapeutic for this condition. We aimed to evaluate its effects in adults with chronic pain. A comprehensive search was performed, including randomized controlled trials published until October 2023, which assessed the effects of noninvasive tVNS. Cohen's d effect size and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were performed. Fifteen studies were included. The results revealed a mean effect size of 0.41 (95% CI 0.17-0.66) in favor of tVNS as compared with control, although a significant heterogeneity was observed (χ2 = 21.7, df = 10, P = 0.02, I 2 = 53.9%). However, when compared with nonactive controls, tVNS shows a larger effect size (0.79, 95% CI 0.25-1.33), although the number of studies was small (n = 3). When analyzed separately, auricular tVNS and cervical tVNS against control, it shows a significant small to moderate effect size, similar to that of the main analysis, respectively, 0.42 (95% CI 0.08-0.76, 8 studies) and 0.36 (95% CI 0.01-0.70, 3 studies). No differences were observed in the number of migraine days for the trials on migraine. This meta-analysis indicates that tVNS shows promise as an effective intervention for managing pain intensity in chronic pain conditions. We discuss the design of future trials to confirm these preliminary results, including sample size and parameters of stimulation.

Effects of forage feeding to calves on performance, rumen fermentation and nutrient digestibility: A meta-analysis

The literature on whether or not to feed forage is marked by inconsistencies, largely due to various factors associated with forage inclusion in calf diets. To elucidate these factors, we conducted a 3-level meta-analysis to comprehensively investigate the overall effects of forage provision in young calves. We searched for studies published between 2000 and 2023 in Google Scholar, ScienceDirect, and X-Mol. Moderator analyses were performed to evaluate the effects of different forage sources, forage provision methods, starter forms, milk levels and forage levels on the heterogeneity of growth performance, rumen fermentation and nutrient digestibility outcomes in studies feeding forage to calves. Mixed-effect model was used to predict the relationship between forage level and performance. Funnel plot and Egger's test were used to determine publication bias. A total of 86 treatment comparisons from 36 articles were included in the final data set. The weighted mean difference (WMD) was used to evaluate the effect size, and the statistical heterogeneity of the effect size was estimated using Cochrane's Q test. The results showed that forage supplementation improved growth performance, structural growth, and development of rumen fermentation in calves. However, moderator analyses revealed that several factors, including forage source, feeding method, physical form of starter, milk feeding level and forage feeding level might contribute considerably to variability, resulting in significant heterogeneity in the effects of forage provision in calves. Larger effect sizes were found for oat hay (OH) supplementation rather than alfalfa hay (AH) or straw, feeding forage as a free-choice (FC) compared with a total mixed ration (TMR; defined as a mixture of calf starter and forage), especially when forage was fed as a FC resulting in higher total dry matter intake (TDMI) and body barrel. Forage supplementation was more effective in boosting calf growth in calves provided ground starter than in calves fed pelleted and textured starter. Greater effects were shown for AH supplementation than OH or straw in improving rumen fermentation parameters. Furthermore, compared with the preweaning period, the effect of providing forage on calves was more noticeable in the postweaning period. The results of the mixed-effects model analysis indicated that calves can be efficiently fed 12% of dry matter as forage during the preweaning period to support their growth and development. Meanwhile, 9% of dry matter might be the optimal level for feeding OH and straw to preweaning calves. More studies are essential to explore how different levels of AH dietary supplementation affects calves during the preweaning period, to improve the consistency and accuracy of the dose-response curve predictions. Overall, growth performance and rumen fermentation of dairy calves were affected by forage inclusion. Moreover, forage source, feeding method, physical form of starter, milk feeding level, and forage level are essential factors that result in different degrees of effect on the calf's performance and rumen fermentation.

Service quality or customer experience: what drives cultural heritage satisfaction and loyalty?

ABSTRACT Previous research suggests that in today’s experience economy, service is no longer the key determinant and that customer experience has taken over. However, few studies compare the relative impact of service quality and customer experiences on outcomes. The aim of this quantitative study is to examine the separate effects of service quality and customer experience on satisfaction, revisit intentions and word-of-mouth communication. Contrary to expectations, service quality has a larger effect on outcomes than customer experience. The mediation analysis shows very small indirect effect sizes, suggesting that that customer experience hardly mediates the relationship between service quality and the three outcomes. The conclusion is that measuring service quality remains essential to explaining consumer behaviour in the experience economy.

Using the visual cliff and pole descent assays to detect binocular disruption in mice.

Amblyopia, a neurodevelopmental visual disorder characterized by impaired stereoacuity, is commonly modeled in animals using monocular deprivation (MD) during a critical period of visual development. Despite extensive research at the synaptic, cellular and circuit levels of analysis, reliable behavioral assays to study stereoscopic deficits in mice are limited. This study aimed to characterize the Visual Cliff Assay (VCA) and the Pole Descent Cliff Task (PDCT) in mice, and to evaluate their utility in detecting binocular dysfunction. Using these assays, we investigated the impact of clinically relevant manipulations of binocular vision, including monocular occlusion, pupillary dilation, and amblyopia induced by long-term MD. Our findings reveal that optimal performance in both the VCA and PDCT are dependent on balanced binocular input. However, deficits after MD in the VCA exhibited relatively small effect sizes (7-14%), requiring large sample sizes for statistical comparisons. In contrast, the PDCT demonstrated larger effect sizes (43-61%), allowing for reliable detection of binocular dysfunction with a smaller sample size. Both assays were validated using multiple monocular manipulations relevant to clinical paradigms, with the PDCT emerging as the preferred assay for detecting deficits in stereoscopic depth perception in mice. These findings provide a robust framework for using the VCA and PDCT in mechanistic and therapeutic studies in mice, offering insights into the neural mechanisms of binocular vision and potential interventions for amblyopia.

Echocardiographic evaluation of left ventricular mechanicsin sarcoidosis patients without overt heart disease: a systematic review and meta-analysis.

During the last decade, a small number of studies have used speckle tracking echocardiography (STE) to investigate sarcoidosis effect on left ventricular (LV) mechanics in patients without overt heart disease. The present systematic review and meta-analysis has been primarily designed to summarize the main findings of these studies and to examine the overall influence of sarcoidosis on LV-global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF). All echocardiographic studies assessing conventional echoDoppler parameters and myocardial strain indices in patients with extracardiac sarcoidosis (ECS) vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LV-GLS and LVEF) were pooled as a standardized mean difference (SMD) comparing sarcoidosis group with healthy controls. The overall SMDs of LV-GLS and LVEF were calculated using the random-effect model. The full-text of 13 studies with 785 ECS patients and 567 healthy controls were analyzed. Both average LVEF (60.5±6.6 vs 63.0±4.8%, P<0.001) and LV-GLS (-17.4±3.3 vs -21.0±2.7%, P<0.001) were significantly lower in ECS patients than controls. However, sarcoidosis showed a significantly larger effect on LV-GLS (SMD: -1.26, 95%CI -1.61,-0.91, P<0.001) rather than on LVEF (SMD: -0.51, 95%CI -0.83,-0.20, P=0.001). Substantial heterogeneity was found for the studies that assessed LV-GLS (I2=86.4%) and LVEF (I2=85.3%). Egger's test gave a P-value of 0.24 for LV-GLS and 0.32 for LVEF assessment, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for both LV-GLS and LVEF (all P <0.05). In patients without overt heart disease, the effect of sarcoidosis on LV-GLS is significantly greater than on LVEF. STE analysis should be implemented in clinical practice for the early detection of myocardial involvement in ECS patients.