Rank Order Research Articles

Evaluation of claims data from a commercial value-based insurance product shows pediatric imaging is not a major driver of overall or pediatric healthcare expenditures.

Initiatives to reduce healthcare expenditures often focus on imaging, suggesting that imaging is a major driver of cost. To evaluate medical expenditures and determine if imaging was a major driver in pediatric as compared to adult populations. We reviewed all claims data for members in a value-based contract between a commercial insurer and a healthcare system for calendar years 2021 and 2022. For both pediatric (<18 years of age) and adult populations, we analyzed average per member per year (PMPY) medical expenditures related to imaging as well as other categories of large medical expenses. Average PMPY expenditures were compared between adult and pediatric patients. Children made up approximately 20% of members and 21% of member months but only 8-9% of expenditures. Imaging expenditures in pediatric members were 0.2% of the total healthcare spend and 2.9% of total pediatric expenditures. Imaging expenditures per member were seven times greater in adults than children. The rank order of imaging expenditures and imaging modalities was also different in pediatric as compared to adult members. Evaluation of claims data from a commercial value-based insurance product shows that pediatric imaging is not a major driver of overall, nor pediatric only, healthcare expenditures.

Quantifying robustness of the gap gene network

Early development of Drosophila melanogaster (fruit fly) facilitated by the gap gene network has been shown to be incredibly robust, and the same patterns emerge even when the process is seriously disrupted. We investigate this robustness using a previously developed computational framework called DSGRN (Dynamic Signatures Generated by Regulatory Networks). Our mathematical innovations include the conceptual extension of this established modeling technique to enable modeling of spatially monotone environmental effects, as well as the development of a collection of graph theoretic robustness scores for network models. This allows us to rank order the robustness of network models of cellular systems where each cell contains the same genetic network topology but operates under a parameter regime that changes continuously from cell to cell. We demonstrate the power of this method by comparing the robustness of two previously introduced network models of gap gene expression along the anterior–posterior axis of the fruit fly embryo, both to each other and to a random sample of networks with same number of nodes and edges. We observe that there is a substantial difference in robustness scores between the two models. Our biological insight is that random network topologies are in general capable of reproducing complex patterns of expression, but that using measures of robustness to rank order networks permits a large reduction in hypothesis space for highly conserved systems such as developmental networks.

Using AI/ML to predict blending performance and process sensitivity for Continuous Direct Compression (CDC)

Utilising three artificial intelligence (AI)/machine learning (ML) tools, this study explores the prediction of fill level in inclined linear blenders at steady state by mapping a wide range of bulk powder characteristics to processing parameters. Predicting fill levels enables the calculation of blade passes (strain), known from existing literature to enhance content uniformity. We present and train three AI/ML models, each demonstrating unique predictive capabilities for fill level. These models collectively identify the following rank order of feature importance: RPM, Mixing Blade Region (MB) size, Wall Friction Angle (WFA), and Feed Rate (FR). Random Forest Regression, a machine learning algorithm that constructs a multitude of decision trees at training time and outputs the mode of the classes (classification) or mean prediction (regression) of the individual trees, develops a series of individually useful decision trees. but also allows the extraction of logic and breakpoints within the data. A novel tool which utilises smart optimisation and symbolic regression to model complex systems into simple, closed-form equations, is used to build an accurate reduced-order model. Finally, an Artificial Neural Network (ANN), though less interrogable emerges as the most accurate fill level predictor, with an r2 value of 0.97. Following training on single-component mixtures, the models are tested with a four-component powdered paracetamol formulation, mimicking an existing commercial drug product. The ANN predicts the fill level of this formulation at three RPMs (250, 350 and 450) with a mean absolute error of 1.4%. Ultimately, the modelling tools showcase a framework to better understand the interaction between process and formulation. The result of this allows for a first-time-right approach for formulation development whilst gaining process understanding from fewer experiments. Resulting in the ability to approach risk during product development whilst gaining a greater holistic understanding of the processing environment of the desired formulation.

N-Nitrosodimethylamine investigations in Muta™Mouse define point-of-departure values and demonstrate less-than-additive somatic mutant frequency accumulations.

The N-nitrosamine, N-nitrosodimethylamine (NDMA), is an environmental mutagen and rodent carcinogen. Small levels of NDMA have been identified as an impurity in some commonly used drugs, resulting in several product recalls. In this study, NDMA was evaluated in an OECD TG-488 compliant Muta™Mouse gene mutation assay (28-day oral dosing across seven daily doses of 0.02-4 mg/kg/day) using an integrated design that assessed mutation at the transgenic lacZ locus in various tissues and at the endogenous Pig-a gene-locus, along with micronucleus frequencies in peripheral blood. Liver pathology was determined together with NDMA exposure in blood and liver. The additivity of mutation induction was assessed by including two acute single-dose treatment groups (i.e. 5 and 10 mg/kg dose on Day 1), which represented the same total dose as two of the repeat dose treatment groups. NDMA did not induce statistically significant increases in mean lacZ mutant frequency (MF) in bone marrow, spleen, bladder, or stomach, nor in peripheral blood (Pig-a mutation or micronucleus induction) when tested up to 4 mg/kg/day. There were dose-dependent increases in mean lacZ MF in the liver, lung, and kidney following 28-day repeat dosing or in the liver and kidney after a single dose (10 mg/kg). No observed genotoxic effect levels (NOGEL) were determined for the positive repeat dose-response relationships. Mutagenicity did not exhibit simple additivity in the liver since there was a reduction in MF following NDMA repeat dosing compared with acute dosing for the same total dose. Benchmark dose modelling was used to estimate point of departure doses for NDMA mutagenicity in Muta™Mouse and rank order target organ tissue sensitivity (liver > kidney or lung). The BMD50 value for liver was 0.32 mg/kg/day following repeat dosing (confidence interval 0.21-0.46 mg/kg/day). In addition, liver toxicity was observed at doses of ≥ 1.1 mg/kg/day NDMA and correlated with systemic and target organ exposure. The integration of these results and their implications for risk assessment are discussed.

Comparing Discrete Choice Experiment with Swing Weighting to Estimate Attribute Relative Importance: A Case Study in Lung Cancer Patient Preferences.

Discrete choice experiments (DCE) are commonly used to elicit patient preferences and to determine the relative importance of attributes but can be complex and costly to administer. Simpler methods that measure relative importance exist, such as swing weighting with direct rating (SW-DR), but there is little empirical evidence comparing the two. This study aimed to directly compare attribute relative importance rankings and weights elicited using a DCE and SW-DR. A total of 307 patients with non-small-cell lung cancer in Italy and Belgium completed an online survey assessing preferences for cancer treatment using DCE and SW-DR. The relative importance of the attributes was determined using a random parameter logit model for the DCE and rank order centroid method (ROC) for SW-DR. Differences in relative importance ranking and weights between the methods were assessed using Cohen's weighted kappa and Dirichlet regression. Feedback on ease of understanding and answering the 2 tasks was also collected. Most respondents (>65%) found both tasks (very) easy to understand and answer. The same attribute, survival, was ranked most important irrespective of the methods applied. The overall ranking of the attributes on an aggregate level differed significantly between DCE and SW-ROC (P < 0.01). Greater differences in attribute weights between attributes were reported in DCE compared with SW-DR (P < 0.01). Agreement between the individual-level attribute ranking across methods was moderate (weighted Kappa 0.53-0.55). Significant differences in attribute importance between DCE and SW-DR were found. Respondents reported both methods being relatively easy to understand and answer. Further studies confirming these findings are warranted. Such studies will help to provide accurate guidance for methods selection when studying relative attribute importance across a wide array of preference-relevant decisions. Both DCEs and SW tasks can be used to determine attribute relative importance rankings and weights; however, little evidence exists empirically comparing these methods in terms of outcomes or respondent usability.Most respondents found the DCE and SW tasks very easy or easy to understand and answer.A direct comparison of DCE and SW found significant differences in attribute importance rankings and weights as well as a greater spread in the DCE-derived attribute relative importance weights.

Food preferences and nutrient composition in captive Southern brown howler monkeys, Alouatta guariba clamitans.

Studies of food preferences in captive primates have so far mainly been restricted to frugivorous species. It was therefore the aim of the present study to assess the occurrence of spontaneous food preferences in a mainly folivorous primate, the captive Southern brown howler monkey, and to analyze whether these preferences correlate with nutrient composition. Using a two-alternative choice test, we presented ten male and five female adult Alouatta guariba clamitans with all possible binary combinations of ten types of food that are part of their diet in captivity and recorded their choice behavior. We found the howler monkeys to display the following rank order of preference: banana > mango > watermelon > papaya > beetroot > apple > pear > orange > cucumber > tomato. This preference ranking significantly and positively correlated with the total carbohydrate content and with the sucrose content of the food items. We also found significant positive correlations between the food preference ranking and the content of the minerals copper and magnesium. Male and female howler monkeys did not differ significantly in their food preference rankings. These results suggest this howler monkeys under human care are not opportunistic, but selective feeders with regard to maximizing their net gain of energy as only the content of carbohydrates, but not the contents of total energy, proteins, or lipids significantly correlated with the displayed food preferences. Thus, the food preferences of this primate are similar to those reported in several species of frugivorous primates tested with cultivated fruits and vegetables.

Magnitude of Fruit Juice-Drug Interactions Due to Osmolality-Dependent Fluid Secretion: Differences among Apple, Orange, and Grapefruit Juices.

We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively. Measurements of intestinal fluid movement following beverage administration by the in situ closed-loop technique revealed the following rank order for fluid volume in rat ileum: AJ > OJ > GFJ > purified water, suggesting that water movement is dependent on the osmolality of these beverages. Such changes in GI fluid volume are expected to alter the luminal drug concentration, potentially contributing to the magnitude of beverage-drug interactions. Indeed, in vivo pharmacokinetic study in rats revealed that the plasma concentration of atenolol, a low-permeability drug, was the highest after oral administration in purified water, followed by GFJ and OJ, and was the lowest after administration in AJ. In contrast, antipyrine, a high-permeability drug, showed no significant difference in plasma concentration after administration in purified water and fruit juices, suggesting that the absorption of high-permeability drugs is less affected by solution osmolality. Our findings indicate that differences in the magnitude of beverage-drug interactions can be at least partly explained by differences in the osmolality of the beverages ingested.

Longitudinal pathways of associations between motor proficiency and physical fitness during earlier and later childhood: The NW-CHILD study.

Understanding the relationships between motor proficiency (MP) and physical fitness (PF) is important for the future health of children, although longitudinal findings of this nature are limited. This study explored the association between MP and PF during earlier childhood (6 and 9 years old) and later childhood (12 years old) in boys and girls. A stratified and randomized research design including a baseline and two follow-up time-point measures (2010, 2013, and 2016) were used. Primary school children (N = 374, boys = 178; girls = 196) were tested with the Bruininks-Oseretsky Test of Motor-Proficiency-2, Short Form, and the Test of Gross Motor Development- 2, at ages 6 and 9 years, and with the Progressive Aerobic Cardiovascular Endurance Run test at age 12. Spearman Rank Order Correlations and stepwise regression analyses were used to analyze the data. Although of a low magnitude, proof of a dynamic longitudinal, but a stable relationship between MP and PF were found and with different gender-specific relationships in this pathway of association. A small but significant percentage of variation in PF at 12 years could be explained by overall motor competence (MC) and object control skills (OCS) at the ages of 6 and 9 years. Among girls, the association with PF at 12 years was influenced by both OCS, and MC, although only MC contributed to the variation found in boys. Socio-economic status made an insignificant contribution at 6 years to later PF in boys, but not in girls. MC, including OCS during early and middle childhood can be considered as possible triggers of physical activity which again, can increase PF during later childhood. Obtaining early competence in these developmental areas is therefore important to promote positive and sustainable trajectories of health with long-term health outcomes.

Profession recommendation based on multiple intelligence for high school students

One of the problems students often face is the lack of understanding of their interests and talents which will cause confusion in making future study choices and career plans. Career selection is an expression of personality into the world of work followed by identification of certain occupational stereotypes. Eight intelligences according to dr. Howard Gardner is linguistic, logical, mathematical, visual spatial, musical, kinesthetic, interpersonal, intrapersonal, and naturalist. This research purpose is to develop a system that produces information and professional recommendations that are in accordance with multiple intelligences of prospective high school students using a combination of Bayes' theorem and weighted product (WP) method. User’s preference value is calculated using the Bayes Theorem method to give each multiple intelligence value which is a criterion. WP method calculation to find professions that match user preferences. Weight of each criterion needed in WP method is calculated by Rank Order Centroid method. WP calculation will produce a ranking of 3 professions according to the input from the user. From system testing results that compared to results from experts, an accuracy of 67.33% is obtained. Based on the accuracy value, it can be said that the accuracy level system is quite good.

Relaxed Rank Order Centroid Weighting MCDM Method With Improved Grey Relational Analysis for Subcontractor Selection: Photothermal Power Station Construction

This article addresses the problem of subcontractor selection in an uncertain decision-making environment by proposing a new hybrid method and improving a classical multicriteria decision-making (MCDM) method. First, the proposed hybrid method combines subjective and objective weighting methods to estimate the weights of criteria that are represented as grey numbers. The subjective weighting method is the PA weighting method. The objective weighting method is the rank order centroid with slacks (ROCS) weighting method used to compensate for the limitation of the rank order centroid weighting method. Second, grey relational analysis (GRA) is improved by introducing both positive and negative reference (PNR) alternatives instead of a single reference alternative as in the classical GRA. Subsequently, the proposed hybrid grey-point allocation-ROCS weighting method and the GRA-PNR evaluation method are applied to select the most suitable subcontractor for the supply of heliostats for photothermal power station construction. Sensitivity analysis is conducted to verify the robustness of the results. Finally, the technique for order preferences by similarity to an ideal solution with grey values, simple additive weighting with grey relations, and additive ratio assessment with grey criteria scores is applied to validate the participation of the selected subcontractor in the project.

Ribonucleotides differentially modulate oral glutamate detection thresholds.

The savory or umami taste of the amino acid glutamate is synergistically enhanced by the addition of the purines inosine 5'-monophosphate (IMP) and guanosine 5'-monophosphate (GMP) disodium salt. We hypothesized that the addition of purinergic ribonucleotides, along with the pyrimidine ribonucleotides, would decrease the absolute detection threshold of (increase sensitivity to) l-glutamic acid potassium salt (MPG). To test this, we measured both the absolute detection threshold of MPG alone and with a background level (3mM) of 5 different 5'-ribonucleotides. The addition of the 3 purines IMP, GMP, and adenosine 5'-monophosphate (AMP) lowered the MPG threshold in all participants (P < 0.001), indicating they are positive modulators or enhancers of glutamate taste. The average detection threshold of MPG was 2.08mM, and with the addition of IMP, the threshold was decreased by approximately 1.5 orders of magnitude to 0.046mM. In contrast to the purines, the pyrimidines uridine 5'-monophosphate (UMP) and cytidine 5'-monophosphate (CMP) yielded different results. CMP reliably raised glutamate thresholds in 10 of 17 subjects, suggesting it is a negative modulator or diminisher of glutamate taste for them. The rank order of effects on increasing sensitivity to glutamate was IMP > GMP> AMP >> UMP// CMP. These data confirm that ribonucleotides are modulators of glutamate taste, with purines enhancing sensitivity and pyrimidines displaying variable and even negative modulatory effects. Our ability to detect the co-occurrence of glutamate and purines is meaningful as both are relatively high in evolutionarily important sources of nutrition, such as insects and fermented foods.

ASSOCIATION BETWEEN OBESITY INDUCED HYPERTENSION AND CONSUMPTION OF JUNK FOOD AMONG UNIVERSITY STUDENTS OF DISTRICT SIALKOT

The principal cause of early death throughout the world is cardiovascular diseases (CVDs). It has been found that, in young adults, high blood pressure (BP) is considered a significant public health concern, with approximately 26.4% of global prevalence. A diet containing junk food is the preliminary cause of obesity, which leads to hypertension and other cardiovascular diseases in adults. The risk factors are prevailing at an alarming rate and have affected university students' physical and mental health. Moreover, these health concerns have caused low productivity among students as well. This problem has not been studied and analyzed in sufficient profundity. This cross-sectional and correlational study investigated the relationship between fast food consumption, obesity, and hypertension among university students. This cross-sectional study was conducted on a sample size of three hundred participants aged twenty-five to forty. To calculate the BMI, the weight and height of the participants were measured, along with the measurements of their systolic and diastolic blood pressure and age, through standard tools and procedures. Their dietary intake was assessed using a questionnaire of food intake that records a 168-hour food intake. The study results revealed that significant positive correlations of high strength between fast food consumption and obesity were found using Spearman rank order correlations (rs = 0.81) and moderate strength of positive correlation between frequent fast-food consumption and hypertension (rs = 0.58). The resultant conclusion of the study shows that junk food is strongly linked with obesity and prehypertension. The findings of the study can reduce the prevalence of obesity and hypertension.

Academic Procrastination and its Association with Academic Achievement among Undergraduate Health Sciences’ Students

Background: Academic procrastination is the postponement of educational activities. Most university students try to keep themselves away from academic activities which might lead to procrastination and unsatisfactory performance. Objective: To assess the level of academic procrastination and its association with academic performance and the demographic characteristics of undergraduate students. Methods: This cross-sectional analytical study using a convenient sampling technique was conducted on 250 health sciences undergraduate students at Sohail University, Karachi, Pakistan from August to October 2022. Ethical approval and data collection permission were obtained. The Procrastination Assessment Scale for Students was used to gather data. The SPSS version-24 was used for statistical analysis. Simple descriptive statistics, spearman’s rank order correlation coefficient tests and independent sample t-test was applied. Results: Mostly participants (53.6%) were female, 93.2% were single, and 46 % in the generic nursing program and 54% were in 3rd &amp; 4th year. Students’ academic performance was insignificant with all the domains except writing a term (p-value 0.22, 0.5, 0.26, 0.37, 0.31 and 0.041 respectively). A significant relationship of students’ gender, education level and study program with academic procrastination was found (p-value 0.004, 0.021 and 0.002 respectively). Bachelor of Science in Nursing (BSN) and Pharm-D programs did not show as much procrastination as compared to Doctor of Physical Therapy (DPT) program (p-value 0.021). Conclusion: This study showed the considerable behaviour of procrastination among undergraduates. There was a significant association between writing a paper and academic achievement. In addition, academic procrastination was significantly associated with gender and the enrolled program of the participants.

Vapor-liquid equilibrium measurements of ionic liquid [DEME][TFSI] with different hydrofluorocarbon refrigerants R152a, R32, and R143a

To overcome the shortages of traditional working pairs (LiBr/H2O and NH3/H2O) for absorption-refrigeration systems (ARSs), novel working pairs consisting of low global warming potential (GWP) hydrofluorocarbons difluoroethane (R152a) and difluoromethane (R32) plus low-viscosity ionic liquid N,N‑diethyl-2‑methoxy-N-methylethan-1-aminium bis((trifluoromethyl)sulfonyl)amide ([DEME][TFSI]) are studied. Firstly, solubilities of R152a and R32 in [DEME][TFSI] are measured by the isochoric saturation method in the temperature range of 293 K ∼ 343 K and pressure range of 0.14 MPa ∼ 1.664 MPa with the relative expanded uncertainty of 0.03. A high-GWP hydrofluorocarbon 1,1,1-trifluoroethane (R143a) is involved in the experiment for further comparison. The non-random two-liquid model is used to correlate the vapor-liquid equilibrium data with average absolute relative errors of 0.55 % (R152a), 0.58 % (R32), and 0.94 % (R143a), respectively. [DEME][TFSI] shows its low viscosity and good solubility of hydrofluorocarbons by contrast with conventional ionic liquids. A refrigerant solubility rank order in [DEME][TFSI]: R152a > trans-1,3,3,3-tetrafluoropropene (R1234ze(E)) > R32 > 2,3,3,3-tetrafluoro-1-propene (R1234yf) > R143a is obtained from the comparison. This work provides the possibility to apply low-GWP working pairs R152a/[DEME][TFSI] and R32/[DEME][TFSI] in ARSs.

Effects of Anesthetics on Cardiac Repolarization in Adults: A Network Meta-Analysis of Randomized Clinical Trials.

Prolongation of cardiac repolarization, especially the heart rate-corrected QT (QTc) interval, is associated with life-threatening dysrhythmias. This study aimed to identify the anesthetic with the lowest risk of prolonging cardiac repolarization and provide guidance for anesthesia management in patients with cardiac diseases or long QT syndrome. Randomized controlled trials (RCTs) comparing the effects of anesthetics on cardiac repolarization indices were searched for in multiple databases. The primary outcome was QTc; and the secondary outcomes were other repolarization indices. A network meta-analysis was conducted using a frequentist approach and registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022304970). Thirteen RCTs investigating 953 adults with normal QTc interval and without cardiovascular diseases were included. Direct meta-analyses found that propofol had less influence than sevoflurane (95% confidence interval (CI): 16.10, 33.54) and desflurane (95% CI: 4.85, 35.36), and sevoflurane had less influence than desflurane (95% CI: 6.96, 19.39) on QTc prolongation. Network analysis found that propofol had less influence than sevoflurane (95% CI: 17.78, 29.63), halothane (95% CI: 11.29, 41.24), desflurane (95% CI: 23.79, 39.88), and isoflurane (95% CI: 20.11, 46.10), and sevoflurane had less influence than desflurane (95% CI: 0.43, 15.82) on QTc prolongation. The rank order of cumulative ranking curve analysis was propofol (100%), sevoflurane (63.8%), halothane (49.5%), desflurane (21.1%), and isoflurane (15.6%). The direct meta-analysis found that propofol had less influence than sevoflurane on QT prolongation (95% CI: 23.12, 57.86). Other secondary outcomes showed no conclusive findings. This meta-analysis found that propofol had a minimal effect on QTc prolongation, followed by sevoflurane and desflurane in adults with normal QTc interval and without cardiovascular diseases. Propofol is the best anesthetic for adult patients with long QT syndrome or cardiac diseases, but still needs more robust evidence.

IMPACT OF NFSM ON CHANGE IN KNOWLEDGE LEVEL OF BENEFICIARY AND NON-BENEFICIARY FARMERS ABOUT RECOMMENDED PACKAGE OF PRACTICES OF CHICKPEA

National Food Security Mission (NFSM) is a centrally sponsored scheme launched in 2007-08, with mission aims to increasing the productivity at the individual farmers through the adoption of improved technologies and farming practices. To assess the effectiveness of the NFSM-pluses in Rajasthan state the chickpea crop is select for this study because India is the single largest producer of chickpea in the world and it is called as King of Pulses. The study was conducted in two Agro-climatic zones of the Rajasthan state i.e. Ic (Hyper arid partial irrigated) and zone IIIa (Semi-arid eastern plains). From these zones 120 Beneficiary Farmers (BFs) and 120 Non-beneficiary Farmers (NBFs) were selected randomly from selected village. Thus, total sample size of 240 respondents. The findings of study shows that majority of beneficiary farmers (46.67%) and non-beneficiary farmers (40 per cent) had medium knowledge level about recommended package of practices of chickpea. According to practice wise extent of knowledge it was found that both BFs and NBFs possessed maximum knowledge level for practice like Time of sowing with (91.53 MPS &amp; 74.03 MPS) and assigned first rank while last rank order assigned for the practices like Physiological aspects (59.50MPS), Plant protection measures (42.25 MPS) and Weed management due to lack of knowledge, its complexity and risky application to the crop. The comparative data related to extent level of knowledge between BFs and NBFs show significance difference in all packages of practice of chickpea cultivation except the Irrigation Management show good impact of NFSM on change in knowledge level of beneficiary farmers of both Agro-climatic zones. The value of rank correlation (rs) was 0.61 which shows positive rank correlation between beneficiary and non-beneficiary farmer’s knowledge level.

Identifying patient preferences for diabetes care: A protocol for implementing a discrete choice experiment in Samoa.

In Samoa, adult Type 2 diabetes prevalence has increased within the past 30 years. Patient preferences for care are factors known to influence treatment adherence and are associated with reduced disease progression and severity. However, patient preferences for diabetes care, generally, are understudied, and other patient-centered factors such as willingness-to-pay (WTP) for diabetes treatment have never been explored in this setting. Discrete Choice Experiments (DCE) are useful tools to elicit preferences and WTP for healthcare. DCEs present patients with hypothetical scenarios composed of a series of multi-alternative choice profiles made up of attributes and levels. Patients choose a profile based on which attributes and levels may be preferable for them, thereby quantifying and identifying locally relevant patient-centered preferences. This paper presents the protocol for the design, piloting, and implementation of a DCE identifying patient preferences for diabetes care, in Samoa. Using an exploratory sequential mixed methods design, formative data from a literature review and semi-structured interviews with n = 20 Samoan adults living with Type 2 diabetes was used to design a Best-Best DCE instrument. Experimental design procedures were used to reduce the number of choice-sets and balance the instrument. Following pilot testing, the DCE is being administered to n = 450 Samoan adults living with diabetes, along with associated questionnaires, and anthropometrics. Subsequently, we will also be assessing longitudinally how preferences for care change over time. Data will be analyzed using progressive mixed Rank Order Logit models. The results will identify which diabetes care attributes are important to patients (p < 0.05), examine associations between participant characteristics and preference, illuminate the trade-offs participants are willing to make, and the probability of uptake, and WTP for specific attributes and levels. The results from this study will provide integral data useful for designing and adapting efficacious diabetes intervention and treatment approaches in this setting.

The β-Blocker Carvedilol and Related Aryloxypropanolamines Promote ERK1/2 Phosphorylation in HEK293 Cells with K A Values Distinct From Their Equilibrium Dissociation Constants as β 2-Adrenoceptor Antagonists: Evidence for Functional Affinity.

The determination of affinity by using functional assays is important in drug discovery because it provides a more relevant estimate of the strength of interaction of a ligand to its cognate receptor than radioligand binding. However, empirical evidence for so-called, "functional affinity" is limited. Herein, we determined whether the affinity of carvedilol, a β-adrenoceptor antagonist used to treat heart failure that also promotes extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, differed between these two pharmacological activities. Four structurally related β-adrenoceptor antagonists (alprenolol, carazolol, pindolol, propranolol) that also activated ERK1/2 were included as comparators to enhance our understanding of how these drugs work in the clinical setting. In HEK293 cells stably expressing the human β 2-adrenoceptor carvedilol and related aryloxypropanolamines were partial agonists of ERK1/2 phosphorylation with potencies ([A]50s) that were lower than their equilibrium dissociation constants (K Bs) as β 2-adrenoceptor antagonists. As the [A]50 of a partial agonist is a good approximation of its K B, then these data indicated that the affinities of carvedilol and related ligands for these two activities were distinct. Moreover, there was a significant negative rank order correlation between the [A]50 of each ligand to activate ERK1/2 and their intrinsic activities (i.e., as intrinsic activity for ERK1/2 phosphorylation increased, so did affinity). Genome editing revealed that the transducer that coupled the β 2-adrenoceptor to ERK1/2 phosphorylation in response to carvedilol and other β 2-adrenoceptor antagonists was Gαs. Collectively, these data support the concept of "functional affinity" and indicate that the ability of the β 2-adrenoceptor to recruit Gαs may influence the affinity of the activating ligand. SIGNIFICANCE STATEMENT: In HEK293 cells overexpressing the human β2-adrenoceptor carvedilol and four related aryloxypropanolamines behaved as β2-adrenoceptor antagonists and partial agonists of ERK1/2 phosphorylation with rank orders of affinity that were distinct. These data imply that carvedilol and other β-blockers can stabilize the β2-adrenoceptor in different affinity conformations that are revealed when functionally distinct responses are measured. This is the basis for the pharmacological concept of "functional affinity."

Relationship between Head Teacher's Motivation Strategies and Teacher's Performance in Secondary Schools in Serere District

Globally, teacher performance is a significant challenge for education, necessitating effective strategies to combat low morale and ensure adequate school performance (Gitonga, 2012). This study investigated the relationship between headteacher motivation strategies and Teacher Performance in secondary schools in the Serere district. Head teachers in Serere District are faced challenges such as lack of supervision, low assessment, absenteeism and non-participation in school activities, leading to a 50% decline in performance. Research was needed to understand the relationship between motivation strategies and teachers’ performance. With a sample size of 246 respondents, including head teachers and teachers, a cross-sectional correlation survey methodology was employed.The Spearman Rank Order Correlation Coefficient was utilized to analyze the data that were collected through surveys.The results showed a favorable relationship between head teachers' motivation and secondary school teachers' performance in the Serere district, suggesting that accommodations, salary increases, and capacity building encourage teachers to work hard.The research findings indicated a positive association between the motivational strategies employed by head teachers and the performance of teachers in secondary schools within the Serere District. The study suggested that additional policies should be introduced to bolster and sustain the existing framework of head teachers' motivational strategies. It further recommended revisiting and refining policies related to their implementation to foster continuous improvement in teachers' performance. Additionally, the study proposed the exploration of further research avenues to delve into motivation strategies and teachers' job satisfaction in secondary schools specifically within the Serere District

Promotional Language (Hype) in Abstracts of Publications of National Institutes of Health–Funded Research, 1985-2020

Investigators applying for National Institutes of Health (NIH) funding increasingly use promotional language (or hype) that has the potential to undermine objective evaluation. Whether or not the same investigators use hype in subsequent research reports has yet to be investigated. To assess changes in the use of hype in journal abstracts reporting research funded by the NIH and to compare those trends with previously reported trends in the associated NIH funding applications. This cross-sectional study assessed trends (from 1985 to 2020) in the use of promotional adjectives in abstracts of journal articles reporting NIH-funded research, and then compared those trends with previously reported trends for the associated NIH funding applications. Articles included in analyses had abstracts available in PubMed. Absolute change for the 139 adjective forms that have previously been identified as representing hype in NIH funding applications was measured as the difference in frequency between 1985 and 2020. Relative change was measured as the percentage change in frequency in 2020 relative to 1985, or the first year of occurrence. Consistency of change was measured by the rank order correlation (Kendall τ). Concordance between longitudinal trends in the journal abstracts and NIH funding applications was measured by the rank-order cross-correlation. In a total of 2 394 480 journal abstracts, all 139 adjective forms were identified in 2 793 592 total occurrences. Among these adjectives, 133 increased in absolute frequency by 5335 words per million (wpm), with a mean (SD) relative increase of 1404% (2371%). The largest absolute increases were for novel (524 wpm), important (414 wpm), and key (378 wpm). The largest relative increases were for scalable (22 wpm [19 964%]), unmet (23 wpm [12 126%]), and tailored (40 wpm [8169%]). The mean (SD) correlation for all adjectives was 0.70 (0.30) with 95 adjectives showing a strong positive correlation (τ > 0.7; P < .001), 24 a moderate positive correlation (0.5 < τ < 0.7; P < .001), and 3 a moderate negative correlation (-0.5 < τ < -0.7; P < .001). The mean (SD) cross-correlation was 0.64 (0.19) with 61 of the 139 adjectives showing a strong positive cross-correlations (τ > 0.7; P < .001), 53 a moderate positive cross-correlations (0.5 < τ < 0.7; P < .001), and 3 a moderate negative cross-correlation (-0.7 < τ < -0.5; P < .001). In this analysis of journal abstracts reporting NIH-funded research from 1985 to 2020, levels of promotional language were found to be increasing and trends were closely associated with previously reported trends in the related NIH funding applications. This suggests that increasing levels of salesmanship may in part be a downstream effect of salesmanship infused during earlier stages of the research cascade.