Incomplete Block Research Articles

Genotype Performance Estimation in Targeted Production Environments by Using Sparse Genomic Prediction

In plant breeding, Multi-Environment Trials (METs) evaluate candidate genotypes across various conditions, which is financially costly due to extensive field testing. Sparse testing addresses this challenge by evaluating some genotypes in selected environments, allowing for a broader range of environments without significantly increasing costs. This approach integrates genomic information to adjust phenotypic data, leading to more accurate genetic effect estimations. Various sparse testing methods have been explored to optimize resource use. This study employed Incomplete Block Design (IBD) to allocate lines to environments, ensuring not all lines were tested in every environment. We compared IBD to Random line allocation, maintaining a consistent number of environments per line across both methods. The primary objective was to estimate grain yield performance of lines using Genomic Estimated Breeding Values (GEBVs) computed through six Genomic Best Linear Unbiased Predictor (GBLUP) methods. In the first five methods, missing values were predicted before cross-environment adjustment; in the sixth, adjustment was performed directly. Using the Bayesian GBLUP model, we analyzed genotype performance under both IBD and random allocation. Results indicate that computing GEBVs for a target population of environments (TPE) using available phenotype and marker data is effective for selection. The IBD method showed superior performance with less variability compared to random allocation. These findings suggest that using IBD designs can enhance selection accuracy and efficiency, and that pre-adjustment prediction of missing lines may not necessarily improve selection outcomes.

Missing Data Imputation in Balanced Construction for Incomplete Block Designs

Observational data with massive sample sizes are often distributed on many local machines. From an experimental design perspective, investigators often desire to identify the effect of new treatments (even ML algorithms) on many blocks of experimental data. With time requirements or budget constraints, assigning all treatments to each block is not always feasible. This creates incomplete responses with respect to a randomized complete block design (RCBD). These incomplete responses are missing by design. However, whether they can be estimated with missing imputation methods is not well understood. Thus, it is challenging to correctly identify the treatment effects with missing data. To this end, this paper provides a method for imputation and analysis of the responses with missing data. The proposed method consists of three steps: Reconstruction, Imputation, and `Complete’-data Analysis (RICA). The incomplete responses are imputed with the expectation-maximization (EM) algorithm. The RCBD model is then fitted by the resulting dataset. The identifiability result suggests that the missing may be nonignorable for each block, but the whole data of an incomplete design are missing by design when the design is balanced. Theoretical results on relative efficiency also inform us when the missingness should be imputed for incomplete designs with the role of balanced variance. Applications on real-world data verify the efficacy of this method.

Diagnostic Utility of Deeper Level Tissue Sections of Negative Peritoneal Biopsies for Clinically Suspected Endometriosis.

Definitive diagnosis of endometriosis is established by histologic confirmation in tissue from surgically visualized lesions; however, the diagnostic sensitivity of this approach varies widely. We hypothesized that incomplete tissue block sampling may contribute to false-negative diagnosis, particularly if the focus of endometriosis in the tissue section is scant. This study defined the diagnostic value of deeper level tissue sections in cases in which none of the specimen parts contained endometriosis on the initial tissue sections, using the World Health Organization essential criteria for diagnosis of endometriosis (presence of endometrial glands and endometrial stroma). Among 135 patients who underwent surgery for suspected endometriosis by a single surgeon at an academic institution from 2015 to 2019, the initial tissue sections resulted in a diagnosis of endometriosis in 73.3% (99/135), at an average diagnostic yield of 5.9 slides per diagnosis of endometriosis. An additional 9 patients were diagnosed with endometriosis by deeper level tissue sections, increasing the diagnostic rate to 80% (108/135). This 6.7% gain in the diagnostic rate came at an increase in resource utilization, with an overall overage diagnostic yield of 9.8 slides per diagnosis of endometriosis. Overall, 8.3% of patients had a false-negative diagnosis on the initial tissue sections. When extrapolated to a population level, the number of patients potentially affected by this source of false-negative diagnosis and the implications for patients merit consideration of the use of deeper level sections if none of the initial sections of any of the specimens contains endometriosis.

Prognostic role of ECG patterns in Anderson Fabry disease

Abstract Background Anderson Fabry disease (AFD) is an X-linked lysosomal storage disorder leading to a deficiency in α-galactosidase A and globotriasylceramide (Gb3) deposition in different organs. Cardiac involvement is extremely common. It has been shown that the ECG abnormalities are directly correlated with the progressive accumulation of glycosphingolipids in the myocardium and cardiac conduction system. However, it is still unclear whether the ECG alterations are correlated with clinical events. Purpose To evaluate the prognostic role of ECG patterns in an unselected population of patients with AFD. Methods We conducted a retrospective multicenter study enrolling 215 consecutive patients. Based on the baseline ECG the study population was divided into the following five groups: 1) normal ECG or minimal alterations; 2) left ventricular hypertrophy (LVH) without signs of overload; 3) isolated negative T waves in the inferior and/or lateral leads; 4) LVH with signs of overload with or without incomplete right bundle branch block (RBBB); 5) complete RBBB. The primary endpoint was the composite of sudden cardiac death, resuscitated cardiac arrest, sustained ventricular tachycardia, and heart failure. Results Median age of study population was 45 years (32-57), and 86 patients (40%) were men. The rate of classic phenotype was 68%. Patients with ECG patterns 3 and 4 were older at baseline, more frequently affected by arterial hypertension, mostly male and showed greater left ventricular thickening, At a median follow up of 60 months (25-83) the overall Kaplan-Meier survival free from the primary endpoint was 57%: the Kaplan-Meier survival estimates of ECG groups were 66%, 75%, 68%, 27% e 52% respectively (log Rank 0.0026). On multivariable analysis patients belonging to either 3 or 4 group showed an increased risk of primary endpoint (HR= 2.45; 95% CI 1.04-5.78, p=0.040) compared to other groups. Conclusion ECG at baseline may be a useful tool to predict the risk of cardiovascular events in Anderson-Fabry Disease. Future studies should investigate if ECG may be useful also to evaluate the clinical response to specific therapy.

Pharmacological manipulation of neurotransmitter activity induces disparate effects on cerebral blood flow and resting-state fluctuations

Abstract Functional MRI methods can assess aspects of drug-induced brain response. Resting blood oxygenation level dependent (BOLD) fMRI and arterial spin labeling (ASL) perfusion MRI indirectly measure brain function through the coupling of activity to cerebral blood flow (CBF) and oxygenation but their relative sensitivity has not been directly compared. We assessed changes in resting measures of BOLD and ASL MRI in response to two neurotransmitter modulators: citalopram, a selective serotonin reuptake inhibitor, and alprazolam, a positive allosteric modulator of GABA type A receptor. Thirty healthy subjects were imaged in a placebo-controlled study, with N=20 subjects receiving each treatment as part of an incomplete block design. Time-averaged CBF images from ASL and measures of resting-state fluctuations of BOLD and ASL images were assessed for significant effects. Following acute citalopram administration, analysis of the ASL data showed a reduction in time-averaged regional CBF in regions associated with high levels of 5-HT1A receptor density. In contrast, following alprazolam administration, BOLD amplitude of low frequency fluctuations showed a highly significant and cortically widespread increase, consistent with the distribution of GABA-A receptors. Only a marginal decrease in ASL CBF was detected after alprazolam intake. BOLD and ASL are each sensitive to drugs targeting neurotransmitter systems, but appear to reflect different aspects of neural metabolism and the balance between excitatory and inhibitory activity. Accordingly, their combination may best capture the effects of neurotransmitter modulations, and thus be advantageous for pharmacological MRI studies.

Experimental investigation of the polyhedral structure of BIBDs

We examine the polyhedral structure of Balanced Incomplete Block Designs (BIBDs) in an effort to improve runtimes for finding optimal solutions via constraint or integer program. For example, an optimal BIBD is one that minimizes the range of blocksums. This range, which we refer to as diffsum, has applications in drug trials and Redundant Arrays of Independent Disks (RAID). The polytope we explore is the convex hull of all lexicographically-ordered BIBD solutions satisfying a given set of parameters, ( v , b , r , k , λ ) , with solutions represented as a vector in R kb . The dimension-reducing equations and the facets for some of the smaller polytopes were found by using the Double-Description Method on a algebraic program modelling these solutions. Because of the presence of the lexicographic ordering, none of these polytopes are full dimensional. After describing some of these smaller BIBD polytopes, we generalize some dimension-reducing equations, and evaluate the efficiency of these equations to optimization models.

Evaluation and identification of high yielding and stable cowpea genotypes using GGE biplot and joint regression analysis for varietal development in East and Southern Africa

Malawi, Mozambique, and Tanzania's cowpea breeding programs have been collaborating on pre-breeding trials in different locations, focusing on key traits such as grain yield. However, there is a lack of information regarding the nature of genotype-environment interaction patterns among these environments. The study was conducted to assess and identify high-yielding and stable cowpea genotypes for the development of improved varieties in these three countries. Thirty genotypes were evaluated in ten environments using an incomplete block design with three replications. Grain yield data was analyzed using genotype (G) × genotype-environment interaction (GGE) biplot and joint regression analysis. The joint analysis of variance showed highly significant differences (P < 0.001) for the main effects of genotypes and environment, as well as their interaction effects. This suggested that the environments assessed were distinct and that the genotypes exhibited varying performances in response to environmental variations. The environmental indices showed that only four environments were favorable for high grain yield, and overall, Guariba was the topmost yielder (1973.5 kg ha−1) across all environments. The analysis identified IT10K-817-7 and MWcp08 as superior and stable genotypes, making them highly desirable and potentially recommended across test environments for their expected ability to achieve economically viable yields. Overall, Chitedze Research Station in Malawi and Nametil Research Station in Mozambique were both discriminating and representative, indicating that they are good test environments for selecting best-performing genotypes that can perform well across a wide range of conditions. These environments can be recommended as the best environments for future cowpea genotype evaluations targeting the release of varieties in the three countries (Malawi, Mozambique and Tanzania) where the METs were carried out.

THE EFFECTS OF INTEGRATED SOIL FERTILITY MANAGEMENT AND CROPPING SYSTEMS ON SOIL WATER CONTENT ON SORGHUM AND COWPEA PRODUCTION IN CENTRAL HIGHLANDS OF KENYA

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Soil fertility degradation remains the major biophysical cause of declining &lt;em&gt;per capita&lt;/em&gt; crop production on smallholder farmers in Central Kenya highlands. The study was carried out for 3 consecutive seasons in Embu County classified as semi-arid lands in Kenya. &lt;strong&gt;Objectives:&lt;/strong&gt; To determine the effect of Soil Water Harvesting (SWH), cropping systems and Integrated Soil Fertility Management technologies on sorghum and cowpea production in Mbeere South Sub-County, Kenya. &lt;strong&gt;Methodology:&lt;/strong&gt; The treatments were arranged in a factorial structure with 3 levels of SWH, 2 cropping systems and 6 soil fertility management options laid out in a partially balanced incomplete block design. The SWC was measured after 2 weeks after planting interval stages in the whole season. Data were analyzed by ANOVA and significant means separated using Least Significant Difference (LSD) at 95% Confidence Interval. &lt;strong&gt;Results:&lt;/strong&gt; There was a two way interactions effect between SWH*Fertility management options on sorghum grain yields was significant (&lt;em&gt;p&lt;/em&gt;=0.0027, &lt;em&gt;p&lt;/em&gt;=0.0008 and&lt;em&gt; p&lt;/em&gt;=0.0057) during long rains (LR) of 2011 and 2012, and short rains (SR) of 2011, respectively. Additionally, SWH methods significantly affected sorghum grain yields in a similar trend (&lt;em&gt;p&lt;/em&gt;=0.002, &lt;em&gt;p&lt;/em&gt;=0.0005 and&lt;em&gt; p&lt;/em&gt;=0.0003) in their respective seasons. In SR 2011 and LR 2012, soil fertility options also produced significant effects (&lt;em&gt;p&lt;/em&gt;=0.0047 and &lt;em&gt;p&lt;/em&gt;=0.0024) on cowpea grain yields, respectively. The results further indicated that there were significant higher SWC measurements at initial stages of 2 WAP, 4 WAP and 6 WAP intervals as compared to the late stages of the season. However, sole cropping systems had significantly more SWC measurement than those in intercropping systems in both seasons. &lt;strong&gt;Implications:&lt;/strong&gt; Manure added treatments positively affected SWC conservation and this could be as a result of increased soil organic carbon which improved soil fertility. The available SWC played a great role in drought effect mitigation by availing moisture to sorghum and cowpea productivity especially when prolonged dry spells coincide with crop’s sensitive phenological growing stages. &lt;strong&gt;Conclusions:&lt;/strong&gt; Water harvesting methods cropping systems and soil fertility management options had positive influence on soil moisture conservation and crop yields production in Central Kenya Highland. &lt;/p&gt;

Nestings of BIBDs with block size four

AbstractIn a nesting of a balanced incomplete block design (or BIBD), we wish to add a point (the nested point) to every block of a ‐BIBD in such a way that we end up with a partial ‐BIBD. In the case where the partial ‐BIBD is in fact a ‐BIBD, we have a perfect nesting. We show that a nesting is perfect if and only if . Perfect nestings were previously known to exist in the case of Steiner triple systems (i.e., ‐BIBDs) when , as well as for some symmetric BIBDs. Here we study nestings of ‐BIBDs, which are not perfect nestings. We prove that there is a nested ‐BIBD if and only if , . This is accomplished by a variety of direct and recursive constructions.

Preoperative electrocardiogram in prediction of 90-day postoperative mortality: retrospective cohort study

BackgroundThere are conflicting data on the relationship between preoperative electrocardiogram and postoperative mortality. We aimed to assess the predictive value of preoperative ECG on postoperative all-cause mortality in patients undergoing non-cardiac surgery (NCS).MethodsWe retrospectively reviewed records of hospitalized patients who underwent an internal preoperative examination and subsequent NCS in the years 2015–2021. We recorded patient comorbidities, vital functions, results of biochemical tests, ECG. The primary end point was 90-day postoperative all-cause mortality, acquired from the hospital records and the nationwide registry run by the Institute of Health Information and Statistics of the Czech Republic.ResultsWe enrolled a total of 2219 patients of mean age 63 years (48% women). Of these, 152 (6.8%) died during the 90-day postoperative period. There were statistically significant associations between increased 90-day postoperative all-cause mortality and abnormal ECG findings in resting heart rate (≥ 80 bpm, relative risk [RR] = 1.82 and ≥ 100 bpm, RR = 2.57), presence of atrial fibrillation (RR = 4.51), intraventricular conduction delay (QRS > 0.12 s, RR = 2.57), ST segment changes and T wave alterations, left bundle branch hemiblock (RR = 1.64), and right (RR = 2.04) and left bundle branch block (RR = 4.13), but not abnormal PQ and QT intervals, paced rhythm, incomplete right bundle branch block, or other ECG abnormalities. A resting heart rate (≥ 80 bpm, relative risk [RR] = 1.95 and ≥ 100 bpm, RR = 2.20), atrial fibrillation (RR = 2.10), and right bundle branch block (RR = 2.52) were significantly associated with 90-day postoperative all-cause mortality even in subgroup of patients with pre-existing cardiac comorbidities.ConclusionsPatients with abnormal preoperative ECG findings face an elevated risk of all-cause mortality within 90 days after surgery. The highest mortality risk is observed in patients with atrial fibrillation and left bundle branch block. Additionally, an elevated heart rate, right bundle branch block, and atrial fibrillation further increase the risk of death in patients with pre-existing cardiac conditions.

PBIB-Designs Arising From BI-Connected Dominating Sets of Cubic Graphs of Order at Most 12

A $(v, b, \gamma_{bc}, r, \lambda_{i})$-design over regular graph $G = (V, E)$ of degree $k$ is an ordered pair $D = (V, B)$, where $|V| = v$ and $B$ is the set of bi-connected dominating sets of $G$ called blocks such that two vertices $\alpha$ and $\beta$ which are $i^{th}$ associates occur together in $ \lambda_{i}$ blocks, the numbers $\lambda_{i}$ being independent of the choice of the pair $\alpha$ and $\beta$. In this paper, we obtain Partially Balanced Incomplete Block (PBIB)-designs arising from bi-connected dominating sets in cubic graphs. Also, we give a complete list of PBIB-designs with respect to the bi-connected dominating sets for cubic graphs of order at most $12$. The discussion of non-existence of some designs corresponding to bi-connected dominating sets from certain graphs concludes the article.

PSLBII-28 Effects of dietary protein manipulation on greenhouse gases and ammonia emissions from feedlot beef steers

Abstract Black Angus steers [n = 112; body weight (BW) = 401 ± 3.6 kg] were used in a randomized incomplete block design to evaluate the effects of 3 rumen available protein to microbial crude protein ratios (RAP:MCP) on growth performance, and gaseous emissions from feedlot steers. Steers were blocked by initial BW and randomly assigned to 1 of 3 treatment rations. Diets were fed rations either Deficient (-150 gּ animal-1ּ d-1; DEF), Balanced (0 gּ animal-1ּ d-1; BAL), or Excess (+150 gּ animal-1ּ d-1; EXS) in RAP: MCP. Steers were allocated and housed in cattle pen enclosures (CPE), and treatment diets were delivered daily as a total mixed ration. The present study consisted of two 42-d periods. Refusals were collected weekly and BW every 14 d. Gas measurements were obtained daily in sequential order from all CPE. Data were analyzed with R statistical software (4.2.3). The linear mixed effect model procedure within the “lme4” package was used with CPE as the experimental unit, treatment and week as fixed effects, and block and period as random effects. A contrast coefficient matrix was constructed to test for linear and quadratic effects. Initial, intermediary and final BW were not different for steers receiving the varying RAP:MCP (P ≥ 0.239). A treatment effect (P = 0.004) was observed for mean dry matter intake (DMI) where EXS steers consumed 0.46 kg more DM compared with BAL steers, but DEF steers had similar DMI to those fed EXS and BAL (P = 0.189). Average daily gain (ADG) was only affected by treatment (P = 0.007) on d 0 to 14 where steers receiving DEF gained 0.6 kg more than those fed BAL (P = 0.010), but those fed EXS had similar ADG. Similar to ADG, gain to feed (G:F) was affected by treatment (P = 0.012) only during d 0 to 14. Mean CH4 production from steers fed DEF and EXS were 20% and 13% greater (P = 0.010) compared with those fed BAL, respectively; however, CH4 from EXS vs. DEF steers was not different (P = 0.149). Mean cumulative NH3 emissions increased linearly by treatment with EXS steers emitting up to 52% more NH3 compared with those receiving DEF (P &amp;lt; 0.001). Similarly, EXS steers had increased SO2 emissions by up to 44% compared with those fed DEF (P &amp;lt; 0.001). Emissions of CO2, N2O, and H2S were similar (P &amp;gt; 0.100). The manipulation of RAP:MCP in the diets of feedlot steers can drastically reduce NH3 emissions without affecting growth performance and may be a valuable tool to reduce air pollution from beef production systems.

On the Selection of Optimal Balanced Incomplete Block Design using Different Types of Designs

The choice of selecting the best among the types of balanced incomplete block designs (BIBDs) have brought about some controversies in combinatorial design. Prominent methods of constructing BIBD have been proposed by different authors, but none has been juxtaposed the designs with respect to type. In this paper, we proposed the adoption of the concept of optimality criteria such as: A-, D-, E- , and T – optimality criterion to select the best design based on their optimality values using a (15, 15, 7, 7, 3) simulated balanced incomplete block design. A dual design, residue design and derived design were selected as the major three types of BIBDs for investigation. The findings revealed that dual design is the best balanced incomplete block design based on its high optimal value. We discovered that residue and derived design obtained from the simulated balanced incomplete block design by method of block selection and intersection becomes a standard balanced incomplete block design.

The Impact of Pedestrian Interactions at Intersections on the Three Levels of Drivers’ Situation Awareness

Evaluating drivers’ situation awareness (SA) is important in the implementation of alert prioritization. This study investigates the relationship between driving performance measures (speed, acceleration and brake usage, steering wheel and lane deviation), pedestrian interaction (location, direction and motion), and driver SA. To achieve this, a controlled study was conducted with 56 participants using a Balanced Incomplete Block Design, where each participant drove 18 out of 48 possible intersections in a driving simulator environment. The Situational Awareness Global Assessment Technique (SAGAT) method was used to assess drivers’ SA. Mixed effects logit models were developed to examine the different SA Levels (perception, comprehension, projection). The driving performance measures were aggregated across three time windows (1, 3, and 5 s). The findings show significant contributions from both driving performance measures and pedestrian interactions in predicting driver SA. More specifically, a one-second time window was useful for predicting pedestrian direction and a three-second time window was best for predicting pedestrian location and intention to cross. The results indicate the importance of considering different time windows for predicting various levels of driver SA responses. These findings offer insights into factors to be considered in driver SA predictive models.

Pulmonary embolism (PE) diagnosed in a 19-year-old lady found to have underlying Antiphospholipid syndrome (APS)

ABSTRACT Background A 19-year-old woman visited a family medicine clinic to obtain her laboratory test results. This case highlights a close call involving a young woman with a potentially serious condition. Pulmonary embolism (PE) is often overlooked during initial assessments in emergency departments or primary care clinics. Case presentation The patient casually mentioned having a cough toward the end of the consultation, revealing she has been using a salbutamol inhaler due to a family history of asthma. Despite appearing well, she had an audible wheezy cough during the examination. Following a chest X-ray (CXR) that indicated a right lung opacity and possible cardiomegaly, an electrocardiogram (ECG) was arranged. The ECG showed an incomplete right bundle branch block (RBBB) and STT changes in leads V3-V6 and lead 3, prompting her transfer to the emergency department for suspected Pulmonary embolism (PE). Further evaluation confirmed acute on chronic PE, with a positive lupus screen leading to the diagnosis of antiphospholipid syndrome (APS) upon detection of anti-phospholipid antibodies in her serology. Discussion The patient’s case was unique, but a basic CXR was performed to investigate their exertional shortness of breath. This led to appropriate action being taken to ensure the patient’s safety. It is important to note that pulmonary embolism can occur in young individuals, highlighting the need for attentive and skilled healthcare professionals. Basic tests such as CXR and ECG can be crucial in cases of ongoing symptoms where uncertainty exists.

Predictors of permanent pacemaker implantation for transcatheter self-expandable aortic valve implant in the cusp overlap era.

Predictors of permanent pacemaker implantation (PPMI) after self-expanding transcatheter aortic valve implant (TAVI) were described. Is unknown if PPMI predictors remain in the era of high implants using the cusp overlap (COP). Single-center, prospective, consecutive case series of patients undergoing self-expanding TAVI with the COP approach. The status of PPMI and other clinical events were ascertained at 30 days. A total of 261 patients were included (84% with Evolut, n = 219). Implant depth >4 mm was infrequent (13.8%). TAVI depth (OR 1.259; p = 0.005), first or second-degree auriculo-ventricular block (OR 3.406; p = 0.033), right-bundle (OR 15.477; p < 0.0001), and incomplete left-bundle branch block (OR 7.964; p = 0.036) were found to be independent predictors of PPMI. The risk of PPMI with deep implant and no electrical disturbances was 3%, and 0% with high implant and no prior electrical disturbances. Those who received PPMI had no statistically significant increased risk of death, myocardial infarction, stroke, bleeding events, or vascular complications at 30 days, but longer hospital stay (mean difference 1.43 days more, p = 0.003). Implant depth and prior conduction abnormalities remain the main predictors of PPMI using self-expanding TAVI in the COP era. Patients with high implants and no prior conduction abnormalities may be candidates for early discharge after uneventful self-expanding TAVI, while the rest may need inpatient monitoring regardless of achieving a high implant. The need for PPMI was associated with longer hospital stays.

Electrocardiographic findings in a group of physically active young adults who reside at 2,600 meters above the sea level: an exploratory study

Purpose: The physiological adaptations to regular physical activity and hypobaric hypoxia associated with high-altitude residence are related to a series of cardiovascular adaptations that can generate electrocardiographic modifications. This study aimed to describe the principal findings and determine the mean values of the electrocardiographic parameters in a group of physically active young adults who reside at a high altitude. Methods: 49 young, physically active subjects (11 women) in a Sports Sciences program participated in the study. Each participant was subjected to a medical interview, a physical examination, and a resting electrocardiogram. Two physicians analyzed the electrocardiogram, searching for criteria of anatomical or physiological abnormalities; a descriptive analysis of the duration of waves and intervals and the amplitude of the T and P waves was also carried out. Results: The mean values of the electrocardiographic parameters were between the expected values. The principal findings involve sinus bradycardia and changes associated with the right side of the heart: incomplete right bundle branch block, right QRS axis deviation, and right ventricular hypertrophy. Conclusions: The findings of this study are related to other studies that describe changes in the right side of the heart in inhabitants of high altitude and sinus bradycardia in physically active subjects and, in some cases, in high-altitude residents. Every young dweller of the altitude who engages in physical activity should be submitted to a resting ECG, considering there is a high probability of finding asymptomatic changes in the ECG that could require further exploration. Keywords: Electrocardiogram, high altitude, hypoxia, exercise

The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

Generalized extended triangular designs: Construction and online generation

Method of constructing new and useful series of m-associate class partially balanced incomplete block (PBIB) designs, named as Generalized Extended Triangular (GET) designs, in m replications has been proposed along with an outline of analytical procedure. Triangular designs, one of the most popular and widely used class of PBIB(2) designs, and the extended triangular PBIB(3) designs form other two important particular cases of this generalized class of designs. To avoid the complexity involved in the construction methodology and to save time, an R package ‘‘GETdesigns’’ has been developed for the generation of the proposed designs. Further, these designs have been effectively used for obtaining mating designs and Latin hypercube designs.

Second type second order slope rotatable designs utilizing symmetrical unequal block arrangements with two unequal block sizes

Kim and Ko developed second order slope rotatable designs (SOSRD) of second type utilizing central composite designs (CCD), in which two numbers are used to represent the positions of star points. In this paper, we suggest second type SOSRD utilizing symmetrical unequal block arrangements (SUBA) with two unequal block sizes. In some cases, the suggested method may develop designs containing fewer design points than second type SOSRD obtained utilizing CCD, pairwise balanced designs (PBD) and balanced incomplete block designs (BIBD). The first order partial derivative's for estimated second order response variance for factors 6≤v≤15 is also obtained.