Interpretive Criteria Research Articles

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates.

Limited treatment options exist for the treatment of carbapenem-resistant Enterobacterales (CRE) bacteria. Fortunately, there are several recently approved antibiotics indicated for CRE infections. Here, we examine the in vitro activity of various novel agents (eravacycline, plazomicin, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) and comparators (tigecycline, amikacin, levofloxacin, fosfomycin, polymyxin B) against 365 well-characterized CRE clinical isolates with various genotypes. Nonduplicate isolates collected from the largest public health hospital in Singapore between 2007 and 2020 were subjected to antimicrobial susceptibility testing (broth microdilution or antibiotic gradient test strips). Susceptibilities were defined using Clinical and Laboratory Standards Institute (CLSI) or Food and Drug Administration (FDA) interpretative criteria. Sequence types and resistance mechanisms were characterized using short-read whole-genome sequencing. Overall, tigecycline and plazomicin exhibited the highest susceptibility rates (89.6% and 80.8%, respectively). However, the tigecycline susceptibility breakpoint utilized here may be outdated in view of prevailing pharmacokinetic-pharmacodynamic (PK/PD) data. Susceptibility varied by carbapenemase genotype; the β-lactam/β-lactamase inhibitor combinations were equally active (92.3 to 99.2% susceptible) against KPC producers, but only ceftazidime-avibactam retained high susceptibility (98.7%) against OXA-48-like producers. Against metallo-β-lactamase producers, only plazomicin exhibited moderate activity (77.0% susceptible). Aminoglycoside activity was also influenced by carbapenemase genotypes. This work provides an insight into the comparative activity and presumptive utility of novel agents in this geographic region. IMPORTANCE This study determined the susceptibilities of carbapenem-resistant Enterobacterales isolates to various novel antimicrobial agents (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, eravacycline, and plazomicin). Whole-genome sequencing was performed for all strains. Our study findings provide insights into the comparative activities of novel agents in this geographic region. Plazomicin and ceftazidime-avibactam exhibited the lowest nonsusceptibility rates and may be considered promising agents in the management of carbapenem-resistant Enterobacterales infections. We note also that antibiotic activity is influenced by genotypes and that understanding the geographic region's molecular epidemiology could aid in the definition of the presumptive utility of novel agents and contribute to antibiotic decision-making.

The Use of Interactive Multimedia on Religious Tolerance Materials Learning for Students of MAN 1 in Bone Regency

This thesis discusses the interactive multimedia in increasing the religion tolerance material for MAN 1 Bone students. The purpose is to obtain empirical data about the students' understanding after learning comprehension of the MAN 1 Bone District students. The research used a one-group pre-test and post-test design methodology, which means the experimental research is only one experimental group. The results of this study were: The first is the motivation of students before being treated in the form of interactive multimedia application was in the high category, namely 71.11% based on interpretation criteria. The second, after being treated in the form of the application in interactive multimedia increases. The results of the t-test, which shows t count (6.621)> t ultimate (2.05553), and the results of the analysis of each indicator are 89.99%. So that the proposed hypothesis is accepted. This shows a significant relationship between the application of interactive multimedia in learning religion and tolerance materials in the students' learning at MAN 1 Bone.

Prostate cancer screening-stepping forward with MRI.

To comprehensively review the literature on the integration of MRI as a diagnostic tool in prostate cancer screening and offer practical recommendations for optimising its use. Existing research studies, clinical guidelines and expert opinions were reviewed to support the optimisation standards for MRI use in screening. Consolidated screening principles were used to make appropriate recommendations regarding the integration of MRI into the diagnostic pathway. To strike a balance between the potential benefits of early detection on mortality and minimising the harm of over-diagnosing indolent cancers, it is necessary to have a clear understanding of the context of MRI use. The key to optimisation is patient selections and MRI-targeted biopsies. For men at higher-than-average risk, it is essential to use screening-specific MRI protocols and establish accuracy levels and interpretation criteria. Optimisation of readings by the automation of data acquisition, image quality monitoring, post-processing, radiologist certification and deep-learning computer-aided software is needed. The optimal utilisation of MRI involves its integration into a multistep diagnostic pathway, supported by a quality-assured and cost-effective infrastructure that ensures community-wide access to imaging. MRI in the prostate cancer screening pathway can bring substantial diagnostic benefits. By carefully considering its advantages, limitations and safety concerns and integrating it into a multistep diagnostic pathway, clinicians can improve outcomes while minimising harm to screening participants. The manuscript discusses the role of MRI in prostate cancer screening, highlighting its potential to improve accuracy and reduce overdiagnosis. It emphasises the importance of optimising protocols and integrating MRI into a multistep diagnostic pathway for successfully delivering screening benefits. • Population screening for prostate cancer is a new indication for prostate MRI that allows the detection of high-risk cancers while reducing the need for biopsies and associated harm. • To optimise prostate cancer screening using MRI, it is essential to redefine MRI protocols; establish accuracy levels, reliability and interpretation criteria; and optimise reading (including post-processing, image quality, radiologist certification, and deep-learning computer-aided software). • The optimal utilisation of MRI for prostate cancer screening would involve its integration into a multistep diagnostic pathway, supported by a quality-assured and cost-effective infrastructure that ensures community-wide access to imaging.

Implementation Of Educational Field Experience Program Activities In Schools With Motivation To Become Teacher In Pkk Program Students

This research was motivated by the unpleasant experiences that were obtained when students carried out the Educational Field Experience Program (PPLK) activities such as students in schools who lacked respect and respect, duties and responsibilities that exceeded the obligations of PPLK students and the time for implementing PPLK that exceeded PPLK standards. Based on the pre-research, there was a decrease in students' desire and interest to become teachers. This study aims to analyze the relationship between the implementation of the Educational Field Experience Program and the motivation to become a teacher for PKK UNP study program students in 2015 and 2016. This type of research uses correlational quantitative. The population in this study were 192 students of the Family Welfare Education study program who had carried out PPLK. For sampling is Proportional Random sampling with the results of 66 people. Data collection was carried out by means of a questionnaire via Google From using a Likert Scale that has been tested for validity and reliability. Data were analyzed using descriptive correlation with the help of SPSS 17 and MS. Excel. The results showed that PPLK data descriptions were in the very high category. For motivation to become a teacher it is in the medium category. The correlation coefficient of PPLK implementation results with motivation to become a teacher in PKK UNP students with a value of r count > r table of 0.465 > 0.242 which means the correlation coefficient is positive. If it is interpreted into the Interpretation criteria, the correlation coefficient is the value r, then the correlation coefficient is at a moderate level because the value of r is in the range 0.400 – 0.599 with a significance value of 0.000 <0.05 which means that Ha is accepted and tcount > ttable, 30.140 > 1.670 It can be concluded that Ha is accepted and Ho is rejected at a significance level of 0.05 and it can be stated that there is a significant and positive relationship between PPLK implementation and the motivation to become a teacher in family welfare education students at Padang State University. Keywords:

Finding the (biomarker-defined) subgroup of patients who benefit from a novel therapy: No time for a game of hide and seek.

An important element of precision medicine is the ability to identify, for a specific therapy, those patients for whom benefits of that therapy meaningfully exceed the risks. To achieve this goal, treatment effect usually is examined across subgroups defined by a variety of factors, including demographic, clinical, or pathologic characteristics or by molecular attributes of patients or their disease. Frequently such subgroups are defined by the measurement of biomarkers. Even though such examination is necessary when pursuing this goal, the evaluation of treatment effect across a variety of subgroups is statistically fraught due to both the danger of inflated false-positive error rate from multiple testing and the inherent insensitivity to how treatment effects differ across subgroups.Pre-specification of subgroup analyses with appropriate control of false-positive (i.e. type I) error is recommended when possible. However, when subgroups are specified by biomarkers, which could be measured by different assays and might lack established interpretation criteria, such as cut-offs, it might not be possible to fully specify those subgroups at the time a new therapy is ready for definitive evaluation in a Phase 3 trial. In these situations, further refinement and evaluation of treatment effect in biomarker-defined subgroups might have to take place within the trial. A common scenario is that evidence suggests that treatment effect is a monotone function of a biomarker value, but optimal cut-offs for therapy decisions are not known. In this setting, hierarchical testing strategies are widely used, where testing is first conducted in a particular biomarker-positive subgroup and then is conducted in the expanded pool of biomarker-positive and biomarker-negative patients, with control for multiple testing. A serious limitation of this approach is the logical inconsistency of excluding the biomarker-negatives when evaluating effects in the biomarker-positives, yet allowing the biomarker-positives to drive the assessment of whether a conclusion of benefit could be extrapolated to the biomarker-negative subgroup.Examples from oncology and cardiology are described to illustrate the challenges and pitfalls. Recommendations are provided for statistically valid and logically consistent subgroup testing in these scenarios as alternatives to reliance on hierarchical testing alone, and approaches for exploratory assessment of continuous biomarkers as treatment effect modifiers are discussed.

Frequency of HER2 protein overexpression and HER2 gene amplification in endometrial clear cell carcinoma

HER2 (ERBB2) overexpression and/or HER2 gene amplification has been well established in several tumors types and when present HER2 directed therapy may be to be efficacious. While recent findings suggests that HER2 overexpression and HER2 amplification are a relatively common in serous endometrial carcinoma, similar data regarding clear cell endometrial carcinoma (CCC) is difficult to interpret due to issues such as diagnostic criteria, sample type and HER2 interpretation criteria. Our goals were to study HER2 expression and HER2 copy number status in hysterectomy specimens from a large series of patients with pure CCC to determine the frequency of HER2 overexpression and HER2 amplification and evaluate applicability of current HER2 interpretation criteria. Pure CCC specimens derived from hysterectomy specimens from 26 patients were identified. All diagnoses were confirmed by two gynecologic pathologists. Immunohistochemistry for HER2 protein and fluorescence in situ hybridization (FISH) studies for HER2 were performed on whole-slide sections from all cases. Results were interpreted according to the 2018 ASO/CAP HER2 guidelines for breast cancer and International Society of Gynecologic Pathologists (ISGyP) HER2 guidelines for serous endometrial carcinoma. Additional testing was performed when indicated by the guidelines. HER2 expression by immunohistochemistry was 3+ in 4% and 0% of cases, and 2+ in 46% and 52% of cases, by 2018 ASCO/CAP and ISGyP criteria, respectively, while the remaining cases were negative. HER2 testing by FISH showed a positive result in 27% of tumors with 2018 ASCO/CAP guidelines, while 23% were positive with the ISGyP criteria. Our findings indicate that HER2 overexpression and HER2 amplification occur in a subset of CCC. Therefore, additional study into the potential benefit of HER2 targeted therapy in patients with CCC is warranted.

Human Pathogenic Monkeypox Disease Recognition Using Q-Learning Approach

While the world is working quietly to repair the damage caused by COVID-19's widespread transmission, the monkeypox virus threatens to become a global pandemic. There are several nations that report new monkeypox cases daily, despite the virus being less deadly and contagious than COVID-19. Monkeypox disease may be detected using artificial intelligence techniques. This paper suggests two strategies for improving monkeypox image classification precision. Based on reinforcement learning and parameter optimization for multi-layer neural networks, the suggested approaches are based on feature extraction and classification: the Q-learning algorithm determines the rate at which an act occurs in a particular state; Malneural networks are binary hybrid algorithms that improve the parameters of neural networks. The algorithms are evaluated using an openly available dataset. In order to analyze the proposed optimization feature selection for monkeypox classification, interpretation criteria were utilized. In order to evaluate the efficiency, significance, and robustness of the suggested algorithms, a series of numerical tests were conducted. There were 95% precision, 95% recall, and 96% f1 scores for monkeypox disease. As compared to traditional learning methods, this method has a higher accuracy value. The overall macro average was around 0.95, and the overall weighted average was around 0.96. When compared to the benchmark algorithms, DDQN, Policy Gradient, and Actor-Critic, the Malneural network had the highest accuracy (around 0.985). In comparison with traditional methods, the proposed methods were found to be more effective. Clinicians can use this proposal to treat monkeypox patients and administration agencies can use it to observe the origin and current status of the disease.

Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hypermobility

Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as pathogenic and likely pathogenic null alleles without downgrading of the PVS1 level of strength and recurrent Glycine substitutions. Adaptations of selected criteria reduced uncertainties on private Glycine substitutions, intronic variants predicted to affect the splicing, and null alleles with a downgraded PVS1 level of strength. Segregation and multigene panel sequencing data mitigated uncertainties on non-Glycine substitutions by the attribution of one or more benignity criteria. These specifications may improve the clinical utility of molecular testing in HCTD by reducing the number of variants with neutral/conflicting interpretations. Close interactions between laboratory and clinicians are crucial to estimate the a priori utility of molecular test and to improve medical reports.

Analysis of mutation rates and haplotypes of 23 Y-chromosomal STRs in Korean father–son pairs

Y-chromosomal short tandem repeats (Y-STRs) have been widely used in forensic genetics, and accurate knowledge of mutation rates at Y-STR loci is essential in kinship analysis. The main aim of this study was to estimate Y-STR mutation rates in Korean males. To obtain locus-specific mutations and haplotypes at 23 Y-STRs, we analyzed samples from 620 Korean father–son pairs. In addition, we also analyzed 476 unrelated individuals using the PowerPlex® Y23 System, with the aim of augmenting the available data for the Korean population. The PowerPlex® Y23 system facilitates analysis of the 23 Y-STR loci (DYS576, DYS570, DYS458, DYS635, DYS389 II, DYS549, DYS385, DYS481, DYS439, DYS456, DYS389 I, DYS19, DYS393, DYS391, DYS533, DYS437, DYS390, Y GATA H4, DYS448, DYS438, DYS392, and DYS643). Locus-specific mutation rate estimates varied from 0.00 to 8.06 × 10−3 per generation, with an average mutation rate of 2.17 × 10−3 (95% CI, 1.5–3.1 × 10−3). To obtain comprehensive genetic values for the Korean population, we combined data obtained in this study with previously reported values, thereby enabling us to estimate the locus-specific mutation rates regarding 22,711 allele transmissions. By combining these data, we obtained an overall average mutation rate of 2.91 × 10−3 (95% CI, 2.3–3.7 × 10−3). In addition, among the 476 unrelated Korean males, we detected 467 different haplotypes, with an overall haplotype diversity value of 0.9999. By extracting haplotypes of Y-STRs described in previous literature on 23 Y-STR reported in Korea, we obtained gene diversities for 1133 Korean individuals. We believe that the values and characteristics of the 23 Y-STRs analyzed in this study will contribute to establishing criteria for forensic genetic interpretation, including kinship analysis.

PHP web-based mathematics learning application: An analysis of student responses

This study aims to analyze and describe students' responses to PHP web-based mathematics learning applications. The research method used is quantitative descriptive. The research sample were 63 students of class X at SMK Al-Ihya Selajambe, Kuningan Jawa Barat. The research instrument uses a student response questionnaire. Data analysis used is quantitative descriptive analysis in the form of percentages. The results of the data in the form of percentages are described using response interpretation criteria. Based on the results of the study, PHP web-based mathematics learning applications gets a percentage of responses 87,04 % for the layout aspect which was in the very good response interpretation criteria, 85,71 % for the display aspect which was in the very good response interpretation criteria, and 88,94 % for the function aspect which was in the very good response interpretation criteria. Overall, the PHP web-based mathematics learning application gets a percentage of responses 87,70% which was in the very good response interpretation criteria. It can be concluded that PHP web-based mathematics learning applications get a very good response from students to use in learning.

C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.

C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification.

Antimicrobial susceptibility surveillance and antimicrobial resistance in Neisseria gonorrhoeae in Africa from 2001 to 2020: A mini-review.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG), compromising gonorrhea treatment, is a global public health concern. Improved, quality-assured NG AMR monitoring at the global level is essential. This mini-review examined NG AMR susceptibility surveillance and AMR data from the African continent from 2001 to 2020. Eligible peer-reviewed publications (n = 30) containing NG AMR data for antimicrobials currently recommended for gonorrhea treatment were included. Overall, very limited NG surveillance and AMR data was available. Furthermore, the NG AMR surveillance studies varied greatly regarding surveillance protocols (e.g., populations and samples tested, sample size, antimicrobials examined), methodologies (e.g., antimicrobial susceptibility testing method [agar dilution, minimum inhibitory concentration (MIC) gradient strip test, disc diffusion test] and interpretative criteria), and quality assurance (internal quality controls, external quality assessments [EQA], and verification of AMR detected). Moreover, most studies examined a suboptimal number of NG isolates, i.e., less than the WHO Global Gonococcal Antimicrobial Surveillance Program (GASP) and WHO Enhanced GASP (EGASP) recommendations of ≥100 isolates per setting and year. The notable inter-study variability and frequently small sample sizes make appropriate inter-study and inter-country comparisons of AMR data difficult. In conclusion, it is imperative to establish an enhanced, standardized and quality-assured NG AMR surveillance, ideally including patient metadata and genome sequencing as in WHO EGASP, in Africa, the region with the highest gonorrhea incidence globally. This will enable the monitoring of AMR trends, detection of emerging AMR, and timely refinements of national and international gonorrhea treatment guidelines. To achieve this aim, national and international leadership, political and financial commitments are imperative.

2022년 형법 중요 판례 평석

First of all, there were six full-bench decisions by the Supreme Court, and the first one related to the crime of trespassing was a ruling based on the purpose of the precedent that had been changed in 2021, reaffirming the precedent's stance once again.
 In property crimes, the Supreme Court has maintained the tendency to strictly limit the application of the crimes of embezzlement and breach of trust.
 Additionally, the judgment related to the interpretation of Article 1 (2) of the Criminal Act is also important, as it abolished the theory of motivation that had been applied in judicial precedents.
 Academics have long criticized the interpretation of Article 1 (2) of the Criminal Act based on the theory of motivation. In this paper, I first reviewed the full-bench decisions by the Supreme Court and provided peer review. For other major judgments, only the issues and reasons for the decisions were briefly introduced.
 To ensure the legitimate exercise of punishment, it is desirable to present clear interpretation criteria for the law, and interpretations beyond the literal meaning of the law cannot be allowed.
 In this regard, it is noteworthy that in 2022, the Supreme Court made positive decisions that presented standards to further clarify the interpretation of each crime element or limit criminal punishment, such as changes in precedents in property crimes to reflect social changes.

How to Monitor Hydration Status and Urine Dilution in Patients with Nephrolithiasis

Maintenance of hydration status requires a tight balance between fluid input and output. An increase in water loss or a decrease in fluid intake is responsible for dehydration status, leading to kidney water reabsorption. Thus, urine volume decreases and concentration of the different solutes increases. Urine dilution is the main recommendation to prevent kidney stone recurrence. Monitoring hydration status and urine dilution is key to preventing stone recurrence. This monitoring could either be performed via spot urine or 24 h urine collection with corresponding interpretation criteria. In laboratory conditions, urine osmolality measurement is the best tool to evaluate urine dilution, with less interference than urine-specific gravity measurement. However, this evaluation is only available during time lab examination. To improve urine dilution in nephrolithiasis patients in daily life, such monitoring should also be available at home. Urine color is of poor interest, but reagent strips with urine-specific gravity estimation are currently the only available tool, even with well-known interferences. Finally, at home, fluid intake monitoring could be an alternative to urine dilution monitoring. Eventually, the use of a connected device seems to be the most promising solution.

Project Based Learning Model Digital Media Assistance in Learning Persuasive Speech Text in SMP/MTs

The purpose of this research is to explain the design of project-based learning model with the help of digital media in teaching persuasive speech texts in SMP/MTs. The method used is descriptive qualitative method. This study uses a qualitative approach with the ADDIE model development method. Data collection was in the form of teacher and student activities in every aspect of learning model design, speech text assessment instrument, viewing instrument sheets and presentation of speech text products. The form of data in this study is in the form of pretest and posttest scores for speech text assessment sheets. From the results of the research and discussion, it can be concluded that the ability to write speech texts in the pretest and posttest obtained an average score of 68,70 in pretest and 86,24 in the posttest, including in the good category. The result of the analysis of the N-gain score are 0,5635 in the range 0.3 ≤ g ≤ 0.7 in the medium category. From user/educator data on the implementation of the digital media-assisted learning model design used with interpretation criteria an average of 89% is included in the very feasible category. That is, the design of a project-based learning model assisted by digital media is able to improve students’ abilities in making speech texts. Which illustrates an increase in effectiveness and value scores after using the project-based learning model. The design of the Digital Media Assisted Project-Based Learning Model in Persuasive Speech Text Learning is a combination of Project Based Learning and Digital media, so the design of this model is very much needed by teachers in persuasive Speech text learning. From the implementation of the use of the digital media-assisted Project based Learning model, it can be concluded that the developed digital media-assisted project-based learning model in learning persuasive speech texts in SMP/MTs is very feasible for teachers and students to use in learning.

Characterizing Touch Discrimination Impairment from Pooled Stroke Samples Using the Tactile Discrimination Test: Updated Criteria for Interpretation and Brief Test Version for Use in Clinical Practice Settings.

Somatosensory loss post-stroke is common, with touch sensation characteristically impaired. Yet, quantitative, standardized measures of touch discrimination available for clinical use are currently limited. We aimed to characterize touch impairment and re-establish the criterion of abnormality of the Tactile Discrimination Test (TDT) using pooled data and to determine the sensitivity and specificity of briefer test versions. Baseline data from stroke survivors (n = 207) and older neurologically healthy controls (n = 100) assessed on the TDT was extracted. Scores were re-analyzed to determine an updated criterion of impairment and the ability of brief test versions to detect impairment. Updated scoring using an area score was used to calculate the TDT percent maximum area (PMA) score. Touch impairment was common for the contralesional hand (83%) but also present in the ipsilesional hand (42%). The criterion of abnormality was established as 73.1 PMA across older adults and genders. High sensitivity and specificity were found for briefer versions of the TDT (25 vs. 50 trials; 12 or 15 vs. 25 trials), with sensitivity ranging between 91.8 and 96.4% and specificity between 72.5 and 95.0%. Conclusion: Updated criterion of abnormality and the high sensitivity and specificity of brief test versions support the use of the TDT in clinical practice settings.

Development of Modernized Acinetobacter baumannii Susceptibility Test Interpretive Criteria for Recommended Antimicrobial Agents Using Pharmacometric Approaches.

Acinetobacter baumannii-Acinetobacter calcoaceticus complex (referred to herein as A. baumannii) treatment guidelines contain numerous older antimicrobial agents with susceptibility test interpretive criteria (STIC, also known as susceptibility breakpoints) set using only epidemiological data. We utilized a combination of in vitro surveillance data, preclinical murine thigh and lung infection models, population pharmacokinetics, simulation, and pharmacokinetic/pharmacodynamic (PK/PD) target attainment analyses to evaluate A. baumannii STIC for four commonly recommended antimicrobials from different classes (amikacin, ceftazidime, ciprofloxacin, and minocycline). Antimicrobial in vitro surveillance data were based on 1,647 clinical A. baumannii isolates obtained from 109 centers in the United States and Europe. Among these isolates, 5 were selected for evaluation in murine infection models based on fitness and MIC variability. PK and dose-ranging studies were conducted using neutropenic murine thigh and lung infection models The MIC ranges for the 5 isolates evaluated were as follows: amikacin, 2 to 32 μg/mL; ceftazidime, 4 to 16 μg/mL; ciprofloxacin, 0.12 to 2 μg/mL; minocycline, 0.25 to 4 μg/mL. All organisms grew ≥1.5 log10 CFU in both models in untreated controls. Plasma and epithelial lining fluid (ELF) pharmacokinetics for all drugs were determined in mice using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. For each isolate, 5 dose levels of each drug were tested individually in the thigh and lung infection model. The inoculum ranged from 7.9 to 8.4 and 6.8 to 7.7 log10 CFU/mL for the lung and thigh models, respectively. PK/PD targets associated with net bacterial stasis and 1- and 2-log10 CFU reductions from baseline were identified for each organism/infection model using Hill-type models. Population pharmacokinetic models for each agent were identified from the literature. Using demographic variables for simulated patients with hospital-acquired or ventilator-associated bacterial pneumonia or urinary tract infections (including acute pyelonephritis) who were administered maximal dosing regimens of each agent, estimates of protein binding, and ELF penetration ratios based on data from the literature, free-drug plasma and total-drug concentration-time profiles were generated, and PK/PD indices by MIC were calculated. Percent probabilities of attaining median and randomly assigned PK/PD targets associated with the above-described endpoints were determined. Recommended susceptible breakpoints for each agent were those representing the highest MIC at which the percent probabilities of achieving PK/PD targets associated with a 1-log10 CFU reduction from baseline approached or were ≥90%. The following susceptible breakpoints for A. baumannii were identified: amikacin, ≤8 μg/mL for pneumonia; ceftazidime, ≤32 and ≤8 μg/mL for pneumonia; ciprofloxacin, ≤1 μg/mL; and minocycline, ≤0.5/≤1 μg/mL which correspond to the standard and high minocycline dosing regimens of 200 mg per day and 200 mg every 12 h, respectively. Implementation of appropriate STIC will help clinicians optimally use the above-described agents and improve the likelihood of successful patient outcomes.

High prevalence of intermediate resistance to ciprofloxacin in Salmonella enterica isolated from a Brazilian poultry production chain, located in Minas Gerais state

We characterized the distribution and diversity of antimicrobial-resistance Salmonella enterica isolated from a poultry production chain in Minas Gerais, Brazil, with special attention to ciprofloxacin and multidrug resistance (MDR). S. enterica (n = 96) of different serotypes and from different processing steps were subjected to broth dilution assay to estimate the minimum inhibitory concentration (MIC) for 12 antibiotics (8 classes) and screened using PCR for the presence of 17 antimicrobial-resistance genes. Isolates presented mainly resistance to ampicillin (11/96), and most presented intermediate resistance to ciprofloxacin (92/96). Roughly one-third (33/96) were resistant to streptomycin based on our interpretive criteria. Most strains resistant to streptomycin and ciprofloxacin were PCR-positive for aphA (51/96) and qnrB (94/96), respectively. Ciprofloxacin resistance was further investigated through high-resolution melting qPCR (HRM-qPCR) and sequencing of quinolone resistance-determining region (QRDR: gyrA, gyrB, parC, and parE). Minor differences were identified in melting temperatures (Tm), and a Thr57Sr mutation was observed in parC. MDR isolates harboring acrA and capable of expressing the AcrAB-TolC multidrug efflux pump were resistant to ethidium bromide at 0.4 mg/mL. The intermediate resistance to ciprofloxacin may be associated with qnrB, and the potential role of Thr57Ser mutation warrants further investigation. The high prevalence of antibiotic related genes and its association with the observed intermediary resistance to ciprofloxacin indicates the widespread of this hazard in the studied poultry production chain.

Physics Teachers’ Perceptions of Senior High Schools in Merauke on Self-Regulation of Digital Instructional Materials

This study describes the high school and MA physics teachers' perceptions of the need for digital teaching materials like e-modules, e-student worksheets, e-comics, and learning videos. The type of research used is descriptive quantitative. Therefore, as many as 12 physics teachers from SMA and MA in Merauke City were sampled in the study. The sample in this study was selected through a purposive sampling technique with criteria based on educational strata, length of teaching, educator certificate and ease of access. Furthermore, data collection was carried out using an instrument in the form of a questionnaire containing 30 statement items with a Likert scale consisting of 5 answer choices. Then, data analysis uses descriptive statistics. The result of this analysis is the accumulation of basic data in the form of the percentage of total responses followed by determining response criteria using interpretation criteria. Based on these criteria, it can be seen that the criteria for physics teachers' perceptions of the need for digital teaching materials. The study results show that the average perception of physics teachers is 88.1% and is included in the criteria for needing digital teaching materials. According to the teacher's perception, the order of priority for teaching material needs is e-module with the TPACK approach (91.3%), e-student worksheets with a scientific approach (83.3%), and interactive multimedia-based learning videos (75%). This research collected data on the perceptions of physics teachers at SMA and MA Merauke as a stage of needs analysis in development research. Based on the results of this analysis, further research will be carried out regarding the development of digital teaching materials in the form of e-modules, e-student worksheets, and learning videos.

The Diagnostic Value of [18F] FDG PET/CT Scan in Characterizing Adrenal Tumors.

Imaging plays an important role in the characterization of adrenal tumors, but findings might be inconclusive. The clinical question is whether [18F] FDG PET/CT is of diagnostic value in this setting. This meta-analysis was aimed at the diagnostic value of [18F] FDG PET/CT in differentiating benign from malignant adrenal tumors discovered either as adrenal incidentaloma or during staging or follow-up of oncologic patients. PubMed, EMBASE, Web of Science and Cochrane Library were searched to select articles between 2000-2021. We included studies describing the diagnostic value of [18F] FDG PET/CT in adult patients with an adrenal tumor. Exclusion criteria were ≤10 subjects, insufficient data on histopathology, clinical follow-up, or PET results. After screening of title and abstract by two independent reviewers, 79 studies were retrieved of which 17 studies met the selection criteria. Data extraction using a protocol and quality assessment according to QUADAS-2 was performed independently by at least two authors. A bivariate random effects model was applied using R (version 3.6.2.). Pooled sensitivity and specificity of [18F] FDG PET/CT for identifying malignant adrenal tumors was 87.3% (95%CI; 82.5%-90.9%) and 84.7% (95%CI; 79.3%-88.9%), respectively. The pooled diagnostic odds ratio (DOR) was 9.20 (95%CI; 5.27-16.08, P < 0.01). Major sources of heterogeneity (I2, 57.1% (95%CI; 27.5%-74.6%)) were in population characteristics, reference standard and interpretation criteria of imaging results. [18F] FDG PET/CT had good diagnostic accuracy for characterization of adrenal tumors. The literature, however, is limited, in particular regarding adrenal incidentalomas. Large prospective studies in well-defined patient populations with application of validated cut-off values are needed.