This book examines test validity in the behavioral, social, and educational sciences by exploring three fundamental problems: measurement, causation and meaning. Psychometric and philosophical ...perspectives receive attention along with unresolved issues. The authors explore how measurement is conceived from both the classical and modern perspectives. The importance of understanding the underlying concepts as well as the practical challenges of test construction and use receive emphasis throughout. The book summarizes the current state of the test validity theory field. Necessary background on test theory and statistics is presented as a conceptual overview where needed.
Each chapter begins with an overview of key material reviewed in previous chapters, concludes with a list of suggested readings, and features boxes with examples that connect theory to practice. These examples reflect actual situations that occurred in psychology, education, and other disciplines in the US and around the globe, bringing theory to life. Critical thinking questions related to the boxed material engage and challenge readers. A few examples include:
What is the difference between intelligence and IQ?
Can people disagree on issues of value but agree on issues of test validity?
Is it possible to ask the same question in two different languages?
The first part of the book contrasts theories of measurement as applied to the validity of behavioral science measures.The next part considers causal theories of measurement in relation to alternatives such as behavior domain sampling, and then unpacks the causal approach in terms of alternative theories of causation.The final section explores the meaning and interpretation of test scores as it applies to test validity. Each set of chapters opens with a review of the key theories and literature and concludes with a review of related open questions in test validity theory.
Researchers, practitione
In 2014 the National Science Foundation (NSF) provided support to the National Academies of Sciences, Engineering, and Medicine for a series of Forums on Open Science in response to a government-wide ...directive to support increased public access to the results of research funded by the federal government. However, the breadth of the work resulting from the series precluded a focus on any specific topic or discussion about how to improve public access. Thus, the main goal of the Workshop on Transparency and Reproducibility in Federal Statistics was to develop some understanding of what principles and practices are, or would be, supportive of making federal statistics more understandable and reviewable, both by agency staff and the public. This publication summarizes the presentations and discussions from the workshop.
Conspectus Long-lived organic room-temperature phosphorescence (RTP) materials have recently drawn extensive attention because of their promising applications in information security, biological ...imaging, optoelectronic devices, and intelligent sensors. In contrast to conventional fluorescence, the RTP phenomenon originates from the slow radiative transition of triplet excitons. Thus, enhancing the intersystem crossing (ISC) rate from the lowest excited singlet state (S1) to the excited triplet state and suppressing the nonradiative relaxation channels of the lowest excited triplet state (T1) are reasonable methods for realizing highly efficient RTP in purely organic materials. Over the past few decades, many strategies have been designed on the basis of the above two crucial factors. The introduction of heavy atoms, aromatic carbonyl groups, and other heteroatoms with abundant lone-pair electrons has been demonstrated to strengthen the spin–orbit coupling, thereby successfully facilitating the ISC process. Furthermore, the rigid environment is commonly constructed through crystal engineering to restrict intramolecular motions and intermolecular collisions to decrease excited-state energy dissipation. However, most crystal-based organic RTP materials suffer from poor processability, flexibility, and reproducibility, becoming a thorny obstacle to their practical application. Amorphous organic polymers with long-lived RTP characteristics are more competitive in materials science. The intertwined structures and long chains of polymers not only ensure the rigid environment with multiple interactions but also protect triplet excitons from the surroundings, which are conducive to realizing ultralong and bright RTP emission. Exploring the fabrication strategies, intrinsic mechanisms, and practical applications of organic long-lived RTP polymers is highly desirable but remains a formidable challenge. In particular, intelligent organic RTP polymer systems that are capable of dynamically responding to external stimuli (e.g., light, temperature, oxygen, and humidity) have been rarely reported. To develop multifunctional RTP materials and expand their potential applications, a great amount of effort has been expended. This Account gives a summary of the significant advances in amorphous organic RTP polymer systems, especially smart stimulus-responsive ones, focusing on the construction of a rigid environment to suppress nonradiative deactivation by abundant inter/intramolecular interactions. The typical interactions in RTP polymer systems mainly include hydrogen bonding, ionic bonding, and covalent bonding, which can change the molecular electronic structures and affect the energy dissipation channels of the excited states. An in-depth understanding of intrinsic mechanisms and an extensive exploration of potential applications for excitation-dependent color-tunable, ultraviolet (UV) irradiation-activated, temperature-dependent, water-responsive, and circularly polarized RTP polymer systems are distinctly illustrated in this Account. Furthermore, we propose some detailed perspectives in terms of materials design, mechanism exploration, and promising application potential with the hope to provide helpful guidance for the future development of amorphous organic RTP polymers.
Lessons Learned
A biweekly TAS‐102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS‐102 plus BEV ...combination.
Biweekly TAS‐102 plus BEV combination could reduce unnecessary dose reduction of TAS‐102, maintain higher doses, and possibly be effective even in cases without chemotherapy‐induced neutropenia (CIN).
The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS‐102 plus BEV.
Background
TAS‐102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS‐102 (70 mg/m2/day on days 1–5 and 8–12, every 4 weeks) plus BEV (5 mg/kg on day 1, every 2 weeks) regimen is complicated by severe hematological toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS‐102 plus BEV combination.
Methods
Patients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS‐102 (twice daily on days 1–5, every 2 weeks) with BEV (5mg/kg on day 1, every 2 weeks). The primary endpoint was progression‐free survival rate at 16 weeks (16‐w PFS rate).
Results
From October 2017 to January 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS‐102 (70 mg/m2/day). Of the 44 eligible patients, the 16‐w PFS rate was 40.9% (95% confidence interval, 26.3%–56.8%), and the null hypothesis was rejected (p < .0001). Median progression‐free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%).
Conclusion
Biweekly TAS‐102 plus BEV showed promising antitumor activity with safety.
Lessons Learned
Monotherapy with prexasertib demonstrated modest activity in BRCA wild‐type, recurrent triple‐negative breast cancer, highlighting the unmet need for combination treatment strategies.
...Neutropenia, anemia, and thrombocytopenia are common with the use of prexasertib but are manageable with supportive care measures. Prophylactic use of granulocyte colony stimulating factor should be considered to avoid dose reductions or treatment delays.
Pharmacodynamic studies showed prexasertib treatment induced DNA damage in peripheral immune cells.
Background
Cell cycle checkpoint kinase 1 (CHK1) is a major G2/M cell cycle regulator in tumors with p53 dysfunction, such as triple‐negative breast cancer (TNBC). We hypothesized the second‐generation CHK1 inhibitor, prexasertib, would yield clinical activity in sporadic TNBC.
Methods
This single arm, phase II trial evaluated prexasertib at 105 mg/m2 IV every 2 weeks in patients with metastatic/recurrent TNBC. The primary endpoint was overall response rate (ORR).
Results
All nine patients enrolled were germline BRCA wild‐type (BRCAwt) and had at least one prior treatment. One partial response (PR) was observed (ORR of 11.1%). Four patients experienced stable disease. The median progression‐free survival (PFS) was 86 days (range 17 to 159 days). Grade 3/4 treatment‐related adverse events included afebrile neutropenia (n = 8; 88.9%), anemia (n = 3; 33.3%), and thrombocytopenia (n = 1; 11.1%). Pharmacodynamic studies showed prexasertib treatment induced DNA damage in peripheral immune cells and demonstrated a decrease in activated/reinvigorated CD8 T cells; however, the one patient with a PR showed evidence of T‐cell recovery.
Conclusion
Prexasertib monotherapy had modest clinical efficacy in BRCAwt TNBC. Further studies of prexasertib in combination with other agents are needed.
Lessons Learned
Palbociclib monotherapy demonstrated minimal clinical activity in patients with previously treated gastroesophageal cancers.
Further clinical evaluation of palbociclib monotherapy is ...not warranted in gastroesophageal cancers, but improved understanding of resistance mechanisms may permit rational combination approaches.
Background
Dysregulation of the cell cycle is a hallmark of cancer. Progression through the G1/S transition requires phosphorylation of retinoblastoma (RB) by cyclin‐dependent kinases (CDKs) 4 and 6, which are regulated by cyclins D and E. Amplifications of cyclin D loci and activating mutations in CDKs are frequent molecular aberrations in gastroesophageal malignancies. We conducted a phase II trial of the CDK4/6 inhibitor palbociclib as an initial test of efficacy.
Methods
Patients with previously treated metastatic gastroesophageal cancers with intact RB nuclear expression by immunohistochemistry were treated with 125 mg daily of palbociclib for days 1–21 of 28‐day cycles. The primary endpoint was overall response rate.
Results
We screened 29 patients and enrolled 21 patients: 5 with gastric adenocarcinoma, 3 with gastroesophageal junction adenocarcinoma, 8 with esophageal adenocarcinoma, and 5 with esophageal squamous cell carcinoma. All 29 tumors screened had intact nuclear RB expression, and four treated patients tested positive for CCND1 overexpression. No objective responses were seen. Median progression‐free survival was 1.8 months, and median overall survival was 3.0 months. All recurrent grade 3 or 4 toxicities were hematologic, with neutropenia in eight patients (38%), anemia in four patients (19%), and thrombocytopenia in two patients (10%).
Conclusion
Palbociclib has limited single‐agent activity in gastroesophageal tumors.
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and ...many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.
The present paper describes the mathematical modeling and dynamics of a novel corona virus (2019-nCoV). We describe the brief details of interaction among the bats and unknown hosts, then among the ...peoples and the infections reservoir (seafood market). The seafood marked are considered the main source of infection when the bats and the unknown hosts (may be wild animals) leaves the infection there. The purchasing of items from the seafood market by peoples have the ability to infect either asymptomatically or symptomatically. We reduced the model with the assumptions that the seafood market has enough source of infection that can be effective to infect people. We present the mathematical results of the model and then formulate a fractional model. We consider the available infection cases for January 21, 2020, till January 28, 2020 and parameterized the model. We compute the basic reproduction number for the data is R0≈2.4829. The fractional model is then solved numerically by presenting many graphical results, which can be helpful for the infection minimization.
More than six billion tests for COVID-19 has been already performed in the world. The testing for SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) virus and corresponding human antibodies ...is essential not only for diagnostics and treatment of the infection by medical institutions, but also as a pre-requisite for major semi-normal economic and social activities such as international flights, off line work and study in offices, access to malls, sport and social events. Accuracy, sensitivity, specificity, time to results and cost per test are essential parameters of those tests and even minimal improvement in any of them may have noticeable impact on life in the many countries of the world. We described, analyzed and compared methods of COVID-19 detection, while representing their parameters in 22 tables. Also, we compared test performance of some FDA approved test kits with clinical performance of some non-FDA approved methods just described in scientific literature. RT-PCR still remains a golden standard in detection of the virus, but a pressing need for alternative less expensive, more rapid, point of care methods is evident. Those methods that may eventually get developed to satisfy this need are explained, discussed, quantitatively compared. The review has a bioanalytical chemistry prospective, but it may be interesting for a broader circle of readers who are interested in understanding and improvement of COVID-19 testing, helping eventually to leave COVID-19 pandemic in the past.
Display omitted
•RT-PCR is a golden standard for COVID-19 detection due to high sensitivity and accuracy.•Other detection methods can get faster time of analysis and lower cost than PCR-based.•FDA approved detection kits have advantage in accuracy vs published not yet approved methods.•Antibodies to virus are detected with ELISA, LFIA and CLIA, which may have an edge in sensitivity and specificity.•CT scan, X-ray scan, and lung ultrasound have comparable clinical accuracy about 93%.
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