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In the era of precision oncology (PO), systemic therapies for patients (pts) with solid tumors have shifted from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). This systematic survey describes features of trials enrolling between 2010 and 2020, focusing on inclusion criteria, type of dose escalation scheme (DES) utilized, and use of expansion cohorts (ECs). A literature search identified phase I studies in adults with solid tumors published January 1, 2000– December 31, 2020 from 12 journals. We included only studies enrolling between 2010 and 2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance. Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I). In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized. [ABSTRACT FROM AUTHOR]

During the past few years, the teachers and staff at Kendall Demonstration Elementary School (KDES) have reviewed research to identify factors that positively impact language development for deaf and hard of hearing children, and established language and communication practices to reflect what they have learned. Based on the research, which details the advantages of early accessible visual language (Baker, 2011) and documents the variations in spoken language outcomes regardless of the use of hearing aids and cochlear implants (Yoshinaga-Itano, 2006), they have examined how an American Sign Language (ASL)/English bilingual program can be designed to benefit children with a wide range of characteristics--from children who have minimal access to spoken language through hearing aids and cochlear implants to those who benefit greatly from these technologies. They refer to this as an "ASL/English bimodal bilingual approach," which includes establishment of language foundations and access to learning through two modalities, e.g., auditory and visual, and two languages, e.g., ASL and English (Berent, 2004; Bishop, 2006; Emmorey, Bornstein, & Thompson, 2005). Through their experience in establishing a bimodal bilingual program at KDES and through their consultations with schools and programs throughout the United States, they are finding that with purposeful planning this multisensory approach can be implemented to effectively support the overall development of deaf and hard of hearing children. (Contains 1 figure.)

Severe coronavirus disease 2019 (COVID‐19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID‐19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID‐19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C‐reactive protein, interleukin‐6, procalcitonin, ferritin, and D‐dimer. In‐hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL‐6 (0.614), D‐dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%–98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%–96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%–96.7%) and NPV of 95.5% (93.1%–97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low‐risk patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: Sclerotinia sclerotiorum is a necrotrophic fungal pathogen causing disease and economic loss on numerous crop plants. This fungus has a broad host range and can infect over 400 plant species, including important oilseed crops such as soybean, canola, and sunflower. S. sclerotiorum isolates vary in aggressiveness of lesion formation on plant tissues. However, the genetic basis for this variation remains to be determined. The aims of this study were to evaluate a diverse collection of S. sclerotiorum isolates collected from numerous hosts and U.S. states for aggressiveness of stem lesion formation on sunflower, to evaluate the population characteristics, and to identify loci associated with isolate aggressiveness using genome-wide association mapping. Methods: A total of 219 S. sclerotiorum isolates were evaluated for stem lesion formation on two sunflower inbred lines and genotyped using genotyping-bysequencing. DNA markers were used to assess population differentiation across hosts, regions, and climatic conditions and to perform a genome-wide association study of isolate aggressiveness. Results and discussion: We observed a broad range of aggressiveness for lesion formation on sunflower stems, and only a moderate correlation between aggressiveness on the two lines. Population genetic evaluations revealed differentiation between populations from warmer climate regions compared to cooler regions. Finally, a genome-wide association study of isolate aggressiveness identified three loci significantly associated with aggressiveness on sunflower. Functional characterization of candidate genes at these loci will likely improve our understanding of the virulence strategies used by this pathogen to cause disease on a wide array of agriculturally important host plants. [ABSTRACT FROM AUTHOR]

Much research casts doubt on the effectiveness of legal norms for improving respect for human rights. But such studies have mostly focused on treaty ratifications or constitutional provisions. In contrast, I focus on national criminal law. I argue that criminalization of torture is more likely to deter police torture than these other forms of legal prohibition, because criminalization more credibly increases the threat of material and social costs of torture, while also helping to catalyze mobilization that amplifies these deterrent effects. Using an original, global dataset on national criminal laws against torture, I find that states that criminalize torture and define it in line with the standards codified in the UN Convention against Torture experience reductions in police torture. These findings highlight a largely unexplored angle on the relationship between law and human rights protection and underscore the general importance of domestic legal internalization for the effectiveness of international law. [ABSTRACT FROM AUTHOR]

Simple Summary: The contribution of access to care to racial/ethnic disparities in cancer outcomes remains insufficiently investigated. Our study showed substantial racial/ethnic disparities in total mortality of the top five major cancers for U.S. men and women, across 4 major racial/ethnic populations. We found that the non-Hispanic (NH)-black and NH-white mortality disparity was most evident among patients with a high socioeconomic status (SES) or those who had private insurance, while the NH-white versus Hispanic and Asian disparities were more evident among patients with low SES, or those with no insurance or Medicare or Medicaid. Our findings highlight the need to develop racial/ethnic-specific strategies to reduce the disparity in mortality among cancer patients, and call for further investigation on factors other than access to care (e.g., lifestyle, treatment adherence, provider/patient relationships, etc.) for their contributions to the racial/ethnic disparities in cancer outcomes. Importance: The reasons underlying racial/ethnic mortality disparities for cancer patients remain poorly understood, especially regarding the role of access to care. Participants: Over five million patients with a primary diagnosis of lung, breast, prostate, colon/rectum, pancreas, ovary, or liver cancer during 2004–2014, were identified from the National Cancer Database. Cox proportional hazards models were applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for total mortality associated with race/ethnicity, and access to care related factors (i.e., socioeconomic status [SES], insurance, treating facility, and residential type) for each cancer. Results: Racial/ethnic disparities in total mortality were observed across seven cancers. Compared with non-Hispanic (NH)-white patients, NH-black patients with breast (HR = 1.27, 95% CI: 1.26 to 1.29), ovarian (HR = 1.20, 95% CI: 1.17 to 1.23), prostate (HR = 1.31, 95% CI: 1.30 to 1.33), colorectal (HR = 1.11, 95% CI: 1.10 to 1.12) or pancreatic (HR = 1.03, 95% CI: 1.02 to 1.05) cancers had significantly elevated mortality, while Asians (13–31%) and Hispanics (13–19%) had lower mortality for all cancers. Racial/ethnic disparities were observed across all strata of access to care related factors and modified by those factors. NH-black and NH-white disparities were most evident among patients with high SES or those with private insurance, while Hispanic/Asian versus NH-white disparities were more evident among patients with low SES or those with no/poor insurance. Conclusions and Relevance: Racial/ethnic mortality disparities for major cancers exist across all patient groups with different access to care levels. The influence of SES or insurance on mortality disparity follows different patterns for racial/ethnic minorities versus NH-whites. Impact: Our study highlights the need for racial/ethnic-specific strategies to reduce the mortality disparities for major cancers. [ABSTRACT FROM AUTHOR]

Cigarette use is one of the leading causes of death in the United States, with most smokers beginning cigarette use in adolescence. Despite not being of legal age to make tobacco purchases, adolescents are quite successful in their acquisition. The current study used latent variable mixture modeling to identify smoking typologies among adolescents and examine associations with various sources of cigarettes (i.e., stealing, obtaining from friends, obtaining from family members, purchasing), social influences (parental objection to smoking, smoking friends), and demographics. Participants were 195 high school students caught with tobacco in school who completed surveys questions about their cigarette use, and cigarette use of family and friends. Results identified three latent classes pertaining to smoking patterns: recent, heavy, frequent smokers (RHFS), low infrequent smokers (LIS), and recent moderate smokers (RMS). Students in the RHFS and RMS groups were more likely to obtain cigarettes by purchasing or borrowing from a friend, and reported more friends who smoke and lower parental objection compared to LIS members. RHFS members also were more likely to obtain cigarettes from family and be of White race compared to the other groups. These findings highlight the need for tailored prevention or intervention programs depending on risk profile. [ABSTRACT FROM AUTHOR]

Children who experience obsessive–compulsive symptoms (OCS) may be at risk for developing Obsessive–Compulsive Disorder (OCD). The current study aimed to investigate developmental trajectories of OCS, as well as possible predictors, within a community-based sample of children. Children (N = 1147) from the longitudinal NICHD Study of Early Child Care and Youth Development (SECCYD) were assessed for OCS, via the Child Behavioral Checklist – Obsessive–Compulsive Scale (OCS-8), eight times between Pre-Kindergarten (54 months; Pre-K) and High School (15 years of age; HS.) Participants were recruited within the United States and included only maternal caregivers. Preliminary analyses indicated that approximately 3% of the sample was above the diagnostic cutoff score on the OCS-8 at the High School time-point. Latent growth models tested symptom trajectories. Findings demonstrated three groups of OCS trajectories. Most children fell within a low symptomatology group (the No Peak group) with low OCS across all time points. Two additional OCS trajectories were also demonstrated: Pre-K Peak (high to low OCS across time) and HS Peak (low to high OCS across time). Both higher attention problems and greater depression/anxiety symptoms at the Pre-K time point predicted children's membership in the Pre-K Peak or HS Peak groups compared to the No Peak group. Membership within the HS Peak group predicted a high likelihood of children's OCS being above previously established cutoff scores for an OCD diagnosis at age 15 years. Membership within either the Pre-K Peak or No Peak groups predicted a low likelihood. This study provides new evidence for the existence of different developmental trajectories for youth with OCS. From a clinical perspective, these results may have important implications when considering the identification and early intervention of childhood OCS and OCD within the community. [ABSTRACT FROM AUTHOR]

Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19).Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival.Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used.Setting: 67 hospitals in the United States.Participants: Adults with COVID-19 admitted to a participating ICU.Measurements: Time to death, censored at hospital discharge, or date of last follow-up.Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]).Limitation: Observational design.Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Teacher education research is in still in the process of developing a robust set of tools that can measure the key features of coursework and fieldwork. This article focuses on the design of measures of "opportunities to learn" (OTLs) in content method courses that can be used across large populations of candidates at diverse preparation programs. We draw on the survey and interview data from a broader, longitudinal study of teacher preparation across four programs in the United States (n = 455 candidates). Variance decomposition suggests far greater within-program variation than between-program variation in reported OTL. More nuanced analyses at a single university indicate significant associations between individual characteristics and reports of OTL, suggesting that self-reports of OTL may tell us more about the candidates who complete a survey than the programs that prepare them. Discussion focuses on implications for teacher education research and next steps for studying OTL in methods coursework. [ABSTRACT FROM AUTHOR]

Immunotherapy is emerging as one of the most effective methods for treating many cancers. However, immunotherapy can still introduce significant off-target toxicity, and methods are sought to enable targeted immunotherapy at tumor sites. Here, we show that relatively large (>100-nm) anionic nanoparticles administered intraperitoneally (i.p.) selectively accumulate in tumor-associated macrophages (TAMs). In a mouse model of metastatic ovarian cancer, fluorescently labeled silica, poly(lactic-co-glycolic acid), and polystyrene nanoparticles administered i.p. were all found to selectively accumulate in TAMs. Quantifying silica particle uptake indicated that >80% of the injected dose was in TAMs. Particles that were smaller than 100 nm or cationic or administered intravenously (i.v.) showed no TAM targeting. Moreover, this phenomenon is likely to occur in humans because when freshly excised human surgical samples were treated with the fluorescent silica nanoparticles no interaction with healthy tissue was seen but selective uptake by TAMs was seen in 13 different patient samples. Ovarian cancer is a deadly disease that afflicts ∼22,000 women per year in the United States, and the presence of immunosuppressive TAMs at tumors is correlated with decreased survival. The ability to selectively target TAMs opens the door to targeted immunotherapy for ovarian cancer. [ABSTRACT FROM AUTHOR]

The article present a case report of a 20 year old Ms. Z. and D. a 3-year-old boy at risk of deportation. Topics include in the cases of D. and Ms. Z., the right and left hands of the state were in tension; mentions the presence of punitive governance in the clinical setting complicates clinicians' ability to fully advocate for the welfare of their patients; and also mentions health professionals can find themselves acting as agents of the punitive state, turning patients into deportees.

Rationale: Dyspnea is a common and distressing physical symptom among patients in the ICU and may be underdetected and undertreated. Objectives: To determine the frequency of dyspnea relative to pain, the accuracy of nurses and personal caregiver dyspnea ratings relative to patient-reported dyspnea, and the relationship between nurse-detected dyspnea and treatment. Methods: This was an observational study of patients (n = 138) hospitalized in a medical ICU (MICU). Nurses and patients' personal caregivers at the bedside reported on their perception of patients' symptoms. Measurements and Main Results: Dyspnea was assessed by patients, caregivers, and nurses with a numerical rating scale. Across all three raters, the frequency of moderate to severe dyspnea was similar or greater than that of pain (P < 0.05 for caregiver and nurse ratings). Personal caregivers' ratings of dyspnea had substantial agreement with patient ratings (κ = 0.65, P < 0.001), but nurses' ratings were not significantly related to patient ratings (κ = 0.19, P = 0.39). Nurse detection of moderate to severe pain was significantly associated with opioid treatment (odds ratio, 2.70; 95% confidence interval, 1.10-6.60; P = 0.03); however, nurse detection of moderate to severe dyspnea was not significantly associated with any assessed treatment. Conclusions: Dyspnea was reported at least as frequently as pain among the sampled MICU patients. Personal caregivers had good agreement with patient reports of moderate to severe dyspnea. However, even when detected by nurses, dyspnea appeared to be undertreated. These findings suggest the need for improved detection and treatment of dyspnea in the MICU. [ABSTRACT FROM AUTHOR]

Purpose: Increase in in situ breast cancer (BCIS) incidence has been reported across Europe and the USA. However, little is known about the trends in BCIS incidence in regions without population-based mammographic screening programs. We set out to investigate these trends in Zurich, Switzerland, where only opportunistic mammographic screening exists.Methods: Data from 989 women diagnosed with a primary BCIS between 2003 and 2014 were used in our analyses. Age-standardized incidence rates per 100,000 person-years (ASR) were computed per year. Additional analyses by BCIS subtype, by age group at diagnosis and by incidence period were conducted. Incidence trends over time were assessed using joinpoint regression analysis.Results: The overall BCIS ASR was 10.7 cases per 100,000 person-years with an increasing trend over the study period. A similar trend was observed for the ductal carcinoma in situ (DCIS) ASR, while the lobular carcinoma in situ (LCIS) ASR decreased. Age-specific analyses revealed that the 50-59 year age group had the highest BCIS ASR. The highest increase in BCIS ASR, even though not statistically significant, was observed for the < 40 year age group.Conclusions: BCIS ASR increased linearly over a 12-year period. The increase was reflected by an increase in DCIS ASR, whereas LCIS ASR decreased over time. The highest increase in BCIS ASR over the study period was observed for the < 40 year age group, even though not statistically significant. Patient and tumor characteristics of this group that may be associated with BCIS development warrant further investigation. [ABSTRACT FROM AUTHOR]

The article talks about graduate education at the master's level. Master's study is complicated as it is shaped by the traditions of Western European universities and factors typical to the American system of education. The goals of master's programs reflect lots of various ideas and vested interests. These are divided into two: "establishment" goals, which are purposes underlying study at the master's level, and faculty goals, which are beliefs about the intent of master's programs set by members of graduate teaching staffs. More information is given.

The institutional review board (IRB) process is often protracted and can be a source of frustration, especially when you want your research and publications to move apace. However, because of historical events, the IRB is an important requirement for conducting research with human participants and is regulated by federal oversite. When conducting research as part of a pedagogical study, it is important to identify which level of IRB review (exempt, expedited, or full board) is required. The purpose of this article is to highlight IRB basics within the United States for pedagogy research. Although there are guidelines internationally, this article specifically focuses on U.S. IRBs, including a brief history of the IRB, pedagogical and community-based participatory research, IRB review, tips for IRB submissions, and example case studies. [ABSTRACT FROM AUTHOR]