Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 ...abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio HR, 0.36 95% confidence interval, 0.18-0.70; P=0.003; RFS: HR, 0.17 0.05-0.54; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 1.09-2.74; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.
Dental educators are challenged to bridge the theory‐practice gap to enhance the educational experience and meet the diverse learning needs of students. The aim of this study was to explore dental ...hygiene students’ perceptions of the effectiveness, appeal, and satisfaction regarding instrumentation videos as a resource to improve learning in the clinical environment. All 152 first‐year students in a U.S. baccalaureate dental hygiene program at two sites in two consecutive years were invited to participate in the study. Survey questions addressed demographics, effectiveness, appeal, and satisfaction with the instrumentation videos along with open‐ended questions to explore students’ perceptions of the videos’ value and benefits. A total of 143 students completed the survey, for a response rate of 94%. The results showed that 50% to 70% of the respondents agreed or strongly agreed with questions relating to effectiveness, appeal, and satisfaction with the videos. Most participants used the videos while practicing (83%). Students who spoke English as a second language were less likely to feel the videos were effective, found them less appealing, and were less satisfied with them (p<0.05). Participants who practiced while using the videos were more likely to report them as being effective and appealing and were more satisfied with the videos than were participants who did not practice with them (p<0.05). Thematic analysis revealed the following themes in the open comments: helpfulness of the videos in clinical practice to clarify, reinforce, and visualize skills learned. These students reported satisfaction with the instrumentation videos, suggesting these learning aids have potential value in closing the theory‐practice gap in clinical dental hygiene education.
Few studies have been published on thesis completion experiences of master's degree students. However, for doctoral students, dissertation completion has been found to be dependent on individual, ...relational, and institutional factors. The aim of this study was to examine dental hygienists’ perceptions of their experiences completing a thesis as a requirement for an advanced degree. A qualitative phenomenological research design was used utilizing virtual focus groups with a national purposive sample of dental hygienists (n=25) who had graduated from a degree program in which a thesis was a requirement for the degree. Data analysis used an inductive approach to identify themes using Liechty et al.'s framework of individual, relational, and institutional factors impacting completion of a dissertation. Liechty et al.'s framework is based on Vygotsky's sociocultural theory of learning. In the results, individual factors identified included family/work responsibilities, lack of understanding of the thesis process, time management, health issues, and reaching personal and professional goals. Relational factors focused primarily on positive and negative experiences with the thesis advisor/committee and support from expert peers/family. Institutional factors included the thesis structure, financial concerns, and challenges in recruiting research participants. This study found many factors influencing the thesis experience that may help guide the process in graduate degree programs. In addition, the findings suggest a need to provide mentoring and support for thesis advisors and committee members to more effectively guide students through the thesis process. Effective modifications of these may improve retention of students and facilitate timely completion of thesis research.
Many health professions have identified characteristics of an effective clinical instructor and used this information to create tools to measure clinical teaching effectiveness (CTE) in their ...disciplines. However, minimal research has been conducted to explore the attributes of an effective clinical instructor in dental hygiene education. The aim of this study was to identify the attributes of dental hygiene clinical instructors associated with effective teaching. This study used a Delphi research design to iteratively survey an expert panel of 14 dental hygiene instructors in dental hygiene programs from 13 U.S. states in 2019. A cumulative overall response rate of 89.3% was achieved after conducting three survey rounds. The results showed statistically significant consensus on 91 CTE characteristics. Participants agreed that effective clinical instructors should possess the ability to clearly communicate, foster interpersonal relationships, encourage a climate of mutual respect, and act as good role models who are emotionally intelligent, caring, trustworthy, fair, honest, and supportive. There was also agreement that effective clinical instructors were those who created a safe learning environment centered on collaboration, motivation, guidance, and positive corrective feedback. These results were similar to those identified in other health professions. However, there is a need for dental hygiene education to develop its own CTE assessment tool for use in professional development.
IntroductionPeripherally inserted central catheters (PICCs) are vital for the delivery of medical therapies, but up to 30% of PICCs are associated with complications such as deep vein thrombosis or ...infection. The integration of antimicrobial and hydrophobic catheter materials, and pressure-activated valves, into polyurethane PICCs are innovations designed to prevent infective and/or thrombotic complications.Methods and analysisA multicentre, parallel group, superiority randomised controlled trial with two experimental arms ((1) hydrophobic PICC (with pressure-activated valve); (2) chlorhexidine gluconate-impregnated PICC (with external clamp)) and one control group ((3) conventional polyurethane PICC (with external clamp)). Recruitment of 1098 adult and paediatric patients will take place over 2 years at three tertiary-referral hospitals in Queensland, Australia. Patients are eligible for inclusion if their PICC is to be inserted for medical treatment, with a vascular size sufficient to support a 4-Fr PICC or larger, and with informed consent. The primary outcome is PICC failure, a composite of thrombotic (venous thrombosis, breakage and occlusion) and infective complications (PICC-associated bloodstream infection and local infection). Secondary outcomes include: all-cause PICC complication; thrombotic complications; infective complications; adverse events (local or systemic reaction); PICC dwell time; patient/parent satisfaction; and healthcare costs. Differences between both intervention groups and the control group will be compared using Cox proportional hazards regression. Effect estimates will be presented as HRs with corresponding 95% CI.Ethics and disseminationEthical approval from Queensland Health (HREC/QCHQ/48682) and Griffith University (Ref. No. 2019/094). Results will be published.Trial registration numberACTRN12619000022167.
Deficits in neurocognition and social cognition are drivers of reduced functioning in schizophrenia spectrum disorders, with potentially shared neurobiological underpinnings. Many studies have sought ...to identify brain-based biomarkers of these clinical variables using a priori dichotomies (e.g., good vs. poor cognition, deficit vs. nondeficit syndrome).
We evaluated a fully data-driven approach to do the same by building and validating a brain connectivity–based biomarker of social cognitive and neurocognitive performance in a sample using resting-state and task-based functional magnetic resonance imaging (n = 74 healthy control participants, n = 114 persons with schizophrenia spectrum disorder, 188 total). We used canonical correlation analysis followed by clustering to identify a functional connectivity signature of normal and poor social cognitive and neurocognitive performance.
Persons with poor social cognitive and neurocognitive performance were differentiated from those with normal performance by greater resting-state connectivity in the mirror neuron and mentalizing systems. We validated our findings by showing that poor performers also scored lower on functional outcome measures not included in the original analysis and by demonstrating neuroanatomical differences between the normal and poorly performing groups. We used a support vector machine classifier to demonstrate that functional connectivity alone is enough to distinguish normal and poorly performing participants, and we replicated our findings in an independent sample (n = 75).
A brief functional magnetic resonance imaging scan may ultimately be useful in future studies aimed at characterizing long-term illness trajectories and treatments that target specific brain circuitry in those with impaired cognition and function
Marine wild-capture fisheries after nuclear war Scherrer, Kim J. N.; Harrison, Cheryl S.; Heneghan, Ryan F. ...
Proceedings of the National Academy of Sciences - PNAS,
11/2020, Volume:
117, Issue:
47
Journal Article
Peer reviewed
Open access
Nuclear war, beyond its devastating direct impacts, is expected to cause global climatic perturbations through injections of soot into the upper atmosphere. Reduced temperature and sunlight could ...drive unprecedented reductions in agricultural production, endangering global food security. However, the effects of nuclear war on marine wild-capture fisheries, which significantly contribute to the global animal protein and micronutrient supply, remain unexplored. We simulate the climatic effects of six war scenarios on fish biomass and catch globally, using a state-of-the-art Earth system model and global process-based fisheries model. We also simulate how either rapidly increased fish demand (driven by food shortages) or decreased ability to fish (due to infrastructure disruptions), would affect global catches, and test the benefits of strong prewar fisheries management. We find a decade-long negative climatic impact that intensifies with soot emissions, with global biomass and catch falling by up to 18 ± 3% and 29 ± 7% after a US–Russia war under business-as-usual fishing—similar in magnitude to the end-of-century declines under unmitigated global warming. When war occurs in an overfished state, increasing demand increases short-term (1 to 2 y) catch by at most ∼30% followed by precipitous declines of up to ∼70%, thus offsetting only a minor fraction of agricultural losses. However, effective prewar management that rebuilds fish biomass could ensure a short-term catch buffer large enough to replace ∼43 ± 35% of today’s global animal protein production. This buffering function in the event of a global food emergency adds to the many previously known economic and ecological benefits of effective and precautionary fisheries management.
Background
In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti‐CD22 immunotoxin, demonstrated a manageable safety ...profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy.
Procedure
This international, multicenter, phase 2 study enrolled children with relapsed/refractory B‐cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21‐day cycle. The primary objective was to evaluate the complete response (CR) rate. Secondary objectives included safety, pharmacokinetics, and immunogenicity evaluations.
Results
Thirty‐two patients (median age, 10 years) were enrolled at 16 sites; 30 received study drug and were evaluable for safety; 28 were evaluable for response. The objective response rate was 28.6%, with three patients (10.7%) achieving morphologic CR, and five patients (17.9%) achieving partial response. Disease progression occurred in 11 patients (39.3%). Ten patients (33.3%) experienced at least one treatment‐related serious adverse event, including capillary leak syndrome (CLS; n = 6), hemolytic uremic syndrome (HUS; n = 4), and treatment‐related death (n = 1) from pulmonary edema. No differences were observed in inflammatory markers in patients who did or did not develop CLS or HUS.
Conclusions
Despite a signal for clinical activity, this phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. Preclinical data suggest enhanced efficacy of moxetumomab pasudotox via continuous infusion or in combination regimens; thus, further studies designed to optimize the efficacy and safety of moxetumomab pasudotox in pediatric ALL may be warranted.
The interest in the topic of spirituality as a more or less independent dimension of quality of life is continuously growing, and research questions are beginning to change as the field of ...religiosity changes, becoming more diverse and pluralistic. Addressing new topics in health research also relies on standardized questionnaires. The number of instruments intended to measure specific aspects of spirituality is growing, and it is particularly difficult to evaluate the new instruments. This Special Issue will focus on some of the established instruments (updating them to different languages and cultures), but will also describe the features and intentions of newly-developed instruments, which may potentially be used in larger studies to develop knowledge relevant to spiritual care and practice. This Special Issue will serve as a resource on the instruments used to study the wide range of organized religiosity, the individual experience of the divine, and an open approach in the search for meaning and purpose in life.
PDF
