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The lymphatics play important roles in chronic diseases/conditions that comprise the bulk of healthcare worldwide. Yet the ability to routinely image and diagnose lymphatic dysfunction, using commonly available clinical imaging modalities, has been lacking and as a result, the development of effective treatment strategies suffers. Nearly two decades ago, investigational near-infrared fluorescence lymphatic imaging and ICG lymphography were developed as routine diagnostic for clinically evaluating, quantifying, and treating lymphatic dysfunction in cancer-related and primary lymphedema, chronic venous disease, and more recently, autoimmune and neurodegenerative disorders. In this review, we provide an overview of what these non-invasive technologies have taught us about lymphatic (dys) function and anatomy in human studies and in corollary animal studies of human disease. We summarize by commenting on new impactful clinical frontiers in lymphatic science that remain to be facilitated by imaging.

Experiences of change from the perspective of both chronically conflictual couples and their therapist has not been explored, thus inhibiting current understanding of what is important for in-session change. The present study examines couple and therapist experiences of therapy for chronically conflictual couples. Sixteen interviews from four couples (n = 8) and their therapists (n = 4) were analyzed using Colaizzi's method of phenomenological inquiry. Results highlight environmental, couple, and therapist factors that are integral to experiencing change in session. Results show the importance of therapists facilitating intentional, non-conflictual, and connecting couple interactions. We discuss clinical implications of the findings. [ABSTRACT FROM AUTHOR]

Temperature fluctuations over long time scales (≳ 1 h) are an insidious problem for precision measurements. In optical laboratories, the primary effect of temperature fluctuations is drifts in optical circuits over spatial scales of a few meters and temporal scales extending beyond a few minutes. We present a lab-scale environment temperature control system approaching 10 mK-level temperature instability across a lab for integration times above an hour and extending to a day. This is achieved by passive isolation of the laboratory space from the building walls using a circulating air gap and an active control system feeding back to heating coils at the outlet of the laboratory's Heating-Ventilation-Air-Conditioning (HVAC) unit. These techniques together result in 20 dB suppression of the temperature power spectrum across the lab at 10−4 Hz—approaching the limit set by statistical coherence of the temperature field—and 10 mK Allan deviation around 15 °C after an hour of averaging, which is an order of magnitude better than any previous report for a full laboratory. [ABSTRACT FROM AUTHOR]

Cultural heritage faces significant threats from environmental challenges and unchecked development. Sustainability has made its way into the field, and there is a growing interest in seeing it thrive. The particular field of the conservation and restoration of tangible movable cultural heritage is also being improved by new concepts and treatment options more aligned with environmental standards. This article investigates the integration of sustainability into the conservation and restoration of this specific cultural heritage by leveraging the SCOPUS and BCIN databases to examine the evolution of scientific content on the topic over the past 24 years. Key trends in research include assessing greener practices in conservation and education and guidance for the promotion of sustainable practices. These themes are also championed by organizations and initiatives that disseminate this message to conservation professionals through effective and less formal communication strategies. The findings emphasize the critical value of bridging the gap between scientific research and practical application, advocating for accessible resources and collaborative efforts to advance sustainable conservation practices. [ABSTRACT FROM AUTHOR]

The "e-rater"® automated scoring engine used at Educational Testing Service (ETS) scores the writing quality of essays. In the current practice, e-rater scores are generated via a multiple linear regression (MLR) model as a linear combination of various features evaluated for each essay and human scores as the outcome variable. This study evaluates alternative scoring models based on several additional machine learning algorithms, including support vector machines (SVM), random forests (RF), and "k"-nearest neighbor regression (k-NN). The results suggest that models based on the SVM algorithm outperform MLR models in predicting human scores. Specifically, SVM-based models yielded the highest agreement between human and e-rater scores. Furthermore, compared with MLR, SVM-based models improved the agreement between human and e-rater scores at the ends of the score scale. In addition, the high correlation between SVM-based e-rater scores with external measures such as examinee's scores on the other parts of the test provided some validity evidence for SVM-based e-rater scores. Future research is encouraged to explore the generalizability of these findings.

The common school philosophy of the nineteenth century in the United States is revisited from a contemporary perspective. Is the basic ethos of the philosophy of Horace Mann and others still relevant today? This question is examined and applied to the conservative advocacy of free markets, individual freedom, and school choice in order to assess the extent to which the delivery of government-supported education is done in a way that upholds the values of the past while simultaneously addressing paramount issues related to social equity, diversity, and social cohesion today.

The current study examined the effect of children's positive relationships and interactions with their teachers and the development of executive function (EF) skills in first grade. A primary objective was to examine externalizing behaviour problems (EBPs) as a potential moderator of the link between teacher-child relationships and interactions and EF skills. Participants for the study included 1,364 first-grade children (48.3% female, M age = 7.02 years, 80.4% White) drawn from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. There was limited evidence suggesting the EBP moderates the relation between teacher--child relationship quality and EF skill development in first grade. Specifically, simple slope trends indicated that teacher-child closeness was positively related to gains in sustained attention for typically developing children but negatively related to sustained attention for children exhibiting borderline to clinical levels of EBPs. Implications of the findings are discussed.

BackgroundThe prevalence of superficial fungal infections in India is believed to have increased substantially in the past decade. We evaluated the treatment outcomes and risk factors associated with clinical response to a treatment course of itraconazole for the management of dermatomycosis in India.MethodsIn this real-world, prospective pilot study (August 2019 to March 2020), adult participants (18-60 years), diagnosed with T. cruris or T. corporis, received itraconazole 200 mg/day (any formulation) orally for 7 days, and were followed for an additional 7 days.ResultsThe study was terminated early due to the COVID-19 pandemic. Of 40 enrolled participants (mean [SD] age, 35.5 [12.73] years; {62.5%}] male; 37 received itraconazole and 20 (50%) completed the study. The median (range) Clinical Evaluation Tool Signs and Symptoms total score at baseline was 5.5 (2-10). Clinical response of "healed" or "markedly improved" based on the Investigator Global Evaluation Tool at day 7 (primary objective) was 42.9% (12/28; 95% CI: 24.53%, 61.19%). Itraconazole minimum inhibitory concentration for identified microorganisms, T. mentagrophytes species complex (91.7%) and T. rubrum (8.3%), was within the susceptibility range (0.015-0.25 mcg/mL). At day 14, 8/13 (61.5%) participants achieved a mycological response, 2/13 participants (15.4%) had a mycological failure and 90% showed a clinical response.ConclusionCOVID-19 pandemic affected patient recruitment and follow-up, so the findings call for a careful interpretation. Nevertheless, this real-world study reconfirmed the clinical efficacy and microbial susceptibility to itraconazole for the fungi causing dermatophytosis in India.Trial registrationTrial registration number: Clinicaltrials.gov NCT03923010.

Abstract Background Window-of-opportunity trials, evaluating the engagement of drugs with their biological target in the time period between diagnosis and standard-of-care treatment, can help prioritise promising new systemic treatments for later-phase clinical trials. Renal cell carcinoma (RCC), the 7th commonest solid cancer in the UK, exhibits targets for multiple new systemic anti-cancer agents including DNA damage response inhibitors, agents targeting vascular pathways and immune checkpoint inhibitors. Here we present the trial protocol for the WIndow-of-opportunity clinical trial platform for evaluation of novel treatment strategies in REnal cell cancer (WIRE). Methods WIRE is a Phase II, multi-arm, multi-centre, non-randomised, proof-of-mechanism (single and combination investigational medicinal product [IMP]), platform trial using a Bayesian adaptive design. The Bayesian adaptive design leverages outcome information from initial participants during pre-specified interim analyses to determine and minimise the number of participants required to demonstrate efficacy or futility. Patients with biopsy-proven, surgically resectable, cT1b+, cN0–1, cM0–1 clear cell RCC and no contraindications to the IMPs are eligible to participate. Participants undergo diagnostic staging CT and renal mass biopsy followed by treatment in one of the treatment arms for at least 14 days. Initially, the trial includes five treatment arms with cediranib, cediranib + olaparib, olaparib, durvalumab and durvalumab + olaparib. Participants undergo a multiparametric MRI before and after treatment. Vascularised and de-vascularised tissue is collected at surgery. A ≥ 30% increase in CD8+ T-cells on immunohistochemistry between the screening and nephrectomy is the primary endpoint for durvalumab-containing arms. Meanwhile, a reduction in tumour vascular permeability measured by K trans on dynamic contrast-enhanced MRI by ≥30% is the primary endpoint for other arms. Secondary outcomes include adverse events and tumour size change. Exploratory outcomes include biomarkers of drug mechanism and treatment effects in blood, urine, tissue and imaging. Discussion WIRE is the first trial using a window-of-opportunity design to demonstrate pharmacological activity of novel single and combination treatments in RCC in the pre-surgical space. It will provide rationale for prioritising promising treatments for later phase trials and support the development of new biomarkers of treatment effect with its extensive translational agenda. Trial registration ClinicalTrials.gov: NCT03741426 / EudraCT: 2018–003056-21 .

Abstract Aim To assess label compliance in prescription of medications approved for treatment of attention‐deficit/hyperactivity disorder (ADHD) in Japan at the time of this study: methylphenidate (MPH), atomoxetine, and guanfacine. Methods Retrospective descriptive study was conducted in prevalent‐user cohorts from the Japan Medical Data Center database. Patients who were prescribed a study drug between January 1, 2013 and September 30, 2018 and were in the database for ≥30 days were included. A prescription was considered compliant if all 4 criteria were satisfied: appropriate age, daily dose not exceeding the approved maximum, no contraindicated concurrent medications, and no contraindicated conditions. Results Among 17 418 patients who were prescribed a study drug during 2013‐2018, 73% were male and 53% were children (aged 85% of patients, all prescriptions were label‐compliant for dose, and for approximately 80%, all prescriptions were label‐compliant for contraindicated conditions. We did not find evidence of widespread abuse or noncompliant use of prescribed ADHD medications.