GRANTSISM: An Excel™ ice sheet model for use in introductory Earth science courses

GRANTISM (GReenland and ANTarctic Ice Sheet Model) is an educational Excel™ model introduced by Pattyn (2006). Here, GRANTISM is amended to simulate the Svalbard-Barents-Sea Ice Sheet during the Last Glacial Maximum, an analogue for the contemporary West Antarctic Ice Sheet. A new name, “GRANTSISM,” is suggested; the added S represents Svalbard. GRANTSISM introduces students of bachelor's or master's programs in Earth sciences (first or second cycle program in the Bologna system for higher education), but with little or no background in numerical modeling, to basic ice sheet modeling. GRANTSISM provides hands-on learning experiences related to ice sheet dynamics in response to climate forcing, and fosters understanding of processes and feedbacks. GRANTSISM was successfully used in noncompulsory courses in which students have been able to reproduce paleo-ice sheet evolution scenarios discussed here as examples. Students progressed further by designing, developing, and analyzing their own modeling scenarios. Here, we describe GRANTSISM and report on how learning activities with GRANTSISM were assessed by students who had no prior experience in ice sheet modeling. The response rate for a noncompulsory survey of the learning activity was less than 40%. A subsequent control experiment with a compulsory survey, however, showed the same patterns of answers, so the student response is considered representative. First, GRANTSISM is concluded to be a highly attractive tool to introduce learners with an interest in ice sheet behavior to ice sheet modeling. Second, it triggers an interest for more in-depth learning experiences related to numerical ice sheet modeling

Diagnostic hysteroscopy and saline infusion sonography in the diagnosis of intrauterine abnormalities: an assessment of patient preference

This study was conducted to assess whether women would prefer to undergo saline infusion sonography (SIS) or office hysteroscopy for the investigation of the uterine cavity. In a randomised controlled trial, 100 patients underwent SIS or office hysteroscopy for assessing patients' pain scores. After the investigation, 92 of them were asked to fill out an anonymous questionnaire addressing their preference regarding the method of evaluation and treatment of the uterine cavity. A control group, consisting of 50 women who never underwent SIS or office hysteroscopy, was also asked to complete an identical questionnaire. The questionnaire was completed by 113 women (83.7%). Twenty-four (21.2%) women would opt for SIS, whereas 52 (46.0%) would opt for office hysteroscopy, and 37 (32.7%) had no preference. If therapy would be necessary, 48.7% of the women would opt for an outpatient treatment, whereas 33.0% of the women would prefer treatment under general anaesthesia. Despite the fact that SIS is less painful, the majority of the women prefer office hysteroscopy. Additionally, therapy in an outpatient setting is preferred to a day case setting

Wnt target genes identified by DNA microarrays in immature CD34+ thymocytes regulate proliferation and cell adhesion

The thymus is seeded by very small numbers of progenitor cells that undergo massive proliferation before differentiation and rearrangement of TCR genes occurs. Various signals mediate proliferation and differentiation of these cells, including Wnt signals. Wnt signals induce the interaction of the cytoplasmic cofactor beta-catenin with nuclear T cell factor (TCF) transcription factors. We identified target genes of the Wnt/beta-catenin/TCF pathway in the most immature (CD4-CD8-CD34+) thymocytes using Affymetrix DNA microarrays in combination with three different functional assays for in vitro induction of Wnt signaling. A relatively small number (approximately 30) of genes changed expression, including several proliferation-inducing transcription factors such as c-fos and c-jun, protein phosphatases, and adhesion molecules, but no genes involved in differentiation to mature T cell stages. The adhesion molecules likely confine the proliferating immature thymocytes to the appropriate anatomical sites in the thymus. For several of these target genes, we validated that they are true Wnt/beta-catenin/TCF target genes using real-time quantitative PCR and reporter gene assays. The same core set of genes was repressed in Tcf-1-null mice, explaining the block in early thymocyte development in these mice. In conclusion, Wnt signals mediate proliferation and cell adhesion, but not differentiation of the immature thymic progenitor pool

Complement activation during OKT3 treatment: A possible explanation for respiratory side effects

Complement activation during OKT3 treatment: A possible explanation for respiratory side effects. Respiratory side effects that sometimes occur during treatment with anti-CD3 MAb OKT3 might result from pulmonary sequestration of activated neutrophils. Therefore, we studied complement activation in relation to activation and pulmonary sequestration of neutrophils during antirejection treatment with OKT3. In each of nine patients studied, plasma C3a-desarg and C4b/c levels increased compared with pretreatment values already in the first sample taken 15 minutes after the first dose of OKT3 (P < 0.05), with peak values at 15 and 30 minutes, respectively. Levels of neutrophil degranulation product elastase (complexed to α1-antitrypsin) also increased already at 15 minutes after the first dose of OKT3 (P < 0.05), which is before elevated levels of the cytokines TNFα, IL-6 or IL-8 were detectable. In contrast, upon subsequent OKT3 administrations or in the control group treated with methylprednisolone, neither complement activation, cytokine release nor neutrophil degranulation occurred. In five studied patients treated with OKT3, pulmonary sequestration of radiolabeled granulocytes was observed from 3 until 15 minutes after the first dose of OKT3, together with peripheral blood granulocytopenia, which lasted at least 30 minutes. In conclusion, we demonstrate a simultaneous activation of complement and pulmonary sequestration of activated granulocytes immediately following the first dose of OKT3. These phenomena may be involved in the development of respiratory side effects complicating this therapy

Tissue Stromal Vascular Fraction Improves Early Scar Healing:A Prospective Randomized Multicenter Clinical Trial

Background Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. The tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound-healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling.Objectives The aim of this study was to investigate the hypothesis that tSVF reduces postsurgical scar formation.Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of 1 breast and a placebo injection in the contralateral breast to serve as an intrapatient control. Primary outcome was scar quality measure by the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes were obtained from photographic evaluation and histologic analysis of scar tissue samples.Results Thirty-four of 40 patients completed follow-up. At 6 months postoperation, injection of tSVF had significantly improved postoperative scar appearance as assessed by the POSAS questionnaire. No difference was observed at 12 months postoperation. No improvement was seen based on the evaluation of photographs and histologic analysis of postoperative scars between both groups.Conclusions Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperation, without any noticeable advantageous effects seen at 12 months.</p

Use of antihypertensive medication after ischemic stroke in young adults and its association with long-term outcome

Background: Knowledge on the use of secondary preventive medication in young adults is limited. Methods: We included 936 first-ever ischemic stroke 30-day survivors aged 15-49, enrolled in the Helsinki Young Stroke Registry, 1994-2007. Follow-up data until 2012 came from Finnish Care Register, Statistics Finland, and Social Insurance Institution of Finland. Usage thresholds were defined as non-users, low (prescription coverage 80%). Adjusted Cox regression allowed assessing the association of usage with all-cause mortality and recurrent vascular events. Results: Of our patients, 40.5% were non-users, 7.8% had low usage, 11.8% intermediate usage and 40.0% high usage. Median follow-up was 8.3 years. Compared to non-users, risk of mortality and recurrent stroke or TIA was lower for patients with low-intermediate (HR 0.40, 95% CI 0.22-0.65; HR 0.31, 95% CI 0.18-0.53) and high usage (HR 0.25, 95% CI 0.15-0.42; HR 0.30, 95% CI 0.19-0.46), after adjustment for confounders. Conclusions: Use of antihypertensives was suboptimal in one-third of patients in whom antihypertensives were initially prescribed. Users were at lower risk of mortality and recurrent stroke or TIA compared to non-users.Key Messages The use of antihypertensive medication is suboptimal in one-third of patients in whom antihypertensive medication was initially prescribed after ischemic stroke at young age. The risk of mortality and recurrent stroke or TIA is lower for users of antihypertensive medication after ischemic stroke at young age compared to non-users, after adjustment for relevant confounders including pre-existing hypertension and prior use of antihypertensive medication. Specific guidelines on antihypertensive medication use after ischemic stroke at young age are lacking. However, our results may motivate doctors and patients in gaining better usage of antihypertensive medication, since better usage was associated with more favorable outcome in this study.Peer reviewe

Cost-Effectiveness of Radiofrequency Denervation for Patients With Chronic Low Back Pain:The MINT Randomized Clinical Trials

OBJECTIVES: To evaluate the cost-effectiveness of radiofrequency denervation when added to a standardized exercise program for patients with chronic low back pain. METHODS: An economic evaluation was conducted alongside 3 pragmatic multicenter, nonblinded randomized clinical trials (RCTs) in The Netherlands with a follow up of 52 weeks. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain; a positive diagnostic block at the facet joints (n = 251), sacroiliac (SI) joints (n = 228), or a combination of facet joints, SI joints, and intervertebral discs (n = 202); and were unresponsive to initial conservative care. Quality-adjusted life-years (QALYs) and societal costs were measured using self-reported questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to estimate statistical uncertainty. RESULTS: After 52 weeks, no difference in costs between groups was found in the facet joint or combination RCT. The total costs were significantly higher for the intervention group in the SI joint RCT. The maximum probability of radiofrequency denervation being cost-effective when added to a standardized exercise program ranged from 0.10 in the facet joint RCT to 0.17 in the SI joint RCT irrespective of the ceiling ratio, and 0.65 at a ceiling ratio of €30 000 per QALY in the combination RCT. CONCLUSIONS: Although equivocal among patients with symptoms in a combination of the facet joints, SI joints, and intervertebral discs, evidence suggests that radiofrequency denervation combined with a standardized exercise program cannot be considered cost-effective from a societal perspective for patients with chronic low back pain originating from either facet or SI joints in a Dutch healthcare setting

Effect of radiofrequency denervation on pain intensity among patients with chronic lowback pain the mint randomized clinical trials

IMPORTANCE Radiofrequency denervation is a commonly used treatment for chronic low back pain, but high-quality evidence for its effectiveness is lacking. OBJECTIVE To evaluate the effectiveness of radiofrequency denervation added to a standardized exercise program for patients with chronic low back pain. DESIGN, SETTING, AND PARTICIPANTS Three pragmatic multicenter, nonblinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain (Mint study) were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral disks (combination trial, 202 participants) and were unresponsive to conservative care. INTERVENTIONS All participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This is usually a 1-Time procedure, but the maximum number of treatments in the trial was 3. MAIN OUTCOMES AND MEASURES The primary outcomewas pain intensity (numeric rating scale, 0-10; whereby 0 indicated no pain and 10 indicated worst pain imaginable) measured 3 months after the intervention. The prespecified minimal clinically important difference was defined as 2 points or more. Final follow-up was at 12 months, ending October 2015. RESULTS Among 681 participants who were randomized (mean age, 52.2 years; 421 wom

Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multilineage development in the human thymus

T cell development in the mouse thymus has been studied extensively, but less is known regarding T cell development in the human thymus. We used a combination of single-cell techniques and functional assays to perform deep immune profiling of human T cell development, focusing on the initial stages of prelineage commitment. We identified three thymus-seeding progenitor populations that also have counterparts in the bone marrow. In addition, we found that the human thymus physiologically supports the development of monocytes, dendritic cells, and NK cells, as well as limited development of B cells. These results are an important step toward monitoring and guiding regenerative therapies in patients after hematopoietic stem cell transplantation