Hands-on Science. Advancing Science. Improving Education

The book herein aims to contribute to the advancement of Science to the improvement of Science Education and to an effective implementation of a sound widespread scientific literacy at all levels of society. Its chapters reunite a variety of diverse and valuable works presented in this line of thought at the 15th International Conference on Hands-on Science “Advancing Science. Improving Education

Selective Radionuclide Localisation in Primary Liver Tumours

The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with cholangiocarcinoma (CCA) and 15 patients with hepatocellullar carcinoma (HCC). Patients received one or two doses of 131I-Lipiodol via hepatic arterial injection. The mean total administered activity was 668 (SD 325) MBq in CCA and 953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to lung. The patient remained asymptomatic with no evidence of tumour 30 months from the start of treatment, whereas the remaining 7 patients exhibited tumour progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was 3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months

Association of Borderline Intellectual Functioning and Adverse Childhood Experience with adult psychiatric morbidity:Findings from a British birth cohort

Background To examine whether Borderline Intellectual Functioning (BIF) and Adverse Childhood Experiences independently predict adult psychiatric morbidity. Methods We performed a secondary analysis of longitudinal data derived from the 1970 British Birth Cohort Study to examine whether BIF and Adverse Childhood Experiences independently predict adult mental distress as measured by the Malaise Inventory. Factor analysis was used to derive a proxy measure of IQ from cognitive testing at age 10 or 5. Variables that could be indicators of exposure to Adverse Childhood Experiences were identified and grouped into health related and socio-economic related adversity. Results Children with BIF were significantly more likely than their peers to have been exposed to Adverse Childhood Experiences (BIF mean 5.90, non-BIF mean 3.19; Mann-Whitney z = 31.74, p < 0.001). As adults, participants with BIF were significantly more likely to score above the cut-off on the Malaise Inventory. We found statistically significant relationships between the number of socio-economic Adverse Childhood Experiences and poorer adult psychiatric morbidity (r range 0.104–0.141, all p < 001). At all ages the indirect mediating effects of Adverse Childhood Experiences were significantly related to adult psychiatric morbidity. Conclusions The relationship between BIF and adult psychiatric morbidity appears to be partially mediated by exposure to Adverse Childhood Experiences. Where possible, targeting Adverse Childhood Experiences through early detection, prevention and interventions may improve psychiatric morbidity in this population group

Intensive follo w-up after liver resection for colorectal liver metastases: results of combined serial tumour marker estimations and computed tomography of the chest and abdomen – a prospective study

The aim of the study was to prospectively evaluate an intensive follow-up programme using serial tumour marker estimations and contrast-enhanced computed tomography (CT) of the chest and abdomen in patients undergoing potentially curative resection of colorectal liver metastases. Seventy-six consecutive patients having undergone potentially curative resections of colorectal liver metastases in a single unit were followed up with a protocol of 3 monthly carcinoembryonic antigen and carbohydrate antigen 19-9 estimations and contrast-enhanced spiral CT of the chest, abdomen and pelvis for the first 2 years following surgery and 6 monthly thereafter. The median period of follow-up was 24 months (range 18–60). Recurrent tumour was classed as early if within 6 months of liver resection. Thirty-seven of the 76 patients (49%) developed recurrence on follow-up. Nineteen recurrences were in the liver alone (51%), 16 liver and extrahepatic (43%) and two extrahepatic alone (6%). Of the 19 patients with isolated liver recurrence, eight developed within 6 months of liver resection none of which were resectable. Of the 11 recurrences after 6 months, five (45%) were resectable. Of the 37 recurrences, CT indicated recurrence despite normal tumour markers in 19 patients. Tumour markers suggested recurrence before imaging in 12 and concurrently with imaging in 6. In the 12 patients who presented with elevated tumour markers before imaging, there was a median lag period of 3 months (range 1–21) in recurrence being detected on further serial imaging. Seventeen patients who developed recurrence had normal tumour markers before initial resection of their liver metastases. Of these 17, 10 (58%) had an elevation of tumour markers associated with recurrence. Over a median follow-up of 2 years following liver resection, the use of CT or tumour markers alone would have failed to demonstrate early recurrence in 12 and 18 patients respectively. A combination of tumour markers and CT detected significantly more (P<0.05) recurrence than either modality alone. Tumour markers and CT should be used in combination in the follow-up of patients with resected colorectal liver metatases, including patients whose markers are normal at the time of initial liver resection

Spanish cohort of VEXAS syndrome : clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion