Search

Background: Abdominal infections account for substantial morbidity after pancreatoduodenectomy. Contaminated bile is the presumed main risk factor, and prolonged antibiotic prophylaxis might prevent these complications. This study compared organ/space infection (OSIs) rates in patients receiving perioperative versus prolonged antibiotic prophylaxis after pancreatoduodenectomy. Methods: Patients undergoing pancreatoduodenectomy in two Dutch centers between 2016 and 2019 were included. Perioperative prophylaxis was compared prolonged prophylaxis (cefuroxime and metronidazole for five days). The primary outcome was an isolated OSI: an abdominal infection without concurrent anastomotic leakage. Odds ratios (OR) were adjusted for surgical approach and pancreatic duct diameter. Results: OSIs occurred in 137 out of 362 patients (37.8%): 93 patients with perioperative and 44 patients with prolonged prophylaxis (42.5% versus 30.8%, P = 0.025). Isolated OSIs occurred in 38 patients (10.5%): 28 patients with perioperative and 10 patients with prolonged prophylaxis (12.8% versus 7.0%, P = 0.079). Bile cultures were obtained in 198 patients (54.7%). Patients with positive bile cultures showed higher isolated OSI rates with perioperative compared to prolonged prophylaxis (18.2% versus 6.6%, OR 5.7, 95% CI: 1.3–23.9). Conclusion: Prolonged antibiotics after pancreatoduodenectomy are associated with fewer isolated OSIs in patients with contaminated bile and warrant confirmation in a randomised controlled trial (Clinicaltrials.gov NCT0578431).

INTRODUCTION: Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking.METHODS: We systematically searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach.RESULTS: Seven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52-0.85; P = 0.001; I 2 = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53-1.12; P = 0.18; I 2 = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44-0.85; P = 0.004; I 2 = 59%). The GRADE certainty of evidence was high for the outcome of OS. CONCLUSIONS: Neoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer.

BACKGROUND: The aim of this study was to determine pancreatic surgery specific short- and long-term complications of pediatric, adolescent and young adult (PAYA) patients who underwent pancreatic resection, as compared to a comparator cohort of adults.METHODS: A nationwide retrospective cohort study was performed in PAYA patients who underwent pancreatic resection between 2007 and 2016. PAYA was defined as all patients RESULTS: A total of 230 patients were included in the PAYA cohort (112 distal pancreatectomies, 99 pancreatoduodenectomies), and 2526 patients in the comparator cohort. For pancreatoduodenectomy, severe morbidity (29.3% vs. 28.6%; P = 0.881), in-hospital mortality (1% vs. 4%; P = 0.179) and textbook outcome (62% vs. 58%; P = 0.572) were comparable between the PAYA and the comparator cohort. These outcomes were also similar for distal pancreatectomy. After pancreatoduodenectomy, new-onset diabetes mellitus (8% vs. 16%) and exocrine pancreatic insufficiency (27% vs. 73%) were lower in the PAYA cohort when compared to adult literature.CONCLUSION: Pancreatic surgery-specific complications were comparable with patients ≥40 years. Development of endocrine and exocrine insufficiency in PAYA patients who underwent pancreatoduodenectomy, however, was substantially lower compared to adult literature.

Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

Introduction Coronavirus disease 2019 (COVID-19) has a high burden on the healthcare system. Prediction models may assist in triaging patients. We aimed to assess the value of several prediction models in COVID-19 patients in the emergency department (ED). Methods In this retrospective study, ED patients with COVID-19 were included. Prediction models were selected based on their feasibility. Primary outcome was 30-day mortality, secondary outcomes were 14-day mortality and a composite outcome of 30-day mortality and admission to medium care unit (MCU) or intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). Results We included 403 patients. Thirty-day mortality was 23.6%, 14-day mortality was 19.1%, 66 patients (16.4%) were admitted to ICU, 48 patients (11.9%) to MCU, and 152 patients (37.7%) met the composite endpoint. Eleven prediction models were included. The RISE UP score and 4 C mortality scores showed very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84, 95% CI 0.79-0.88 for both), significantly higher than that of the other models. Conclusion The RISE UP score and 4 C mortality score can be used to recognise patients at high risk for poor outcome and may assist in guiding decision-making and allocating resources.

The prognosis of kidney transplant recipients (KTR) with vascular calcification (VC) in the aorto-iliac arteries is unclear. We performed a systematic review and meta-analysis to investigate their survival outcomes. Studies from January 1st, 2000 until March 5th, 2019 were included. Outcomes for meta-analysis were patient survival, (death-censored) graft survival and delayed graft function (DGF). Twenty-one studies were identified, eight provided data for meta-analysis. KTR with VC had a significantly increased mortality risk [1-year: risk ratio (RR) 2.19 (1.39–3.44), 5-year: RR 2.28 (1.86–2.79)]. The risk of 1-year graft loss was three times higher in recipients with VC [RR 3.15 (1.30–7.64)]. The risk of graft loss censored for death [1-year: RR 2.26 (0.58–2.73), 3-year: RR 2.19 (0.49–9.82)] and the risk of DGF (RR 1.24, 95% CI 0.98–1.58) were not statistically different. The quality of the evidence was rated as very low. To conclude, the presence of VC was associated with an increased mortality risk and risk of graft loss. In this small sample size, no statistical significant association between VC and DGF or risk of death-censored graft loss could be demonstrated. For interpretation of the outcomes, the quality and sample size of the evidence should be taken into consideration.

Background. FOLFIRINOX chemotherapy is the current Dutch standard of care for locally advanced (LAPC) and metastatic pancreatic cancer (PDAC) patients with good performance status. The objective of this study was to evaluate real-world response rates and survival in advanced PDAC and to assess conditional survival after FOLFIRINOX. Methods. A multicenter, retrospective cohort study was conducted in four hospitals in the Netherlands. Consecutive patients with LAPC or metastatic PDAC, treated with FOLFIRINOX, were included. Results. Between 2012 and 2018, 284 patients were included: n = 136 with LAPC and n = 148 with metastatic PDAC. Objective response rates were similar in both the groups: 14.0% in LAPC and 18.2% in metastatic patients. The disease control rate was higher in LAPC patients (77.2%) compared to metastatic PDAC (51.4%, P < 0.001 ). Median overall survival (OS) in LAPC patients was 12.7 months (95% CI 11.4–14.1 months). Their 2-year survival probability increased from 14% to 26% one year after the completion of FOLFIRINOX. Median OS in metastatic PDAC patients was 8.1 months (95% CI 6.5–9.6 months); 2-year survival probability increased from 10% to 29% after one year. Discussion. Our study provides real-world estimates of response rates, survival, and conditional survival in patients with advanced PDAC treated with FOLFIRINOX. These results are useful for patient counseling and clinical decision making.

OBJECTIVES: The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS). METHODS: This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010-2017). In addition, a systematic literature search was performed. RESULTS: In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized. CONCLUSIONS: Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized.

Biofuel crops, including annuals such as maize (Zea mays L.), soybean [Glycine max (L.) Merr.], and canola (Brassica napus L.), as well as high‐biomass perennial grasses such as miscanthus (Miscanthus × giganteus J.M. Greef & Deuter ex Hodkinson & Renvoiz), are candidates for sustainable alternative energy sources. However, large‐scale conversion of croplands to perennial biofuel crops could have substantial impacts on regional water, nutrient, and C cycles due to the longer growing seasons and differences in rooting systems compared with most annual crops. However, due to the limited tools available to nondestructively study the spatiotemporal patterns of root water uptake in situ at field scales, these differences in crop water use are not well known. Geophysical imaging tools such as electrical resistivity (ER) reveal changes in water content in the soil profile. In this study, we demonstrate the use of a novel coupled hydrogeophysical approach with both time domain reflectometry soil water content and ER measurements to compare root water uptake and soil properties of an annual crop rotation with the perennial grass miscanthus, across three growing seasons (2009–2011) in southwest Michigan, USA. We estimated maximum root depths to be between 1.2 and 2.2 m, with the vertical distribution of roots being notably deeper in 2009 relative to 2010 and 2011, likely due to the drought conditions during that first year. Modeled cumulative ET of both crops was underestimated (2–34%) relative to estimates obtained from soil water drawdown in prior studies but was found to be greater in the perennial grass than the annual crops, despite shallower modeled rooting depths in 2010 and 2011.

This qualitative study explores the youth-initiated mentoring (YIM) approach for youth at risk for out-of-home placement. In this approach, a youth nominates someone from within their social network, and positions this person as a YIM to function as an ally for the youth and as a partner for parents and professional caregivers. Through interviews with six youth, six YIMs, and seven parents ( N = 19), we examined the positioning of a YIM and sustainability. The results indicated that attitudes from participants toward asking someone or being asked to become a YIM varied from enthusiastic to cautious. Participants reported increased contact intensity and relationship quality. Two parents did not experience YIM as beneficial. Most participants expected that the YIM–mentee relationship lasts after professional care terminates. The results reveal that YIM is experienced as an ally, but it also has the potential to increase relational conflicts between social network members.

Background: The value of neoadjuvant radiotherapy (RT) after 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. Methods: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012–2019) from the Trans-Atlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score ≥2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (≤70 vs >70 years), WHO performance score (0 vs 1), tumor size (0–20 vs 21–40 vs >40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1–4 vs 5–8 vs >8), and baseline CA 19-9 level (≤500 vs >500 U/mL). Primary outcome was overall survival (OS) from diagnosis. Results: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score–matched. After matching, median OS was 26.2 months (95% CI, 24.0–38.4) with RT versus 32.8 months (95% CI, 25.3–42.0) without RT (P=.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P=.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (>1 mm) (70.6% vs 64.8%; P=.51), more node-negative disease (57.3% vs 37.6%; P=.01), and more major pathologic response with P=.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P=.92). Conclusions: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data.

TPS4171 Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials (including the Dutch PREOPANC trial) have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including gemcitabine-based chemoradiotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether total neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine (i.e. the intervention arm of the PREOPANC trial) in patients with resectable or borderline resectable pancreatic cancer. Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) added during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients, assuming an accrual period of 3 years and 1.5 years follow-up. Between June 2018 and January 2021, 375 patients were enrolled in 20 centers in the Netherlands and accrual is complete. Final analyses are expected at the end of 2022. Netherlands Trial Register: NL7094. Clinical trial information: NL7094.

Background and Aims B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study aimed to identify minimal residual autoimmunity (MRA) in the B-cell compartment of AAV patients treated with RTX. Method EuroFlow-based highly-sensitive flow cytometry (HSFC) was employed to study B-cell and plasma cell (PC) subsets in-depth in AAV patients before and after RTX treatment. Additionally, peripheral blood mononuclear cells (PBMCs) of these RTX-treated AAV patients were cultured and in vitro stimulated with CpG, IL-2, and IL-21 to induce antibody-secreting cells (ASC). (ANCA)-IgG was measured in these supernatants by ELISA. Results By employing EuroFlow-based HSFC, we detected circulating CD19+ B-cells at all timepoints after RTX treatment, in contrast to conventional low-sensitive flow cytometry. Pre-germinal center (Pre-GC) B-cells, memory B-cells and CD20+CD138− plasmablasts (PBs) were rapidly and strongly reduced, while CD20−CD138− PrePC and CD20-CD138+ mature (m)PCs were reduced slower and remained detectable. Both memory B-cells and CD20− PCs remained detectable after RTX. Serum ANCA-IgG decreased significantly upon RTX. Changes in ANCA levels strongly correlated with changes in naive, switched CD27+ and CD27− (double-negative) memory B-cells, but not with plasma cells. Lastly, we demonstrated in vitro ANCA production by AAV PBMCs, 24 and 48 weeks after RTX treatment reflecting MRA in the memory compartment of AAV patients. Conclusion We demonstrated that RTX induced strong reductions in circulating B-cells, but never resulted in complete B-cell depletion. Despite strongly reduced B-cell numbers after RTX, ANCA-specific memory B-cells were still detectable in AAV patients. Thus, MRA is identifiable in AAV and can provide a potential novel approach in personalizing RTX treatment in AAV patients.

ObjectiveTo mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed RISE UP score has very good discriminatory value with respect to short-term mortality in older patients in the emergency department (ED). It consists of six items: age, abnormal vital signs, albumin, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and bilirubin. We hypothesized that the RISE UP score could have discriminatory value with regard to 30-day mortality in ED patients with COVID-19.SettingTwo EDs of the Zuyderland Medical Centre (MC), secondary care hospital in the Netherlands.ParticipantsThe study sample consisted of 642 adult ED patients diagnosed with COVID-19 between March 3rd until May 25th 2020. Inclusion criteria were: 1) admission to the hospital with symptoms suggestive of COVID-19, and 2) positive result of the polymerase chain reaction (PCR), or (very) high suspicion of COVID-19 according to the chest computed tomography (CT) scan.OutcomePrimary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU).ResultsWithin 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value with respect to 30-day mortality (AUC 0.77, 95% CI 0.73-0.81), and to the composite outcome (AUC 0.72, 95% CI 0.68-0.76). Patients with RISE UP scores below 10% (121 patients) had favourable outcome (0% mortality and 5% ICU admissions). Patients with a RISE UP score above 30% (221 patients) were at high risk of adverse outcome (46.6% mortality and 19% ICU admissions).ConclusionThe RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome, and may help guiding decision-making and allocating healthcare resources.

IntroductionCoronavirus disease 2019 (COVID-19) has a high burden on the healthcare system and demands information on the outcome early after admission to the emergency department (ED). Previously developed prediction models may assist in triaging patients when allocating healthcare resources. We aimed to assess the value of several prediction models when applied to COVID-19 patients in the ED.MethodsAll consecutive COVID-19 patients who visited the ED of a combined secondary/tertiary care center were included. Prediction models were selected based on their feasibility. The primary outcome was 30-day mortality, secondary outcomes were 14-day mortality, and a composite outcome of 30-day mortality and admission to the medium care unit (MCU) or the intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC).ResultsA total of 403 ED patients were diagnosed with COVID-19. Within 30 days, 95 patients died (23.6%), 14-day mortality was 19.1%. Forty-eight patients (11.9%) were admitted to the MCU, 66 patients (16.4%) to the ICU and 152 patients (37.7%) met the composite endpoint. Eleven models were included: RISE UP score, 4C mortality score, CURB-65, MEWS, REMS, abbMEDS, SOFA, APACHE II, CALL score, ACP index and Host risk factor score. The RISE UP score and 4C mortality score showed a very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84 respectively, 95% CI 0.79-0.88 for both), for 14-day mortality (AUC 0.83, 95% CI: 0.79-0.88, for both) and for the composite outcome (AUC 0.79 and 0.77 respectively, 95% CI 0.75-0.84). The discriminatory performance of the RISE UP score and 4C mortality score was significantly higher compared to that of the other models.ConclusionThe RISE UP score and 4C mortality score have good discriminatory performance in predicting adverse outcome in ED patients with COVID-19. These prediction models can be used to recognize patients at high risk for short-term poor outcome and may assist in guiding clinical decision-making and allocating healthcare resources.

We employ early-time signal (ETS) amplitude analysis of ground-penetrating radar (GPR) data collected during a controlled irrigation study in a sandy soil agricultural field. We carried out two irrigation experiments, one with 250 MHz, 400 MHz, and 1000 MHz GPR antennae, and a second with 1000 MHz antennae only. Supporting data on the effects of irrigation on soil water content were provided by direct measurement and the extent of soil wetting by electrical resistivity tomography (ERT). We compare two statistics used to quantify the ETS: (1) average envelope amplitude (AEA), and (2) carrier frequency amplitude (CFA), which has recently been proposed as a more robust alternative to AEA analysis. We also investigate the dependence of these statistics on the time window used to calculate them. In the first experiment, both statistics successfully relate the GPR ETS to increasing water content for the 250 MHz and 400 MHz antennae, although the CFA was sensitive to changes across a wider range of moisture contents. The 1000 MHz data did not show the expected relationships, especially in the CFA data. This is likely due to signal associated with shallow reflections. In the second experiment, the effect of this signal was removed by using a shorter, earlier time window when calculating ETS statistics, rather than using the first positive half cycle (FPHC). Our work suggests the cautious use of time window for ETS analysis, as the FPHC may not be an acceptable choice when shallow reflectors are present. At our field site, the AEA was less affected than time window selection while CFA appears more robust over a wider range of soil moisture content values.

Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. We present a case of a 26-year-old man who presented to our hospital after intentionally ingesting 30 tablets of Triumeq. An intoxication with Triumeq can lead to several side effects. An overdose of abacavir and lamivudine can cause mitochondrial toxicity and lactic acidosis. An intoxication with dolutegravir appears to be relatively harmless. As Triumeq will be used on a regular basis as treatment for patients with HIV-1 infection, these intoxications are expected to be encountered more often.

Introduction/Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) to guide physicians in clinical management. Methodology Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3–37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth (figure 1). Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n=62) and advanced stage (n=15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n=62, figure 2), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n=45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusion Survival of patients diagnosed with early stage HL during pregnancy appears not statistically different from matched non-pregnant controls, however future prospective research is necessary to investigate the efficacy of chemotherapy during pregnancy. Awareness of complications as preterm delivery and low birth weight is important. Disclosure This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. We are grateful to the Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) for their support. FA is senior clinical investigator of the F.W.O. MJH was supported by Charles University research project Progres Q28 and Q34 and by grant MH CZ - DRO (‘Kralovske Vinohrady University Hospital - FNKV, 00064173’). The funding sources did not influence study design. There are no conflicting interests to declare.

Background. Patients with end-stage renal disease and aortoiliac stenosis are often considered ineligible for kidney transplantation, although kidney transplantation has been acknowledged as the best therapy for end-stage renal disease. The clinical outcomes of kidney transplantation in patients with aortoiliac stenosis are not well-studied. This study aimed to assess the impact of aortoiliac stenosis on graft and patient survival. Methods. This retrospective, single-center study included kidney transplant recipients transplanted between January 1, 2000, and December 31, 2016, who received contrast-enhanced imaging. Patients with aortoiliac stenosis were classified using the Trans-Atlantic Inter-Society Consensus (TASC) II classification and categorized as having TASC II A/B lesions or having TASC II C/D lesions. Patients without aortoiliac stenosis were functioning as controls. Results. A total number of 374 patients was included in this study (n = 88 with TASC II lesions, n = 286 as controls). Death-censored graft survival was similar to the controls. Patient and uncensored graft survival was decreased in patients with TASC II C/D lesions (log-rank test P < 0.001). Patients with TASC II C/D lesions had a higher risk of 90-day mortality (hazard ratio, 3.96; 95% confidence interval, 1.12-14.04). In multivariable analysis, having a TASC II C/D lesion was an independent risk factor for mortality (hazard ratio, 3.25; 95% confidence interval, 1.87-5.67; P < 0.001). Having any TASC II lesion was not a risk factor for graft loss (overall P = 0.282). Conclusions. Kidney transplantation in patients with TASC II A/B is feasible and safe without increased risk of perioperative mortality. TASC II C/D decreases patient survival. Death-censored graft survival is unaffected.

Supplemental material, supplementary_material for An Exploration of Youth–Parent–Mentor Relationship Dynamics in a Youth-Initiated Mentoring Intervention to Prevent Out-of-Home Placement by L. Van Dam, R. E. Bakhuizen, S. E. O. Schwartz, M. De Winter, M. Zwaanswijk, I. B. Wissink and G. J. J. M. Stams in Youth & Society

Core Ideas Early‐time analysis extends the use of GPR to attenuating, clay‐rich soils. Early‐time GPR can upscale point measurements of water content when calibrated. Ongoing work studies alternative statistics to represent the early‐time signal. We used a recent ground‐penetrating radar (GPR) methodology, early‐time amplitude analysis, with the goal of monitoring changes in soil water content (SWC) in response to irrigation in clayey soils. We hypothesized that early‐time analysis could be used to monitor changes in SWC in clay‐rich soil where ground wave and reflection‐based GPR methods traditionally fail. An overnight irrigation experiment was performed in a 20‐ by 14‐m section of natural grassland at the Samford Ecological Research Facility in southeastern Queensland, Australia. Both GPR reflection surveys and ground wave velocity analysis were ineffective at the site due to the signal attenuation associated with the clay‐rich soil. We collected daily GPR and time‐domain reflectometry (TDR) data sets during a 5‐d period in August 2014, with soil samples collected for gravimetric analysis at the conclusion of data collection. The GPR data display a clear response of the early‐time signal amplitude to changes in SWC. The GPR data sets exhibit a strong correlation with SWC, as measured by TDR and gravimetric analysis of soil cores, which is consistent with the dependence of GPR early‐time amplitude on relative permittivity. The results suggest that the early‐time method can be used to obtain spatially distributed information on subsurface moisture content in clay‐rich soils.

Large-scale sediment deformation structures formed by glaciotectonic processes have been identified south of Ludington, USA. Here, several apparent clay diapirs rise from below beach level to near the top of an approximately 60 m high bluff along the eastern shore of Lake Michigan. Throughout the area, the surface topography and locations of springs indicate a complicated subsurface structure and a preferred pattern of groundwater drainage. Since public borehole information is sparse, it is not known whether the structures exposed in the bluff are true diapirs or ridges, and if the latter, what is their orientation. In this paper we present the results of field, laboratory, and modeling studies to characterize the inland extent and orientation of these deformation structures using galvanic-source electrical geophysical methods. We exploit the large electrical contrast between a sandy sedimentary layer and an underlying clayey silt sedimentary layer in which the deformation occurred. Constant-spread traverses and multi-electrode tomographic data demonstrate that at least one of the narrow structures extends a significant distance inland.

Quantifying the unfrozen water content of permafrost is critical for assessing impacts of surface warming on the reactivation of groundwater flow and release of greenhouse gasses from degrading permafrost. Unfrozen water content was determined along a ~12 km transect in the Adventdalen valley in Svalbard, an area with continuous permafrost, using surface nuclear magnetic resonance and controlled source audio-magnetotelluric data. This combination of measurements allowed for differentiation of saline from fresh, and frozen from unfrozen pore water. Above the limit of Holocene marine transgression no unfrozen water was detected, associated with high electrical resistivity. Below the marine limit, within several kilometers of the coast, up to ~10% unfrozen water content was detected, associated with low resistivity values indicating saline pore water. These results provide evidence for unfrozen water within continuous, thick permafrost in coastal settings, which has implications for groundwater flow and greenhouse gas release in similar Arctic environments.

Plot- to field-scale root distribution data are relatively rare and difficult to measure with traditional methods. Nevertheless, these data are needed to accurately model root water uptake (RWU) processes within agronomic, hydrologic, and terrestrial biosphere models. New tools are needed to effectively observe root distributions and model dynamic root growth processes. In the past decade, geophysical tools have increasingly been used to study the vadose zone, and hydrogeophysical inversions have shown promise to noninvasively characterize water dynamics. In such an approach, the hydrology is modeled and hydrological data are inverted with the geophysical data, constraining the geophysical inversion results and decreasing uncertainty and the number of nonunique solutions. In this study, we developed and tested a coupled hydrogeophysical inversion approach that uses electrical resistivity data to estimate soil hydraulic, petrophysical, and root dynamic parameters. This builds on prior research that used either a coupled hydrogeophysical inversion to estimate soil hydraulic parameters only, or a hydrological inversion to estimate root distribution or root water uptake parameters. Our results indicate that under the conditions tested, this approach accurately captures root water dynamics and soil hydraulic parameters. This opens up opportunities to noninvasively image a variety of root distributions and soil systems, better understand the dynamics of RWU processes, and improve estimates of transpiration for systems models.

Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P

Oral presentation Eliminating Occupational Disease: Translating Research into Action, EPICOH 2017, EPICOH 2017, 28–31 August 2017, Edinburgh, UK. Objective To identify the main determinants of occupational diseases at both the individual and the population level. Methods This study used data from the Dutch National Working Conditions Survey (NWCS 2014; occupational disease confirmed by a doctor, self-reported, employees). Multivariate regression analyses were performed to assess the independent association at the individual level (OR) between each determinant and the presence of at least one occupational disease. Additionally, the Population Attributable Risk (PAR) was calculated for each determinant in order to assess the risk at the population level as well. Results The top three determinants that may be influenced and also contributed most to musculoskeletal occupational diseases, were the same at the individual and the population level: ‘Repetitive movements‘ (PAR=40.0%; OR=2.25), ‘Working in uncomfortable positions/bad posture‘ (PAR=17.7%; OR=1.62), and ‘High job demands‘ (PAR=17.6%; OR=1.57). Determinants that contributed most to psychological occupational diseases were also the same on the individual and population level: ‘Low engagement‘ (PAR=33.6%; OR=2.27), ‘Conflict with supervisor‘ (PAR=16.7%; OR=1.51), and ‘High emotional demands‘ (PAR=14.4%; OR=2.85). Conclusion These determinants may be influenced through education, measures and/or policies at the workplace or on higher levels, in order to decrease the prevalence of occupational diseases in the working population.

Introduction Female sex workers (FSW) are at risk for HPV-induced diseases but are currently not targeted by the HPV vaccination program in the Netherlands. We explored the determinants of their intention to get vaccinated against HPV in case vaccination would be offered to them in the near future. Methods In 2016, FSW aged >18 years having an STI consultation with the Prostitution and Health Centre (P and G292) in Amsterdam, either at the clinic or at their working location, were invited to complete a questionnaire assessing the socio-psychological determinants of their HPV vaccination intention (scale ranging from −3 to +3). Determinants of HPV vaccination intention were assessed with uni- and multivariable linear regression. Additionally, we explored the effect of out-of-pocket payment on intention. Results Between May and September 2016, 293 FSW participated; 98 (34%) worked in clubs/private houses/massage salons, 111 (38%) worked at ‘prostitution windows’, and 81 (28%) worked as escorts or from home. The median age was 29 years (IQR 25–37). HPV vaccination intention was relatively high (mean 2.0; 95% CI:1.8–2.2). In multivariable analysis attitude (β=0.6; 95% CI:0.5–0.7), descriptive norm (β=0.3; 95% CI:0.2–0.4), self-efficacy (β=0.2; 95% CI:0.1–0.3), beliefs (β=0.1; 95% CI:0.0–0.2) and anticipated regret (β=0.1; 95% CI:0.0–0.2) were the strongest predictors of HPV vaccination intention. Demographic variables did not improve the multivariable regression model. The explained variance in the model (R2) was 0.54. HPV vaccination intention decreased significantly when vaccination would require out-of-pocket payment (€50 mean: 1.2 (95%CI: 0.8–1.7); €100 mean: 1.6 (95%CI: 1.1–2.0); € 200 mean: 1.0 (95%CI: 0.5–1.5); € 350 mean: 0.2 (95%CI: −0.2–0.7). Conclusion HPV vaccination intention among FSW in Amsterdam appears to be very high. The included socio-psychological factors explained most of the variance in HPV vaccination intention among FSW. Out-of-pocket payment had a significant negative effect on HPV vaccination intention.

Summary We propose a new framework to compare alternative geostatistical descriptions of a given site. Multiple realizations of each of the considered geostatistical models and their corresponding tomograms (based on inversion of noise-contaminated simulated data) are used as a multivariate training image. The training image is scanned with a direct sampling algorithm to obtain conditional realizations of hydraulic conductivity that are not only in agreement with the geostatistical model, but also honor the spatially varying resolution of the site-specific tomogram. Model comparison is based on the quality of the simulated geophysical data from the ensemble of conditional realizations. The tomogram in this study is obtained by inversion of cross-hole ground-penetrating radar (GPR) first-arrival travel time data acquired at the MAcro-Dispersion Experiment (MADE) site in Mississippi (USA). Various heterogeneity descriptions ranging from multi-Gaussian fields to fields with complex multiple-point statistics inferred from outcrops are considered. Under the assumption that the relationship between porosity and hydraulic conductivity inferred from local measurements is valid, we find that conditioned multi-Gaussian realizations and derivatives thereof can explain the crosshole geophysical data. A training image based on an aquifer analog from Germany was found to be in better agreement with the geophysical data than the one based on the local outcrop, which appears to under-represent high hydraulic conductivity zones. These findings are only based on the information content in a single resolution-limited tomogram and extending the analysis to tracer or higher resolution surface GPR data might lead to different conclusions (e.g., that discrete facies boundaries are necessary). Our framework makes it possible to identify inadequate geostatistical models and petrophysical relationships, effectively narrowing the space of possible heterogeneity representations.

Successful prediction of groundwater flow and solute transport through highly heterogeneous aquifers has remained elusive due to the limitations of methods to characterize hydraulic conductivity (K) and generate realistic stochastic fields from such data. As a result, many studies have suggested that the classical advective-dispersive equation (ADE) cannot reproduce such transport behavior. Here we demonstrate that when high-resolution K data are used with a fractal stochastic method that produces K fields with adequate connectivity, the classical ADE can accurately predict solute transport at the macrodispersion experiment site in Mississippi. This development provides great promise to accurately predict contaminant plume migration, design more effective remediation schemes, and reduce environmental risks.

In deciduous forests, soil moisture is an important driver of numerous physical, microbial, and biogeochemical processes. Therefore, characterizing the interactions between vegetation and soil moisture is critical to forecast long-term water resources and ecosystem health. However, these interactions are difficult to measure, both in time and space. Recent studies have shown the ability of electrical resistivity imaging (ERI) to characterize the spatial and temporal dynamics of soil moisture at a range of scales. However, no study has yet attempted to use ERI to describe spatiotemporal variability of soil water in relation to vegetation structure and throughfall. In this study, at a mature forest site in Michigan, USA, we captured spatial and temporal dynamics of soil moisture using weekly ERI measurements augmented with throughfall and soil temperature measurements, and a detailed vegetation survey for five adjacent quadrats. Our results show that throughout the growing season, the soil moisture gradually declined despite strong variations in cumulative monthly rainfall. This decline was occasionally halted, but not reversed, during weeks with high precipitation. Spatial variability of electrical resistivity and soil moisture was not related to soil temperature differences but showed a strong correlation with canopy variables.

Free to read Unstable density-driven flow can lead to enhanced solute transport in groundwater. Only recently has the complex fingering pattern associated with free convection been documented in field settings. Electrical resistivity (ER) tomography has been used to capture a snapshot of convective instabilities at a single point in time, but a thorough transient analysis is still lacking in the literature. We present the results of a 2 year experimental study at a shallow aquifer in the United Arab Emirates that was designed to specifically explore the transient nature of free convection. ER tomography data documented the presence of convective fingers following a significant rainfall event. We demonstrate that the complex fingering pattern had completely disappeared a year after the rainfall event. The observation is supported by an analysis of the aquifer halite budget and hydrodynamic modeling of the transient character of the fingering instabilities. Modeling results show that the transient dynamics of the gravitational instabilities (their initial development, infiltration into the underlying lower-density groundwater, and subsequent decay) are in agreement with the timing observed in the time-lapse ER measurements. All experimental observations and modeling results are consistent with the hypothesis that a dense brine that infiltrated into the aquifer from a surficial source was the cause of free convection at this site, and that the finite nature of the dense brine source and dispersive mixing led to the decay of instabilities with time. This study highlights the importance of the transience of free convection phenomena and suggests that these processes are more rapid than was previously understood.

Ground-penetrating radar (GPR) is widely used for assessment of soil moisture variability in field soils. Because GPR does not measure soil water content directly, it is common practice to use calibration functions that describe its relationship with the soil dielectric properties and textural parameters. However, the large variety of models complicates the selection of the appropriate function. In this article an overview is presented of the different functions available, including volumetric models, empirical functions, effective medium theories, and frequency-specific functions. Using detailed information presented in summary tables, the choice for which calibration function to use can be guided by the soil variables available to the user, the frequency of the GPR equipment, and the desired level of detail of the output. This article can thus serve as a guide for GPR practitioners to obtain soil moisture values and to estimate soil dielectric properties.

Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) registered by the International Network on Cancer, Infertility and Pregnancy (INCIP) to guide physicians in clinical management. Methods Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the INCIP registry. For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3 – 37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth. Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n = 62) and advanced stage (n = 15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n = 62), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n = 45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusions Although further prospective research on the efficacy of chemotherapy during pregnancy is necessary, survival of patients diagnosed with early stage HL during pregnancy appears not to be statistically different from matched non-pregnant controls, Awareness of complications as preterm delivery and low birth weight is important in this population. Clinical trial identification NTC00330447. Legal entity responsible for the study The authors. Funding European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 647047 Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) Charles University Research Project Progres Q28 and Q34 and by grant MH CZ - DRO ("Kralovske Vinohrady University Hospital - FNKV, 00064173"). Disclosure All authors have declared no conflicts of interest.

Large concentrations of magnetite in sedimentary deposits and soils with igneous parent material have been reported to affect geophysical sensor performance. We have undertaken the first systematic experimental effort to understand the effects of magnetite for ground-penetrating radar (GPR) characterization of the shallow subsurface. Laboratory experiments were conducted to study how homogeneous magnetite-sand mixtures and magnetite concentrated in layers affect the propagation behavior (velocity, attenuation) of high-frequency GPR waves and the reflection characteristics of a buried target. Important observations were that magnetite had a strong effect on signal velocity and reflection, at magnitudes comparable to what has been observed in small-scale laboratory experiments that measured electromagnetic properties of magnetite-silica mixtures. Magnetite also altered signal attenuation and affected the reflection characteristics of buried targets. Our results indicated important implications for several fields, including land mine detection, Martian exploration, engineering, and moisture mapping using satellite remote sensing and radiometers.

[1] Hydraulic conductivity (K) fields are used to parameterize groundwater flow and transport models. Numerical simulations require a detailed representation of the K field, synthesized to interpolate between available data. Several recent studies introduced high-resolution K data (HRK) at the Macro Dispersion Experiment (MADE) site, and used ground-penetrating radar (GPR) to delineate the main structural features of the aquifer. This paper describes a statistical analysis of these data, and the implications for K field modeling in alluvial aquifers. Two striking observations have emerged from this analysis. The first is that a simple fractional difference filter can have a profound effect on data histograms, organizing non-Gaussian ln K data into a coherent distribution. The second is that using GPR facies allows us to reproduce the significantly non-Gaussian shape seen in real HRK data profiles, using a simulated Gaussian ln K field in each facies. This illuminates a current controversy in the literature, between those who favor Gaussian ln K models, and those who observe non-Gaussian ln K fields. Both camps are correct, but at different scales.

Introduction Uptake is an important determinant of the effectiveness of population-based screening. Uptake of colorectal cancer (CRC) screening generally remains sub-optimal. Aim To determine factors influencing the decision whether to participate or not among individuals invited for faecal occult blood test (FOBT) or flexible sigmoidoscopy (FS) screening. Methods A questionnaire was sent to a stratified random sample of individuals aged 50–74, previously invited for a randomised CRC screening trial offering FOBT or FS, and a reference group from the same population not previously invited (screening naive group). The questionnaire assessed reasons for (non)-participation, individuals’ characteristics associated with participation, knowledge, attitudes and level of informed choice. Results The response rate was 75% ( n = 341/452) for CRC screening participants, 21% ( n = 676/3212) for non-participants and 38% ( n = 192/500) for screening-naive individuals. The main reasons for FOBT and FS participation were acquiring certainty about CRC presence and possible early CRC detection. Anticipated regret and positive attitudes towards CRC screening were strong predictors of actual participation and intention to participate in a next round. The main reason for non-participation in FOBT screening was lack of abdominal complaints. Non-participation in FS screening was additionally influenced by worries about burden. Eighty-one percent of participants and 12% of non-participants made an informed choice on participation. Conclusion Only 12% of non-participants made an informed choice not to participate. These results imply that governments and/or organizations offering screening should focus on adequately informing and educating target populations about the harms and benefits of CRC screening. This may impact uptake of CRC screening.

Time limitations and unwanted health effects may act as barriers to participation in colorectal cancer (CRC) screening. The aim of the study was to measure the time requirements and health effects of colonoscopy and computed tomography colonography (CTC) screening. This was a prospective diary study in a consecutive sample within a randomized controlled CRC screening trial, comparing primary colonoscopy and CTC screening for average-risk individuals aged 50 - 74 years. The diary ended when all screening-related complaints had passed. The diary was returned by 75 % (241/322) of colonoscopy and 75 % (127/170) of CTC screenees. The median interval between leaving home and returning from the examination was longer for colonoscopy (4 hours and 18 minutes [4:18], interquartile range [IQR] 3:30 - 5:00) than for CTC (2:30 hours, IQR 2:06 - 3:00; P < 0.001). Similarly, the time to return to routine activities was longer after colonoscopy (3:54 hours, IQR 1:48 - 15:00) than after CTC (1:36 hours, IQR 0:54 - 4:42). The duration of screening-related symptoms after the examination was shorter for colonoscopy (11:00 hours, IQR 2:54 - 20:00) than for CTC (22:00 hours; IQR 5:30 - 47:00; P < 0.001). Abdominal complaints were reported more frequently after CTC. Anxiety, pain, and quality of life worsened during the screening process, with no differences between the two examinations. Compared with colonoscopy, CTC screening required less time and allowed screenees to return to their daily activities more quickly. In contrast, CTC was associated with a twofold longer duration of screening-related symptoms. Feelings of anxiety, pain, and quality of life scores were similar during colonoscopy and CTC screening. These results should be incorporated into cost-effectiveness analyses of CRC screening techniques

BACKGROUND: Little is known about the effect of participating in a colorectal cancer (CRC) screening programme on quality of life (QOL), neither for participants with a negative nor for those with a positive test result. These findings, however, are important to evaluate the impact of CRC screening. METHODS: Participants from CRC screening trials were sent a questionnaire, which included validated measures on generic health-related QOL, generic anxiety and screen-specific anxiety. Both faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) participants, either with negative or positive test results, were addressed. RESULTS: The response rate was 73% (1289 out of 1772) for FIT and 78% (536 out of 689) for FS participants, with mean ages varying from 63-66 years. Positive FIT participants had worse physical (PCS-12, 47.1 vs 48.3, P = 0.02), but equal mental QOL scores (MCS-12, 51.1 vs 51.6, P = 0.26). Positive and negative FS participants had similar QOL scores. Both FIT and FS participants with a positive test result reported more screen-specific anxiety than negative FIT and FS participants. Positive and n CONCLUSION: Our findings indicate that the burden of participating in CRC screening may be limited. Conducting a prospective study to confirm these results is recommended. British Journal of Cancer (2012) 107, 1295-1301. doi:10.1038/bjc.2012.386 www.bjcancer.com Published online 6 September 2012 (C) 2012 Cancer Research UK

The Cenozoic tectonic history of NW Europe is generally attributed to some combination of three principal controlling factors: North Atlantic opening, Alpine collision and formation of the Icelandic mantle plume. Using constraints from the high-resolution Tellus aeromagnetic survey of Northern Ireland, we show that Palaeogene tectonics can be attributed to approximately north–south Alpine-related compression, forming NNW–SSE-trending dextral and ENE–WSW-trending sinistral conjugate strike-slip faults, with the latter defined by kilometre-scale displacements along reactivated Caledonian or Carboniferous faults. This tectonism was, however, punctuated by pulsed magmatic intrusive and extrusive events, including four distinct dyke swarms that are attributed to NE–SW- to east–west-directed plume-related extension. Although this evidence shows, for the first time, that north–south Alpine compression was periodically overwhelmed by the dynamic stresses and uplift associated with pulsed mantle plume-related deformation, associated strike-slip faulting may have controlled the locus of volcanic activity and central igneous complexes, and the location of sedimentary depocentres.