Submillimetre Common-User Bolometer Array 2 (SCUBA-2) is an innovative 10 000 pixel bolometer camera operating at submillimetre wavelengths on the James Clerk Maxwell Telescope (JCMT). The camera has ...the capability to carry out wide-field surveys to unprecedented depths, addressing key questions relating to the origins of galaxies, stars and planets. With two imaging arrays working simultaneously in the atmospheric windows at 450 and 850 μm, the vast increase in pixel count means that SCUBA-2 maps the sky 100-150 times faster than the previous SCUBA instrument. In this paper, we present an overview of the instrument, discuss the physical characteristics of the superconducting detector arrays, outline the observing modes and data acquisition, and present the early performance figures on the telescope. We also showcase the capabilities of the instrument via some early examples of the science SCUBA-2 that have already been undertaken. In 2012 February, SCUBA-2 began a series of unique legacy surveys for the JCMT community. These surveys will take 2.5 yr and the results are already providing complementary data to the shorter wavelength, shallower, larger area surveys from Herschel. The SCUBA-2 surveys will also provide a wealth of information for further study with new facilities such as ALMA, and future telescopes such as CCAT and SPICA.
Background
As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients ...treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored.
Patients and Methods
Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS–HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm.
Results
Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue mean difference (MD) + 14,
p
= 0.001, loss of appetite (MD + 15,
p
= 0.003), hair loss (MD + 18,
p
< 0.001), and loss of taste (MD + 27,
p
< 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively.
Conclusions
In patients with resectable CPM randomized to perioperative systemic therapy or CRS–HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial’s previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.
Relatively limited data have been published on the chemical composition of wet deposition for South Africa, which is considered an important source region for atmospheric pollutants. Concentrations ...and wet deposition fluxes of ionic species determined in rain samples collected from December 2014 to April 2018 at a regional site, Welgegund, are presented, and contextualised by wet deposition composition in the northeastern interior of South Africa. 89% of rain samples collected during the sampling period complied with the data quality objectives of the World Meteorological Organisation. The total ionic concentration of rainwater at Welgegund was similar to that at two regional sites located within proximity of industrial activities. The pH of rainwater (4.80) was comparable to that determined at two rural background sites, which indicated increased neutralisation. Similarly to the other sites located in the South African interior, SO4 2- was the most abundant species in rain, with concentrations thereof in the same order as SO4 2- levels determined at the two industrially influenced sites. Lower sulphur and nitrogen fluxes at Welgegund were attributed to lower average annual rainfall. The anthropogenic (industrial) source group had the largest contribution to wet deposition chemical composition, which signified the influence of major source regions in the South African interior that impact Welgegund. Relatively large contributions were also calculated from marine and crustal sources. The influence of agricultural activities was also evident, while biomass burning had the lowest contribution due to open biomass burning occurring mainly during the dry season
Workloads in nursing wards depend highly on patient arrivals and lengths of stay, both of which are inherently variable. Predicting these workloads and staffing nurses accordingly are essential for ...guaranteeing quality of care in a cost-effective manner. This paper introduces a stochastic method that uses hourly census predictions to derive efficient nurse staffing policies. The generic analytic approach minimizes staffing levels while satisfying so-called nurse-to-patient ratios. In particular, we explore the potential of flexible staffing policies that allow hospitals to dynamically respond to their fluctuating patient population by employing float nurses. The method is applied to a case study of the surgical inpatient clinic of the Academic Medical Center Amsterdam (AMC). This case study demonstrates the method׳s potential to evaluate the complex interaction between staffing requirements and several interrelated planning issues such as case mix, care unit partitioning and size, as well as surgical block planning. Inspired by the quantitative results, the AMC concluded that implementing this flexible nurse staffing methodology will be incorporated in the redesign of the inpatient care operations in the upcoming years.
This multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)‐specific fluorescence imaging during cytoreductive surgery–hyperthermic intraperitoneal chemotherapy ...surgery in peritoneal metastasized colorectal cancer. A correct change in peritoneal carcinomatosis index (PCI) owing to fluorescence imaging was seen in four of the 14 included patients. The use of SGM‐101 in patients with peritoneally metastasized colorectal carcinoma is feasible, and allows intraoperative detection of tumour deposits and alteration of the PCI.
Augmented reality guidance
Anastomotic leakage (AL) is still a common and feared complication after low anterior resection (LAR) for rectal cancer. The multifactorial pathophysiology of AL and lack of standardised treatment ...options requires a multi-modal approach to improve long-term anastomotic integrity. The objective of the IMARI-trial is to determine whether the one-year anastomotic integrity rate in patients undergoing LAR for rectal cancer can be improved using a multi-interventional program.
IMARI is a multicentre prospective clinical effectiveness trial, whereby current local practice (control cohort) will be evaluated, and subsequently compared to results after implementation of the multi-interventional program (intervention cohort). Patients undergoing LAR for rectal cancer will be included. The multi-interventional program includes three preventive interventions (mechanical bowel preparation with oral antibiotics, tailored full splenic flexure mobilization and intraoperative fluorescence angiography using indocyanine green) combined with a standardised pathway for early detection and active management of AL. The primary outcome is anastomotic integrity, confirmed by CT-scan at one year postoperatively. Secondary outcomes include incidence of AL, protocol compliance and association with AL, temporary and permanent stoma rate, reintervention rate, quality of life and functional outcome. Microbiome analysis will be conducted to investigate the role of the rectal microbiome in AL. In a Dutch nationwide study, the AL rate was 20%, with anastomotic integrity of 90% after one year. Based on an expected reduction of AL due to the preventive approaches of 50%, and increase of anastomotic integrity by a standardised pathway for early detection and active management of AL, we hypothesised that the anastomotic integrity rate will increase from 90 to 97% at one year. An improvement of 7% in anastomotic integrity at one year was considered clinically relevant. A total number of 488 patients (244 per cohort) are needed to detect this difference, with 80% statistical power.
The IMARI-trial is designed to evaluate whether a multi-interventional program can improve long-term anastomotic integrity after rectal cancer surgery. The uniqueness of IMARI lies in the multi-modal design that addresses the multifactorial pathophysiology for prevention, and a standardised pathway for early detection and active treatment of AL.
Trialregister.nl ( NL8261 ), January 2020.
Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS ...could serve as an effective treatment for patients with MICCH.
The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks’ baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25–48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21–24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631).
Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p<0·0001) in weeks 21–24, a median change of –5·21 (–11·18 to –0·19; p<0·0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17·58 (9·83 to 29·33) at baseline to 9·50 (3·00 to 21·25) at 21–24 weeks (median change from baseline –4·08, –11·92 to –0·25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15·00 (9·25 to 22·33) to 6·75 (1·50 to 16·50; –6·50, –10·83 to –0·08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21–24 was –2·42 (95% CI –5·17 to 3·33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage.
In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action.
The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.
Abstract Relativistic electron-positron plasmas are ubiquitous in extreme astrophysical environments such as black-hole and neutron-star magnetospheres, where accretion-powered jets and pulsar winds ...are expected to be enriched with electron-positron pairs. Their role in the dynamics of such environments is in many cases believed to be fundamental, but their behavior differs significantly from typical electron-ion plasmas due to the matter-antimatter symmetry of the charged components. So far, our experimental inability to produce large yields of positrons in quasi-neutral beams has restricted the understanding of electron-positron pair plasmas to simple numerical and analytical studies, which are rather limited. We present the first experimental results confirming the generation of high-density, quasi-neutral, relativistic electron-positron pair beams using the 440 GeV/c beam at CERN’s Super Proton Synchrotron (SPS) accelerator. Monte Carlo simulations agree well with the experimental data and show that the characteristic scales necessary for collective plasma behavior, such as the Debye length and the collisionless skin depth, are exceeded by the measured size of the produced pair beams. Our work opens up the possibility of directly probing the microphysics of pair plasmas beyond quasi-linear evolution into regimes that are challenging to simulate or measure via astronomical observations.
The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. ...We hypothesized that conformational flexibility and transient exposure of non-neutralizing, immunodominant epitopes could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo receptor-induced conformational changes and a decreased exposure of non-neutralizing V3-directed antibody epitopes. In rabbits, the stabilized trimers induced similar autologous Tier-1B or Tier-2 NAb titers to those elicited by the corresponding wild-type trimers but lower levels of V3-directed Tier-1A NAbs. Stabilized, closed trimers might therefore be useful components of vaccines aimed at inducing bNAbs.
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•Rational design improves native-like HIV-1 envelope trimers•Design improvements facilitate the generation of trimers from multiple isolates•Modified trimers are more stable and less conformationally flexible•Immunogenicity of non-neutralizing epitopes is reduced
Native-like HIV-1 envelope trimers with improved stability and reduced exposure of non-neutralizing epitopes present a new platform for developing vaccines that induce broadly neutralizing anti-HIV antibodies.
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