The efficiency of perovskite solar cells is affected by open-circuit voltage losses due to radiative and non-radiative charge recombination. When estimated using sensitive photocurrent measurements ...that cover the above- and sub-bandgap regions, the radiative open-circuit voltage is often unphysically low. Here we report sensitive photocurrent and electroluminescence spectroscopy to probe radiative recombination at sub-bandgap defects in wide-bandgap mixed-halide lead perovskite solar cells. The radiative ideality factor associated with the optical transitions increases from 1, above and near the bandgap edge, to ~2 at mid-bandgap. Such photon energy-dependent ideality factor corresponds to a many-diode model. The radiative open-circuit voltage limit derived from this many-diode model enables differentiating between radiative and non-radiative voltage losses. The latter are deconvoluted into contributions from the bulk and interfaces via determining the quasi-Fermi level splitting. The experiments show that while sub-bandgap defects do not contribute to radiative voltage loss, they do affect non-radiative voltage losses.
Background
Patients with colorectal peritoneal carcinomatosis have a very poor prognosis. The recently developed consensus molecular subtype (CMS) classification of primary colorectal cancer ...categorizes tumours into four robust subtypes, which could guide subtype‐targeted therapy. CMS4, also known as the mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4 status and histopathological features of colorectal peritoneal carcinomatosis were investigated in this study.
Methods
Fresh‐frozen tissue samples from primary colorectal cancer and paired peritoneal metastases from patients who underwent cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy were collected. Histopathological features were analysed, and a reverse transcriptase–quantitative PCR test was used to assess CMS4 status of all collected lesions.
Results
Colorectal peritoneal carcinomatosis was associated with adverse histopathological characteristics, including a high percentage of stroma in both primary tumours and metastases, and poor differentiation grade and high‐grade tumour budding in primary tumours. Furthermore, CMS4 was significantly enriched in primary tumours with peritoneal metastases, compared with unselected stage I–IV tumours (60 per cent (12 of 20) versus 23 per cent; P = 0.002). The majority of peritoneal metastases (75 per cent, 21 of 28) were also classified as CMS4. Considerable intrapatient subtype heterogeneity was observed. Notably, 15 of 16 patients with paired tumours had at least one CMS4‐positive tumour location.
Conclusion
Significant enrichment for CMS4 was observed in colorectal peritoneal carcinomatosis.
Surgical relevance
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC) improves survival of selected patients with colorectal peritoneal carcinomatosis, but recurrence is common. Histopathological and molecular analysis of colorectal peritoneal carcinomatosis could provide clues for development of novel therapies.
In this study, colorectal peritoneal carcinomatosis was found to be enriched for tumours with high stromal content and CMS4‐positive status.
To further improve prognosis for patients with colorectal peritoneal carcinomatosis, therapies that target tumour–stroma interaction could be added to CRS‐HIPEC.
Mesenchymal subtype predominates
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is ...challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging.
The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis.
This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC.
Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue ...recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement.
DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue.
Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement.
This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175 .
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Evidence of benefits of laparoscopic and laparoscopic-assisted colectomies (LAC) over open procedures in gastrointestinal surgery has continued to accumulate. With its wide implementation, ...technical difficulties and limitations of LAC have become clear. Hand-assisted laparoscopic surgery (HALS) was introduced in an attempt to facilitate the transition from open techniques to minimally invasive procedures. Continuing debate exists about which approach is to be preferred, HALS or LAC. Several studies have compared these two techniques in colorectal surgery, but no single study provided evidence which procedure is superior. Therefore, a systematic review was carried out comparing HALS with LAC colorectal resection.
Methods
Eligible studies were identified from electronic databases (Medline, Embase Cochrane) and cross-reference search. The database search, quality assessment, and data extraction were independently performed by two reviewers. Minimal outcome criteria for inclusion were operating time, conversion rate, hospital stay, and morbidity.
Results
Out of 468 studies a total of 13 studies were selected for comprehensive review. Two randomized controlled trials (RCT) and 11 non-RCTs, comprising 1017 patients, met the inclusion criteria. Because of possible clinical heterogeneity two groups of procedures were created: segmental colectomies and total (procto)colectomies. In the segmental colectomy group significant differences in favor of the HALS group were seen in operating time (WMD 19 min) and conversion rate (OR of 0.3 conversions). In the total (procto)colectomy group a significant difference in favor of the HALS group was seen in operating time (WMD 61 min).
Conclusions
This systematic review indicates that HALS provides a more efficient segmental colectomy regarding operating time and conversion rate, particularly accounting for diverticulitis. A significant operating time advantage exists for HALS total (procto)colectomy. HALS must therefore be considered a valuable addition to the laparoscopic armamentarium to avoid conversion and speed up complicated colectomies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Liquid xenon time-projection chambers are the world's most sensitive detectors for a wide range of dark matter candidates. We show that the statistical analysis of their data can be improved by ...replacing detector response Monte Carlo simulations with an equivalent deterministic calculation. This allows the use of highdimensional undiscretized models, yielding up to ∼2 times better discrimination of the dominant backgrounds. In turn, this could significantly extend the physics reach of upcoming experiments such as XENONnT and LZ, and bring forward a potential 5σ dark matter discovery by over a year.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Proof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis ...(RA). For the treatment of RA patients, we engineered a recombinant adeno-associated serotype 5 vector (rAAV5) encoding human (h)IFN-β under control of a nuclear factor κB promoter (ART-I02).
The potency of ART-I02 in vitro as well as biodistribution in vivo in arthritic animals was evaluated to characterize the vector prior to clinical application. ART-I02 expression and bioactivity after transduction was evaluated in fibroblast-like synoviocytes (FLS) from different species. Biodistribution of the vector after local injection was assessed in a rat adjuvant arthritis model through qPCR analysis of vector DNA. In vivo imaging was used to investigate transgene expression and kinetics in a mouse collagen induced arthritis model.
Transduction of RA FLS in vitro with ART-I02 resulted in high expression levels of bioactive hIFN-β. Transduction of FLS from rhesus monkeys, rodents and rabbits with ART-I02 showed high transgene expression, and hIFN-β proved bioactive in FLS from rhesus monkeys. Transgene expression and bioactivity in RA FLS were unaltered in the presence of methotrexate. In vivo, vector biodistribution analysis in rats after intra-articular injection of ART-I02 demonstrated that the majority of vector DNA remained in the joint (>93%). In vivo imaging in mice confirmed local expression of rAAV5 in the knee joint region and demonstrated rapid detectable and sustained expression up until 7 weeks.
These data show that hIFN-β produced by RA FLS transduced with ART-I02 is bioactive and that intra-articular delivery of rAAV5 drives expression of a therapeutic transgene in the joint, with only limited biodistribution of vector DNA to other tissues, supporting progress towards a phase 1 clinical trial for the local treatment of arthritis in patients with RA.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Detection of peritoneal metastases (PM) is key in the staging and management of gastrointestinal and ovarian cancer patients. The purpose of this meta-analysis was to determine the diagnostic ...performance of CT, PET(CT), and (DW)MRI in detecting PM.
Methods
A literature search in Pubmed, Embase (Ovid), and Scopus was performed (January 1997–May 2018) to identify studies reporting on the accuracy of imaging PM in the diagnostic workup of gastrointestinal or ovarian cancers. Inclusion criteria were region-based or patient-based studies comprising > 15 patients, surgery/histology/radiological follow-up as a reference standard, and sufficient data to construct a 2 × 2 contingency table. Two observers performed data extraction. The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model and hierarchical summary operating curves (HSROC) were generated.
Results
Of 3457 citations retrieved, twenty-four articles met all inclusion criteria. Thirty-seven datasets could be extracted for analysis including 20 for CT, 10 for PET(CT), and 7 for (DW)MRI. The pooled sensitivity, specificity, and DOR for the detection of PM for region-based studies for CT were 68% (CI, 46–84%), 88%(CI, 81–93%), and 15.9 (CI, 4.4–58.0) respectively; 80% (CI, 57–92%), 90% (CI, 80–96%), and 36.5 (CI, 6.7–199.5) for PET(CT), respectively; 92% (CI, 84–96%), 85% (CI, 78–91%), 63.3 (CI, 31.5–127.3) for (DW)MRI. In the patient-based group, not enough studies were included to make a pooled analysis for (DW)MRI and PET(CT).
Conclusion
(DW)MRI and PET(CT) showed comparable diagnostic performance for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients. Since MRI is more widely available than PET(CT) in clinical practice, this potentially is the imaging method of choice in most centers in the future.
Key Points
• Detection of peritoneal metastases plays an important role in the accurate staging of cancer patients, however, there is no accepted reference standard for the imaging of peritoneal metastases
• This meta-analysis shows that (DW)MRI provided the highest sensitivity for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients
• Although (DW)MRI and PET(CT) show a comparable overall diagnostic performance, (DW)MRI seems to be the imaging method of choice since it is more available in daily practice than PET(CT).
The aims of this study were to investigate the extent of heavy metal contamination in the Philippi horticultural area in the Western Cape Province, South Africa. Concentrations of Cd, Cr, Cu, Mn, Ni, ...Pb and Zn were determined in the irrigation water, soils and vegetables in both winter and summer cropping seasons with an ICP-AES and tested against certified standards. Differences were found in heavy metal concentrations between the winter and summer cropping seasons in the irrigation water, soils and vegetables. Certain heavy metals exceeded the maximum permissible concentrations in the irrigation water, soils and vegetables produced in South Africa. These toxic concentrations were predominantly found in the summer cropping season for the soils and in the crops produced in winter. It is thus suggested that further studies are carried out in the Philippi horticultural area to determine the sources of the heavy metals to try and mitigate the inputs thereof and therefore reduce the amount of heavy metals entering the human food chain.
Abstract
We present FlameNEST, a framework providing explicit likelihood evaluations in noble element particle detectors using data-driven models from the Noble Element Simulation Technique. ...FlameNEST provides a way to perform statistical analyses on real data with no dependence on large, computationally expensive Monte Carlo simulations by evaluating the likelihood on an event-by-event basis using analytic probability elements convolved together in a single TensorFlow multiplication. Furthermore, this robust framework creates opportunities for simple inter-collaboration analyses which will be fundamental for the future of experimental dark matter physics.
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