On the Consequences of Retaining the General Validity of Locality in Physical Theory

The empirical validity of the locality (LOC) principle of relativity is used to argue in favour of a local hidden variable theory (HVT) for individual quantum processes. It is shown that such a HVT may reproduce the statistical predictions of quantum mechanics (QM), provided the reproducibility of initial hidden variable states is limited. This means that in a HVT limits should be set to the validity of the notion of counterfactual definiteness (CFD). This is supported by the empirical evidence that past, present, and future are basically distinct. Our argumentation is contrasted with a recent one by Stapp resulting in the opposite conclusion, i.e. nonlocality or the existence of faster-than-light influences. We argue that Stapp's argumentation still depends in an implicit, but crucial, way on both the notions of hidden variables and of CFD. In addition, some implications of our results for the debate between Bohr and Einstein, Podolsky and Rosen are discussed.Comment: revtex, 11 page

The prevalence of middle ear pathogens in the outer ear canal and the nasopharyngeal cavity of healthy young adults

AbstractCulturing middle ear fluid samples from children with chronic otitis media with effusion (OME) using standard techniques results in the isolation of bacterial species in approximately 30–50% of the cases. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, the classic middle ear pathogens of acute otitis media, are involved but, recently, several studies suggested Alloiococcus otitidis as an additional pathogen. In the present study, we used species-specific PCRs to establish the prevalence, in both the nasopharyngeal cavity and the outer ear, of H. influenzae, M. catarrhalis, S. pneumoniae and A. otitidis. The study group consisted of 70 healthy volunteers (aged 19–22 years). The results indicate a high prevalence (>80%) of A. otitidis in the outer ear in contrast to its absence in the nasopharynx. H. influenzae was found in both the outer ear and the nasopharynx (6% and 14%, respectively), whereas S. pneumoniae and M. catarrhalis were found only in the nasopharynx (9% and 34%, respectively). A. otitidis, described as a fastidious organism, were able to be cultured using an optimized culture protocol, with prolonged incubation, which allowed the isolation of A. otitidis in five of the nine PCR-positive samples out of the total of ten samples tested. Given the absence of the outer ear inhabitant A. otitidis from the nasopharynx, its role in the aetiology of OME remains ambiguous because middle ear infecting organisms are considered to invade the middle ear from the nasopharynx through the Eustachian tube

Interventional oncology at the time of COVID-19 pandemic: Problems and solutions.

The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data

Quality Improvement for Portal Vein Embolization

Fibrin sealant is used in many areas of surgery. We present a novel aspect of flap insetting in the ischial region using fibrin spray to seal the transferred tissue. We analyzed 10 patients suffering from decubital ulcers and assessed drainage output, time of drain removal, as well as complications following fasciocutaneous flap surgery. Patients were randomized to receive sprayed fibrin glue (study group) or not (control group) before wound closure. The mean drainage time was 4 +/- 1 days in the study group and 6 +/- 1 days in the control group ( P = 0.06). The mean drainage volume was 100 +/- 20 mL in the study group and 168 +/- 30 mL in the control group ( P < 0.01). Fibrin sealant led to reduced drainage volumes and duration of drainage, indicating a beneficial effect of the application of fibrin glue in fasciocutaneous flap surgery for pressure sore coverage

Interventional management of gastroduodenal lesions complicating intra-arterial hepatic chemotherapy.

Herein we report the efficacy of embolization of small patent gastric or duodenal vessels for treating gastroduodenal complications after hepatic arterial infusion therapy (HAIC). Catheter ports were implanted percutaneously from a femoral approach in three cases or surgically in the gastroduodenal artery in two cases. Acute abdominal pain developed on average after four HAIC courses of 5FU-oxaliplatin, mytomycin, oxaliplatin or fotemustine. Esophagogastroduodenoscopy showed gastroduodenal lesions (gastroduodenitis with or without ulcerations) in all cases. Despite the interruption of the HAIC, symptoms persisted and led to selective hepatic arteriography showing a patent right gastric artery (n = 4) or a recanalized gastroduodenal artery (n = 1) responsible for gastroduodenal misperfusion. Successful embolizations of the arteries responsible for gastroduodenal misperfusion (right gastric artery in four cases and gastroduodenal artery in one case) using 0.018 platinium coils relieved the patients' symptoms and allowed the HAIC to continue. In gastroduodenal complications of HAIC, a selective hepatic arteriography should be performed to search any artery responsible for the misperfusion of the toxic agent in the gastroduodenal area. Embolization of these arteries allowed the HAIC to be restored

Long-Read Sequencing to Unravel Complex Structural Variants of CEP78 Leading to Cone-Rod Dystrophy and Hearing Loss

Inactivating variants as well as a missense variant in the centrosomal CEP78 gene have been identified in autosomal recessive cone-rod dystrophy with hearing loss (CRDHL), a rare syndromic inherited retinal disease distinct from Usher syndrome. Apart from this, a complex structural variant (SV) implicating CEP78 has been reported in CRDHL. Here we aimed to expand the genetic architecture of typical CRDHL by the identification of complex SVs of the CEP78 region and characterization of their underlying mechanisms. Approaches used for the identification of the SVs are shallow whole-genome sequencing (sWGS) combined with quantitative polymerase chain reaction (PCR) and long-range PCR, or ExomeDepth analysis on whole-exome sequencing (WES) data. Targeted or whole-genome nanopore long-read sequencing (LRS) was used to delineate breakpoint junctions at the nucleotide level. For all SVs cases, the effect of the SVs on CEP78 expression was assessed using quantitative PCR on patient-derived RNA. Apart from two novel canonical CEP78 splice variants and a frameshifting single-nucleotide variant (SNV), two SVs affecting CEP78 were identified in three unrelated individuals with CRDHL: a heterozygous total gene deletion of 235 kb and a partial gene deletion of 15 kb in a heterozygous and homozygous state, respectively. Assessment of the molecular consequences of the SVs on patient’s materials displayed a loss-of-function effect. Delineation and characterization of the 15-kb deletion using targeted LRS revealed the previously described complex CEP78 SV, suggestive of a recurrent genomic rearrangement. A founder haplotype was demonstrated for the latter SV in cases of Belgian and British origin, respectively. The novel 235-kb deletion was delineated using whole-genome LRS. Breakpoint analysis showed microhomology and pointed to a replication-based underlying mechanism. Moreover, data mining of bulk and single-cell human and mouse transcriptional datasets, together with CEP78 immunostaining on human retina, linked the CEP78 expression domain with its phenotypic manifestations. Overall, this study supports that the CEP78 locus is prone to distinct SVs and that SV analysis should be considered in a genetic workup of CRDHL. Finally, it demonstrated the power of sWGS and both targeted and whole-genome LRS in identifying and characterizing complex SVs in patients with ocular diseases

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity