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Background: The restructuring of healthcare systems to cope with the demands of the COVID-19 pandemic has led to a reduction in clinical services such as cancer screening and diagnostics., Methods: Data from the four Northern Ireland pathology laboratories were used to assess trends in pathological cancer diagnoses from 1st March to 12th September 2020 overall and by cancer site, sex and age. These trends were compared to the same timeframe from 2017 to 2019., Results: Between 1st March and 12th September 2020, there was a 23% reduction in cancer diagnoses compared to the same time period in the preceding 3 years. Although some recovery occurred in August and September 2020, this revealed inequalities across certain patient groups. Pathological diagnoses of lung, prostate and gynaecological malignancies remained well below pre-pandemic levels. Males and younger/middle-aged adults, particularly the 50-59-year-old patient group, also lagged behind other population demographic groups in terms of returning to expected numbers of pathological cancer diagnoses., Conclusions: There is a critical need to protect cancer diagnostic services in the ongoing pandemic to facilitate timely investigation of potential cancer cases. Targeted public health campaigns may be needed to reduce emerging inequalities in cancer diagnoses as the COVID-19 pandemic continues., (© 2021. The Author(s).)

We address the inverse Frobenius-Perron problem: given a prescribed target distribution ρ, find a deterministic map M such that iterations of M tend to ρ in distribution. We show that all solutions may be written in terms of a factorization that combines the forward and inverse Rosenblatt transformations with a uniform map; that is, a map under which the uniform distribution on the d -dimensional hypercube is invariant. Indeed, every solution is equivalent to the choice of a uniform map. We motivate this factorization via one-dimensional examples, and then use the factorization to present solutions in one and two dimensions induced by a range of uniform maps.

We describe a new and computationally efficient Bayesian methodology for inferring species trees and demographics from unlinked binary markers. Likelihood calculations are carried out using diffusion models of allele frequency dynamics combined with novel numerical algorithms. The diffusion approach allows for analysis of data sets containing hundreds or thousands of individuals. The method, which we call Snapper, has been implemented as part of the BEAST2 package. We conducted simulation experiments to assess numerical error, computational requirements, and accuracy recovering known model parameters. A reanalysis of soybean SNP data demonstrates that the models implemented in Snapp and Snapper can be difficult to distinguish in practice, a characteristic which we tested with further simulations. We demonstrate the scale of analysis possible using a SNP data set sampled from 399 fresh water turtles in 41 populations. [Bayesian inference; diffusion models; multi-species coalescent; SNP data; species trees; spectral methods.]., (© The Author(s) 2020. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Doxorubicin (DOX) is a potent anticancer agent that binds both DNA and cardiolipin (CL). To investigate DOX binding to CL versus DNA, aqueous soluble, CL-enriched nanoparticles, termed nanodisks (ND), were employed. Upon incubation with CL-ND, but not with phosphatidylcholine ND, DOX binding was detected. DOX binding to CL-ND was sensitive to buffer pH and ionic strength. To investigate if a DOX binding preference for DNA versus CL-ND exists, an agarose gel-based dye binding assay was developed. Under conditions wherein the commercial fluorescent dye, GelRed, detects a 636 bp DNA template following electrophoresis, DOX staining failed to visualize this DNA band. Incubation of the template DNA with DOX prior to electrophoresis resulted in a DOX concentration-dependent attenuation of GelRed staining intensity. When the template DNA was pre-incubated with equivalent amounts of free DOX or DOX-CL-ND, no differences in the extent of GelRed staining intensity attenuation were noted. When DOX was incubated with DNA alone, or a mixture of DNA and CL-ND, the extent of DOX-induced GelRed staining intensity attenuation was equivalent. Thus, DOX has a binding preference for DNA versus CL and, moreover, DOX-CL-ND offer a potential strategy to prevent DOX-induced cardiotoxicity while not affecting its affinity for DNA., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Miniature membranes comprised of tetramyristoylcardiolipin (CL) and apolipoprotein (apo) A-I, termed nanodisks (ND), are stable, aqueous soluble, reconstituted high density lipoproteins. When CL ND, but not dimyristoylphosphatidylcholine (PC) ND, were incubated with CaCl 2 , a concentration dependent increase in sample turbidity occurred, consistent with CL undergoing a bilayer to non-bilayer transition. To assess the cation specificity of this reaction, CL ND were incubated with various mono- and divalent cations. Whereas monovalent cations had no discernable effect, MgCl 2 and SrCl 2 induced a response similar to CaCl 2 . When ND were formulated using different weight ratios of CL and PC, those possessing 100% CL or 75% CL remained susceptible to CaCl 2 induced sample turbidity development while ND possessing 50% CL displayed reduced susceptibility. ND comprised of 25% CL and 75% PC were unaffected by CaCl 2 under these conditions. SDS PAGE analysis of insoluble material generated by incubation of CL ND with CaCl 2 revealed that nearly all apoA-I was recovered in the insoluble fraction along with CL. One h after addition of EDTA to CaCl 2 -treated CL ND, sample clarity was restored. Collectively, the data are consistent with a model wherein Ca 2+ forms a bidentate interaction with anionic phosphates in the polar head group of CL. As phosphate group repositioning occurs to maximize Ca 2+ binding, CL acyl chains reposition, accentuating the conical shape of CL to an extent that is incompatible with the ND bilayer structure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Producing practical designs for light-weight timber-framed structures that achieve high sound isolation remains a challenging task, in part because of the lack of models that can accurately predict the sound transmission through proposed designs. This work develops detailed modeling of structural vibration in timber floor/ceiling systems, from which sound transmission in the low-frequency regime (10-150 Hz) can be computed, as a design tool for producing practical timber floor/ceiling details that achieve high isolation for low-frequency sound. The mathematical model uses a variational formulation that enables straightforward modeling of complex composite structures, and introduces the notion of coupling layers to model the movement between joined materials that occurs with practical bonding methods, thereby improving on existing models that assume either perfectly bonded or perfectly slipping interfaces. The composite model structure is assembled only at the computational step, giving an efficient computational scheme that also fits well into the design-development cycle. Results from a parallel experimental program are used to validate the model and to determine effective coupling and damping parameters. The influence of coupling parameters is shown for an example floor, demonstrating that finite slippage at joints is required for the model to predict low-frequency vibration in practical constructions.

Optimal sequential inference, or filtering, for the state of a deterministic dynamical system requires simulation of the Frobenius-Perron operator, that can be formulated as the solution of a continuity equation. For low-dimensional, smooth systems, the finite-volume numerical method provides a solution that conserves probability and gives estimates that converge to the optimal continuous-time values, while a Courant-Friedrichs-Lewy-type condition assures that intermediate discretized solutions remain positive density functions. This method is demonstrated in an example of nonlinear filtering for the state of a simple pendulum, with comparison to results using the unscented Kalman filter, and for a case where rank-deficient observations lead to multimodal probability distributions.

Background: Population based cancer registration provides a critical role in disease surveillance in terms of incidence, survival, cancer cluster investigations and prevalence trends, and therefore high levels of completeness and timeliness are required. This study estimates completeness and variation between early and late registrations in the N. Ireland Cancer Registry (NICR) and assesses the implications for reporting cancer incidence and for registry-based research., Methods: Two main approaches assessed completeness. For the period 2010-2012, incidence reported in the first year of data publication was compared to incidence reported in subsequent years until 2015. Demographic characteristics and survival of incident cases ascertained before the first publication year were compared to those ascertained in subsequent years. The flow method approach was used to estimate completeness annually after the incident year., Results: Overall incidence for all cancers increased between the first year of data publication and subsequent years up to 2015, irrespective of year of diagnosis. Late registrations had poorer survival. The flow method approach estimated the completeness of case ascertainment of NICR data to be 96% complete at five years for all cancers combined., Conclusion: The estimated completeness levels for the NICR are comparable to other high quality cancer registries internationally. While data timeliness has little impact on incidence estimates, delays in registration may have implications for specific research studies into incidence and survival. This means that improvements in the timeliness of reporting should be a target for all registries but not at the expense of completeness., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To evaluate precision and recall rates for the automatic extraction of information from free-text pathology reports. To assess the impact that implementation of pattern-based methods would have on cancer registration completeness., Method: Over 300,000 electronic pathology reports were scanned for the extraction of Gleason score, Clark level and Breslow depth, by a number of Perl routines progressively enhanced by a trial-and-error method. An additional test set of 915 reports potentially containing Gleason score was used for evaluation., Results: Values for recall and precision of over 98 and 99%, respectively, were easily reached. Potential increase in cancer staging completeness of up to 32% was proved., Conclusions: In cancer registration, simple pattern matching applied to free-text documents can be effectively used to improve completeness and accuracy of pathology information.

Introduction: The objective of this work was to evaluate the safeguards implemented by surgical trainees to protect the confidentiality of electronic patient data through a structured questionnaire sent to Northern Ireland surgical trainees., Participants and Methods: A group of 32 basic and higher surgical trainees attending a meeting of the Northern Ireland Association of Surgeons-in-Training were invited to complete a questionnaire regarding their computer use, UK Data Protection Act, 1988 registration and electronic data confidentiality practices., Results: Of these 32 trainees, 29 returned completed questionnaires of whom 26 trainees regularly stored sensitive patient data for audit or research purposes on a computer. Only one person was registered under the Data Protection Act, 1988. Of the computers used to store and analyse sensitive data, only 3 of 14 desktops, 8 of 19 laptops and 3 of 14 hand-held computers forced a password logon. Of the 29 trainees, 16 used the same password for all machines, and 25 of 27 passwords were less than 8 characters long. Two respondents declined to reveal details of their secure passwords. Half of all trainees had never adjusted their internet security settings, despite all 14 desktops, 16 of 19 laptops and 5 of 14 hand-helds being routinely connected to the internet. Of the 29 trainees, 28 never encrypted their sensitive data files. Ten trainees had sent unencrypted sensitive patient data over the internet, using a non-secure server., Conclusions: Electronic data confidentiality practices amongst Northern Ireland surgical trainees are unsafe. Simple practical measures to safeguard confidentiality are recommended.