Orthogonal spatial coding with stimulated parametric down-conversion.

Orthogonal optical coding is widely used in classical multi-user communication networks. Using the phase conjugation property of stimulated parametric down-conversion, we extend the current time-domain orthogonal optical coding scheme to the spatial domain to encode and decode image information. In this process, the idler beam inherits the complex conjugate of the field information encoded in the seed beam. An encoding phase mask introduced onto the input seed beam blurs the image transferred to the idler. The original image is restored by passing the coded transferred image through a corrective phase mask placed in the momentum space of the idler beam. We expect that this scheme can also inspire new techniques in secure image transmission, aberration cancellation, and frequency conversion imaging.

Multiomics analysis of adaptation to repeated DNA damage in prostate cancer cells.

DNA damage is frequently utilized as the basis for cancer therapies; however, resistance to DNA damage remains one of the biggest challenges for successful treatment outcomes. Critically, the molecular drivers behind resistance are poorly understood. To address this question, we created an isogenic model of prostate cancer exhibiting more aggressive characteristics to better understand the molecular signatures associated with resistance and metastasis. 22Rv1 cells were repeatedly exposed to DNA damage daily for 6 weeks, similar to patient treatment regimes. Using Illumina Methylation EPIC arrays and RNA-seq, we compared DNA methylation and transcriptional profiles between the parental 22Rv1 cell line and the lineage exposed to prolonged DNA damage. Here we show that repeated DNA damage drives the molecular evolution of cancer cells to a more aggressive phenotype and identify molecular candidates behind this process. Total DNA methylation was increased while RNA-seq demonstrated these cells had dysregulated expression of genes involved in metabolism and the unfolded protein response (UPR) with Asparagine synthetase (ASNS) identified as central to this process. Despite the limited overlap between RNA-seq and DNA methylation, oxoglutarate dehydrogenase-like (OGDHL) was identified as altered in both data sets. Utilising a second approach we profiled the proteome in 22Rv1 cells following a single dose of radiotherapy. This analysis also highlighted the UPR in response to DNA damage. Together, these analyses identified dysregulation of metabolism and the UPR and identified ASNS and OGDHL as candidates for resistance to DNA damage. This work provides critical insight into molecular changes which underpin treatment resistance and metastasis.

Sut-6/NIPP1 modulates tau toxicity.

Neurodegenerative diseases exhibiting the pathological accumulation of tau such as Alzheimer's disease and related disorders still have no disease-modifying treatments and the molecular mechanisms of neurodegeneration remain unclear. To discover additional suppressor of tauopathy (sut) genes that mediate or modulate the toxicity of pathological tau, we performed a classical genetic screen using a tau transgenic Caenorhabditis elegans model. From this screen, we identified the suppressing mutation W292X in sut-6, the C. elegans homolog of human NIPP1, which truncates the C-terminal RNA-binding domain. Using CRISPR-based genome editing approaches, we generated null and additional C-terminally truncated alleles in sut-6 and found that loss of sut-6 or sut-6(W292X) suppresses tau-induced behavioral locomotor deficits, tau protein accumulation and neuron loss. The sut-6(W292X) mutation showed stronger and semi-dominant suppression of tau toxicity while sut-6 deletion acted recessively. Neuronal overexpression of SUT-6 protein did not significantly alter tau toxicity, but neuronal overexpression of SUT-6 W292X mutant protein reduced tau-mediated deficits. Epistasis studies showed tauopathy suppression by sut-6 occurs independent of other known nuclear speckle-localized suppressors of tau such as sut-2, aly-1/aly-3 and spop-1. In summary, we have shown that sut-6/NIPP1 modulates tau toxicity and found a dominant mutation in the RNA-binding domain of sut-6 which strongly suppresses tau toxicity. This suggests that altering RNA-related functions of SUT-6/NIPP1 instead of complete loss of SUT-6/NIPP1 will provide the strongest suppression of tau.

Generation of volumetrically full Poincaré beams.

Optical communications, remote sensing, particle trapping, and high-resolution imaging are a few research areas that benefit from new techniques to generate structured light. We present a method of generating polarization-structured laser beams that contain both full and partial polarization states. We demonstrate this method by generating an optical beam that contains every state of partial and full polarization. We refer to this beam as a volumetrically full Poincaré beam to distinguish it from full Poincaré beams, which contain all states of full polarization only. In contrast to methods relying upon spatial coherence to generate polarization-structured beams with partial polarization, our method creates well-collimated beams by relying upon temporal coherence.

Suppression of Nonlinear Optical Rogue Wave Formation Using Polarization-Structured Beams.

A nonlinear self-focusing material can amplify random small-amplitude phase modulations present in an optical beam, leading to the formation of amplitude singularities commonly referred to as optical caustics. By imposing polarization structuring on the beam, we demonstrate the suppression of amplitude singularities caused by nonlinear self-phase modulation. Our results are the first to indicate that polarization-structured beams can suppress nonlinear caustic formation in a saturable self-focusing medium and add to the growing understanding of catastrophic self-focusing effects in beams containing polarization structure.

Evaluation of the performance of a lateral flow device for quantitative detection of anti-SARS-CoV-2 IgG.

INTRODUCTION: The AbC-19™ lateral flow immunoassay (LFIA) performance was evaluated on plasma samples from a SARS-CoV-2 vaccination cohort, WHO international standards for anti-SARS-CoV-2 IgG (human), individuals ≥2 weeks from infection of RT-PCR confirmed SARS-CoV-2 genetic variants, as well as microorganism serology. METHODS: Pre-vaccination to three weeks post-booster samples were collected from a cohort of 111 patients (including clinically extremely vulnerable patients) from Northern Ireland. All patients received Oxford-AstraZeneca COVID-19 vaccination for the first and second dose, and Pfizer-BioNTech for the third (first booster). WHO international standards, 15 samples from 2 variants of concern (Delta and Omicron) and cross-reactivity with plasma samples from other microorganism infections were also assessed on AbC-19™. RESULTS: All 80 (100%) participants sampled post-booster had high positive IgG responses, compared to 38/95 (40%) participants at 6 months post-first vaccination. WHO standard results correlated with information from corresponding biological data sheets, and antibodies to all genetic variants were detected by LFIA. No cross-reactivity was found with exception of one (of five) Dengue virus samples. CONCLUSION: These findings suggest BNT162b2 booster vaccination enhanced humoral immunity to SARS-CoV-2 from pre-booster levels, and that this antibody response was detectable by the LFIA. In combination with cross-reactivity, standards and genetic variant results would suggest LFIA may be a cost-effective measure to assess SARS-CoV-2 antibody status.

iBDecide: A web-based tool to promote engagement in shared decision-making among adolescents with ulcerative colitis.

BACKGROUND: Adolescents and young adults (AYAs) seek increased autonomy and self-efficacy. AYAs must learn to manage their medical care in preparation for transition to adult healthcare. Our team's research found that AYAs need more information about their disease and treatment OBJECTIVE: To develop and test the usability of a decision tool "iBDecide" to promote shared decision-making among AYAs with ulcerative colitis (UC) who are beginning to manage their treatment and medications METHODS: Using design thinking, 14 AYAs, 6 healthcare providers, 4 designers, a social worker, and a human factors researcher developed a shared decision-making tool. The System Usability Scale (SUS) assessed usability RESULTS: AYAs preferred an application with information on treatment, medication, nutrition, and symptom tracking. A web-based application, 'iBDecide', was developed to include these options. SUS results indicated that participants on average "agree" that: 'they would use iBDecide' and that 'it was easy to use and streamlined'. The mean SUS score was 78.25 (+/-12.91), range 70-90 DISCUSSION: Including AYAs in tool development helps ensure usability and improves engagement in shared decision-making. Co-designed tools may remove barriers for engagement and skill-building needed for the transition to adult care. CONCLUSION: iBDecide can stimulate AYA engagement in shared decision-making in treating UC.

Operando Synchrotron X-ray Diffraction in Calcium Batteries: Insights into the Redox Activity of 1D Ca3CoMO6 (M = Co and Mn).

1D Ca3Co2-z M z O6 (M = Co z = 0, M = Mn z = 1, and M = Fe z = 0.4) were prepared and tested electrochemically. While the iron-containing phase was not found to be active, the iron- and manganese-containing phases were found to be potentially interesting as positive electrode materials for calcium metal-based high-energy battery technologies and were investigated by operando synchrotron X-ray diffraction. Results indicate that electrochemically driven calcium deintercalation from the crystal structure (ca. 0.7 mol per formula unit) takes place upon oxidation in both cases. The oxidized phases have incommensurate modulated crystal structures with the space group R 3m(00γ)0s and a = 9.127(1) Å, c 1 = 2.4226(3) Å and c 2 = 4.1857(3) Å, and γ = 0.579 (M = Co) and a = 9.217(1) Å, c 1 = 4.9076(4) Å and c 2 = 4.3387(4) Å, and γ = 1.139 (M = Mn), which exhibit differences due to the presence of manganese and Mn/Co ordering. The degree of calcium re-intercalation within the structure was found to be extremely limited, if any. Complementary experiments carried out in lithium cells did not show any reversibility either, thus pointing at intrinsic structural/migration constraints in the oxidized phase rather than slow kinetics of high desolvation energies associated with divalent ion charge carriers.

Introducing mobile fracture prevention services with DXA in Northern Scotland: a comparative study of three rural communities.

Mobile fracture prevention services, with DXA, significantly improved access to care for those at high risk of fracture living in rural areas. Introduction of mobile services facilitated access to fracture liaison services and development of integrated of care pathways across community- and secondary-based care. INTRODUCTION: The ageing population is growing faster in rural areas, yet most fracture prevention services are located in urban areas. As part of a wider study, evaluating the introduction of mobile fracture prevention services, we focus on whether mobile services improve access to care for those at highest risk of fracture. METHODS: Services outcomes were assessed against the Royal Osteoporosis Society clinical standards for fracture liaison services. This included standardised, age-specific referral rates, FRAX 10-year probability of major osteoporotic and hip fracture of referrals, pre- and post-introduction of the mobile service across two island and one rural mainland sites. This was compared with referrals from a similar rural mainland region with local access to a comprehensive service. RESULTS: Greatest impact occurred in areas with most limited service provision at baseline. Mean age of patients referred increased from 59 to 68 years (CI 6.8-10.1, p < 0.001). Referral rates increased from 2.8 to 5.4 per 1000 population between 2011 and 2018, with a 5-fold rise in those ≥ 75 years (0.4 to 2.0 per 1000). Mean FRAX 10-year risk of major osteoporotic fracture increased from 12.7 to 17.7% (CI 3.2-5.7, p < 0.001). Mean hip fracture risk probability increased from 3.0 to 5.7% (CI 2.0-3.4, p < 0.001). However, referral rates from the mobile sites remained lower than the comparator site. CONCLUSIONS: Mobile fracture prevention services, including DXA, greatly improved uptake amongst high-risk individuals. Mobile services facilitated development of integrated of care pathways, including fracture liaison services, across community- and secondary-based care.

Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer.

BACKGROUND: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. PATIENTS AND METHODS: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models. RESULTS: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m. CONCLUSION: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

Quantification of the regional bioarchitecture in the human aorta.

Regional variance in human aortic bioarchitecture responsible for the elasticity of the vessel is poorly understood. The current study quantifies the elements responsible for aortic compliance, namely, elastin, collagen and smooth muscle cells, using histological and stereological techniques on human tissue with a focus on regional heterogeneity. Using donated cadaveric tissue, a series of samples were excised between the proximal ascending aorta and the distal abdominal aorta, for five cadavers, each of which underwent various staining procedures to enhance specific constituents of the wall. Using polarised light microscopy techniques, the orientation of collagen fibres was studied for each location and each tunical layer of the aorta. Significant transmural and longitudinal heterogeneity in collagen fibre orientations were uncovered throughout the vessel. It is shown that a von Mises mixture model is required accurately to fit the complex collagen fibre distributions that exist along the aorta. Additionally, collagen and smooth muscle cell density was observed to increase with increasing distance from the heart, whereas elastin density decreased. Evidence clearly demonstrates that the aorta is a highly heterogeneous vessel which cannot be simplistically represented by a single compliance value. The quantification and fitting of the regional aortic bioarchitectural data, although not without its limitations, including mean cohort age of 77.6 years, facilitates the development of next-generation finite element models that can potentially simulate the influence of regional aortic composition and microstructure on vessel biomechanics.

Quantum Nonlocal Aberration Cancellation.

Phase distortions, or aberrations, can negatively influence the performance of an optical imaging system. Through the use of position-momentum entangled photons, we nonlocally correct for aberrations in one photon's optical path by intentionally introducing the complementary aberrations in the optical path of the other photon. In particular, we demonstrate the simultaneous nonlocal cancellation of aberrations that are of both even and odd order in the photons' transverse degrees of freedom. We also demonstrate a potential application of this technique by nonlocally canceling the effect of defocus in a quantum imaging experiment and thereby recover the original spatial resolution.

Ecological momentary assessment studies of comorbid PTSD and alcohol use: A narrative review.

INTRODUCTION: PTSD and harmful alcohol use, including alcohol use disorder (AUD), frequently co-occur. Recent research has used ecological momentary assessment (EMA) to examine the associations between PTSD symptoms and alcohol-related variables, such as craving for alcohol, alcohol use, and the presence of alcohol-related problems. The overall purpose of this narrative review is to summarize this emerging literature. METHODS: Inclusion criteria for studies were: 1) Use of ecological momentary assessment as the method for gathering data on alcohol use and/or craving in populations with both problematic alcohol use and PTSD, and the inclusion of an assessment of both PTSD symptoms and at least one alcohol use variable during EMA; and 2) At screening, participants were required to meet study criteria for a) elevated PTSD symptoms or trauma exposure, and b) alcohol use. RESULTS: The pertinent extant literature is reviewed in terms of four underlying themes: Methodological considerations of EMA research in a population with PTSD symptoms and harmful alcohol use; Associations between PTSD symptoms and alcohol use variable/s; Moderators of PTSD-alcohol use associations; Mediators of PTSD-alcohol use associations. CONCLUSIONS: Collectively, studies provide support for the self-medication hypothesis. Several variables were found to moderate association between PTSD symptoms and alcohol-related variables. EMA data may ultimately be useful in identifying when individuals are at risk for harm due to increased symptoms or alcohol misuse and may inform treatment approaches administered remotely.

More than a messenger: Alternative splicing as a therapeutic target.

Alternative splicing of pre-mRNA is an essential post- and co-transcriptional mechanism of gene expression regulation that produces multiple mature mRNA transcripts from a single gene. Genetic mutations that affect splicing underlie numerous devastating diseases. The complexity of splicing regulation allows for multiple therapeutic approaches to correct disease-associated mis-splicing events. In this review, we first highlight recent findings from therapeutic strategies that have used splice switching antisense oligonucleotides and small molecules that bind directly to RNA. Second, we summarize different genetic and chemical approaches to target components of the spliceosome to correct splicing defects in pathological conditions. Finally, we present an overview of compounds that target kinases and accessory pathways that intersect with the splicing machinery. Advancements in the understanding of disease-specific defects caused by mis-regulation of alternative splicing will certainly increase the development of therapeutic options for the clinic. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.

Electrical and geometrical tuning of MoS2 field effect transistors via direct nanopatterning.

Mechanically exfoliated van der Waals materials can be used to prepare proof-of-concept electronic devices. Their optoelectronic properties strongly depend on the geometry and number of layers present in the exfoliated flake. Once the device fabrication steps have been completed, tuning the device response is complex, since the geometry and number of layers cannot be easily modified. In this work, we employ Pulsed Focused Electron Beam Induced Etching (PFEBIE) to tailor the geometry and electronic properties of field effect transistors based on mechanically exfoliated Molybdenum Disulfide (MoS2) flakes. First, MoS2 field effect transistors are fabricated via optical lithography and conventional methods. Then, the geometry of the MoS2 source-drain conduction channel is modified employing a Xenon difluoride (XeF2) gas injection nozzle combined with a pulsed electron beam pattern-generation system. Electrical characterization of devices carried out before and after the nanopatterning step via PFEBIE reveals a shift in the doping from N-type towards P-type. We attribute this change to sulfur vacancies induced during the direct nanopatterning step. This is confirmed by micro-Raman and micro-Photoluminescence spectroscopy experiments. The direct nanopatterning method allows us to fine-tune the geometry and thus the electronic properties of the devices, once the conventional fabrication steps have been completed. The success rate of our tailoring method exceeds 85% when tuning the geometry of the flake into a 250 nm wide and straight conduction channel between source and drain.

Maternal and neonatal characteristics of a Canadian urban cohort receiving treatment for opioid use disorder during pregnancy.

The epidemic of prescription and non-prescription opioid misuse is of particular importance in pregnancy. The Society of Obstetricians and Gynaecologists of Canada currently recommends opioid replacement therapy with methadone or buprenorphine for opioid-dependent women during pregnancy. This vulnerable segment of the population has been shown to be at increased risk of blood-borne infectious diseases, nutritional insecurity and stress. The objective of this study was to describe an urban cohort of pregnant women on opioid replacement therapy and to evaluate potential effects on the fetus. A retrospective chart review of all women on opioid replacement therapy and their infants who delivered at The Ottawa Hospital General and Civic campuses between January 1, 2013 and March 24, 2017 was conducted. Data were collected on maternal characteristics, pregnancy outcomes, neonatal outcomes and corresponding placental pathology. Maternal comorbidities identified included high rates of infection, tobacco use and illicit substance use, as well as increased rates of placental abruption compared with national averages. Compared with national baseline averages, the mean neonatal birth weight was low, and the incidence of small for gestational age infants and congenital anomalies was high. The incidence of NAS was comparable with estimates from other studies of similar cohorts. Findings support existing literature that calls for a comprehensive interdisciplinary risk reduction approach including dietary, social, domestic, psychological and other supports to care for opioid-dependent women in pregnancy.

Development of consensus-based national antimicrobial stewardship competencies for UK undergraduate healthcare professional education.

BACKGROUND: Healthcare professionals are involved in an array of patient- and medicine-related stewardship activities, for which an understanding and engagement with antimicrobial stewardship (AMS) is important. Undergraduate education provides an ideal opportunity to prepare healthcare professionals for these roles and activities. AIM: To provide UK national consensus on a common set of antimicrobial stewardship competencies appropriate for undergraduate healthcare professional education. METHODS: A modified Delphi approach comprising two online surveys delivered to a UK national panel of 21 individuals reflecting expertise in prescribing and medicines management with regards to the education and practice of nurses and midwives, pharmacists, physiotherapists, and podiatrists; and antimicrobial prescribing and stewardship. Data collection took place between October and December 2017. FINDINGS: A total of 21 participants agreed to become members of the expert panel, of whom 19 (90%) completed round 1 questionnaire, and 17 (89%) completed round 2. Panelists reached a consensus, with consistently high levels of agreement reached, on six overarching competency statements (subdivided into six domains), and 55 individual descriptors essential for antimicrobial stewardship by healthcare professionals. CONCLUSION: Due to the consistently high levels of agreement reached on competency statements and their associated descriptors, this competency framework should be used to direct education for undergraduate healthcare professionals, and those working in new clinical roles to support healthcare delivery where an understanding of, and engagement with, AMS is important. Although the competencies target basic education, they can also be used for continuing education.