Thermo-electro-optical properties of seamless metallic nanowire networks for transparent conductor applications.

Rapid reaction time, high attainable temperatures, minimum operating voltage, excellent optical transmittance, and tunable sheet resistance are all desirable properties of transparent conductors, which are important thin-film components in numerous electronic devices. A seamless nanowire network (NWN) refers to a structure composed of nanowires that lack interwire contact junctions, resulting in a continuous and uninterrupted network arrangement. This seamless nature leads to unique properties, including high conductivity and surface area-to-volume ratios, which make it a promising candidate for a vast application range in nanotechnology. Here, we have conducted an in-depth computational investigation to study the thermo-electro-optical properties of seamless nanowire networks and understand their geometrical features using in-house computational implementations and a coupled electrothermal model built in COMSOL Multiphysics software. Sheet resistance calculations were performed using Ohm's law combined with Kirchhoff circuit laws for a random resistor network and compared with those obtained employing COMSOL. In this work, aluminium, gold, copper, and silver nanowires are the materials of choice for testing the transparent conduction performance of our systems. We have studied a wide range of tuning parameters, including the network area fraction, the width-to-depth aspect ratio, and the length of the nanowire segments. We obtained corresponding figures of merit (optical transmittance versus sheet resistance) and temperature distributions to provide a complete characterization of the performance of real-world transparent conductors idealized with seamless NWNs. Our analysis accounted for the thermo-electro-optical responses of the NWNs and the inspection of various controlling parameters depending on system design considerations to shed light on how the electrical transport, optical qualities, and thermal management of these systems can be optimized.

Implementation lessons learnt when trialling palliative care interventions in the intensive care unit: relationships between determinants, implementation strategies, and models of delivery-a systematic review protocol.

BACKGROUND: Heterogeneity amongst palliative care interventions in the intensive care unit (ICU) and their outcomes has meant that, even when found to be effective, translation of evidence into practice is hindered. Previous evidence reviews have suggested that the field of ICU-based palliative care would benefit from well-designed, targeted interventions, with explicit knowledge translation research demonstrating valid implementation strategies. Reviewing effectiveness studies alongside process evaluations for these interventions will give insight into the implementation barriers or constraints identified, and the implementation strategies adopted. METHODS: A systematic review to identify and synthesise knowledge on how models of integrating palliative care into the ICU have been implemented and provide critical recommendations for successful future development and implementation of complex interventions in the field. The search will be carried out using MEDLINE, Embase, Cochrane, CINAHL, and PsycINFO. The search strategy will combine terms related to palliative care, intensive care, and implementation. Only full-text articles will be considered and conference abstracts excluded. There will be no date or language restrictions. The Implementation Research Logic Model will be used as a framework for synthesis. Findings will be reported following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. DISCUSSION: This review will provide understanding of implementation facilitators, barriers, and strategies, when employing palliative care interventions within the ICU. This will provide valuable recommendations for successful future development of complex interventions using implementation frameworks or theories. This can increase the potential for sustained change in practice, reduce heterogeneity in interventions, and therefore help produce measurable and comparable outcomes. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic reviews PROSPERO (CRD42022311052).

Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

PURPOSE: A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. PATIENTS AND METHODS: A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. RESULTS: A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41-24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). CONCLUSIONS: HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

Stormwater runoff reduction benefits of distributed curbside infiltration devices in an urban catchment.

Distributed infiltration systems can benefit downstream water bodies by reducing the runoff flowrate and volume discharges from the catchment. Investigating their runoff flowrate and volume reduction potential at the catchment scale will inform decision makers regarding their efficacy for managing catchment outflows. To this end, we conducted field investigations at the residential catchment scale for three years. The study monitored the catchment for one year before the installation of leaky well systems (preinstallation) and two years after installation (postinstallation). The hydrological model, calibrated to preinstallation catchment outflows, acted as a virtual control tool. Runoff flow outputs from the control model and two years of monitored runoff flow data from the postinstallation period were analysed using statistical methods. The statistical tests showed a significant 13% reduction in average flowrates in storms with a corresponding runoff flowrate of up to 50 L/s. The study further reported the ability of infiltration systems to reduce runoff volume in the catchment by 9%. This reduction was not significant, however, as per the results of the statistical analysis. We then fitted the generalized linear model (GLM) to the monitored and simulated runoff volume data. This enabled us to break down the effect of curbside infiltration systems on runoff volume according to corresponding peak flowrates during the storm. The results of the two-way ANOVA performed to detect significant differences in the regression slopes of the GLM indicated that curbside infiltration systems significantly reduced runoff volume for storms when the runoff flowrates remained below 100 L/s.

A case series study of an innovative community-based brief psychological model for men in suicidal crisis.

OBJECTIVES: To conduct a 1-year evaluation of James' Place, a suicidal crisis centre delivering a clinical intervention in a community setting. DESIGN: A case series study, following men entering the service during the first year of operation. PARTICIPANTS: Men experiencing a suicidal crisis referred to the service (N = 265), with N = 176 going on to engage in therapy. INTERVENTION: The James' Place Model is a therapeutic intervention offered to men who are in a suicidal crisis. Trained therapists provide a range of therapeutic approaches and interventions, focusing on decreasing suicidal distress and supporting men to develop resilience and coping strategies. MAIN OUTCOME MEASURES: CORE-34 Clinical Outcome Measure (CORE-OM). RESULTS: For all subscales of the CORE-OM there was a significant reduction in mean scores between assessment and discharge (p < 0.001), with all outcomes demonstrating a large effect size. All reductions illustrated a clinically significant change or a reliable change. CONCLUSIONS: Our results support the use of the James' Place Model for men in suicidal distress to aid in potentially preventing suicides in this high-risk group of the population.HighlightsEvaluates a brief psychological clinical intervention delivered in the community.Model effectively reduces suicide risk and findings can inform future services.Accessed men receiving an innovative intervention at the time of suicidal crisis.

The Mars Environmental Dynamics Analyzer, MEDA. A Suite of Environmental Sensors for the Mars 2020 Mission.

NASA's Mars 2020 (M2020) rover mission includes a suite of sensors to monitor current environmental conditions near the surface of Mars and to constrain bulk aerosol properties from changes in atmospheric radiation at the surface. The Mars Environmental Dynamics Analyzer (MEDA) consists of a set of meteorological sensors including wind sensor, a barometer, a relative humidity sensor, a set of 5 thermocouples to measure atmospheric temperature at ∼1.5 m and ∼0.5 m above the surface, a set of thermopiles to characterize the thermal IR brightness temperatures of the surface and the lower atmosphere. MEDA adds a radiation and dust sensor to monitor the optical atmospheric properties that can be used to infer bulk aerosol physical properties such as particle size distribution, non-sphericity, and concentration. The MEDA package and its scientific purpose are described in this document as well as how it responded to the calibration tests and how it helps prepare for the human exploration of Mars. A comparison is also presented to previous environmental monitoring payloads landed on Mars on the Viking, Pathfinder, Phoenix, MSL, and InSight spacecraft.

The 2021 ultrafast spectroscopic probes of condensed matter roadmap.

In the 60 years since the invention of the laser, the scientific community has developed numerous fields of research based on these bright, coherent light sources, including the areas of imaging, spectroscopy, materials processing and communications. Ultrafast spectroscopy and imaging techniques are at the forefront of research into the light-matter interaction at the shortest times accessible to experiments, ranging from a few attoseconds to nanoseconds. Light pulses provide a crucial probe of the dynamical motion of charges, spins, and atoms on picosecond, femtosecond, and down to attosecond timescales, none of which are accessible even with the fastest electronic devices. Furthermore, strong light pulses can drive materials into unusual phases, with exotic properties. In this roadmap we describe the current state-of-the-art in experimental and theoretical studies of condensed matter using ultrafast probes. In each contribution, the authors also use their extensive knowledge to highlight challenges and predict future trends.

Phosphaturic mesenchymal tumors: what an endocrinologist should know.

Tumor-induced osteomalacia (TIO), also known as "oncogenic osteomalacia", is a rare cause of osteomalacia. TIO often has an insidious onset characterized clinically by progressive muscle weakness and bone pain with fractures. The hallmark biochemical finding is a persistent low serum phosphorus concentration due to renal phosphate wasting. The vast majority of cases of TIO result from production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) by a histologically distinctive mesenchymal tumor, termed "phosphaturic mesenchymal tumor" (PMT). Circulating FGF23 induces internalization of renal sodium/phosphate co-transporters resulting in reduced proximal tubular phosphate reabsorption. FGF23 also inhibits production of 1α,25-dihydroxyvitamin D which is inappropriately low or normal in the context of hypophosphatemia. Diagnosis is often delayed owing to the rarity of the condition and an underappreciation for the role of phosphorus as a cause for the constellation of symptoms. Primary treatment for TIO is identification of the offending tumor and surgical removal. However, these tumors are notoriously difficult to find, precluding the opportunity for a curative surgery in many. In such cases, phosphate and calcitriol therapy is used to improve symptoms and heal the osteomalacia. Recently, molecular genetic studies have shown recurrent genetic events in PMT, including the novel fusions FN1-FGFR1 and less commonly FN1-FGF1. These fusion events are hypothesized to result in autocrine/paracrine signaling loops within the tumor, spurring tumorigenesis. This review will cover the clinical features, imaging characteristics, pathologic features, molecular genetic aspects, and therapy of PMT, with a brief discussion of other neoplasms that may cause TIO.

Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD.

Stimulant medication has long been effective in treating attention-deficit/hyperactivity disorder (ADHD) and is currently the first-line pharmacological treatment for children. Both methylphenidate and amphetamine modulate extracellular catecholamine levels through interaction with dopaminergic, adrenergic and serotonergic system components; it is therefore likely that catecholaminergic molecular components influence the effects of ADHD treatment. Using meta-analysis, we sought to identify predictors of pharmacotherapy to further the clinical implementation of personalized medicine. We identified 36 studies (3647 children) linking the effectiveness of methylphenidate treatment with DNA variants. Pooled-data revealed a statistically significant association between single nucleotide polymorphisms (SNPs) rs1800544 ADRA2A (odds ratio: 1.69; confidence interval: 1.12-2.55), rs4680 COMT (odds ratio (OR): 1.40; confidence interval: 1.04-1.87), rs5569 SLC6A2 (odds ratio: 1.73; confidence interval: 1.26-2.37) and rs28386840 SLC6A2 (odds ratio: 2.93; confidence interval: 1.76-4.90), and, repeat variants variable number tandem repeat (VNTR) 4 DRD4 (odds ratio: 1.66; confidence interval: 1.16-2.37) and VNTR 10 SLC6A3 (odds ratio: 0.74; confidence interval: 0.60-0.90), whereas the following variants were not statistically significant: rs1947274 LPHN3 (odds ratio: 0.95; confidence interval: 0.71-1.26), rs5661665 LPHN3 (odds ratio: 1.07; confidence interval: 0.84-1.37) and VNTR 7 DRD4 (odds ratio: 0.68; confidence interval: 0.47-1.00). Funnel plot asymmetry among SLC6A3 studies was identified and attributed largely to small study effects. Egger's regression test and Duval and Tweedie's 'trim and fill' were used to examine and correct for publication bias. These findings have major implications for advancing our therapeutic approach to childhood ADHD treatment.

Growth pattern-based grading of pulmonary adenocarcinoma-Analysis of 534 cases with comparison between observers and survival analysis.

OBJECTIVES: The 2015 WHO classification of pulmonary adenocarcinoma recommends recording observed architectural growth patterns in 5% increments for resected tumors, and determining the predominant growth pattern, which seems to be prognostic. There is debate over the best way to implement pattern-based grading, and whether such systems are reproducible. MATERIALS AND METHODS: 534 resected adenocarcinomas were reviewed by 2 pulmonary pathologists to determine predominant pattern and percentages of all observed patterns. Three different grading schemes were applied based on predicted prognosis scores: score 1 (lepidic), score 2 (acinar/papillary), and score 3 (solid/micropapillary/cribriform). Mucinous tumors were separately evaluated as both scores 2 and 3 since their prognosis is more ambiguous. The first grading scheme used the score of the predominant pattern; the second used the worst observed pattern score; and the third scored tumors with ≥80% lepidic growth as 1, tumors with ≥20% of any score 3 pattern(s) as 3, and all remaining as 2. RESULTS: The predominant pattern assigned by each observer was an exact match in 51.7% of cases, a "close match" in 27.3% (same prognosis score), and a mismatch in 21%. Predominant pattern determined by both observers showed significant stratification of overall and progression-free survival (OS and PFS, respectively). All 3 grading schemes showed a significant difference in OS and PFS determined by both observers; but the worst score scheme provided suboptimal results, likely due to a very small score 1 group, and this scheme did not maintain significance on multivariable analysis. Survival differences for all grading schemes maintained significance whether mucinous was considered score 2 or 3, but mucinous tumors trended towards poor survival. CONCLUSION: Pattern-based grading has prognostic significance in pulmonary adenocarcinoma. Interobserver variation is present, but two observers were able to predict significant differences in OS and PFS using various pattern-based grading schemes.

Material characterisation of nanowires with intrinsic stress.

When fabricating nanowires (NWs) in a doubly-clamped beam configuration it is possible for a residual axial stress to be generated. Here, we show that material characterisation of metal and semiconductor NWs subjected to residual axial stress can be problematic. Benchmark measurements of the Young's modulus of NWs are performed by sectioning a doubly-clamped NW into two cantilevered wires, eliminating residual axial stress. Use of models for doubly-clamped beams that incorporate the effects of residual stress are found to lead to ambiguity in the extracted Young's modulus as a function of displacement fit range, even for NWs with no residual stress. This is due to coupling of bending and axial stress effects at small displacements, and the limited displacement range of force curves prior to fracture or plastic deformation. This study highlights the importance of fabricating metal and semiconductor NWs that exhibit little or no residual axial stress for materials characterisation.

Implementation of the Needs Assessment Tool for patients with interstitial lung disease (NAT:ILD): facilitators and barriers.

A Needs Assessment Tool (NAT) was developed previously to help clinicians identify the supportive/palliative needs of people with interstitial lung disease (ILD) (NAT:ILD). This letter presents barriers and facilitators to clinical implementation. Data from (1) a focus group of respiratory clinicians and (2) an expert consensus group (respiratory and palliative clinicians, academics, patients, carers) were analysed using Framework Analysis. Barriers related to resources and service reconfiguration, and facilitators to clinical need, structure, objectiveness, flexibility and benefits of an 'aide-memoire'. Identified training needs included communication skills and local service knowledge. The NAT:ILD was seen as useful, necessary and practical in everyday practice.

The primacy of NF1 loss as the driver of tumorigenesis in neurofibromatosis type 1-associated plexiform neurofibromas.

Neurofibromatosis type 1 (NF1) is a common tumor-predisposition disorder due to germline mutations in the tumor suppressor gene NF1. A virtually pathognomonic finding of NF1 is the plexiform neurofibroma (PN), a benign, likely congenital tumor that arises from bi-allelic inactivation of NF1. PN can undergo transformation to a malignant peripheral nerve sheath tumor, an aggressive soft-tissue sarcoma. To better understand the non-NF1 genetic contributions to PN pathogenesis, we performed whole-exome sequencing, RNASeq profiling and genome-wide copy-number determination for 23 low-passage Schwann cell cultures established from surgical PN material with matching germline DNA. All resected tumors were derived from routine debulking surgeries. None of the tumors were considered at risk for malignant transformation at the time; for example, there was no pain or rapid growth. Deep (~500X) NF1 exon sequencing was also conducted on tumor DNA. Non-NF1 somatic mutation verification was performed using the Ampliseq/IonTorrent platform. We identified 100% of the germline NF1 mutations and found somatic NF1 inactivation in 74% of the PN. One individual with three PNs had different NF1 somatic mutations in each tumor. The median number of somatic mutations per sample, including NF1, was one (range 0-8). NF1 was the only gene that was recurrently somatically inactivated in multiple tumors. Gene Set Enrichment Analysis of transcriptome-wide tumor RNA sequencing identified five significant (FDR<0.01) and seven trending (0.01⩽FDR<0.02) gene sets related to DNA replication, telomere maintenance and elongation, cell cycle progression, signal transduction and cell proliferation. We found no recurrent non-NF1 locus copy-number variation in PN. This is the first multi-sample whole-exome and whole-transcriptome sequencing study of NF1-associated PN. Taken together with concurrent copy-number data, our comprehensive genetic analysis reveals the primacy of NF1 loss as the driver of PN tumorigenesis.

TET2 binds the androgen receptor and loss is associated with prostate cancer.

Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine proximal to KLK3. A gene co-expression network identified using TCGA prostate tumour RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signalling. Decreased TET2 mRNA expression in TCGA PCa tumours is strongly associated with reduced patient survival, indicating reduced expression in tumours may be an informative biomarker of disease progression and perhaps metastatic disease.

Co-percolation to tune conductive behaviour in dynamical metallic nanowire networks.

Nanowire networks act as self-healing smart materials, whose sheet resistance can be tuned via an externally applied voltage stimulus. This memristive response occurs due to modification of junction resistances to form a connectivity path across the lowest barrier junctions in the network. While most network studies have been performed on expensive noble metal nanowires like silver, networks of inexpensive nickel nanowires with a nickel oxide coating can also demonstrate resistive switching, a common feature of metal oxides with filamentary conduction. However, networks made from solely nickel nanowires have high operation voltages which prohibit large-scale material applications. Here we show, using both experiment and simulation, that a heterogeneous network of nickel and silver nanowires allows optimization of the activation voltage, as well as tuning of the conduction behavior to be either resistive switching, memristive, or a combination of both. Small percentages of silver nanowires, below the percolation threshold, induce these changes in electrical behaviour, even for low area coverage and hence very transparent films. Silver nanowires act as current concentrators, amplifying conductivity locally as shown in our computational dynamical activation framework for networks of junctions. These results demonstrate that a heterogeneous nanowire network can act as a cost-effective adaptive material with minimal use of noble metal nanowires, without losing memristive behaviour that is essential for smart sensing and neuromorphic applications.

Paediatric learning in a clinical attachment: undergraduate medical students' perspectives.

BACKGROUND: The clinical environment in paediatrics presents many unique challenges for medical students to achieve clinical proficiency. AIMS: Our study aimed to explore how different elements of the paediatric rotation aid medical students in achieving learning outcomes at the undergraduate stage. METHODS: Using a small-scale exploratory case study, three focus group interviews were conducted with 19 participants by an independent facilitator. Students' self-reported levels of achievement of module learning outcomes were also analysed. Qualitative data were recorded, transcribed and thematically analysed. Open coding was initially employed; codes were then refined into categories and grouped. Themes were identified, reviewed and defined. RESULTS: Students highlighted several key themes including trainee factors, teacher factors and environmental factors that were associated with positive learning environments. These included the opportunity to contribute to the patient care, feeling like part of the team. CONCLUSIONS: A clinical learning environment that allows medical students to become actively involved in patient care and to contribute as members to the clinical team can enhance their learning experience.

Programmability of nanowire networks.

Electrical connectivity in networks of nanoscale junctions must be better understood if nanowire devices are to be scaled up from single wires to functional material systems. We show that the natural connectivity behaviour found in random nanowire networks presents a new paradigm for creating multi-functional, programmable materials. In devices made from networks of Ni/NiO core-shell nanowires at different length scales, we discover the emergence of distinct behavioural regimes when networks are electrically stressed. We show that a small network, with few nanowire-nanowire junctions, acts as a unipolar resistive switch, demonstrating very high ON/OFF current ratios (>10(5)). However, large networks of nanowires distribute an applied bias across a large number of junctions, and thus respond not by switching but instead by evolving connectivity. We demonstrate that these emergent properties lead to fault-tolerant materials whose resistance may be tuned, and which are capable of adaptively reconfiguring under stress. By combining these two behavioural regimes, we demonstrate that the same nanowire network may be programmed to act both as a metallic interconnect, and a resistive switch device with high ON/OFF ratio. These results enable the fabrication of programmable, multi-functional materials from random nanowire networks.