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Abstract The field of digital identity innovation has grown significantly over the last 30 years, with over 6000 technology patents registered worldwide. However, many questions remain about who controls and owns our digital identity and intellectual property and, ultimately, where the future of digital identity is heading. To investigate this further, this research mines digital identity patents and explores core themes such as identity, systems, privacy, security, and emerging fields like blockchain, financial transactions, and biometric technologies, utilizing natural language processing (NLP) methods including part-of-speech (POS) tagging, clustering, topic classification, noise reduction, and lemmatisation techniques. Finally, the research employs graph modelling and statistical analysis to discern inherent trends and forecast future developments. The findings significantly contribute to the digital identity landscape, identifying key players, emerging trends, and technological progress. This research serves as a valuable resource for academia and industry stakeholders, aiding in strategic decision-making and investment in emerging technologies and facilitating navigation through the dynamic realm of digital identity technologies.

Cerebrospinal fluid (CSF)-venous fistula represents a formidable yet often overlooked neurosurgical dilemma. Despite its disabling consequences, it remains significantly underdiagnosed. This abstract sheds light on the clinical intricacies, diagnostic challenges, and therapeutic interventions associated with CSF-venous fistula. Early diagnosis is paramount, yet hindered by its rarity and diverse and often unspecific clinical presentations. The importance of heightened awareness among clinicians and radiologists for timely detection and management cannot be overstated. This presentation will draw upon a review of clinical cases operated in the Royal Hallamshire Hospital, supplemented by a concise surgical video which is focused on surgical technique and benefit of microscope mediated augmented reality.

Abstract Complex multi-element alloys are gaining prominence for structural applications, supplementing steels, and superalloys. Understanding the impact of each element on alloy surfaces due to oxidation is vital in maintaining material integrity. This study investigates oxidation mechanisms in these alloys using a model five-element equiatomic CoCrFeNiMn alloy, in a controlled oxygen environment. The oxidation-induced surface changes correlate with each element’s interactive tendencies with the environment, guided by thermodynamics. Initial oxidation stages follow atomic size and redox potential, with the latter becoming dominant over time, causing composition inversion. The study employs in-situ atom probe tomography, transmission electron microscopy, and X-ray absorption near-edge structure techniques to elucidate the oxidation process and surface oxide structure evolution. Our findings deconvolute the mechanism for compositional and structural changes in the oxide film and will pave the way for a predictive design of complex alloys with improved resistance to oxidation under extreme conditions.

Background: Taeniosis and cysticercosis are human infections caused by the pork tapeworm, Taenia solium. This study is a baseline for community-based intervention. We determined the prevalence of human cysticercosis and associated risk factors following a deworming program conducted throughout the country, with Mbulu District being among the districts in Northern Tanzania. Methods: Human cysticercosis was determined by enzyme-linked immunosorbent assay (Ag- ELISA). Household interviews and observations were conducted to identify risk factors for cysticercosis transmissions among households and communities. Results: Three hundred individuals participated in this study. The age ranged from 5 to 89 years, with a median of 19 years. The prevalence of human cysticercosis was 23 (7.67%). The prevalence was high with 6 (11.76%) among individuals aged 26 to 35 years and ±45 years. There was no statistically significant difference in the prevalence by age group, sex, or occupation. Among the 300 participants, 82 (27.3%) had received anthelmintics during the previous year; among these, 5 (21.7%) were infected. The likelihood of infection was low among anthelmintic users by 28% [0.72 (0.26–2.01)], but the protection was not significant. The communities differed in risk factors on the availability of a clean and safe water supply; 52.7% (46/86) of households visited had no pit latrine. The cysticercosis prevalence showed a significant difference in communities. Conclusions: The prevalence of human cysticercosis was high and associated with higher age groups. The prevalence was low among those who had taken anthelmintics and was associated with lower age groups. The current school deworming program has a positive effect on school children, while the elderly are at higher risk because the intervention did not target them. It is recommended to scale up anthelmintic intervention to higher age groups.

Taeniosis and cysticercosis are infections caused by cestodes, Taenia solium is among them. T.solium neurocysticercosis accounts for 30% of acquired epilepsy in human in developing countries. This study was carried out to determine the prevalence of cysticercosis among domestic pigs in Mbulu district following deworming intervention. The study was conducted among three rural communities monitoring community intervention in Mbulu district between March 2020 and September 2021. Live pigs were diagnosed by lingual examination for the presence of T. solium cysticerci, and pig-rearing practices were recorded. Logistic regression was performed to determine the role of risk factors on pig infection outcome. We conveniently sampled 510 pigs; 267 (52.4%) were sampled in the year 2020 and 243 (47.6%) in 2021. All pigs were examined by lingual examination for the presence of pork tapeworm larvae, and 43 (8.4%) pigs were found to be infected. Twenty-one (48.8%) of the infected pigs were males and 22 (51.2%) were females, and the overall annual prevalence of tapeworm larvae was 9% and 7.8% for 2020 and 2021, respectively. The pigs were twice more likely to be found infected during the rainy season compared to the dry season in 2020 (OR = 2.27, 95%CI of 1.16–7.22). The reported pig-rearing practices were free-range, penned, and tethered, 141 (52.8%), 64 (24%), and 62 (23.2%), respectively. Of the 94 visited households in 2020, 78 (83%) reported drinking water without boiling, and 59 (62.8%) household leaders reported having heard about taeniosis/cysticercosis. The prevalence of cysticercosis among domestic pigs in this study was high, with seasonal variations. Despite the ongoing national school deworming and community deworming program, there was no significant change in the prevalence of cysticercosis over two consecutive years. The reported pig infections imply fecal-oral transmission with humans tapeworm eggs released from infected humans. Most households reported consuming unboiled drinking water that might be contaminated. Integrating pig vaccination and deworming, health education and school or community deworming along with improved pig management practice and general community water sanitation hygiene (WASH) are recommended to reduce the burden of pork tapeworm in the study communities.

Background: Advances in targeted therapy development and tumor sequencing technology are reclassifying cancers into smaller biomarker-defined diseases. Randomized controlled trials (RCTs) are often impractical in rare diseases, leading to calls for single-arm studies to be sufficient to inform clinical practice based on a strong biological rationale. However, without RCTs, favorable outcomes are often attributed to therapy but may be due to a more indolent disease course or other biases. When the clinical benefit of targeted therapy in a common cancer is established in RCTs, this benefit may extend to rarer cancers sharing the same biomarker. However, careful consideration of the appropriateness of extending the existing trial evidence beyond specific cancer types is required. A framework for extrapolating evidence for biomarker-targeted therapies to rare cancers is needed to support transparent decision-making. Objectives: To construct a framework outlining the breadth of criteria essential for extrapolating evidence for a biomarker-targeted therapy generated from RCTs in common cancers to different rare cancers sharing the same biomarker. Design: A series of questions articulating essential criteria for extrapolation. Methods: The framework was developed from the core topics for extrapolation identified from a previous scoping review of methodological guidance. Principles for extrapolation outlined in guidance documents from the European Medicines Agency, the US Food and Drug Administration, and Australia’s Medical Services Advisory Committee were incorporated. Results: We propose a framework for assessing key assumptions of similarity of the disease and treatment outcomes between the common and rare cancer for five essential components: prognosis of the biomarker-defined cancer, biomarker test analytical validity, biomarker actionability, treatment efficacy, and safety. Knowledge gaps identified can be used to prioritize future studies. Conclusion: This framework will allow systematic assessment, standardize regulatory, reimbursement and clinical decision-making, and facilitate transparent discussions between key stakeholders in drug assessment for rare biomarker-defined cancers.

**Introduction**: The authors reviewed close/positive margins in cutaneous squamous cell carcinoma of the head and neck, ensuing recurrence, regional or systemic metastasis, mortality and follow-up management. **Methods**: The design was a systematised review from January 2000 to July 2021. The MEDLINE database was searched with 15 articles out of 3104 meeting the inclusion criteria. Pertinent references underpinning the National Comprehensive Cancer Network’s Squamous Cell Skin Cancer Guidelines Version 2.2022 were reviewed. **Results**: Overall, there were 13,671 cutaneous squamous cell carcinoma lesions. We found pooled rates for positive excision (14.6% at 99% CI [12.97, 16.26]), ensuing recurrence (14.7% at 99% CI [13.51, 15.83]), regional or systemic metastasis (33.8% at 99% CI [33.77, 33.87]), and mortality (46.6% at 99% CI [42.53, 50.65]). Positive excisions most frequently involved the deep margin (73.7%), nose (34.5%) and ear (33.14%). Re-excision of positive margins appeared to confer worse recurrence (35.4%). We found pooled rates for close/positive excision (17% at 99% CI [15.22, 18.84]), ensuing recurrence (17% at 99% CI [15.76, 18.16]), regional or systemic metastasis (30.4% at 99% CI [26.15, 34.73]), and mortality (46.6% at 99% CI [42.53, 50.65]). Mean follow up was 51 months. Surgical re-excision with adequate margins appeared to be most efficacious, followed by radiotherapy. Chemoradiation and chemotherapy appeared less efficacious. **Conclusion**: Surgical re-excision with adequate margins remains the gold standard for close/positive margins in cutaneous squamous cell carcinoma of the head and neck, followed by radiotherapy.

Cyber attacking is easier than cyber defending—attackers only need to find one breach, while the defenders must successfully repel all attacks. This research demonstrates how cyber defenders can increase their capabilities by joining forces with eXplainable-AI (XAI) utilizing interactive human-machine collaboration. With a global shortfall of cyber defenders there is a need to amplify their skills using AI. Cyber asymmetries make propositional machine learning techniques impractical. Human reasoning and skill is a key ingredient in defense and must be embedded in the AI framework. For Human-Machine collaboration to work requires that the AI is an ultra-strong machine learner and can explain its models. Unlike Deep Learning, Inductive Logic Programming can communicate what it learns to a human. An empirical study was undertaken using six months of eavesdropped network traffic from an organization generating up-to 562K network events daily. Easier-to-defend devices were identified using a form of the Good-Turing Frequency estimator which is a promising form of volatility measure. A behavioral cloning grammar in explicit symbolic form was then produced from a single device's network activity using the compression algorithm SEQUITUR. A novel visualization was generated to allow defenders to identify network sequences they wish to explain. Interactive Inductive Logic Programming (the XAI) is supplied the network traffic meta data, sophisticated pre-existing cyber security background knowledge, and one recurring sequence of events from a single device to explain. A co-inductive process between the human cyber defender and the XAI where the human is able to understand, then refute and shape the XAI's developing model, to produce a model that conforms with the data as well as the original device designers programming. The acceptable model is in a form that can be deployed as an ongoing active cyber defense.

BackgroundMultiple myeloma is diagnosed in 5,800 people in the United Kingdom (UK) each year with up to 64% having vertebral compression fractures at the time of diagnosis. Painful vertebral compression fractures can be of significant detriment to patients’ quality of life. Percutaneous vertebroplasty aims to provide long-term pain relief and stabilize fractured vertebrae.Methods and materialsData was collected from all cases of percutaneous vertebroplasty performed on patients with multiple myeloma from November 2017 to January 2019. Pain scores were measured using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) pre-procedure, 2 months post procedure and 4 years post-procedure. Procedure related complications and analgesia use were also documented.Results22 patients were included with a total of 119 vertebrae treated. Patients reported a significant improvement in overall pain score with a median pre-procedure VAS of 8 and a median post-procedure VAS of 3.5 (p

The per capita municipal solid waste (MSW) generation per day in Ghana is estimated to be 0.47 kg/person/day, which translates to over 14,000 tonnes of solid waste generation daily. The disposal and management of this amount of solid waste has been challenging worldwide, and in Ghana, this is evident with the creation of unsanitary dumping sites scattered across most communities in the country, especially urban communities. The indiscriminate disposal of solid waste in Ghana is known to cause flooding, the pollution of water bodies, and the spread of diseases. The purpose of this review is to highlight the prospects of waste incineration with energy recovery as a waste-to-energy (WtE) technology which has contributed immensely to the disposal and management of MSW in nations worldwide (especially developed ones). The review indicates that waste incineration with energy recovery is a matured waste-to-energy technology in developed nations, and there are currently about 492 waste incineration plants in operation in the EU, over 77 in operation in about 25 states in the USA, and about 1900 in operation in Japan. Waste incineration with energy recovery is also gradually gaining prominence in developing nations like China, Brazil, Bangladesh, Nigeria, Indonesia, and Pakistan. The adoption of waste incineration with energy technology can reduce Ghana’s overdependence on fossil fuels as primary sources of energy. It is, however, recommended that a techno-economic assessment of proposed waste incineration facilities is performed considering the MSW generated in Ghana. Additionally, it is also recommended that the possibility of incorporating the use of artificial intelligence technology into the management of MSW in Ghana be investigated.

Background The Medicare Annual Wellness Visit (AWV) allows providers to acquire critical information about patients’ health through a review of vitals, environmental risks, and medical and family history. These visits are free to those enrolled in Medicare and prioritize patient–provider relationship building and preventative care. Despite this, AWV completion rates are suboptimal.Methods A quality improvement project was aimed to increase the percentage of AWVs among Medicare patients in a primary care internal medicine practice from a baseline of 1.7% completion to 2.7% in 3 months from January to April 2023.Intervention With eligible patients identified, a standardized approach was created where an AWV appointment was ordered, and a patient message explaining the benefit of the appointment was sent by the patient portal.Results Our AWV intervention resulted in 72 patients being seen for an AWV, which increased the percentage of completed AWVs in the division by 2.1% from 1.7% to 3.8% in 3 months.Conclusion This intervention will continue to improve AWV rates and improve patient care for Medicare patients in internal medicine. It could be applied to other areas of primary care and within other health systems.

BackgroundTuberculosis remains a significant global health concern, especially for People Living with HIV, who are at an increased risk of severe TB disease. Despite the availability of TB Preventive Treatment, knowledge gaps persist among People Living with HIV regarding its importance, accessibility, and administration. The study aimed to assess TPT knowledge levels and determinants among People Living with HIV in Tanzania.MethodsA cross-sectional survey was conducted from April to May 2023 in 12 regions of mainland Tanzania. The study included PLHIV aged 18 years and above, receiving HIV care in selected Care and Treatment Centers. Data were collected through face-to-face interviews using a semi-structured questionnaire covering sociodemographic characteristics and Tuberculosis preventive treatment knowledge. Descriptive statistics, chi-square tests, and logistic regression analyses were employed for data analysis.ResultsOut of the 391 People Living with HIV interviewed, 71.4% demonstrated adequate Tuberculosis preventive treatment knowledge. Female participants, those attending urban health facilities, and individuals with longer durations of HIV care exhibited higher Tuberculosis preventive treatment knowledge levels. However, knowledge disparities persisted based on demographic characteristics such as gender and location of health facilities.ConclusionWhile a considerable portion of People Living with HIV demonstrated adequate higher Tuberculosis preventive treatment knowledge, addressing gaps among those with lower understanding is crucial. Targeted education campaigns tailored to the needs of People Living with HIV, especially in rural areas and among male populations, are essential. Collaborative efforts between national health programs and community organizations are vital to integrate Tuberculosis preventive treatment awareness effectively into comprehensive HIV care programs, ultimately reducing the burden of Tuberculosis among People Living with HIV and the general population.

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. High levels of free fatty acids in the liver impair hepatic lysosomal acidification and reduce autophagic flux. We investigate whether restoration of lysosomal function in NAFLD recovers autophagic flux, mitochondrial function, and insulin sensitivity. Here, we report the synthesis of novel biodegradable acid-activated acidifying nanoparticles (acNPs) as a lysosome targeting treatment to restore lysosomal acidity and autophagy. The acNPs, composed of fluorinated polyesters, remain inactive at plasma pH, and only become activated in lysosomes after endocytosis. Specifically, they degrade at pH of ~6 characteristic of dysfunctional lysosomes, to further acidify and enhance the function of lysosomes. In established in vivo high fat diet mouse models of NAFLD, re-acidification of lysosomes via acNP treatment restores autophagy and mitochondria function to lean, healthy levels. This restoration, concurrent with reversal of fasting hyperglycemia and hepatic steatosis, indicates the potential use of acNPs as a first-in-kind therapeutic for NAFLD.

Abstract Tuberculosis (TB) disproportionally affects persons and families who are economically and socially disadvantaged. Therefore, a patient cost survey was conducted in Tanzania to evaluate the costs incurred by patients and their households before and after the diagnosis of TB. It was the first survey in Tanzania to ascertain baseline information and experience for subsequent surveys. This paper aims to share the experience encountered during the survey to ensure a standardized approach and elimination of potential barriers for the implementation of future surveys. A total of 777 TB patients from 30 clusters selected based on probability proportional to the size were interviewed during the study period. As the sample size was calculated based on notification data from the previous year, some health facilities experienced an inadequate number of TB patients during the study to meet the allocated cluster size for the survey. Most facilities had poor recording and recordkeeping in TB registers where deaths were not registered, and some patients had not been assigned district identification numbers. Fixed days for TB drug refills in health facilities affected the routine implementation of the survey as the interviews were conducted when patients visited the facility to pick up the drugs. Tablets used to collect data failed to capture the geographic location in some areas. The households of TB patients lost to follow-up and those who had died during TB treatment were not included in the survey. When planning and preparing for patient costs surveys, it is important to consider unforeseen factors which may affect planned activities and findings. During the survey in Tanzania, the identified challenges included survey logistics, communications, patient enrollment, and data management issues. To improve the quality of the findings of future surveys, it may be reasonable to revise survey procedures to include households of TB patients who were lost to follow-up and those who died during TB treatment; the households of such patients may have incurred higher direct and indirect costs than households whose patient was cured as a result of receiving TB treatment.

Abstract Background Mycobacterium tuberculosis presents several lineages each with distinct characteristics of evolutionary status, transmissibility, drug resistance, host interaction, latency, and vaccine efficacy. Whole genome sequencing (WGS) has emerged as a new diagnostic tool to reliably inform the occurrence of phylogenetic lineages of Mycobacterium tuberculosis and examine their relationship with patient demographic characteristics and multidrug-resistance development. Methods 191 Mycobacterium tuberculosis isolates obtained from a 2017/2018 Tanzanian drug resistance survey were sequenced on the Illumina Miseq platform at Supranational Tuberculosis Reference Laboratory in Uganda. Obtained fast-q files were imported into tools for resistance profiling and lineage inference (Kvarq v0.12.2, Mykrobe v0.8.1 and TBprofiler v3.0.5). Additionally for phylogenetic tree construction, RaxML-NG v1.0.3(25) was used to generate a maximum likelihood phylogeny with 800 bootstrap replicates. The resulting trees were plotted, annotated and visualized using ggtree v2.0.4 Results Most [172(90.0%)] of the isolates were from newly treated Pulmonary TB patients. Coinfection with HIV was observed in 33(17.3%) TB patients. Of the 191 isolates, 22(11.5%) were resistant to one or more commonly used first line anti-TB drugs (FLD), 9(4.7%) isolates were MDR-TB while 3(1.6%) were resistant to all the drugs. Of the 24 isolates with any resistance conferring mutations, 13(54.2%) and 10(41.6%) had mutations in genes associated with resistance to INH and RIF respectively. The findings also show four major lineages i.e. Lineage 3[81 (42.4%)], followed by Lineage 4 [74 (38.7%)], the Lineage 1 [23 (12.0%)] and Lineages 2 [13 (6.8%)] circulaing in Tanzania. Conclusion The findings in this study show that Lineage 3 is the most prevalent lineage in Tanzania whereas drug resistant mutations were more frequent among isolates that belonged to Lineage 4.

Right ventricular outflow tract ventricular tachycardia (RVOT VT) is a well-recognised subtype of idiopathic ventricular tachyarrhythmia and often described in young healthy individuals. This arrhythmia typically occurs in patients with a structurally normal heart, and in this context is generally considered benign. In this case we present a rare association between RVOT VT and a ruptured sinus of Valsalva aneurysm in a patient known to have a restrictive ventricular septal defect. Prompt surgical intervention was necessary to prevent potentially life threatening consequences.The diagnostic and surgical evaluation learnt from this case would be useful to remind clinicians to explore rarer causes of RVOT VT especially when patients have underlying congenital heart disease. This case also highlights the importance of utilizing multi-modality imaging for the anatomical assessment of this pathology, which aids definitive management.

Abstract Background Although tuberculosis (TB) care is free in Tanzania, TB-associated costs may compromise access to services and treatment adherence resulting in poor outcomes and increased risk of transmission in the community. TB can impact economically patients and their households. We assessed the economic burden of TB on patients and their households in Tanzania and identified cost drivers to inform policies and programs for potential interventions to mitigate costs. Methods We conducted a nationally representative cross-sectional survey using a standard methodology recommended by World Health Organization. TB patients of all ages and with all types of TB from 30 clusters across Tanzania were interviewed during July – September 2019. We used the human capital approach to assess the indirect costs and a threshold of 20% of the household annual expenditure to determine the proportion of TB-affected households experiencing catastrophic cost. We descriptively analyzed the cost data and fitted multivariable logistic regression models to identify potential predictors of catastrophic costs. Results Of the 777 TB-affected households, 44.9% faced catastrophic costs due to TB. This proportion was higher (80.0%) among households of patients with multi-drug resistant TB (MDR-TB). Overall, cost was driven by income loss while accessing TB services (33.7%), nutritional supplements (32.6%), and medical costs (15.1%). Most income loss was associated with hospitalization and time for picking up TB drugs. Most TB patients (85.9%) reported worsening financial situations due to TB, and over fifty percent (53.0%) borrowed money or sold assets to finance TB treatment. In multivariable analysis, the factors associated with catastrophic costs included hospitalization (adjusted odds ratio [aOR] = 34.9; 95% confidence interval (CI):12.5–146.17), living in semi-urban (aOR = 1.6; 95% CI:1.0–2.5) or rural areas (aOR = 2.6; 95% CI:1.8–3.7), having MDR-TB (aOR = 3.4; 95% CI:1.2–10.9), and facility-based directly-observed treatment (DOT) (aOR = 7.2; 95% CI:2.4–26.6). Conclusion We found that the cost of TB care is catastrophic for almost half of the TB-affected households in Tanzania; our findings support the results from other surveys recently conducted in sub-Saharan Africa. Collaborative efforts across health, employment and social welfare sectors are imperative to minimize household costs due to TB disease and improve access to care, patient adherence and outcomes.

BackgroundPneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data.MethodsWe used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from diverse domain areas. The model performance was evaluated based on both quantitative metrics and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of a particularly high degree of uncertainty around data or domain expert knowledge.ResultsDesigned to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an area under the receiver operating characteristic curve of 0.8 in predicting clinically-confirmed bacterial pneumonia with sensitivity 88% and specificity 66% given certain input scenarios (i.e., information that is available and entered into the model) and trade-off preferences (i.e., relative weightings of the consequences of false positive versus false negative predictions). We specifically highlight that a desirable model output threshold for practical use is very dependent upon different input scenarios and trade-off preferences. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures.ConclusionsTo our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. We have shown how the method works and how it would help decision making on the use of antibiotics, providing insight into how computational model predictions may be translated to actionable decisions in practice. We discussed key next steps including external validation, adaptation and implementation. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.

BackgroundCerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis.MethodsA dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score.ResultsCSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches.ConclusionNeural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling.

IntroductionThe BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine.MethodsHere, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.Results and discussionOverall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P

Several studies highlight how the coronavirus (COVID-19) lockdowns have permanently changed the way people travel, but there has been less focus on impacts outside major metropolitan areas, where alternative transportation modes are more limited or scarce. This case study focuses on the long-term effects of the COVID-19 lockdowns on public transit and bikesharing using micro-level data in Lane County, Oregon. Lane County reflects the nearly 3,000 small U.S. counties that are a mixture of rural and urban landscape. Findings show that both transportation modes have begun to recover after large reductions in usage, though bikesharing seems to be less resilient relative to public transit 18-months post-lockdown. Additionally, findings show changes in bus ridership and bikeshare trips differed based on sociodemographic characteristics, though bikeshare trips were more sensitive to change. For example, there were statistically significant differences in bikeshare trips among tracts with a higher proportion of Black, Hispanic, or low-income residents, but no such differences for bus ridership. Given that small U.S. counties are typically less diverse, if not addressed, inequitable access could worsen in the long-run. Results from this case study could help inform other small U.S. counties, especially those that do not have the resources to collect micro-level data and are based around a university or where public transit is free for a large portion of the population, on future local policies regarding urban mobility and equity.

Sea ice is a key habitat in the high latitude Southern Ocean and is predicted to change in its extent, thickness and duration in coming decades. The sea-ice cover is instrumental in mediating ocean–atmosphere exchanges and provides an important substrate for organisms from microbes and algae to predators. Antarctic krill, Euphausia superba, is reliant on sea ice during key phases of its life cycle, particularly during the larval stages, for food and refuge from their predators, while other small grazers, including copepods and amphipods, either live in the brine channel system or find food and shelter at the ice-water interface and in gaps between rafted ice blocks. Fish, such as the Antarctic silverfish Pleuragramma antarcticum, use platelet ice (loosely-formed frazil crystals) as an essential hatching and nursery ground. In this paper, we apply the framework of the Marine Ecosystem Assessment for the Southern Ocean (MEASO) to review current knowledge about relationships between sea ice and associated primary production and secondary consumers, their status and the drivers of sea-ice change in this ocean. We then use qualitative network modelling to explore possible responses of lower trophic level sea-ice biota to different perturbations, including warming air and ocean temperatures, increased storminess and reduced annual sea-ice duration. This modelling shows that pelagic algae, copepods, krill and fish are likely to decrease in response to warming temperatures and reduced sea-ice duration, while salp populations will likely increase under conditions of reduced sea-ice duration and increased number of days of >0°C. Differences in responses to these pressures between the five MEASO sectors were also explored. Greater impacts of environmental pressures on ice-related biota occurring presently were found for the West and East Pacific sectors (notably the Ross Sea and western Antarctic Peninsula), with likely flow-on effects to the wider ecosystem. All sectors are expected to be impacted over coming decades. Finally, we highlight priorities for future sea ice biological research to address knowledge gaps in this field.

ObjectiveDespite progress in endonasal skull-base neurosurgery, cerebrospinal fluid (CSF) rhinorrhoea remains common and significant. The CRANIAL study sought to determine 1) the scope of skull-base repair methods used, and 2) corresponding rates of postoperative CSF rhinorrhoea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull-base tumors.MethodsA prospective observational cohort study of 30 centres performing endonasal skull-base neurosurgery in the UK and Ireland (representing 91% of adult units). Patients were identified for 6 months and followed up for 6 months. Data collection and analysis was guided by our published protocol and pilot studies. Descriptive statistics, univariate and multivariable logistic regression models were used for analysis.ResultsA total of 866 patients were included - 726 TSA (84%) and 140 EEA (16%). There was significant heterogeneity in repair protocols across centres. In TSA cases, nasal packing (519/726, 72%), tissue glues (474/726, 65%) and hemostatic agents (439/726, 61%) were the most common skull base repair techniques. Comparatively, pedicled flaps (90/140, 64%), CSF diversion (38/140, 27%), buttresses (17/140, 12%) and gasket sealing (11/140, 9%) were more commonly used in EEA cases. CSF rhinorrhoea (biochemically confirmed or requiring re-operation) occurred in 3.9% of TSA (28/726) and 7.1% of EEA (10/140) cases. A significant number of patients with CSF rhinorrhoea (15/38, 39%) occurred when no intraoperative CSF leak was reported. On multivariate analysis, there may be marginal benefits with using tissue glues in TSA (OR: 0.2, CI: 0.1-0.7, p

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging modality that enables observation of metabolites. Applications of MRSI for neuroimaging have shown promise for monitoring and detecting various diseases. This study builds off previously developed techniques of short TR, 1H FID MRSI by correcting for T1-weighting of the metabolites and utilizing an internal water reference to produce quantitative (mmol kg−1) metabolite maps. This work reports and shows quantitative metabolite maps for 12 metabolites for a single slice. Voxel-specific T1-corrections for water are common in MRSI studies; however, most studies use either averaged T1-relaxation times to correct for T1-weighting of metabolites or omit this correction step entirely. This work employs the use of voxel-specific T1-corrections for metabolites in addition to water. Utilizing averaged T1-relaxation times for metabolites can bias metabolite maps for metabolites that have strong differences between T1-relaxation for GM and WM (i.e. Glu). This work systematically compares quantitative metabolite maps to single voxel quantitative results and qualitatively compares metabolite maps to previous works.

There is very little knowledge regarding autistic adult services, practices, and delivery. The study objective was to improve understanding of current services and practices for autistic adults and opportunities for improvement as part of the Autism Spectrum Disorder in the European Union (ASDEU) project. Separate survey versions were created for autistic adults, carers of autistic adults, and professionals in adult services. 2,009 persons responded to the survey and 1,085 (54%) of them completed at least one of the services sections: 469 autistic adults (65% female; 55% 50% responded “don’t know”). Five of seven residential services features recommended for autistic adults were experienced by

Abstract Ice-associated microalgae make a significant seasonal contribution to primary production and biogeochemical cycling in polar regions. However, the distribution of algal cells is driven by strong physicochemical gradients which lead to a degree of microspatial variability in the microbial biomass that is significant, but difficult to quantify. We address this methodological gap by employing a field-deployable hyperspectral scanning and photogrammetric approach to study sea-ice cores. The optical set-up facilitated unsupervised mapping of the vertical and horizontal distribution of phototrophic biomass in sea-ice cores at mm-scale resolution (using chlorophyll a [Chl a] as proxy), and enabled the development of novel spectral indices to be tested against extracted Chl a (R2 ≤ 0.84). The modelled bio-optical relationships were applied to hyperspectral imagery captured both in situ (using an under-ice sliding platform) and ex situ (on the extracted cores) to quantitatively map Chl a in mg m−2 at high-resolution (≤ 2.4 mm). The optical quantification of Chl a on a per-pixel basis represents a step-change in characterising microspatial variation in the distribution of ice-associated algae. This study highlights the need to increase the resolution at which we monitor under-ice biophysical systems, and the emerging capability of hyperspectral imaging technologies to deliver on this research goal.

Abstract Background National institutes and education initiatives emphasize the need to prepare future biologists to apply discoveries in science towards solving problems that are both social and scientific in nature. Research from socio-scientific, design-based, and problem-based learning demonstrates that contextualized, real-world tasks can improve students’ ability to apply their scientific knowledge in practical ways to navigate social problems. Biomimicry Design is an interdisciplinary field requiring biology and design skills; it informs the creation of sustainable designs through emulation of biological structures and functions that arise as a result of natural selection. Notably, engaging in biomimicry design targets an important biology and engineering learning outcome: understanding of how structure influences function. This study leveraged the practices of biomimicry along with those of design-based learning (DBL) to improve student outcomes in an evolutionary biology undergraduate course. Through DBL, the authors aimed to (1) ignite deeper understanding of how structure determines function in nature (a cross-disciplinary concept) and (2) help students to consider new ways this concept can benefit society (a science process skill). Results We randomly assigned two sections of an upper-division evolutionary biology course to either a biomimicry DBL (DBL group) or species comparison (comparison group) curricular design. Students in the course were exposed to a 1-day lesson, then 1-weeklong case study, and then a final project focused on either biomimicry species-to-human design comparisons (DBL condition) or species-to-species comparisons (comparison condition). To assess the targeted outcomes, we analyzed students’ responses from a pre-post assessment. Students in the biomimicry section were more likely to apply their biological structure–function knowledge to societal benefits when leaving the course. Students in both sections showed comparable gains in structure–function understanding, but there was no change in the number of students who used misconception language in their post-course compared to pre-course responses. Conclusions We conclude that our DBL curriculum, above and beyond the comparison curriculum, may support students’ ability to apply biological concepts to societal benefits without compromising structure–function understanding. Overall, these results provide rationale for incorporating tasks situated in DBL to address socio-scientific issues in biology courses.

Abstract Background We meta‐analyzed the efficacy and safety of catheter (CA) vs thoracoscopic (TA) ablation for atrial fibrillation (AF). Methods PubMed, Embase, and Cochrane databases were searched until 31/12/2019 for relevant randomized trials and subsequent pooled analyses. Results In six trials totaling 465 patients (254 CA/211 TA), 1‐year AF recurrences were higher for CA (46% vs 26%, odds ratio 2.90 [95% CI 1.32‐6.38]), whereas total adverse events were lower (10% vs 25%, 0.35 [0.14‐0.86], respectively). Conclusion CA has lower efficacy but higher safety than TA. CA should remain the first‐line AF ablation strategy, and TA reserved for selected CA‐resistant patients where rhythm control is clinically necessary.

Abstract Background In Canada alone, almost 3000 VLBW infants are born and treated annually with almost 1200 going onto death or survival with severe brain injury, chronic lung disorders, aggressive retinopathy of prematurity, late-onset sepsis, or significant necrotizing enterocolitis. Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying, bifidogenic glycoprotein found in all vertebrates and in mammalian milk, leukocytes and exocrine secretions. Lactoferrin aids in creating an environment for growth of beneficial bacteria in the gut, thus reducing colonization with pathogenic bacteria. It is hypothesized that oral bovine lactoferrin (bLF), through its antimicrobial, antioxidant and anti-inflammatory properties, will reduce the rate of mortality or major morbidity in very low birth weight preterm infants. Method Lactoferrin Infant Feeding Trial_Canada (LIFT_Canada) is a multi-centre, double-masked, randomized controlled trial with the aim to enroll 500 infants whose data will be combined with the data of the 1542 infants enrolled from Lactoferrin Infant Feeding Trial_Australia/New Zealand (LIFT_ANZ) in a pooled intention-to-treat analysis. Eligible infants will be randomized and allocated to one of two treatment groups: 1) a daily dose of 200 mg/kg bLF in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier; 2) no bLF with daily feeds. The primary outcome will be determined at 36 weeks corrected gestation for the presence of neonatal morbidity and at discharge for survival and treated retinopathy of prematurity. The duration of the trial is expected to be 36 months. Discussion Currently, there continues to be no clear answer related to the benefit of bLF in reducing mortality or any or all of the significant neonatal morbidities in very low birth weight infants. LIFT_Canada is designed with the hope that the pooled results from Australia, New Zealand, and Canada may help to clarify the situation. Trial registration Clinical Trials.Gov, Identifier: NCT03367013, Registered December 8, 2017.

Biomass-based, small-scale Combined Cooling, Heating and Power (CCHP) systems can increase the energy autonomy of building complexes while reducing their Greenhouse Gases (GHG) emissions. In combination with air-to-water Heat Pumps (HP), highly efficient energy systems can be designed, which allow for high flexibility in serving thermal and electric demands. This study presents an exergy evaluation of such a small-scale CCHP/HP system using a dynamic modelling approach based on gasification of various types of woody biomass. The transient model takes into account the effects of the biomass chemical composition as well as of ambient temperatures on the exergy performance of all key components for various CCHP system sizes supporting an HP system. The model has been applied in a case study for a historic building complex, where the CCHP sub-system would support an HP-subsystem allowing for downsizing the latter. The results show that smaller CCHP systems operate with higher exergy efficiency, because for larger systems the heat transfer from the engine and the operation of the absorption chiller are less exergy efficient. The electric load-following CCHP subsystem reaches exergy efficiencies of up to 13.3%, indicating huge improvement potential for system and sub-system design. It was also found that the biomass composition heavily influences the exergy efficiency of the gasifier and in turn changes the exergy efficiency of the syngas engine and the entire CCHP sub-system.

The use of waste incineration with energy recovery is a matured waste-to-energy (WtE) technology. Waste incineration can reduce the volume and mass of municipal solid waste significantly. However, the generation of high volumes of polluting flue gases is one of the major drawbacks of this technology. Acidic gases are constituents in the flue gas stream which are deemed detrimental to the environment. The wet flue gas desulphurization (FGD) method is widely employed to clean acidic gases from flue gas streams, due to its high efficiency. A major setback of the wet FGD technology is the production of wastewater, which must be treated before reuse or release into the environment. Treating the wastewater from the wet FGD presents challenges owing to the high level of contamination of heavy metals and other constituents. Membrane distillation (MD) offers several advantages in this regard, owing to the capture of low-grade heat to drive the process. In this study the wet FGD method is adopted for use in a proposed waste incineration plant located in Ghana. Through a mass and energy flow analysis it was found that MD was well matched to treat the 20 m3/h of wastewater generated during operation. Thermal performance of the MD system was assessed together with two parametric studies. The thermal efficiency, gained output ratio, and specific energy consumption for the optimized MD system simulated was found to be 64.9%, 2.34 and 966 kWh/m3, respectively, with a total thermal energy demand of 978.6 kW.

Carlos II of Spain (1661–1700), last of the Spanish Habsburgs, was known as The ‘Bewitched’ due to his multiple medical issues and feeble nature. He suffered from a range of ailments extending beyond the well-known Habsburg jaw, including developmental delay, intellectual disability, dysarthria, skeletal deformity, recurrent infections, epilepsy and infertility, among others. The Habsburg dynasty of Spain was characterised by marked inbreeding, and the male line died out with Carlos II. Various diagnoses have been proffered to explain Carlos II’s infirmity, though none have been full satisfactory to explain the full breadth of his ailments. As illustrated here, it may be that aspartylglucosaminuria, an autosomal recessively inherited lysosomal storage disorder, can account for both the characteristic facial features and the wide variety of other features exhibited by Carlos II.

Background: Teaching is a core activity for universities, and pedagogic research is essential for improving student experience, staff satisfaction, and research and teaching quality. Pedagogic research is often performed as a secondary research area or by part-time staff, requiring good collaboration. Existing research structures in universities often result in pedagogic research falling through the gaps and for quality work and pedagogic improvements to be missed. Aim: The aim was to develop a clear and flexible structure to improve participation and output of pedagogic research in the School of Pharmacy and Biomedical Sciences at the University of Central Lancashire. Method: A collaborative adhocracy called the Pedagogic Interest Group (PIG) was created in January 2020. It was designed to allow collaborative, flexible research projects to be easily set up by any staff member. The group supervises and organises a bespoke team of people for each project, drawing on all previously involved staff's expertise and contacts through an initial project meeting organised by an independent group chair. Each project group runs independently, with further help available from the group chairs. Results: Under the PIG structure, seven projects have been undertaken in less than one year. Two papers were published, one under review, two in preparation, one abstract accepted at an international conference, and fifteen funded undergraduate research projects completed. Part-time teaching staff are more involved in the research. Internally, three departments and externally, three other UK universities have been collaboratively involved in research projects. Conclusion: The PIG structure works and depends on staff's continued engagement and at least two independent chairs for impartiality and transparency.

Abstract Background Vascular complications are common during invasive cardiac electrophysiology procedures. This meta‐analysis compares outcomes following ultrasound and nonultrasound‐guided vascular access for these procedures. Methods PubMed, Embase and Cochrane 01/01/1980‐30/09/2018 were searched for relevant studies to meta‐analyse. Results Seven studies (6269 patients) were included. Pooled rates and odds ratio(95% confidence interval) for ultrasound and nonultrasound subgroups were 1.2% vs 3.0%, 0.32 (0.21‐0.49) for all vascular complications, with less hematomas and arterial punctures but similar arteriovenous fistulas, pseudoaneurysms or retroperitoneal bleeds. Conclusion Ultrasound guidance had less complications due to less hematoma and arterial puncture, and is generally recommended for electrophysiology procedures.

Abstract Many applications are built upon private algorithms, and executing them in untrusted, remote environments poses confidentiality issues. To some extent, these problems can be addressed by ensuring the use of secure hardware in the execution environment; however, an insecure software-stack can only provide limited algorithm secrecy. This paper aims to address this problem, by exploring the components of the Trusted Computing Base (TCB) in hardware-supported enclaves. First, we provide a taxonomy and give an extensive understanding of trade-offs during secure enclave development. Next, we present a case study on existing secret-code execution frameworks; which have bad TCB design due to processing secrets with commodity software in enclaves. This increased attack surface introduces additional footprints on memory that breaks the confidentiality guarantees; as a result, the private algorithms are leaked. Finally, we propose an alternative approach for remote secret-code execution of private algorithms. Our solution removes the potentially untrusted commodity software from the TCB and provides a minimal loader for secret-code execution. Based on our new enclave development paradigm, we demonstrate three industrial templates for cloud applications: ① computational power as a service, ② algorithm querying as a service, and ③ data querying as a service.

Abstract Background Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. Methods Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. Results From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination. Conclusions Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.

The Autism Spectrum Disorders in the European Union (ASDEU) survey investigated the knowledge and health service experiences of users and providers to generate new hypotheses and scientific investigations that would contribute to improvement in health care for autistic adults. An online survey designed for autistic adults, carers of autistic adults, and professionals in adult services was translated into 11 languages and distributed electronically by organizations and in-country adult service facilities in 2017; 522 autistic adults, 442 carers, and 113 professionals provided answers to the health questions. Professionals, the majority in non-medical services, appeared to be poorly informed about whether certain co-occurring conditions were more frequent in autistic adults than typical adults—especially some medical conditions, suicide attempts, accidents, and pain. A minority of autistic adults reported preventive health behaviors such as routine health check-ups. The majority of users and providers expressed the desire to make health care services more user-friendly for autistic adults. Among the three groups,

The chronically increased blood pressure characteristic of essential hypertension represents an insidious and cumulative risk for cardiovascular disease. Essential hypertension is a multifactorial condition, with no known specific aetiology but a strong genetic component. The Spontaneously Hypertensive rat (SHR) shares many characteristics of human essential hypertension, and as such is a commonly used experimental model. The mammalian hypothalamo-neurohypophyseal system (HNS) plays a pivotal role in the regulation of blood pressure, volume and osmolality. In order to better understand the possible role of the HNS in hypertension, we have used microarray analysis to reveal differential regulation of genes in the HNS of the SHR compared to a control normotensive strain, the Wistar Kyoto rat (WKY). These results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). One of the genes identified and validated as being downregulated in SHR compared to WKY was that encoding the neuropeptide urocortin (Ucn). Immunohistochemical analyses revealed Ucn to be highly expressed within magnocellular neurons of the PVN and SON, with pronounced localisation in dendritic projections containing oxytocin and vasopressin. When Ucn was overexpressed in the PVN of the SHR by in vivo lentiviral mediated gene transfer, blood pressure was unaffected but there were significant, transient reductions in the VLF spectra of systolic blood pressure consistent with an action on autonomic balance. We suggest that Ucn may act, possibly via dendritic release, to subtly regulate neurohumoral aspects of arterial pressure control.

The purpose of this multi-study article was to investigate the roles of adaptability and social support in predicting a variety of psychological outcomes. Data were collected from Year 12 college students (N = 73; Study 1), university students (N = 102; Study 2), and non-studying members of the general public (N = 141; Study 3). Findings showed that, beyond variance attributable to social support, adaptability made a significant independent contribution to psychological wellbeing (life satisfaction, psychological wellbeing, flourishing, and general affect) and psychological distress across all studies. Beyond the effects of adaptability, social support was found to make a significant independent contribution to most wellbeing outcomes (but not psychological distress in university students). In a multi-group analysis comparing predictors of psychological wellbeing in university students and non-studying adults, where the same outcome measures were used (Study 4; N = 243), it was found that adaptability played a stronger role (relative to social support) for university students, whereas social support played a stronger role for non-studying adults. Finally, (contrary to expectations) there was no evidence of an interaction between adaptability and social support predicting psychological outcomes—adaptability and social support operated as independent main effects. These findings demonstrate the importance of adaptability and social support in uniquely predicting psychological wellbeing in different sample groups. It is argued here that these two factors, should be given greater consideration in discussions of psychological wellbeing, and are relevant to psychological wellbeing at different major developmental life stages.

The regolith environment and associated organic material on Ceres is analogous to environments that existed on Earth 3–4 billion years ago. This has implications not only for abiogenesis and the theory of transpermia, but it provides context for developing a framework to contrast the limits of Earth’s biosphere with extraterrestrial environments of interest. In this study, substrate utilisation by the ice-associated bacterium Colwellia hornerae was examined with respect to three aliphatic organic hydrocarbons that may be present on Ceres: dodecane, isobutyronitrile, and dioctyl-sulphide. Following inoculation into a phyllosilicate regolith spiked with a hydrocarbon (1% or 20% organic concentration wt%), cell density, electron transport activity, oxygen consumption, and the production of ATP, NADPH, and protein in C. hornerae was monitored for a period of 32 days. Microbial growth kinetics were correlated with changes in bioavailable carbon, nitrogen, and sulphur. We provide compelling evidence that C. hornerae can survive and grow by utilising isobutyronitrile and, in particular, dodecane. Cellular growth, electron transport activity, and oxygen consumption increased significantly in dodecane at 20 wt% compared to only minor growth at 1 wt%. Importantly, the reduction in total carbon, nitrogen, and sulphur observed at 20 wt% is attributed to biotic, rather than abiotic, processes. This study illustrates that short-term bacterial incubation studies using exotic substrates provide a useful indicator of habitability. We suggest that replicating the regolith environment of Ceres warrants further study and that this dwarf planet could be a valid target for future exploratory missions.

Sea ice supports a unique assemblage of microorganisms that underpin Antarctic coastal food-webs, but reduced ice thickness coupled with increased snow cover will modify energy flow and could lead to photodamage in ice-associated microalgae. In this study, microsensors were used to examine the influence of rapid shifts in irradiance on extracellular oxidative free radicals produced by sea-ice algae. Bottom-ice algal communities were exposed to one of three levels of incident light for 10 days: low (0.5 μmol photons m−2 s−1, 30 cm snow cover), mid-range (5 μmol photons m−2 s−1, 10 cm snow), or high light (13 μmol photons m−2 s−1, no snow). After 10 days, the snow cover was reversed (either removed or added), resulting in a rapid change in irradiance at the ice-water interface. In treatments acclimated to low light, the subsequent exposure to high irradiance resulted in a ~400× increase in the production of hydrogen peroxide (H2O2) and a 10× increase in nitric oxide (NO) concentration after 24 h. The observed increase in oxidative free radicals also resulted in significant changes in photosynthetic electron flow, RNA-oxidative damage, and community structural dynamics. In contrast, there was no significant response in sea-ice algae acclimated to high light and then exposed to a significantly lower irradiance at either 24 or 72 h. Our results demonstrate that microsensors can be used to track real-time in-situ stress in sea-ice microbial communities. Extrapolating to ecologically relevant spatiotemporal scales remains a significant challenge, but this approach offers a fundamentally enhanced level of resolution for quantifying the microbial response to global change.

Background Detection of pneumonia-causing respiratory viruses in the nasopharynx of asymptomatic children has made their actual contribution to pneumonia unclear. We compared nasopharyngeal viral density between children with and without pneumonia to understand if viral density could be used to diagnose pneumonia.Methods Nasopharyngeal swabs (NPS) were collected from hospitalised pneumonia cases at Princess Margaret Hospital (PMH) and contemporaneous age-matched controls at PMH outpatient clinics and a local immunisation clinic in Perth, Australia. The density (copies/mL) of respiratory syncytial virus (RSV), influenza A virus (InfA), human metapneumovirus (HMPV) and rhinovirus in NPS was determined using quantitative PCR. Linear regression analysis was done to assess the trend between viral density and age in months. The association between viral density and disease status was examined using logistic regression. Area under receiver operating characteristic (AUROC) curves were assessed to determine optimal discriminatory viral density cut-offs.Results Through May 2015 to October 2017, 230 pneumonia cases and 230 controls were enrolled. Median nasopharyngeal density for any respiratory virus was not substantially higher in cases than controls (p>0.05 for each). A decreasing density trend with increasing age was observed—the trend was statistically significant for RSV (regression coefficient −0.04, p=0.004) but not for other viruses. After adjusting for demographics and other viral densities, for every log10 copies/mL density increase, the odds of being a case increased by six times for RSV, three times for HMPV and two times for InfA. The AUROC curves were

Purpose This study aimed to evaluate the impact of Patient as teacher (PAT) sessions on the knowledge, communication skills, and participation of pharmacy students in the United Kingdom. Methods During the academic year 2019–2020, year 1 and 2 pharmacy students at the University of Central Lancashire were invited to complete a questionnaire following PAT sessions. Data were analyzed by means of descriptive statistics, including mean and standard deviation for: continuous variables and reliability analysis. Pearson’s chi-square or Fisher exact test, odds ratio, and phi were used for analyzing dichotomous variables. Thematic analysis was used for free text comments. Results Sixty eight of 228 students participated (response rate of 29.8%). No statistical difference was found between gender (P=0.090); a statistically significant difference was found between year (P=0.008). Cronbach’s α (0.809) confirmed a good internal consistency. Ninety-seven percent of the students learned a lot, and 85.3% appreciated and valued the PAT sessions; 89.7% wanted more sessions. Ninety-two point seven percent perceived the sessions to contextualize their learning. Five questions were dichotomized by grouping the responses into negative and positive; 90.3% of responses were positive and did not show statistically significant differences in gender and year of study. Overall students’ free text comments were positive, but active listening and consultation appeared in the positive and negative domains, highlighting the need for more student engagement. Conclusion PAT sessions had a positive impact on students’ knowledge, communication skills and participation, and contextualized learning. They provide a valuable contribution to the pharmacy students’ experience in the United Kingdom.

The main challenge for implementing an industrial-scale membrane distillation (MD) system is its associated thermal power demand and resulting operational cost, which hinders the commercialization of the technology, even after forty years of its evolution and development. Nevertheless, an enormous amount of waste heat releasing from the nano-electronics facilities provides MD an opportunity to showcase its potential for treating industrial wastewater discharging from the facilities. In this work, a waste heat driven MD system for a plant capacity of 15 m3/h was analyzed in terms of its thermal power demand and unit wastewater treatment cost. The economic analysis was performed using the factored estimate method. The results show that the thermal power requirement of the industrial-scale MD system was 12.38 MW, and the unit water treatment cost can vary between 3-23 $/m3, based on plant type (i.e., retrofitted facility or new wastewater treatment facility). • Determination of various industrial waste heat sources in typical nano-electronics fabrication facilities via interviews of related professionals, and designed industrial-scale waste heat integrated MD system for nano-electronics industries • Mass and energy balances around the industrial-scale MD system for wastewater treatment in nano-electronics industries • Equipment design for the purpose and performed economic evaluation of the MD system by customizing factored estimate method

Abstract Background Bleomycin, etoposide, and cisplatin (BEP) chemotherapy administered every 3 weeks for 4 cycles remains the standard first line treatment for patients with intermediate- and poor-risk metastatic germ cell tumours (GCTs). Administering standard chemotherapy 2-weekly rather than 3-weekly, so-called ‘accelerating chemotherapy’, has improved cure rates in other cancers. An Australian multicentre phase 2 trial demonstrated this regimen is feasible and tolerable with efficacy data that appears promising. The aim of this trial is to determine if accelerated BEP is superior to standard BEP as first line chemotherapy for adult and paediatric male and female participants with intermediate and poor risk metastatic GCTs. Methods This is an open label, randomised, stratified, 2-arm, international multicentre, 2 stage, phase 3 clinical trial. Participants are randomised 1:1 to receive accelerated BEP or standard BEP chemotherapy. Eligible male or female participants, aged between 11 and 45 years with intermediate or poor-risk metastatic GCTs for first line chemotherapy will be enrolled from Australia, the United Kingdom and the United States. Participants will have regular follow up for at least 5 years. The primary endpoint for stage 1 of the trial (n = 150) is complete response rate and for the entire trial (n = 500) is progression free survival. Secondary endpoints include response following treatment completion (by a protocol-specific response criteria), adverse events, health-related quality of life, treatment preference, delivered dose-intensity of chemotherapy (relative to standard BEP), overall survival and associations between biomarkers (to be specified) and their correlations with clinical outcomes. Discussion This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and pediatric age groups open to both males and females. It is also the largest, current randomised trial for germ cell tumours in the world. Positive results for this affordable intervention could change the global standard of care for intermediate and poor risk germ cell tumours, improve cure rates, avoid the need for toxic and costly salvage treatment, and return young adults to long, healthy and productive lives. Trial registration ACTRN 12613000496718 on 3rd May 2013 and Clinicaltrials.gov NCT02582697 on 21st October 2015.

Abstract Background Falls are a common cause of hospitalization, morbidity, and mortality among the elderly in the United States. Evidence-based imaging recommendations for evaluation of delayed intracranial hemorrhage (DICH) are not generally agreed upon. The purpose of this project was to evaluate the incidence of DICH detected by head computer tomography (CT) among an elderly population on pre-injury anticoagulant or antiplatelet (ACAP) therapy. Methods Data from a Level 1 Trauma Center trauma registry was used to assess the incidence of DICH in an elderly population of patients (≥65 years) who sustained a minor fall while on pre-injury ACAP medications. Counts and percentages are reported. Results Data on 1076 elderly trauma patients were downloaded, of which 838 sustained a minor fall and 513 were found to be using a pre-injury ACAP medication. One patient (0.46%) with a DICH was identified out of 218 patients who received a routine repeat head CT. Aspirin and warfarin were the most common pre-injury ACAP medications and 19.27% (42/218) of patients were found to be using multiple ACAP medications. Conclusions Universal screening protocols promote immediate-term patient safety, but do so at a great expense with respect to health expenditures and increased radiation exposure. This analysis highlights the need for an effective risk assessment tool for DICH that would reduce the burden of unnecessary screenings while still identifying life-threatening intracranial hemorrhages in affected patients.

Abstract Background Lung cancer is the leading cause of cancer mortality worldwide. Early diagnosis and treatment is a key factor in reducing mortality and improving patient outcomes. To achieve this, it is important to understand the diagnostic pathways of cancer patients. Patients from Culturally and Linguistically Diverse (CALD) are a vulnerable group for lung cancer with higher mortality rates than Caucasian patients. The aim of this study is to explore differences in the lung cancer diagnostic pathways between CALD and Anglo-Australian patients and factors underlying these differences. Methods This is a prospective, observational cohort study using a mixed-method approach. Quantitative data regarding time intervals in the lung cancer diagnostic pathways will be gathered via patient surveys, General practitioner (GP) review of general practice records, and case-note analysis of hospital records. Qualitative data will be gathered via structured interviews with lung cancer patients, GPs, and hospital specialists. The study will be conducted in five study sites across three states in Australia. Anglo-Australian patients and patients from five CALD groups (i.e., Arabic, Chinese, Greek, Italian and Vietnamese communities) will mainly be identified through the list of new cases presented at lung multidisciplinary team meetings. For the quantitative component, it is anticipated that 724 patients (362 Anglo-Australian and 362 CALD patients) will be recruited to obtain a final sample of 290 (145 per group) assuming a 50% patient survey completion rate and a 80% GP record review completion rate. For the qualitative component, 60 interviews with lung cancer patients (10 Anglo-Australian and 10 patients per CALD group), 20 interviews with GPs, and 20 interviews with specialists will be conducted. Discussion This is the first Australian study to compare the time intervals along the lung cancer diagnostic pathway between CALD and Anglo-Australian patients. The study will also explore the underlying patient, healthcare provider, and health system factors that influence the time intervals in the two groups. This information will improve our understanding of the effect of ethnicity on health outcomes among lung cancer patients and will inform future interventions aimed at early diagnosis and treatment for lung cancer, particularly patients from CALD backgrounds. Trial registration The project was retrospectively registered with Australian New Zealand Clinical Trials Registry (registration number: ACTRN12617000957392, date registered: 4th July 2017).