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Abstract Background Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011–2020. Methods Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011–2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. Results The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. Conclusion This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. Clinical Trial Number. Not applicable.

The high cost of using the niobium (Nb) barrier for manufacturing magnesium diboride (MgB2) mono-and multi-filamentary wires for large-scale applications has become one of the barriers to replacing current commercial niobium-titanium superconductors. The potential of replacing the Nb barrier with a low-cost iron (Fe) barrier for multifilament MgB2 superconducting wires is investigated in this manuscript. Therefore, MgB2 wires with Fe barrier sintered with different temperatures are studied (from 650 °C to 900 °C for 1 h) to investigate the non-superconducting reaction phase of Fe-B. Their superconducting performance including engineering critical current density (Je) and n-value are tested at 4.2 K in various external magnetic fields. The best sample sintered at 650 °C for 1 h has achieved a Je value of 3.64 × 104 A cm−2 and an n-value of 61 in 2 T magnetic field due to the reduced formation of Fe2B, better grain connectivity and homogenous microstructure. For microstructural analysis, the focused ion beam (FIB) is utilised for the first time to acquire three-dimensional microstructures and elemental mappings of the interface between the Fe barrier and MgB2 core of different wires. The results have shown that if the sintering temperature can be controlled properly, the Je and n-value of the wire are still acceptable for magnet applications. The formation of Fe2B is identified along the edge of MgB2, as the temperature increases, the content of Fe2B also increases which causes the degradation in the performance of wires.

In neurons, a diverse range of coding and non-coding RNAs localize to axons, dendrites, and synapses, where they facilitate rapid responses to local needs, such as axon and dendrite extension and branching, synapse formation, and synaptic plasticity. Here, we review the extent of our current understanding of RNA subclass diversity in these functionally demanding subcellular compartments. We discuss the similarities and differences identified between axonal, dendritic and synaptic local transcriptomes, and discuss the reported and hypothesized fates and functions of localized RNAs. Furthermore, we outline the RNA composition of exosomes that bud off from neurites, and their implications for the biology of neighboring cells. Finally, we highlight recent advances in third-generation sequencing technologies that will likely provide transformative insights into splice isoform and RNA modification diversity in local transcriptomes.

Almost half of Scottish people who die currently die in hospital, which may represent a complex need or lack of alternative options. Nearly 95% of people use unscheduled care in their last year of life, which includes the Emergency Department (ED) – the outcome of ED attendance is often hospital admission. This increased use of unscheduled care services is associated with high costs and poor patient outcomes. This study analyses sequences of patient visits and describes patterns of ED attendance and inpatient admissions in the patients' final year of life to help understand their healthcare journeys. This work examines the use of ED attendance and hospital admissions in NHS Tayside and NHS Fife between 2000 and 2021 for people in the last year of life. The retrospective cohort consists of all patients 18+ who died and visited the ED or were admitted to the hospital at least once. From a study population of 981,879, 164,506 (17%) people died, with 148,734 (90%) people having an ED visit or hospital admission. Data was divided for the 52 weeks before death, with three possible states for each week: home, ED visit, and admission. A preliminary analysis shows high and significant variability in ED attendance and hospital admissions with distinct usage patterns. A better understanding of the patients' characteristics within each pattern may allow for potential interventions that improve patient care by reducing avoidable ED attendances or hospital admissions in the last year of life.

Background: Fiji is a Pacific Island nation with the predominant ethnic groups indigenous Fijians (iTaukei) (62 %) and Fijians of Indian descent (31 %). This study reports on the effect of a Parental Assistance Payment Program (PAPP) tied to on-time birth registration, available in Fiji from August 2018 to July 2020. Methods: Unit record birth registration data (n = 117,829) for children born during 2016–22 were used to calculate mean birth-to-registration intervals and the likelihood of on-time birth registration (within 365 days) before the PAPP (January 2016–July 2018) compared to during the PAPP (August 2018–July 2020), by population disaggregations (sex, ethnicity, age, marital status). Results: During the PAPP, mean birth-to-registration intervals declined sharply by 81 %, from 665 days (95 %CI: 658–671) to 124 days (121–127). The largest declines were among i-Taukei children (803 to 139 days, 83 %) compared to non-iTaukei (283 to 76 days, 73 %); mothers aged 10–19 years (880 to 134 days, 85 %) compared to ≥20 years (653 to 123 days, 81 %); and single mothers (983 to 145 days, 85 %) compared to married mothers (570 to 115 days, 80 %). On-time birth registration increased from 57 % to 93 %, and the adjusted hazard ratio showed children born during the PAPP were 2.3 times more likely (95 %CI: 2.2–2.4) to have their birth registered on-time compared to children born before the PAPP. When the PAPP was discontinued in August 2020, the birth-to-registration interval increased sharply in all population groups. Conclusions: During the two-year period the PAPP was available, it was highly effective at improving the timeliness of birth registration, particularly among iTaukei children, young mothers, and single mothers. After the PAPP was discontinued, the timeliness of birth registration deteriorated sharply. Longer post-PAPP follow-up time (≠5 years) is required to determine whether the timeliness of birth registration has deteriorated to levels similar to those during the pre-PAPP period.

Background: Sustainable Development Goal 3.4.1 (SDG3.4.1) targets a one-third reduction in non-communicable disease (NCD) mortality in ages 30–69-years by 2030 (relative to 2015). Directing interventions to achieve this aim requires reliable estimates of underlying cause of death (UCoD). This may be problematic when both cardiovascular diseases (CVD) and diabetes are present due to a lack of consistency in certification of such deaths. We estimate empirically 2013–17 NCD mortality in Fiji, by sex and ethnicity, from CVD, diabetes, cancer, and chronic lower respiratory diseases (CRD), and aggregated as NCD4. Methods: UCoD was determined from Medical Certificates of Cause-of-Death (MCCD) from the Fiji Ministry of Health after pre-processing of mortality data where diabetes and/or hypertension were present in order to generate internationally comparable UCoD. If no potentially fatal complications from diabetes or hypertension accompanied these causes in Part I (direct cause) of the MCCD, these conditions were re-assigned to Part II (contributory cause). The probability of a 30-year-old dying before reaching age 70-years (PoD30–70), by cause, was calculated. Findings: The PoD30–70 from NCD4 over 2013–17 differed by sex and ethnicity: in women, it was 36% (95%CI 35–37%) in i-Taukei and 27% (26–28%) in Fijians of Indian descent (FID); in men, it was 41% (40–42%) in both i-Taukei and FID.PoD30–70 from CVD, diabetes, cancer and CRD in women was: 18%, 10%, 13% and 1·0% in i-Taukei; 13%, 10%, 5·6% and 1·1% in FID; in men was: 28%, 8.4%, 7·6% and 2·2% in i-Taukei; 31%, 8.3%, 3.5% and 3·1% in FID. Interpretation: To achieve SDG3.4.1 goals in Fiji by 2030, effective population wide and ethnic-specific interventions targeting multiple NCDs are required to reduce PoD30–70 from NCD4: from 36% to 24% in i-Taukei, and 27% to 18% in FID women; and from 41% to 27% in i-Taukei and FID men. Funding: Not applicable.

Pavement service life is an important factor that affects both the whole life cost and carbon footprint of a pavement. The service life of a pavement is affected by several different parameters which can be broadly classified into climate conditions, binder and mixture properties, pavement design, workmanship, and maintenance strategies. The current practice for determining service life of pavements involves the use of pavement design tools, which are used while constructing a new pavement or performing a reconstruction/resurfacing or pavement maintenance. In addition, field measurements using ground penetration radar, falling weight deflectometer, traffic speed deflectometer, and other techniques are also used to assess the condition of an existing pavement. The information from these measurements is then combined with pavement design software to predict potential pavement service life. The accuracy of the predicted pavement service life is affected by the associated uncertainties in the parameters that affect pavement life. The following paper presents various approaches that could be potentially used to determine the associated uncertainties in the estimation of pavement service life. The various uncertainty quantification techniques have been applied to a specific design, and the outcomes are discussed in this paper. The Monte Carlo simulation method, a system-level uncertainty quantification technique, can estimate a probabilistic pavement service life. The other uncertainty quantification schemes are software specific and provide probabilistic life factors by assumed statistical distributions. Hence, the Monte Carlo simulation technique could be one potential method that can be used for estimating a generalized pavement service utilizing predictions from various design software.

Magnesium diboride (MgB2) magnets have the potential to be the next-generation liquid-helium-free magnet for magnetic resonance imaging (MRI) application due to their relatively high superconducting transition temperature, high current density and low raw material cost compared with current commercial niobium-titanium (Nb-Ti) magnets. A typical superconducting magnet includes several coils. To produce an ultra-stable magnetic field for imaging in MRI, a superconducting electromagnet operating in a persistent mode is crucial. Superconducting coils of the electromagnet in MRI are short-circuited to operate in the persistent mode by connecting coils with superconducting joints. Persistent joints have been demonstrated for in-situ and ex-situ wires of both mono- and multi-filamentary structures, made predominantly by PIT techniques similar to those used in wire production. To realise further engagement of MgB2 in MRI applications, enhancing the performance of MgB2 superconducting joints is essential. This literature review summarises research and development on MgB2 superconducting joining technology.

Addressing the large carbon footprint of conferences such as the UN Climate Change Convention Conference of the Parties (COP) will be important for maintaining public confidence in climate policy. Transparency is also a vital aspect of creating equitable outcomes in climate policies, as often those most likely to be affected or who are able to create change on the ground are often unable to attend in person because of the high financial costs as well as having a large carbon footprint. The selection of host locations for the regular meetings of the UN Climate Change Convention is based on a rotation in amongst the five UN regions, which for 2022 is Africa. Here, we present UCL’s own carbon footprint calculator and use it to weigh the benefits of certain modes of transport to the 2021 COP 26 in Glasgow, UK and the 2022 COP 27 to be held in Sharm El-Sheikh, Egypt. The calculator demonstrates the well-known carbon-efficiency of coach and rail over flights, but shows that these benefits are only partly mitigated in the case of COP 27 due to insufficient transport links from Europe to the conference location. However, we also highlight some of the benefits of hosting a COP in the global South, particularly in the context of climate justice. Incorporating these principles into the calculator, we invite visitors to COP this year to carefully consider their options for carbon offsetting and how the tenets of climate justice could be integrated into the carbon accounting framework.

Abstract Background Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology. Method A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients’ presenting renal function to eGFR categories: 61–90 ml/min/1.73m2 (complete remission– CR) to 31–60 ml/min/1.73m2 (partial remission– PR) and 0–30 ml/min/1.73m2 no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching

Using qualitative self-reported and observational evidence combined with a quantitative breakdown of linked administrative justice system data, this before-and-after study demonstrates the beneficial impacts of a First Nations community-controlled adult literacy campaign in six rural and remote communities in New South Wales, Australia. The most significant quantitative finding is a 50% reduction in reported serious offences in a sample of 162 campaign participants. Qualitative data from interviews found an increased use of legal assistance services following the campaign.. These findings are contextualised through the lived experiences and perceptions of First Nations campaign staff and participants, community leaders and government and non-government agency personnel.

Nuclear depletion and cytoplasmic accumulation of splicing factor SFPQ are hallmarks of ALS. Here the authors demonstrate a relationship between loss of SFPQ and the emergence in neurites of intron-retaining mRNAs enriched in ALS models and tissues.

Abstract Participatory methods for researching human–environmental interactions seek detailed inputs on all manner of issues, but the outputs are often only understandable to the technically literate. On the other hand, participatory methods that involve the co-design of structured outputs (maps, models, games, stories, etc.) can be used to represent and integrate the knowledge and views of participants authentically and can be interpretable to both ‘scientist’ and ‘non-scientist’ alike, thereby creating ‘sideways’ rather than top-down or bottom-up perspectives. This paper is both a methodological paper and a treatise that looks at some of the theory underpinning such approaches, drawing on the theory of citizen or ‘bottom-up’ stakeholder engagement in science but also co-created engagement, emphasising the learning and trust-building benefits of this ‘sideways’ engagement. It describes how some established and novel methods (participatory agent-based modelling; co-constructing computer games; and participatory social network mapping), can be used to engage stakeholders in iterative, constructivist communication, allowing researchers and stakeholders to co-create a structured ‘reality’ separate from the reality it represents. We discuss how such approaches support and contribute to scientific outputs that better represent participants’ reality. Our findings show that, when applied to ecosystem services, agricultural adaptation and disaster risk management, such representations provide communication opportunities and spaces for reflection and constructivist learning. The structured outputs allow stakeholders—both participant and researcher—to ‘mirror’ their human-environmental system to collaboratively think about gaps and problems in understanding.

Abstract The complexity in the styles of 1200 Byzantine icons painted between 13th and 16th from Greece, Russia and Romania was investigated through the Kolmogorov algorithmic information theory. The aim was to identify specific quantitative patterns which define the key characteristics of the three different painting schools. Our novel approach using the artificial surface images generated with Inverse FFT and the Midpoint Displacement (MD) algorithms, was validated by comparison of results with eight fractal and non-fractal indices. From the analyzes performed, normalized Kolmogorov compression complexity (KC) proved to be the best solution because it had the best complexity pattern differentiations, is not sensitive to the image size and the least affected by noise. We conclude that normalized KC methodology does offer capability to differentiate the icons within a School and amongst the three Schools.

Abstract Background Fiji, a Pacific Island nation of 884,887 (2017 census), has experienced a prolonged epidemiological transition. This study examines trends in mortality and life expectancy (LE) in Fiji by sex and ethnicity over 1996–2017, with comparisons to published estimates. Methods Trends in infant mortality rates (IMR), under-5 mortality (U5M), adult mortality (probability of dying), LE (at birth) and directly age-standardised death rates (DASRs) by sex and ethnicity, are calculated (with 95% confidence limits) using unit death records from the Fiji Ministry of Health and Medical Services. The LE gap between populations, or within populations over time, is examined using decomposition by age. Period trends are assessed for statistical significance using linear regression. Results Over 1996–98 to 2014–17: IMR and U5M for i-Taukei and Fijians of Indian descent declined; U5M decline for i-Taukei (24.6 to 20.1/1000 live births) was significant (p = 0.016). Mortality (15–59 years) for i-Taukei males was unchanged at 27% but declined for Indians 33 to 30% (p = 0.101). Mortality for i-Taukei females increased 22 to 24% (p = 0.011) but declined for Indians 20 to 18% (p = 0.240). DASRs 1996–2017 were lower for i-Taukei (9.3 to 8.2/1000 population) than Indian males (10.6 to 9.8/1000). DASRs declined for i-Taukei (both sexes, p 0.05). Over 22 years, LE at birth increased by 1 year or less (p = 0.030 in male i-Taukei). In 2014–17, LE (years) for males was: i-Taukei 64.9, Indians 63.5; and females: i-Taukei 67.0 and Indians 68.2. Mortality changes in most 5-year age groups increased or decreased the LE gap less than 10 weeks over 22 years. Compared to international agency reports, 2014–17 empirical LE estimates (males 64.7, females 67.8) were lower, as was IMR. Conclusions Based on empirical data, LE in Fiji has minimally improved over 1996–2017, and is lower than some international agencies report. Adult mortality was higher in Indian than i-Taukei men, and higher in i-Taukei than Indian women. Exclusion of stillbirths resulted in IMRs lower than previously reported. Differing mortality trends in subgroups highlight the need to collect census and health data by ethnicity and sex, to monitor health outcomes and inform resource allocation.

Translational RelevanceEvaluation of targeted therapies is urgently needed for the majority of patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC) who progress after immunochemotherapy. Erlotinib, a targeted inhibitor of epidermal growth factor receptor pathway, lacks FDA approval in HNSCC due to inadequate tumor response. This study identifies two potential avenues to improve tumor response to erlotinib among patients with HNSCC. For the first time, this study shows that an increased erlotinib dose of 300 mg in smokers is well-tolerated and produces similar plasma drug concentration as the regular dose of 150 mg in non-smokers, with increased study-specific defined tumor response. The study also highlights the opportunity for improved patient selection for erlotinib treatment by demonstrating that early in-treatment [18]FDG PET/CT is a potential predictor of tumor response, with robust statistical correlations between metabolic changes on early in-treatment PET (4-7 days through treatment) and anatomic response measured by end-of-treatment CT.PurposePatients with advanced HNSCC failing immunochemotherapy have no standard treatment options. Accelerating the investigation of targeted drug therapies is imperative. Treatment with erlotinib produced low response rates in HNSCC. This study investigates the possibility of improved treatment response through patient smoking status-based erlotinib dose optimization, and through early in-treatment [18]FDG PET evaluation to differentiate responders from non-responders.Experimental designIn this window-of-opportunity study, patients with operable HNSCC received neoadjuvant erlotinib with dose determined by smoking status: 150 mg (E150) for non-smokers and 300 mg (E300) for active smokers. Plasma erlotinib levels were measured using mass spectrometry. Patients underwent PET/CT before treatment, between days 4-7 of treatment, and before surgery (post-treatment). Response was measured by diagnostic CT and was defined as decrease in maximum tumor diameter by ≥ 20% (responders), 10-19% (minimum-responders), and < 10% (non-responders).ResultsNineteen patients completed treatment, ten of whom were smokers. There were eleven responders, five minimum-responders, and three non-responders. Tumor response and plasma erlotinib levels were similar between the E150 and E300 patient groups. The percentage change on early PET/CT and post-treatment PET/CT compared to pre-treatment PET/CT were significantly correlated with the radiologic response on post-treatment CTs: R=0.63, p=0.0041 and R=0.71, p=0.00094, respectively.ConclusionThis pilot study suggests that early in-treatment PET/CT can predict response to erlotinib, and treatment with erlotinib dose adjusted according to smoking status is well-tolerated and may improve treatment response in HNSCC. These findings could help optimize erlotinib treatment in HNSCC and should be further investigated.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT00601913, identifier NCT00601913.

Abstract Background Virtual Learning Collaboratives (VLC), learning communities focused on a common purpose, are used frequently in healthcare settings to implement best practices. Yet, there is limited research testing the effectiveness of this approach compared to other implementation strategies. This study evaluates the effectiveness of a VLC compared to Technical Assistance (TA) among community oncology practices implementing ENABLE (Educate, Nurture, Advise, Before Life Ends), an evidence-based, early palliative care telehealth, psycho-educational intervention for patients with newly diagnosed advanced cancer and their caregivers. Methods Using Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) and Proctor’s Implementation Outcomes Frameworks, this two-arm hybrid type-III cluster-randomized controlled trial (RCT) will compare two implementation strategies, VLC versus TA, among the 48 National Cancer Institute Community Oncology Research Program (NCORP) practice clusters that have not historically provided palliative care to all patients with advanced cancer. Three cohorts of practice clusters will be randomized to the study arms. Each practice cluster will recruit 15–27 patients and a family caregiver to participate in ENABLE. The primary study outcome is ENABLE uptake (patient level), i.e., the proportion of eligible patients who complete the ENABLE program (receive a palliative care assessment and complete the six ENABLE sessions over 12 weeks). The secondary outcome is overall program implementation (practice cluster level), as measured by the General Organizational Index at baseline, 6, and 12 months. Exploratory aims assess patient and caregiver mood and quality of life outcomes at baseline, 12, and 24 weeks. Practice cluster randomization will seek to keep the proportion of rural practices, practice sizes, and minority patients seen within each practice balanced across the two study arms. Discussion This study will advance the field of implementation science by evaluating VLC effectiveness, a commonly used but understudied, implementation strategy. The study will advance the field of palliative care by building the capacity and infrastructure to implement an early palliative care program in community oncology practices. Trial registration Clinicaltrials.gov . NCT04062552; Pre-results. Registered: August 20, 2019. https://clinicaltrials.gov/ct2/show/NCT04062552?term=NCT04062552&draw=2&rank=1

Abstract Background Tonga is a South Pacific Island country with a population of 100,651 (2016 Census). This study examines Tongan infant mortality rates (IMR), under-five mortality rates (U5MR), adult mortality and life expectancy (LE) at birth from 2010 to 2018 using a recent collation of empirical mortality data over the past decade for comparison with other previously published mortality estimates. Methods Routinely collected mortality data for 2010–2018 from the Ministry of Health, national (Vaiola) hospital, community nursing reports, and the Civil Registry, were consolidated by deterministic and probabilistic linkage of individual death records. Completeness of empirical mortality reporting was assessed by capture-recapture analysis. The reconciled data were aggregated into triennia to reduce stochastic variation, and used to estimate IMR and U5MR (per 1000 live births), adult mortality (15–59, 15–34, 35–59, and 15–64 years), and LE at birth, employing the hypothetical cohort method (with statistical testing). Mortality trends and differences were assessed by Poisson regression. Mortality findings were compared with published national and international agency estimates. Results Over the three triennia in 2010–2018, levels varied minimally for IMR (12–14) and U5MR (15–19) per 1000 births (both ns, p > 0.05), and also for male LE at birth of 64–65 years, and female LE at birth 69–70 years. Cumulated risks of adult mortality were significantly higher in men than women; period mortality increases in 15–59-year women from 18 to 21% were significant (p 95%. International agencies reported generally comparable estimates of IMR and U5MR, with varying uncertainty intervals; but they reported significantly lower adult mortality and higher LE than the empirical estimates from this study. Conclusions Life expectancy in Tonga over 2010–2018 has remained relatively low and static, with low IMR and U5MR, indicating the substantial impact from premature adult mortality. This analysis of empirical data (> 95% complete) indicates lower LE and higher premature adult mortality than previously reported by international agencies using indirect and modelled methods. Continued integration of mortality recording and data systems in Tonga is important for improving the completeness and accuracy of mortality estimation for local health monitoring and planning.

Future Force Design (FFD) is a strategic planning activity that decides the programming of defence capability options. This is a complex problem faced by the Australian Department of Defence (DoD) and requires the simultaneous selection and scheduling of projects. Specifically, this is a NP-hard problem known as the Project Portfolio Selection and Scheduling Problem (PPSSP). While the PPSSP is a complex problem itself, its complexity is further increased when coupled with the additional characteristics that arise in the context of defence-oriented planning, such as long planning periods and complex operational constraints. As a result, many previous studies examined only a small number of projects over a short planning period and are largely unsuitable for the scale required in the defence sector. To address this issue, two primary contributions are made in this paper. Firstly, this study describes a complex practical PPSSP, inspired by the FFD process, and develops a corresponding mathematical model. Problem instances are derived from real-world, publicly-available defence data. Secondly, to address instances of the problem, two existing meta-heuristics are considered and a hybrid, multi-population approach is proposed. Results are compared against those attained by a commercial exact solver and indicate that there is no statistically significant difference in performance between the proposed multi-population approach and the exact solver. A key benefit of the proposed meta-heuristic approach is that its run time is not significantly influenced by the complexity of the problem instance. Additionally, many interesting practical insights regarding the solution of selection and scheduling problems are uncovered.

The problem of designing an effective future defense force is quite complex and challenging. One methodology that is often employed in this domain is portfolio optimization, whereby the objective is to select a diverse set of assets that maximize the return on investment. In the defense context, the return on investment is often measured in terms of the capabilities that the investments will provide. While the field of portfolio optimization is well established, applications in the defense sector pose unique challenges not seen in other application domains. However, the literature regarding portfolio optimization for defense applications is rather sparse. To this end, this paper provides a structured review of recent applications and identifies a number of areas that warrant further investigation.

Abstract Objectives: To describe and compare vaccination coverage for Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) adults in 2004–05 and 2012–13, including the impact of national vaccination funding initiatives. Methods: National Aboriginal and Torres Strait Islander Health cross‐sectional surveys – 2004–05 (n=5,757) and 2012–13 (n=5,482) – were compared. Self‐reported influenza and pneumococcal vaccination coverage among Indigenous adults was analysed by age, remoteness, gender and risk factor status. Results: Influenza vaccination coverage among Indigenous adults in 2004–05 and 2012–13 remained low. While coverage increased for those aged 18–49 years from 23% to 29%, it declined for those aged ≥65 years from 84% to 74%. For remote areas, influenza coverage among those aged 50–64 years declined from 76% to 66%. Pneumococcal vaccination coverage remained very low and declined across all age groups in 2004–05 and 2012–13 (50–64 years: 30% to 23%). For remote areas, pneumococcal coverage declined among those aged 50–64 years from 52% to 32%. Conclusions: Indigenous adult vaccination coverage for influenza and pneumococcal disease remains unacceptably low. Between 2004–05 and 2012–13, declines occurred in pneumococcal vaccination coverage across all age groups ≥18 years. Despite national funding of influenza vaccine in 2010, there was no increase in influenza coverage, except for the 18–49‐year age group. Implications for public health: Current approaches to promote, deliver and monitor vaccination of Indigenous adults are inadequate.

COVID-19 has caused excessive morbidity and mortality worldwide. COVID-19 vaccines, including the two mRNA vaccines, were developed to help mitigate COVID-19 and to move society towards herd immunity. Despite the strong efficacy and effectiveness profile of these vaccines, there remains a degree of vaccine hesitancy among the population. To better understand hesitancy associated with COVID-19 vaccines and to delineate between those who are vaccine acceptors, vaccine refusers, and the moveable middle, we conducted a cross-sectional survey to understand respondents’ decision to receive, or not, a COVID-19 vaccine at the onset of mRNA vaccine availability in Central Texas. A total of 737 individuals responded, with 685 responses classified to one of eight domains: A: End to the Pandemic (n = 48); B: Trust in Medical Community (n = 27); C: Illness-Focused Perceptions (n = 331); D: Social Motivation (n = 54); E: Vaccine-Focused Perceptions (n = 183); F: Knowledge Gap (n = 14); G: Underlying Health Concern (n = 9); and H: Undecided (n = 19). Vaccine acceptors (n = 535) were primarily represented in domains A–E, while vaccine refusers (n = 26) were primarily represented in domains C, E, G, and H. The moveable middle (n = 124) was primarily represented by domains C–H. These findings show clear delineations between vaccine acceptors, vaccine refusers, and the moveable middle across eight domains that can assist public health professionals in addressing vaccine hesitancy.

Abstract Background The United States appears to be in the midst of an opioid epidemic. National data indicate a rise in emergency department visits for opioid-related causes over the past decade. This data, while important in helping to explain the magnitude of the epidemic nationally offers only a glimpse of what can be expected to occur locally. The objective of this secondary data analysis was to describe the impact that opioid abuse, adverse events, poisoning, and dependence have on emergency department utilization for individuals who purchased health insurance under the Affordable Care Act in Central Texas from a community-based health maintenance organization. Methods Individuals who purchased health insurance from Sendero Health Plans in calendar years 2016, 2017, and 2018 were eligible for participation if they had both an emergency department encounter and an opioid-related ICD-10-CM diagnosis. Eligible individuals were assessed to determine if they were dispensed an opioid agonist or opioid antagonist prescription during the year of their emergency department encounter. Sendero medical claims data for calendar years 2016, 2017, and 2018 were used to calculate both the incidence and ratio of emergency department visits per 100,000-person Sendero member population. Sendero data were compared to available national data estimates. Results A total of 55 individuals had an emergency department encounter with a primary or secondary opioid-related diagnosis from January 1, 2016 through December 31, 2018. These 55 individuals had 69 unique emergency department encounters during this time period. The incidence of new claims per 100,000-member Sendero population was 67.1, 64.5, and 62.6 in 2016, 2017, and 2018 respectively. The ratio of unique emergency department encounters per 100,000-member Sendero population was 95.9, 82.6, and 66.5 in 2016, 2017, and 2018 respectively. Conclusion Health insurance claims data from a community-based health plan can be used as a source of local information by policy makers and officials as they seek to address the impact of opioid abuse, adverse events, poisoning, and dependence in Central Texas as national data may not represent the local impact of this epidemic.

Abstract Background Many developing countries are experiencing the epidemiological transition, with the majority of deaths attributed to cardiovascular disease, cancer, Type 2 diabetes (T2DM) and others. In some countries, large proportional mortality attributed to diabetes is evident in official mortality statistics, with Mauritius and Fiji rated as the highest in the world. Methods This study investigates trends in recorded diabetes and cardiovascular disease mortality in Mauritius and Fiji under coding from the International Classification of Diseases (ICD) versions 9 and 10, using mortality data reported from these countries to the World Health Organization (WHO). Results In Mauritius over 1981–2004, T2DM proportional mortality varied between 4% and 7% in males (M) and 5% and 9% in females (F). In 2005 there was a sudden increase to M 20% and F 25%, which continued to M 25% and F 30% by 2012. Over 1981–2004 the proportion of circulatory disease mortality rose from 44% to 49% in males, and from 46% to 57% in females. In 2005, circulatory disease mortality proportions fell precipitously to 34% in males and 37% in females, and declined to 31% and 34% by 2013. ICD–10 coding was introduced in 2005. In Fiji, sharp rises in proportional T2DM mortality from 3% in both sexes in 2001 to M 15% and F 20% in 2002 were followed by more gradual trend increases to M 20% and F 26% by 2012–13. Circulatory disease proportions fell steeply from M 57% and F 53% in 2001 to M 44% and M 38% by 2004, with subsequent less steep declines to M 39% and F 30% by 2012. ICD–10 coding was introduced in 2001. Conclusions Large, abrupt changes in diabetes and circulatory disease proportional mortality in Fiji and Mauritius coincided with the local introduction of ICD–10 coding in different years. There is also evidence for diabetes-related misclassification of underlying cause of death in Australia and the USA. These artefacts can undermine accurate monitoring of cause of death for evaluation of effectiveness of prevention and control, especially of circulatory disease mortality which is demonstrably reversible in populations.

Abstract Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. Methods The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving. Results These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity. Conclusion Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes.

Objective: Mass vaccination planning is occurring at all levels of government in advance of regulatory approval and manufacture of a SARS-CoV-2 vaccine for distribution sometime in 2021. We outline a methodology in which both health insurance provider network data and publicly available data sources can be used to identify and plan for SARS-CoV-2 vaccinator capacity at the county level.Methods: Sendero Health Plans, Inc. provider network data, Texas State Board of Pharmacy data, US Census Bureau data, and H1N1 monovalent vaccine data were utilized to identify providers with demonstrated capacity to vaccinate the population in Travis County, Texas to achieve an estimated SARS-CoV-2 herd immunity target of 67%.Results: Within the Sendero network, 2,356 non-pharmacy providers were identified with 788 (33.4%) practicing in primary care and 1,569 (66.6%) practicing as specialists. Of the total, 686 (29.1%) provided at least one immunization between January 1, 2019 and September 30, 2020. There are 300 pharmacies with active licenses in Travis County with 161 (53.7%) classified as community pharmacies. We estimate that 1,707,098 doses of a 2-dose SARS-CoV-2 vaccine series will need to be administered within Travis County, Texas to achieve the estimated 67% herd immunity threshold to disrupt person-to-person transmission of the SARS-CoV-2 virus based on 2020 census data.Conclusion: A community-based health insurance plan can use data from its provider network and public data sources to support the CDC call to action to identify SARS-CoV-2 vaccinators in the community, including physicians, nurse practitioners, physician assistants, and pharmacies in order to provide macro level estimates of SARS-CoV-2 administration and throughput.

Abstract Background To analyse trends over the period 1991–2013 in systolic blood pressure (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension in adults aged 25–64 years in Samoa; and to assess the contribution of rising obesity levels to period trends. Methods Unit record data from seven population-based surveys (n = 10,881) conducted between 1991 and 2013 were included for analysis. Surveys were adjusted to the nearest previous census to improve national representativeness. Hypertension was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg and/or on medication for hypertension. Obesity was measured by body mass index (BMI). Poisson, linear and meta-regression were used to assess period trends. Results Over 1991–2013 mean SBP and DBP (mmHg), and the prevalence of hypertension (%) increased in both sexes. Increases in hypertension were: from 18.3 to 33.9% (p

Abstract Background Young adult (aged 20–34) males experience higher mortality than females, and in age groups immediately younger and older, and with considerable variation in death rates over time. Trends in mortality and the cause structure of deaths among young adult Australian males over 1979–2011 are investigated, with a focus on suicide and drug overdose. Methods Mortality data by age for the period 1979 to 2011 and Australian population figures were obtained from the Australian Bureau of Statistics (ABS). Cause of death was investigated using relevant International Classification of Diseases (ICD) codes, and mortality by cause was examined graphically over time according to various ICD aggregations. Mortality trends were contextualised in relation to labour market changes occurring in Australia from the 1980s to early 2000s. Results Although motor vehicle accident (MVA) mortality declined by half between 1980 and 1998 in males, this did not translate into a reduction in total young male mortality because of simultaneous increases in suicide, and drug-related deaths classified as either poisoning (external cause) or drug dependence (mental disorders). When both suicide and drug-related deaths declined concurrently after 1998, total 20–34 year male mortality declined by almost half (46%) over 1998–2011. Declines in external cause mortality accounted for 63% of the total mortality decline in 20–34 year males over 1998–2011. The close temporal coincidence (statistically significant) of increases and declines in suicide and drug-related deaths over a decade suggests related causality. Conclusions The coincidence of young male suicide and drug overdose mortality epidemics over the study period (excess deaths: 5000) suggest related causality such as exposure to common factors, including the labour market liberalisation and de-regulation of the 1990s, and deserves further investigation.

Abstract Background Reliable and timely data on maternal and neonatal mortality is required to implement health interventions, monitor progress, and evaluate health programs at national and sub-national levels. In most South Asian countries, including Pakistan, vital civil registration and health information systems are inadequate. The aim of this study is to determine accurate maternal and perinatal mortality through enhanced surveillance of births and deaths, compared with prior routinely collected data. Methods An enhanced surveillance system was established that measured maternal, perinatal and neonatal mortality rates through more complete enumeration of births and deaths in a rural district of Pakistan. Data were collected over a period of 1 year (2015/16) from augmentation of the existing health information system covering public healthcare facilities (n = 19), and the community through 273 existing Lady Health Workers; and with the addition of private healthcare facilities (n = 10), and 73 additional Community Health Workers to cover a total study population of 368,454 consisting of 51,690 eligible women aged 18 to 49 years with 7580 pregnancies and 7273 live births over 1 year. Maternal, neonatal, perinatal and stillbirth rates and ratios were calculated, with comparisons to routine reporting from the previous period (2014–15). Results Higher maternal mortality, perinatal mortality and neonatal mortality rates were observed through enhanced surveillance compared to mortality rates in the previous 1.5 years from the routine monitoring system from increased completeness and coverage. Maternal mortality was 247 compared to 180 per 100, 000 live births (p = 0.36), neonatal mortality 40 compared to 20 per 1, 000 live births (p

The effects and consequences of global warming on the productivity of the Patagonian forest are still unknown. The use of Unmanned Aerial Vehicles (UAV) promotes new knowledge of the most pristine and unknown sub-antarctic forests located in Chilean Patagonia. This work presents an initial approach to spatialize biochemicals over the Patagonian forests using ultra-high spatial resolution imagery acquired from UAVs equipped with a multispectral (visible, near-infrared, and thermal) sensor. The images were obtained in multiple flights over the Cerro Castillo National Park (Aysén Region, Chile), and several Vegetation Indices (VIs) were estimated. Leaves of Nothofagus pumilio (Poepp. et Endl.) Krasser (Nothofagaceae) individuals were extracted after the flights and were then used to determine the biochemicals traits of chlorophylls (Chl-a and Chl-b) and carotenoids pigments, as well as the total phenolic content (TPC), total flavonoids content (TFC), and the DPPH radical scavenging assay. Their relationships with multiple VIs was analyzed in order to assess the spatiality of the biochemicals traits in the forest during it most productive phenological stage. Results showed high correlations for the biochemical traits pigments (R2 > 0.75) with the indices DVI, MCARI, and MSAVI1 as the best performing indices, while further spectral availability is needed for significant correlations with biochemicals traits related to the antioxidant capacity. Spatialization of the biochemical traits within UAV imagery was also performed evaluating their representation in the forest. This work allowed us to identify the different spectral behavior of the N. pumilio species, its relation to biochemical traits, and their spatialization, thus presenting the first step to developing a monitoring protocol for the evaluation of the Patagonian forests under the current global warming scenarios in the region.