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Background: While mid-life hypertension represents a risk factor for the development of Alzheimer's disease (AD), the risk after the age of 65 is less certain. Establishing relationships between late life hypertension and the pathological changes of AD could be crucial in understanding the relevance of blood pressure as a risk factor for this disorder. Objective: We investigated associations between self-reported late-life hypertension, cognitive status and AD pathology at death. The impact of antihypertensive medication was also examined. Methods: Using the Cornell Medical Index questionnaire, we ascertained whether participants had ever reported hypertension. We also noted use of antihypertensive medication. The donated brains of 108 individuals were assessed for AD pathology using consensus guidelines. Statistical analysis aimed to elucidate relationships between hypertension and AD pathology. Results: We found no associations between self-reported hypertension and cognitive impairment at death. However, those with hypertension were significantly more likely to exhibit lower levels of AD pathology as measured by Thal phase, Braak stage, CERAD score, and NIA-AA criteria—even after controlling for sex, level of education and presence of APOEɛ4 allele(s). No significant associations could be found when examining use of antihypertensive medications. Conclusions: Our findings suggest that late-life hypertension is associated with less severe AD pathology. We postulate that AD pathology may be promoted by reduced cerebral blood flow. [ABSTRACT FROM AUTHOR]

This article explores how the immunoreactivity of phosphorylated TDP-43 (pTDP-43) in fixed post-mortem brain tissue can be affected by factors such as long-term storage and prolonged formalin fixation. The study reveals that extended fixation and long-term storage can weaken the immunoreactivity of pTDP-43, but it remains detectable for diagnostic purposes. These findings have implications for the use of brain tissue stored in brain banks for scientific research. The study also found that other proteins, such as amyloid-β and phosphorylated α-synuclein, are not affected by extended fixation or long-term storage, suggesting that existing tissue samples in brain banks can still be used for research, even if they have been stored for many years. [Extracted from the article]

Working with people living with dementia in residential facilities for older adults can be challenging, and this is exacerbated when staff have a limited understanding of dementia. However, the relationship between knowledge of dementia and strain in caring for people with dementia among residential facility staff is unclear. This cross-sectional study investigated the relationship between dementia knowledge and strain in caring for people with dementia. A questionnaire containing the Dementia Knowledge Assessment and Strain in Dementia Care Scales was administered in 2017 and 2019 to 141 staff in three southern Australian residential facilities for older adults. Bivariate and hierarchical regression analysis examined inter-scale relationships and the power of dementia strain to explain knowledge variance. It was found that staff had substantial gaps in dementia knowledge (mean score 32/50) and low strain in dementia care (mean score 4/16). A positive relationship was found between higher dementia knowledge and greater strain in dementia care (rs = 0.319, p <.001), particularly with feeling that residents are not receiving appropriate care from colleagues (Factor 1 Frustrated Empathy; rs = 0.392, p <.001). Frustrated Empathy explained a significant amount of variance in dementia knowledge beyond demographic variables. The findings suggest that more comprehensive dementia knowledge is associated with higher strain in care of people with dementia, particularly in the context of perceived lapses in the quality of care provided by colleagues. Arguably, organisational-wide dementia education to address identified gaps should be supported by facilitating staff enaction of their knowledge to improve care. [ABSTRACT FROM AUTHOR]

This study investigates the development of the Festival of Nine Lessons and Carols, considers how in this context the Christmas story is told in word and music, and examines how this service contributes to the Church's mission of proclaiming the story of faith today. It focuses on the initial development of the service in Truro 1880, its subsequent adaptation at King's College, Cambridge, and how the tradition is reflected in and developed throughout the twentieth and twenty-first century, using examples from four Cathedrals in England: Coventry, Salisbury, Durham, and Truro. This paper shows how, with adaption and careful planning, this service can continue to be used as a missional tool to tell the story of faith in the twenty-first century. [ABSTRACT FROM AUTHOR]

Background: Environmental co-exposure to allergen and traffic-related air pollution is common globally and contributes to the exacerbation of respiratory diseases. Individual responses to environmental insults remain variable due to gene-environment interactions. Objective: This study examined whether single nucleotide polymorphisms (SNPs) in lung cell surface receptor genes modifies lung function change and immune cell recruitment in allergen-sensitized individuals exposed to diesel exhaust (DE) and allergen. Methods: In this randomized, double-blinded, four-arm, crossover study, 13 allergen-sensitized participants underwent allergen inhalation challenge following a 2-hour exposure to DE, particle-depleted diesel exhaust (PDDE) or filtered air (FA). Lung function tests and bronchoscopic sample collection were performed up to 48 h after exposures. Transient receptor potential channel (TRPA1 and TRPV1) and toll-like receptor (TLR2 and TLR4) risk alleles were used to construct an unweighted genetic risk score (GRS). Exposure-by-GRS interactions were tested using mixed-effects models. Results: In participants with high GRS, allergen exposure was associated with an increase in airway hyperresponsiveness (AHR) when co-exposed to PDDE (p = 0.03) but not FA or DE. FA and PDDE also were associated with a relative increase in macrophages and decrease in lymphocytes in bronchoalveolar lavage. Conclusions: TRPs and TLRs variants are associated with increased AHR and altered immune cellularity in allergen-exposed individuals. This effect is blunted by DE exposure, suggesting greater influence of unmeasured gene variants as primary meditators of a particulate-rich co-exposure. Trial registration: The study was registered with ClinicalTrials.gov on December 20, 2013 (NCT02017431). [ABSTRACT FROM AUTHOR]

Objectives: The study investigated how senior residential aged care staff perceived the purpose, function, impact and challenges of implementing a new role in their organisation for an unregistered care worker with a Bachelor of Dementia Care: the Dementia Care Support Worker. The role was piloted over two years in an Australian organisation with three aged care facilities to examine its potential to address gaps in service provision for people with dementia. Background: The residential aged care workforce is under pressure to care for residents with increasingly complex health conditions and where most care is provided by care workers. Presently no formal leadership role exists for care workers with specialised dementia knowledge in the aged care setting. Study design and methods: A qualitative descriptive approach was taken to explore senior staff members' perceptions of the role at two time points. Twenty-three semi-structured interviews held in July-August 2017 (n = 12), soon after role commencement, and in February-March 2019 (n = 11) were thematically analysed. Results: Three themes reflected senior staff members' expectations of the role: enhancing staff and management knowledge about dementia and dementia care practices; facilitating changes to improve care for residents living with dementia; and educating and supporting residents' families. Eighteen months later, participants felt the role was helping meet the need for improved care of residents with dementia, and staff understanding of dementia. They suggested communication and support structures to improve role effectiveness. Discussion: Staff were receptive to the establishment of the Dementia Care Support Worker role and felt it resulted in improvement in dementia care. Success was contingent on strong organisational support and resourcing. Conclusion: Improving dementia knowledge of care staff is an essential first step in driving care quality improvements. The Dementia Care Support Worker role for care workers has the potential to address knowledge needs and support improved care practices. Implications for research, policy, and practice: This research models how a new role might be configured for unregistered care workers with specialist dementia knowledge. Further research is needed to explore the establishment of such a role more widely in other organisations, to investigate whether it could provide a new career development pathway for care workers and improve the skills and capacity of the aged care workforce. Substantial policy changes would also be required to support role viability, such as around increased salary. Research which examines the impact of such roles on care outcomes would complement the findings. What is already known about the topic? • While dementia is common in residential aged care, knowledge of dementia is typically low among the care staff. • Consequently, care staff are not equipped to meet the complex needs of residents with dementia and their families. • New roles for unregistered care workers with specialised dementia knowledge have been proposed, but not tested. What this paper adds • This research models how a new role might be configured for care workers with specialist dementia knowledge. • Aged care facility leaders support a role for care workers with formal specialist dementia knowledge and skills, and perceive the role helps improve the quality of resident care and develop stakeholders' dementia knowledge. • Appropriate communication and support structures are required for the effective establishment of the role. [ABSTRACT FROM AUTHOR]

Architected lattices are gaining prominence for structural applications as additive manufacturing technologies mature. Emergent behavior, such as material jetting and wave propagation, arising from the open architecture has been observed under dynamic loading conditions. The origin of the observed jetting and how it might come about across a broad spectrum of lattice types, material compositions, length scales, and dynamic loading conditions is still an open question. The jetting behavior due to lattice structures was studied through a series of dynamic compression plate impact experiments with in situ x-ray imaging. The role of the impact conditions, the lattice spacing, the lattice architecture, and the lattice base material is explored in the context of promoting or suppressing jet formation. A transition from lattice-led to impactor-led jetting is observed above a certain impact threshold. Complementary direct numerical simulations were also performed to compare with the experiments, to study the underlying stress state giving rise to jetting, and to provide insight into conditions not accessed experimentally. We present a geometric argument on the competitive process leading to lattice and/or impactor jetting which incorporates base material properties, the periodicity of the lattice, and basic tunable length scales of the lattice. Using two-dimensional calculations, we further look at how tuning of a single parameter of the studied systems changes the observed jetting transition. [ABSTRACT FROM AUTHOR]

Exposure to trauma, high-stress situations, and disrupted sleep are well known risk factors affecting firefighters' mental health. Little is known about the association between firefighters' exposure to fire contaminants and mental health disorders. The UK Firefighter Contamination Survey assessed firefighters' health and capacity for occupational exposure to contaminants. Participants were invited to anonymously complete its 64 questions online. Logistic regression analyses assessed the associations between self-reported mental health disorders and proxies of contaminant exposure. Results found that firefighters who notice soot in their nose/throat for more than a day after attending fires (Odds Ratio (OR) = 1.8, 1.4–2.4), and those who remain in their personal protective equipment (PPE) for over 4 h after fires (OR = 1.9, 1.2–3.1), were nearly twice as likely to report mental health disorders. Significantly increased odds ratios for all three outcomes of interest (anxiety, depression and/or any mental health disorders) were also found among firefighters who take PPE home to clean. Sleeping problems were reported by 61% of firefighters. These firefighters were 4.2 times more likely to report any mental health disorder (OR = 4.2, 3.7–4.9), 2.9 times more likely to report anxiety (OR = 2.9, 2.4–3.5) and 2.3 times more likely to report depression (OR = 2.3, 1.9–2.8) when compared to firefighters who did not report sleep issues. Effective decontamination measures within UK Fire and Rescue Services, together with firefighters' wellness, may play a crucial role in protecting firefighters' mental health. [ABSTRACT FROM AUTHOR]

Firefighters suffer an increased risk of cancer from exposures to chemicals released from fires. Our earlier research has found that fire toxicants not only remain on firefighters' PPE, but are also tracked back to fire stations. The UK Firefighter Contamination Survey assesses firefighters' risk of developing cancer due to occupational exposure to fire toxins. Over 4% of surveyed firefighters were found to have a cancer diagnosis, with the age-specific cancer rate up to 323% higher (35–39 year olds) than that of the general population. Firefighters who had served ≥ 15 years were 1.7 times more likely to develop cancer than those who had served less time. Firefighters were at least twice as likely to be diagnosed with cancer if they noticed soot in their nose/throat (odds ratio (OR) = 2.0, 1.1–3.5), or remained in their PPE for more than four hours after attending a fire incident (OR = 2.3, 1.1–5.2). Also associated with an increased likelihood of cancer was: eating while wearing PPE (OR = 1.8, 1.2–2.7); failing to store clean/dirty PPE separately (OR = 1.3, 1.0–1.7); working in a station that smells of fire (OR = 1.3, 1.0–1.8) or not having designated (separated) clean and dirty areas (OR = 1.4, 1.1–1.7); using an on-site washing machine to launder fire hoods (OR = 1.3, 1.0–1.7); feeling that cleaning is not taken seriously at work (OR = 1.5, 1.2–2.0). [ABSTRACT FROM AUTHOR]

The Centre for the AIDS Programme of Research in South Africa (CAPRISA), performs world-leading research on the epidemiology, pathogenesis, prevention and treatment of HIV/AIDS, tuberculosis, and - more recently - COVID-19. A rigorous yet supportive academic culture has nurtured the careers of many successful health sciences researchers, some of whom have worked for the organization since its inception over 20 years ago. This focus on professional development is founded on a training programme that invests heavily in the individual with the payoff of strengthening the science base for HIV and tuberculosis research in South Africa. Those selected for mentorship are typically medical students from the University of KwaZulu-Natal, adjoining the headquarters of CAPRISA in Durban. Increasingly, however, the institute attracts international fellows from partnering organizations to experience the intellectually demanding, scientifically robust, cutting-edge research environment. The purpose of this voices piece is to narrate and critically evaluate the experience from the dual perspectives of host and visitor of a research training programme undertaken by three undergraduate health sciences students from Vietnam, enrolled at VinUniversity. This was the inaugural running of what is expected to be an annual summer trip to CAPRISA by Hanoi-based medical and nursing students. The formative educational experience in best practice tackling of infectious diseases in challenging clinical contexts demonstrated the importance of investing in research placement programmes for public health impact. The exchange has inspired each student to become a future leader in seeking bold, innovative, and strategic approaches to improve global health issues in their home country. [ABSTRACT FROM AUTHOR]

We report on a patient with atypical parkinsonism due to coexistent Lewy body disease (LBD) and diffuse anaplastic astrocytoma. The patient presented with a mixed cerebellar and parkinsonian syndrome, incomplete levodopa response, and autonomic failure. The clinical diagnosis was multiple system atrophy (MSA). Supportive features of MSA according to the consensus diagnostic criteria included postural instability and early falls, early dysphagia, pyramidal signs, and orofacial dystonia. Multiple exclusion criteria for a diagnosis of idiopathic Parkinson's disease (iPD) were present. Neuropathological examination of the left hemisphere and the whole midbrain and brainstem revealed LBD, neocortical‐type consistent with iPD, hippocampal sclerosis, and widespread neoplastic infiltration by an anaplastic astrocytoma without evidence of a space occupying lesion. There were no pathological features of MSA. The classification of atypical parkinsonism was difficult in this patient. The clinical features and disease course were confounded by the coexistent tumor, leading to atypical presentation and a diagnosis of MSA. We suggest that the initial features were due to Lewy body pathology, while progression and ataxia, pyramidal signs, and falls were accelerated by the occurrence of the astrocytoma. Our case reflects the challenges of an accurate diagnosis of atypical parkinsonism, the potential for confounding co‐pathology and the need for autopsy examination to reach a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the impacts of changing a model of care and employing general practitioners (GPs) within residential aged care facilities (RACFs) on costs to the aged care provider (ACP) and state and federal governments of Australia.Methods: This study was a cost analysis of a prospective, stepped-wedge, cluster randomised trial. All financial data from the ACP for every RACF involved, before and after implementation of the new model were obtained. Costs of hospital transfers, admissions, ambulance usage and GP consultations were calculated. Costs of new infrastructure, recruiting and training new staff were accounted for. Costs were standardised to 2019 Australian Dollars per occupied bed day (OBD).Results: Implementation of the new model of care resulted in overall cost savings of $9.7 per OBD to the ACP, with increased salary costs offset by increased federal government subsidies and Medicare claims income. Costs to the federal government increased by $19.6 per OBD, driven by increases in subsides. Costs savings of $3.0 per OBD to state governments were seen, driven by decreased costs of hospital transfers.Conclusions: Implementation of a model of care including GPs employed at RACFs had a mixed impact on costs depending on perspective, with overall savings to the ACP and state government perspective. [ABSTRACT FROM AUTHOR]

Globally, there has been an increasing amount of wood harvested from younger, fast-growing trees derived from plantation forests. As a consequence, producers and industrial consumers of wood products are becoming increasingly concerned with not only growth rates, but specific wood attributes that affect processing efficiencies and final product quality. Intra-ring checking is a problem that down-grades an unacceptably high proportion of radiata pine clearwood. Methods of identifying trees prone to this undesirable behaviour have been relatively destructive and time consuming, and from a breeding perspective, to date, there is no reliable method of predicting which selected progeny will later show a propensity to check. Using 120, 7-year-old Pinus radiata clones sampled from a common site, displaying difference in the propensity to form intra-ring checks, a GC/MS-based global metabolic profiling technique was employed to demonstrate that metabolomics can be used to accurately identify the checking phenotype. Metabolic profiling coupled with statistical tests was then used to develop models with greater than 90% efficiency to predict the intra-ring checking phenotype. Moreover, an inspection of unique metabolites contributing to the models indicated that coniferin, which is often found as a storage compound in rays, is a strong indicator of intra-ring checking, and indeed those genotypes that displayed the propensity to check inherently had a greater number of ray cells per unit area. [ABSTRACT FROM AUTHOR]

(1) Background: To date, data addressing the antibody response of cancer patients to SARS-CoV-2 vaccines are limited. To our knowledge, this is the first report to evaluate humoral immunity. responses in Canadian cancer patients. (2) Methods: 116 cancer patients and 35 healthy participants were enrolled in this cross-sectional study. The interval between the first and second doses were closely matched during analysis. IgG antibodies against the SARS-CoV-2 spike receptor–binding domain were determined using an enzyme-linked immunosorbent assay (ELISA). (3) Results: Following two doses of SARS-CoV-2 vaccine (including BNT162b2, AZD1222, and mRNA-1273), the mean serum anti-spike protein antibody level was 382.4 BAU/mL (binding antibody unit, SD ± 9.4) in the control group, 265.8 BAU/mL (±145.7) in solid cancer patients, and 168.2 BAU/mL (±172.9) in hematological cancer patients. Observed differences were significantly lower in both solid and hematological groups when comparing to the control group (p ≤ 0.0001). In solid cancer group, patients with cytotoxic chemotherapy demonstrated significantly lower antibody levels (p < 0.01), whereas the rest of the patients showed similar antibody levels as the healthy control. Antibody levels were lower in those on treatment than those off treatment in patients with hematological malignancies (p < 0.0001) but not for those with solid cancers (p = 0.4553). (4) Conclusions: After two doses of the SARS-CoV-2 vaccination, patients with solid and hematological malignancies demonstrated impaired serological responses. This was particularly prominent if there was cytotoxic chemotherapy or systemic therapy in solid and hematological cancer, respectively. [ABSTRACT FROM AUTHOR]

Between-country tourism is established as a facilitator of the spread of invasive alien species; however, little attention has been paid to the question of whether tourism contributes to the arrival and subsequent dispersal of exotic organisms within national borders. To assess the strength of evidence that tourism is a driver for the accidental introducing and dispersal of exotic organisms, we sourced three national databases covering the years 2011 to 2017, namely international and domestic hotel guest nights and national population counts, along with records of exotic organism detections collected by the Ministry for Primary Industries, New Zealand's government agency that oversees biosecurity. We fitted statistical models to assess the strength of the relationship between monthly exotic organism interception rate, guest nights and population, the latter as a baseline. The analysis showed that levels of incursion detection were significantly related to tourism records reflecting the travel of both international and domestic tourists, even when population was taken into account. There was also a significant positive statistical correlation between the levels of detection of exotic organisms and human population. The core take-home message is that a key indicator of within-country human population movement, namely the number of nights duration spent in specific accommodation, is statistically significantly correlated to the contemporaneous detection of exotic pests. We were unable to distinguish between the effects of international as opposed to domestic tourists. We conclude that this study provides evidence of impact of within-country movement upon the internal spread of exotic species, although important caveats need to be considered. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of Alzheimer's disease (AD) provides an opportunity for early intervention. Cognitive testing has proven to be a reliable way to identify individuals who may be at risk of AD. The Telephone Assessment for Cognitive Screening (TICS) is proficient in screening for cognitive impairment. However, its ability to identify those at risk of developing AD pathology is unknown.Objective: We aim to investigate associations between TICS scores, collected over a period of 13 years, and the cognitive status of participants at death. We also examine relationships between TICS scores and neuropathological indices of AD (CERAD score, Thal phase, and Braak stage).Methods: Between 2004 and 2017, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent cognitive assessment using TICS. Scores from four time points were available for analysis. Cognitive impairment and AD pathology at death was evaluated in 101 participants.Results: TICS scores at time points 2, 3, and 4 were significantly lower in those cognitively impaired at death compared to those considered cognitively normal. There were significant negative correlations between TICS scores and CERAD score and Braak stage at time points 2 and 4. No correlations between Thal phase and TICS were found.Conclusion: Findings indicate that TICS could be used not only to screen for cognitive impairment, but also to identify individuals at risk of developing AD pathology, many years before any overt symptoms occur. Once identified, 'at risk' individuals could be targeted for early interventions which could attenuate the progression of the disease. [ABSTRACT FROM AUTHOR]

A galaxy merger is expected to cause the formation of a supermassive black hole (SMBH) binary, which itself eventually coalesces through the anisotropic emission of gravitational waves. This may result in the merged SMBH receiving a recoil kick velocity ∼100–1000 kms−1, causing it to oscillate in the gravitational potential of the host galaxy. The luminous quasar E1821+643, identified as an SMBH recoil candidate via spectropolarimetry observations, shows Doppler shifting of the broad emission lines in direct and scattered light, consistent with a relative velocity of 2100 km s−1 between the quasar nucleus and host galaxy. In this paper, we attempt to detect the expected spatial displacement using a combination of optical spectroastrometry and Hubble Space Telescope (HST) narrow-band images. The spectroastrometry reveals a relative spatial displacement between the quasar nucleus and the gas emitting the [O  iii ] λλ4959, 5007 lines of ∼130 mas (∼580 pc) to the north-west. Our HST images resolve the [O  iii ] emission on sub-arcsecond scales, showing that it is asymmetrically distributed, extending to radial distances ∼0.5−0.6 arcsec from the nucleus in a wide arc running from the north-east around to the west. A simulated spectroastrometry observation based on the HST [O  iii ] image indicates that only a small fraction of the measured displacement can be attributed to the asymmetric [O  iii ] emission. This displacement therefore appears to be a real spatial offset of the quasar nucleus with respect to the narrow-line region, presumed to be located at the host galaxy centre, further supporting the interpretation that a post-merger gravitational recoil of the SMBH has occurred in E1821+643. [ABSTRACT FROM AUTHOR]

Using single-molecule fluorescence microscopes, individual biomolecules can be observed within live bacterial cells. Using differently coloured probes, physical associations between two different molecular species can be assessed through co-localisation measurements. However, bacterial cells are finite and small (~ 1 μm) relative to the resolution limit of optical microscopes (~ 0.25 μm). Furthermore, the images produced by optical microscopes are typically two-dimensional projections of three-dimensional objects. These limitations mean that a certain proportion of object pairs (molecules) will inevitably be assigned as being co-localised, even when they are distant at molecular distance scales (nm). What is this proportion? Here, we attack this problem, theoretically and computationally, by creating a model of the co-localisation expected purely due to chance. We thus consider a bacterial cell wherein objects are distributed at random and evaluate the co-localisation in a fashion that emulates an experimental analysis. We consider simplified geometries where we can most transparently investigate the effect of a finite size of the cell and the effect of probing a three-dimensional cell in only two dimensions. Coupling theory to simulations, we also study the co-localisation expected due to chance using parameters relevant to bacterial cells. Overall, we show that the co-localisation expected purely due to chance can be quite substantial and describe the parameters that it depends upon. [ABSTRACT FROM AUTHOR]

For patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after an androgen receptor axis–targeted therapy and docetaxel, poly (ADP-ribose) polymerase (PARP) inhibitors and chemotherapy with cabazitaxel have shown promise. We address the trials for the two approaches and consider possible sequencing of these drugs. We suggest that only patients with a BRCA2 mutation should receive a PARP inhibitor, and docetaxel or cabazitaxel should be favored in the absence of BRCA2 alterations, provided the patient is naïve to these drugs. [ABSTRACT FROM AUTHOR]

Prior studies examining the nonlinear material properties of 6000 series aluminum alloys have predominantly concentrated on analyzing the stress–strain characteristics of these materials under monotonic tensile loading. Limited research has been conducted on their behavior under cyclic loading conditions. To address these gaps, a series of monotonic tensile and variable increasing amplitude cyclic loading tests was conducted on coupons made from 6082-T6, 6063-T6, and 6060-T5 aluminum alloys. The experimental results revealed that as strain amplitude increased the material showed isotropic strain hardening. This combined with the adequate hysteretic energy dissipation capacity demonstrates their potential advantage to be used as in structural components in earthquake prone regions. The experimental results are used to calibrate the material parameters of the uniaxial Giuffrè–Menegotto–Pinto constitutive model to be able to predict the nonlinear stress–strain behavior under monotonic and cyclic loading. Furthermore, using fiber element modeling in OpenSees software, employing a modified Giuffrè–Menegotto–Pinto model, the flexural buckling performance of 6082-T6 aluminum alloy columns is analyzed. The results are compared with existing experimental and finite element data, demonstrating the accuracy of the model in predicting the flexural buckling behavior. [ABSTRACT FROM AUTHOR]

Objectives: Early diagnosis of Alzheimer's disease (AD) is essential for early interventions. Symptoms of depression could represent a prodromal stage of AD. Very early mood alterations may help to stratify those at highest risk of late-life AD. We aim to investigate associations between baseline/longitudinal scores for depression, presence of cognitive impairment and/or AD pathology at death.Methods/design: Between 1991 and 2015, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent 10 waves of assessment using the Geriatric Depression Scale (GDS). AD pathology at death was evaluated in 106 eligible cases. Analyses aimed to examine associations between GDS scores, cognitive status and AD pathology (as measured by Braak stage, Thal phase and CERAD).Results: Baseline GDS scores were significantly higher for those cognitively impaired at death than those cognitively normal. Significantly higher baseline GDS scores were found for those with greater Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores than those with lower CERAD scores. Similarly, significantly higher baseline GDS scores were found for those with a greater Braak stage than those with lower tau burden. These correlations remained after controlling for age at death, education and APOE ε4, but were less robust. Mean longitudinal GDS scores associated with cognition but not pathology.Conclusions: GDS scores collected approximately 20 years before death were associated with cognitive status and AD pathology at death. We postulate that early AD-related pathological change produces raised GDS scores due to an overlapping neural basis with depression, and that this may be considered as an early diagnostic marker for AD. [ABSTRACT FROM AUTHOR]

Advances in technology have opened multiple formats of rapid communication for Extension personnel to communicate with clientele. Today, Extension personnel at many universities use webpages, social media, applications on smart phones, and many other ways to deliver timely messages to clientele. For example, the University of Maine Cooperative Extension provides a hotline for the latest information for pest and disease occurrence, distribution, and control. This has been expanded into text-based information delivery, which has been well accepted. North Dakota State University and University of Minnesota potato Extension website contains information on potato production, current issues and provides many resources for potato growers. In addition to the website, information is shared by Twitter and Facebook. An application providing growers with late blight and early blight risk, current weather information, and inversion warnings is a new project being delivered to growers since 2017. North Dakota State University provides pesticide information on the Pest Management application. This application also allows users to submit a picture for pest identification assistance. The use of the web as an archival source for traditional extension documents has been expanded to distance education with videos for continuing education credits. These methods, mixed with traditional field days, winter meetings, and Extension bulletins, are how Extension is reaching today's potato farmer and industry with timely information. [ABSTRACT FROM AUTHOR]

The term "Primary age-related tauopathy" (PART) was coined in 2014 to describe the common neuropathological observation of neurofibrillary tangles without associated beta-amyloid (Aβ) pathology. It is possible for PART pathology to be present in both cognitively normal and cognitively impaired individuals. Genetically, Apolipoprotein E (APOE) ε4 has been shown to occur less commonly in PART than in Alzheimer's disease (AD). Here, we investigate the relationships between PART, AD and those pathologically normal for age, with an emphasis on APOE and cognition, using 152 selected participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age and the Manchester arm of the Brains for Dementia Research cohort. APOE genotype differed between PART and AD with APOE ε2 more common in the former and APOE ε4 more common in the latter. Individuals with definite PART were less likely to be cognitively impaired than those with AD and those with pathology considered pathologically normal for age. We postulate that the lack of Aβ in definite PART cases may be due either to an increased frequency of APOE ε2 or decreased frequency of APOE ε4 as their resulting protein isoforms have differing binding properties in relation to Aβ. Similarly, an increased frequency of APOE ε2 or decreased frequency of APOE ε4 may lead to decreased levels of cognitive impairment, which raises questions regarding the impact of Aβ pathology on overall cognition in elderly subjects. We suggest that it may be possible to use the increased frequency of APOE ε2 in definite PART to assist neuropathological diagnosis. [ABSTRACT FROM AUTHOR]

Fragile X‐associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG trinucleotide expansion from 55 to 200 repeats in the non‐coding region of the fragile X mental retardation 1 (FMR1) gene (FMR1). Clinical features include cognitive decline, progressive tremor, and gait ataxia. Neuropathologically, FXTAS shows white matter changes, hippocampal and cerebellar involvement, and p62‐positive eosinophilic intranuclear inclusions in astrocytes and neurons. Here, we document the neuropathological findings from a subject who developed cognitive impairment but not tremor and was proved to have genetically confirmed FMR1 premutation. Microscopically, typical p62‐postive intranuclear inclusions were present in all the regions examined. Neocortical regions demonstrated gliosis of layer I and mild degree of neuronal loss and atrophy across the other layers. The molecular, Purkinje's cell, and granule cell layers of the cerebellar folia demonstrated mild gliosis, and cerebellar white matter was mildly affected. Aside from p62‐positive inclusions, the hippocampus was spared. Arteries in the deep white matter often showed changes consistent with moderate small vessel disease (SVD). Reactive gliosis and severe SVD were features of basal ganglia. Florid reactive astrocytosis was found in the white matter of all regions. Axonal loss and features of axonal damage were found in the white matter of the centrum semiovale. Microglial activation was widespread and evenly seen in both the white matter and grey matter, although the grey matter appeared more severely affected. Pathology associated with Alzheimer's disease was limited. Similarly, no abnormal accumulations of α‐synuclein were present. We postulate that age at death and disease duration may play a role in the extent of the pathological features associated with FXTAS. The present results suggest that immunohistochemical staining for p62 can help with the diagnosis of cases with atypical phenotype. In addition, it is likely that the cognitive impairment observed was a result of white matter changes. [ABSTRACT FROM AUTHOR]

Relying on analysis of Ktunaxa v. British Columbia (2017) and the law and jurisprudence that shaped it, this article assesses the implementation of UNDRIP rights concerning Indigenous sacred sites in Canada. It describes sacred sites and relevant aspects of the UNDRIP and assesses Canadian law and jurisprudence against these. It reaches three main conclusions. First, as interpreted by the courts, the Canadian constitution does not fulfil Canada's UNDRIP obligations concerning sacred sites: whether a group enjoys these rights depends largely upon the legal status of the land on which the site is situated; whether a group can secure these rights depends largely upon how the law treats the group's relationship to its site; and whether the state may limit these rights is determined by reasons that do not satisfy UNDRIP standards. Second, the Canadian Supreme Court's decision to stick with its jurisprudence rather than use Ktunaxa to more closely align Canadian law with the UNDRIP suggests that governments must not rely upon the courts to implement their UNDRIP obligations for them. Thus, third, political actors who seek UNDRIP compliance must take the initiative themselves to address legal imperfections like those identified in this article through regulatory, legislative, and constitutional action. [ABSTRACT FROM AUTHOR]

Background: The pathological features of Alzheimer's disease (AD) are well described but little is known as to how both neurodegeneration and vascular changes might interact in causing cognitive impairment.Objective: The present study aims to investigate relationships between vascular and AD pathology in cognitively healthy and cognitively impaired individuals with a particular emphasis on those at intermediate Braak tau stages.Methods: We investigated the interplay between Braak tau stage and measures of vascular pathology as described by the vascular cognitive impairment neuropathology guidelines (VCING) in 185 brains from the Brains for Dementia Research programme and The University of Manchester Longitudinal Study of Cognition in Healthy Old Age. VCING asserts that at least one large (>10 mm) infarct, moderate/severe occipital leptomeningeal cerebral amyloid angiopathy, and moderate/severe arteriosclerosis in occipital white matter accurately predicts the contribution of cerebrovascular pathology to cognitive impairment.Results: We found that the extent of arteriosclerosis in the occipital white matter did not differ between cognitive groups at intermediate (III-IV) Braak stages whereas moderate/severe leptomeningeal occipital cerebral amyloid angiopathy was greater in cognitively impaired than normal individuals at Braak stage III-IV. This finding remained significant after controlling for effects of age, sex, CERAD score, Thal phase, presence/severity of primary age-related tauopathy, presence/severity of limbic-predominant age-related TDP43 encephalopathy and small vessel disease in basal ganglia.Conclusion: Interventions targeting cerebral amyloid angiopathy may contribute to delay the onset of cognitive impairment in individuals with intermediate Alzheimer's type pathology. [ABSTRACT FROM AUTHOR]

Vaginal stents are used to prevent fibrosis after vaginal reconstruction. Currently, physicians must create their own makeshift stents in the operating room. There is a critical need for a new pediatric vaginal stent. We have developed a biodegradable shape-memory polymer (SMP) foam stent that can assume a secondary compressed shape for deployment and expand at physiological temperatures. Herein, we describe the development of the SMP chemistry with target transition temperature and emulsion-templating approach to generate SMP foams with shape memory behavior. Polycaprolactone diacrylate (linear-PCL-DA) and tetracrylate (star-PCL-TA) macromers were synthesized. Differential scanning calorimetry was used to characterize the transition temperature (Tm) and percent crystallinity. Foams were fabricated via emulsion templating. Briefly, PCL-DA and -TA solutions in toluene were emulsified with water (25:75) using a polyglycerol polyricinoleate 4125 (10%w/w) surfactant and 2.5% BAPO photoinitiator. The emulsion was photocrosslinked, vacuum dried, and subsequently annealed at 85°C for 1 hour. SEM image analysis was used to characterize the pore structure and compressive testing performed. Shape fixity/recovery of the foams were evaluated by crimping to 50% with the percent change determined against pre-crimped dimensions. Linear-PCL-DA displayed a transition temperature at Tm=55 °C compared to new star-PCL-TA at Tm=43°C. Emulsion templating provided uniform pore architectures. Functional evaluations of the foams determined self-expansion of the linear-PCL-DA at ∼55°C compared to the new 10 kDa star-PCL-TA at 37°C in less than 5 minutes. Despite a concomitant reduction in crystallinity, all scaffolds retained strong fixity behavior. The compressive modulus of star-PCL-TA (modulus = 0.45 MPa) scaffolds were lower than that of linear-PCL-DA (modulus = 0.8 MPa). The reduced stiffness of the star-PCL-TA provided a softer foam towards balancing the maintaining of caliber and comfort while preventing substantial deformation (10.2%) under Valsalva forces. This new SMP foam shows promise in generating a self-fitting vaginal stent. By altering the architecture of the PCL macromer from a linear to a star architecture, we have successfully lowered the transition temperature to allow for effective deployment at physiological temperatures. Supporting Figures or Tables https://www.abstractscorecard.com/uploads/Tasks/upload/19245/RGXGDRUQ-1377960-2-ANY(1).pdf [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 70-year-old man who presented with visual memory loss. Despite not meeting the clinical criteria for either condition at presentation, post-mortem examination revealed concomitant progressive supranuclear palsy (PSP) and Lewy body pathology. The study suggests that interactions between these two pathologies in mesial temporal regions may result in this atypical clinical phenotype. The article provides detailed clinical and neuropsychological information and highlights the importance of considering multiple pathologies in cases of neurodegenerative diseases. [Extracted from the article]

If later time points had been available, a more severe decline in MC scores in AD compared to possible/definite PART would have been anticipated as the rate of both A and tau pathology accelerates compared to PART. This early detectable difference in cognition however is transient, being overcome by onset and progression of A and tau pathology in AD and possible PART, and tau pathology in definite PART. AD pathology, as measured by Braak stage, Thal phase and CERAD score, also correlated with MC test scores at time point 2. [Extracted from the article]

Maternal immune priming is the transfer of immunity from mother to offspring, which may reduce the offspring's risk of disease from a pathogen that previously infected its mother. Maternal immune priming has been described in at least 25 invertebrate taxa, including Crassostrea gigas. Larvae of C. gigas have improved survival to Ostreid herpesvirus (OsHV-1) if their mothers are either infected with OsHV-1 or were injected with a virus mimic called poly(I:C). However, fitness costs associated with maternal immune priming in C. gigas are unknown. Here, we show C. gigas larvae produced from poly(I:C)-treated mothers are smaller, and have higher total bacteria and Vibrio loads compared to control larvae. These results suggest that the improved offspring survival of C. gigas to OsHV-1 due to maternal immune priming with poly(I:C) is potentially traded off with other important life history traits, such as larval growth rate and destabilisation of the microbiome. • Fitness costs associated with maternal immune priming using a viral mimic (poly(I:C)) was investigated in Crassostrea gigas. • Maternal immune priming reduced the size of C. gigas offspring. • Maternal immune priming altered the microbiome of C. gigas offspring. • Offspring from poly(I:C)-primed mothers had higher abundance of Vibrio sp. [ABSTRACT FROM AUTHOR]

The goal of cryopreservation is to retain the original stage of gametes and embryos after they have endured cooling and warming. Slow freezing is a standard method for in vivo-derived bovine embryo cryopreservation, threefifths of such embryos being frozen by this method globally. However, it is evident that slow freezing is not efficient for cryopreserving in vitro-produced bovine embryos. Hence, only one-third of in vitro-produced bovine embryos are cryopreserved. Vitrification is a preferred method for storage of human embryos; consequently, it has been explored as a novel means to store in vitro-produced bovine embryos, for which it shows considerable promise as an alternative to slow freezing. This is due to several reasons: vitrification is often less time-consuming than slow freezing; it does not need expensive slow rate freezing machines; and it has been proven to have comparatively higher survival rates. Yet, in the cattle industry vitrification continues to present shortcomings, such as possible toxicity of vitrification solutions and failure to standardize methods, which pose a challenge for its application to in vitro-produced bovine embryos. Therefore, determining the most suitable procedure is crucial to make vitrification more practical in commercial settings. [ABSTRACT FROM AUTHOR]

Objective:Design:Setting:Subjects:Outcome measures:Results:Conclusions:The aim of this study was to explore how participants and physicians experienced a plant-based dietary approach to type 2 diabetes mellitus (T2DM) in South Africa.A multiple-case study was undertaken.The pilot ‘Diabetes Reversal Challenge’ was initiated and led by UBUNTU Wellness Institute. Participants with T2DM consume a whole-food plant-based diet for 21 days and are assigned to private physicians for clinical monitoring of health outcomes.South African adults with T2DM (n = 10) and physicians (n = 4) participated in the challenge between April 2021 and May 2022.Participants’ health outcomes and contextual factors influencing how participants and physicians experienced the plant-based dietary approach in South Africa were the measures used.The plant-based dietary approach resulted in positive health outcomes for South African adults with T2DM, such as improved glycaemic control, weight loss, reduced need for medication and psychological benefits. Multiple layers of contextual factors influenced the plant-based dietary approach to T2DM in South Africa, mapped into a socio-ecological framework that includes (1) individual, (2) interpersonal, (3) organisational, (4) community and (5) healthcare system factors.These results encourage healthcare systems to explore plant-based dietary approaches as an option in the management of T2DM in South Africa. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to measure the impact of meditation on participants' ability to regulate brain wave activity in high-stress situations, control physiological stress responses and improve subjective wellbeing.Methods: Twelve obstetrics and gynaecology (O&G) doctors meditated for 20 minutes daily for 21 days utilising a portable EEG (electroencephalogram) providing instantaneous audio feedback. Their brain activity levels and salivary cortisol were measured before and after performing three surgical procedures. Participants were interviewed about their experiences and completed self-ratings of distress (e.g. DASS-21, Depression, Anxiety and Depression Scale). Data were analysed statistically and thematically.Results: (a) Measures of pre- and post-operative brain activity showed no significantly higher levels of alpha waves. (b) Pre- and post-operative salivary cortisol levels did not significantly decrease. (c) DASS-21 scores showed significant decreases in levels of anxiety and stress.Conclusion: Results suggest that, with biofeedback meditation, O&G doctors can learn to reduce situational stress and improve mood overall through a focussed intervention. [ABSTRACT FROM AUTHOR]

Background: Dengue virus, an Aedes mosquito-borne flavivirus, is associated with close to 400 million reported infections per annum worldwide. Reduction of dengue virus transmission depends entirely on limiting Aedes breeding or preventing adult female contact with humans. Currently, the World Health Organization promotes the strategic approach of integrated vector management in order to optimise resources for mosquito control. Main text: Neglected tropical disease researchers focus on geographical zones where the incidence of clinical cases, and prevalence of vectors, are high. In combatting those infectious diseases such as dengue that affect mainly low-income populations in developing regions, a mosquito-centric approach is frequently adopted. This prioritises environmental factors that facilitate or impede the lifecycle progression of the vector. Climatic variables (such as rainfall and wind speed) that impact the vector's lifecycle either causally or by happenstance also affect the human host's 'lifecycle', but in very different ways. The socioeconomic impacts of the same variables that influence vector control impact host vulnerability but at different points in the human lifecycle to those of the vector. Here, we argue that the vulnerability of the vector and that of the host interact in complex and unpredictable ways that are characteristic of (complex and intransigent) 'wicked problems'. Moreover, they are treated by public health programs in ways that may ignore this complexity. This opinion draws on recent evidence showing that the best climate predictors of the scale of dengue outbreaks in Bangladesh cannot be explained through a simple vector-to-host causal model. Conclusions: In mapping causal pathways for vector-borne diseases this article makes a case to elevate the lifecycle of the human host to a level closer in equivalence to that of the vector. Here, we suggest value may be gained from transferring Rittel and Webber's concept of a wicked (social) problem to dengue, malaria and other mosquito-transmitted public health concerns. This would take a 'problem definition' rather than a 'solution-finding' approach, particularly when considering problems in which climate impacts simultaneously on human and vector vulnerability. [ABSTRACT FROM AUTHOR]

Clinical infection with malaria, caused by parasites of the genus Plasmodium, is considered a serious medical condition with the potential to become a life-threatening emergency. This is especially relevant to low-income countries in tropical and subtropical regions of the world where high rates of malaria-related morbidity and mortality are recorded. As a means to combat this major global public health threat, rapid and effective diagnosis remains the frontline action to initiate a timely and appropriate medical intervention. From all the approaches to parasite detection, rapid diagnostic tests, so-called RDTs, are the easiest to use and most cost-effective. However, some of the limitations inherent in this methodology could hinder effective patient treatment. A primary drawback is that the vast majority of commercially available RDTs detect only one of the five species of human malaria, P. falciparum. While this is the main cause of infection in many areas, it excludes the possibility of infection with another parasite (P. vivax, P. ovale, P. malariae, and P. knowlesi) or of mixed infections containing different species. Hence, a diagnosis of non-P. falciparum malaria is missed. In turn, in resource-constrained settings where optimal microscopy is not available, a misdiagnosis of bacterial infection based on signs and symptoms alone often results in an inappropriate prescription of antibiotics. Here, we discuss how effective diagnosis of malaria and indiscriminate use of antibiotics in sub-Saharan Africa, a hot spot for P. falciparum transmission, may both be addressed by the development of innovative multiplexing RDTs that detect two or more species of Plasmodium. [ABSTRACT FROM AUTHOR]

Development of pharmacotherapies that promote remyelination is a high priority for multiple sclerosis (MS), due to their potential for neuroprotection and restoration of function through repair of demyelinated lesions. A novel preparation of clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response to demyelinating agents in both chronic cuprizone and acute lysolecithin rodent animal models. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of myelin differentiation markers. Additional in vitro data demonstrated that these gold nanocrystals act via a novel energy metabolism pathway involving the enhancement of key indicators of aerobic glycolysis. In response to gold nanocrystals, co-cultured central nervous system cells exhibited elevated levels of the redox coenzyme nicotine adenine dinucleotide (NAD+), elevated total intracellular ATP levels, and elevated extracellular lactate levels, along with upregulation of myelin-synthesis related genes, collectively resulting in functional myelin generation. Based on these preclinical studies, clean-surfaced, faceted gold nanocrystals represent a novel remyelinating therapeutic for multiple sclerosis. [ABSTRACT FROM AUTHOR]

In the present study, we have characterized and compared individuals whose brains were donated as part of The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (UoM) with those donated through the Manchester arm of the UK Brains for Dementia Research (BDR) program. The aim of this study was to investigate how differences in study recruitment may affect final pathological composition of cohort studies. The UoM cohort was established as a longitudinal study of aging and cognition whereas the BDR program was established, prima facie, to collect brains from both demented and non-demented individuals for the purpose of building a tissue research resource. Consequently, the differences in recruitment patterns generated differences in demographic, clinical, and neuropathological characteristics. There was a higher proportion of recruits with dementia [mostly Alzheimer's disease (AD)] within the BDR cohort than in the UoM cohort. In pathological terms, the BDR cohort was more 'polarized', being more composed of demented cases with high Braak pathology scores and non-demented cases with low Braak scores, and fewer non-AD pathology cases, than the UoM cohort. In both cohorts, cerebral amyloid angiopathy tended to be greater in demented than non-demented individuals. Such observations partly reflect the recruitment of demented and non-demented individuals into the BDR cohort, and also that insufficient study time may have elapsed for disease onset and development in non-demented individuals to take place. Conversely, in the UoM cohort, where there had been nearly 30 years of study time, a broader spread of AD-type pathological changes had 'naturally' evolved in the brains of both demented and non-demented participants. [ABSTRACT FROM AUTHOR]

More than 75 arboviruses (arthropod-borne viruses) have been identified in Australia. While Alfuy virus (ALFV), Barmah Forest virus (BFV), Edge Hill virus (EHV), Kokobera virus (KOKV), Murray Valley encephalitis virus (MVEV), Sindbis virus (SINV), Ross River virus (RRV), Stratford virus (STRV), and West Nile virus strain Kunjin (KUNV) have been associated with human infection, there remains a paucity of data regarding their respective transmission cycles and any potential nonhuman vertebrate hosts. It is likely that these viruses are maintained in zoonotic cycles involving native animals rather than solely by human-to-human transmission. A serosurvey (n = 100) was undertaken to determine the prevalence of neutralizing antibodies against a panel of Australian arboviruses in western gray kangaroos (Macropus fuliginosus) obtained from 11 locations in the midwest to southwest of Western Australia. Neutralizing antibodies against RRV were detected in 25%, against BFV in 14%, and antibodies to both viruses in 34% of serum samples. The prevalence of antibodies against these two viruses was the same in males and females, but higher in adult than in subadult kangaroos (p < 0.05). Twenty-one percent of samples had neutralizing antibodies against any one or more of the flaviviruses ALFV, EHV, KOKV, MVEV, and STRV. No neutralizing antibodies against SINV and KUNV were detected. If this sample of kangaroo sera was representative of the broader Australian population of macropods, it suggests that they are common hosts for RRV and BFV. The absence or low seroprevalence of antibodies against the remaining arboviruses suggests that they are not prevalent in the region or that kangaroos are not commonly infected with them. The detection of neutralizing antibodies to MVEV requires further investigation as this virus has not been identified previously so far south in Western Australia. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a Gram-positive bacterium found frequently on a person's skin and sometimes in their upper respiratory tract. Although regarded primarily as a commensal of the human microbiota S. aureus shows the ability to become an opportunistic pathogen. Hence, it is a common cause of skin and lung infections and of food poisoning. S. aureus forms biofilms, complex communities of bacteria inside an exopolysaccharide matrix, which adhere to different surfaces, including those associated with hospital-acquired infections such as catheters, shunts and other implanted medical devices. In this instance, the presence of proteins adsorbed to the surface of the biomaterial provides a nutrient source for bacterial growth. Due to antimicrobial resistance, use of longstanding antibiotics alone is increasingly an ineffective therapeutic intervention for biofilm-related infections. Therefore, a growing concern is the treatment of medical devices in order to prevent antibiotic resistance associated with routine handling of these items in a healthcare setting. Consequently, several different biotechnological approaches have targeted a practical solution to S. aureus biofilm formation. These include novel antibiotics administered alone or combined with other compounds, application of natural products like enzymes and antimicrobial peptides, and harnessing of nanoparticles and phage therapy. This brief article provides an overview of each of these cutting-edge methods aimed at inhibition of S. aureus biofilms. Development of an effective agent to prevent and treat biofilm formation would represent a significant step forward for infection control of methicillin-resistant S. aureus (MRSA) and other antibiotic-resistant strains that provides a major global public health challenge. [ABSTRACT FROM AUTHOR]

Objectives: Head injury with loss of consciousness (HI-LOC) is a common occurrence. Some studies have linked such injuries with an increased risk of Alzheimer disease (AD). However, recent large clinicopathologic studies have failed to find a clear relationship between HI-LOC and the pathological changes associated with AD. The present study aims to further investigate the relationship between HI-LOC and AD pathology in the elderly.Methods/design: History of HI-LOC in participants in the University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age was ascertained. The donated brains of 110 of these individuals were assessed for AD pathology using consensus guidelines. Analyses aimed to elucidate relationships between HI-LOC and AD pathology.Results: No associations were found between incidence of HI-LOC and regional AD pathology or any of the three established measures of the neuropathology associated with AD: CERAD score, Thal phase, or Braak stage.Conclusions: Single incidences of HI-LOC may not be sufficient to cause the pathology associated with late-stage AD. Other routes of damage, such as diffuse axonal injury or Lewy body pathology, may play a greater role in causing cognitive impairment associated with head injury. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the current NCI-CTEP recommendation and the clinical use of Calvert Formula-derived carboplatin dosing pattern in the treatment of advanced lung cancer patients and assess carboplatin-related toxicity in relation to the degree of dose fluctuation. Methodology: This retrospective study involved all histologically confirmed inoperable lung cancer patients receiving palliative-intent carboplatin or carboplatin-combination chemotherapy from 2012 to 2016 at Kingston Health Sciences Centre. The carboplatin dosing pattern and carboplatin-related toxicity were collected and analysed on SPSS IBM for Windows version 24.0 (IBM Corp., Armonk, NY, USA). Results were expressed in percentages and P values. Results: Our findings (N = 75) suggested that 24% of patients had a high-degree of fluctuation in carboplatin dose (>10% variation from initial dose) if carboplatin dose was readjusted with each new creatinine. In practice, 16% of patients had a fluctuation of greater than 10% in ordered dose in the absence of planned dose reductions. Our study found no significant association between prescribed high-risk dosing fluctuation (>10% increased from initial dose) and carboplatin-related toxicities. Discussion and conclusion: In contrast to some prescribing recommendations such as NCI-CTEP, our study suggested that most medical oncologists incorporate new serum creatinine in calculating carboplatin dose for each cycle. Only 9% of patients were treated with a fixed dosing pattern (i.e. no fluctuation). Nonetheless, no significant associations were found between high-risk carboplatin dosing fluctuation and its-related toxicity. Whether such practice was due to the forcing function of the computer order entry system (CPOE), or conscious decisions by medical oncologists was unknown. Further analysis in evaluating physicians' preferences and influencing factors on dosing pattern decision would be recommended. [ABSTRACT FROM AUTHOR]

• Experimental testing of corrosion damage low-strength concrete columns under compressive loading. • Influence of corrosion damage on inelastic buckling of stocky low-strength concrete columns. • Impact of corrosion on confined low-strength concrete behaviour under cyclic loading. • Influence of cross sectional shape on failure modes of corroded column under cyclic loading. New codes have recently introduced seismic detailing for new structures. However, there are still older reinforced concrete (RC) structures without proper ductile detailing for earthquake resistance in seismic-prone areas. These structures are further impacted by the corrosion of their embedded reinforcing bars, which further reduces the strength and ductility under axial cyclic loading. This paper summarises the results of an experimental investigation performed on low-strength short RC columns, with different confinement configurations, subject to varying degrees of corrosion to investigate their structural responses to axial cyclic loading. The experiment was conducted on 30 short RC columns (square and circular) with three levels of confinement and steel reinforcement corrosion loss ranging from 0% to ∼ 30% subjected to cyclic compressive loading. The test results show that corrosion and inadequate confinements have a significant negative impact on the structural responses of corroded columns. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma (UC) harbors many oncogenic alterations and the limited efficacy of first-line immunotherapy in this setting suggests that oncogenic alterations could have potential as a predictive biomarker for treatment decision-making. Antibody-drug conjugates (ADCs) may offer new avenues for biomarker-driven treatment in advanced UC, especially for patients with oncogenic alterations. [ABSTRACT FROM AUTHOR]

The plant pathogen Fusarium culmorum represents an inoculum source capable of contaminating grains with deoxynivalenol in the Inland Northwest region of the United States. A multilevel modeling approach utilizing varying intercepts for different sampling quadrats, fields, and iterations in the dataset was performed to characterize differences in isolation frequency of F. culmorum collected during a 2-year soil survey. Differences in the isolation frequency of F. culmorum varied the most by sampled field followed by quadrat and iteration, respectively. Higher relative elevation within the sampling region of a field limited the amount of F. culmorum recovered. The effect of annual climate variables was investigated using combinations of single-variable and multivariable model equations with linear and polynomial terms. The same data analysis approach was applied to an external dataset of F. culmorum isolation frequencies in grains from fields across eastern Australia. These results represent a case study for investigating variability within datasets containing overdispersed fungal counts and incorporating climate summaries as predictor variables. [ABSTRACT FROM AUTHOR]