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Meaningful collaborations between archaeologists and descendant communities and nations is a necessary component of archaeological practice in the 2020s and beyond. While calls for decolonising the social sciences and humanities have become a common refrain, practical methodologies for supplanting settler-colonial research practice have been less apparent. We detail how the development of independent radiocarbon-based chronologies in archaeology is one such substantive path forward. As a joint group of Indigenous and Euro-American and Euro-Canadian researchers, we outline how collaborative research agendas that privilege the knowledge and interests of descendant communities and include independent chronology building can be developed and achieved, securing mutual benefit and distributing authority in the construction of archaeologically derived Indigenous histories.

Abstract In this paper, we show how we developed a visualisation tool to challenge perceived notions about biosecurity on poultry farms. Veterinarians and veterinary public health professionals tend to present biosecurity measures as a universal and cost-effective solution for preventing and controlling diseases on farms. However, we illustrate how biosecurity is an ill-defined term, making it difficult to talk about or apply in practice. As a result, we demonstrate how we moved away from using the term biosecurity in our research by designing a visualisation tool. The tool was to allow us to open up dialogue around disease prevention and control, and make tangible the tacit situated practices of stakeholders working along the poultry supply chain. Our findings show that for those working along the poultry supply chain, the term biosecurity was either consistently open to interpretation, or too rigid to reflect or allow for local variations. We conclude by highlighting how our visualisation tool offers insights into why researchers must move beyond using biosecurity as a term, and instead envisage, design, and develop local solutions to prevent and control diseases on poultry farms.

Abstract Integration is often considered the core challenge and the defining characteristic of inter- and trans-disciplinary (ITD) research. Given its importance, it is surprising that the current system of higher education does not provide permanent positions for integration experts; i.e., experts who lead, administer, manage, monitor, assess, accompany, and/or advise others on integration within ITD projects or programs. Based on empirical results of an ITD 2019 Conference Workshop entitled “Is there a new profession of integration experts on the rise?” held in Gothenburg, Sweden, and our own experience in leading and studying ITD integration, the present article sheds light on the overarching question, “What are integration experts?”, thus contributing to the emerging literature on integration and integration expertise. We use direct quotes from participants to substantiate workshop results and triangulate them with recent literature on ITD research as well as Science of Team Science (SciTS) and Science and Technology Studies (STS). We conclude our article by discussing possible unintended consequences of establishing academic careers for integration experts, and suggest four complementary ways to support them, while mitigating potentially negative consequences: (a) establishing an international Community of Practice (CoP) to foster peer-to-peer exchange among integration experts, create greater visibility, and develop ideas for transforming academic structures; (b) studying academic careers of integration experts to provide empirical evidence of “successful” examples and disclose different ways of establishing related academic positions; (c) funding respective positions and aligning metrics for ITD research to foster integration within ITD projects or programs; and (d) engaging in collaborative dialog with academic institutions and funding agencies to present empirical results and lessons learnt from (a) and (b) to support them in establishing and legitimating careers for integration experts. If academia is to be serious about addressing the most pressing environmental and societal problems of our time, it needs to integrate its integrators.

Background: Underutilization of implantable cardioverter defibrillators (ICD) to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients remains an issue across several geographies. A better understanding of risk factors for SCD in post-MI patients from regions with low ICD adoption rates will help identify those who will benefit from an ICD. This analysis assessed risk factors for all-cause and cardiovascular-related mortality in post-MI patients from the Improve Sudden Cardiac Arrest (SCA) Bridge Trial. Results: For the entire cohort, the overall 1-year mortality rate was 5.9% (88/1491) and 3.4% (51/1491) for all-cause and cardiovascular mortality, respectively, with 76.5% of all cardiac deaths being from SCD. A multivariate model determined increased age, reduced left ventricular ejection fraction (LVEF), increased time from myocardial infarction to hospital admission, being female, being from Southeast Asia (SEA), and having coronary artery disease to be significant risk factors for all-cause mortality. The risk factors for cardiovascular-related mortality revealed increased age, reduced LVEF, and being from SEA as significant risk factors. Conclusions: We show several characteristics as being predictors of cardiovascular-related mortality in post-MI patients from the Improve SCA Bridge study. Patients who experience an MI and present with these characteristics would benefit from a referral to an electrophysiologist for further SCD risk stratification and management and possible subsequent ICD implantation to reduce unnecessary death. [ABSTRACT FROM AUTHOR]

Abstract Mitochondrial disorders are clinically and genetically diverse, with isolated complex III (CIII) deficiency being relatively rare. Here, we describe two affected cousins, presenting with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy. Genetic investigations in both cases identified a homozygous deletion of exons 2 and 3 of UQCRH, which encodes a structural complex III (CIII) subunit. We generated a mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh−/−), which also presented with lactic acidosis and hyperammonaemia, but had a more severe, non‐episodic phenotype, resulting in failure to thrive and early death. The biochemical phenotypes observed in patient and Uqcrh−/− mouse tissues were remarkably similar, displaying impaired CIII activity, decreased molecular weight of fully assembled holoenzyme and an increase of an unexpected large supercomplex (SXL), comprising mostly of one complex I (CI) dimer and one CIII dimer. This phenotypic similarity along with lentiviral rescue experiments in patient fibroblasts verifies the pathogenicity of the shared genetic defect, demonstrating that the Uqcrh−/− mouse is a valuable model for future studies of human CIII deficiency.

Abstract Glioma‐derived cell‐free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma‐derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by analysis of matched tumor biopsies. By sequencing cfDNA across thousands of mutations, identified individually in each patient’s tumor, we detected tumor‐derived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.4 × 10−3, 3.1 × 10−5, and 4.7 × 10−5, respectively. We identified a shift in the size distribution of tumor‐derived cfDNA fragments in these body fluids. We further analyzed cfDNA fragment sizes using whole‐genome sequencing, in urine samples from 35 glioma patients, 27 individuals with non‐malignant brain disorders, and 26 healthy individuals. cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with non‐malignant brain disorders (P = 1.7 × 10−2) and healthy individuals (P = 5.2 × 10−9). Machine learning models integrating fragment length could differentiate urine samples from glioma patients (AUC = 0.80–0.91) suggesting possibilities for truly non‐invasive cancer detection.

Abstract Leigh syndrome is a progressive neurodegenerative disorder, most commonly observed in paediatric mitochondrial disease, and is often associated with pathogenic variants in complex I structural subunits or assembly factors resulting in isolated respiratory chain complex I deficiency. Clinical heterogeneity has been reported, but key diagnostic findings are developmental regression, elevated lactate and characteristic neuroimaging abnormalities. Here, we describe three affected children from two unrelated families who presented with Leigh syndrome due to homozygous variants (c.346_*7del and c.173A>T p.His58Leu) in NDUFC2, encoding a complex I subunit. Biochemical and functional investigation of subjects’ fibroblasts confirmed a severe defect in complex I activity, subunit expression and assembly. Lentiviral transduction of subjects’ fibroblasts with wild‐type NDUFC2 cDNA increased complex I assembly supporting the association of the identified NDUFC2 variants with mitochondrial pathology. Complexome profiling confirmed a loss of NDUFC2 and defective complex I assembly, revealing aberrant assembly intermediates suggestive of stalled biogenesis of the complex I holoenzyme and indicating a crucial role for NDUFC2 in the assembly of the membrane arm of complex I, particularly the ND2 module.

Efforts to discourage academic misconduct in online learning environments frequently include the use of remote proctoring services. While these services are relatively commonplace in undergraduate science courses, there are open questions about students' remote assessment environments and their concerns related to remote proctoring services. Using a survey distributed to 11 undergraduate science courses engaging in remote instruction at three American, public, research-focused institutions during the spring of 2021, we found that the majority of undergraduate students reported testing in suboptimal environments. Students' concerns about remote proctoring services were closely tied to technological difficulties, fear of being wrongfully accused of cheating, and negative impacts on mental health. Our results suggest that remote proctoring services can create and perpetuate inequitable assessment environments for students, and additional research is required to understand the efficacy of their intended purpose to prevent cheating. We also advocate for continued conversations about the broader social and institutional conditions that can pressure students into cheating. While changes to academic culture are difficult, these conversations are necessary for higher education to remain relevant in an increasingly technological world. [ABSTRACT FROM AUTHOR]

Abstract In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non‐fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human‐type receptor specificity could enable transmission in the human population. Despite mutations in the receptor‐binding pocket of the human H6N1 isolate, it has retained avian‐type (NeuAcα2‐3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human‐type (NeuAcα2‐6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human‐type receptor, stabilizing human receptor binding.

Abstract OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase family, is required for the assembly of oxidative phosphorylation complexes IV and V in yeast. However, depletion of human OXA1 (OXA1L) was previously reported to impair assembly of complexes I and V only. We report a patient presenting with severe encephalopathy, hypotonia and developmental delay who died at 5 years showing complex IV deficiency in skeletal muscle. Whole exome sequencing identified biallelic OXA1L variants (c.500_507dup, p.(Ser170Glnfs*18) and c.620G>T, p.(Cys207Phe)) that segregated with disease. Patient muscle and fibroblasts showed decreased OXA1L and subunits of complexes IV and V. Crucially, expression of wild‐type human OXA1L in patient fibroblasts rescued the complex IV and V defects. Targeted depletion of OXA1L in human cells or Drosophila melanogaster caused defects in the assembly of complexes I, IV and V, consistent with patient data. Immunoprecipitation of OXA1L revealed the enrichment of mtDNA‐encoded subunits of complexes I, IV and V. Our data verify the pathogenicity of these OXA1L variants and demonstrate that OXA1L is required for the assembly of multiple respiratory chain complexes.

Abstract Multidrug‐resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource‐poor hospital settings. Through whole‐genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high‐dependency wards in a hospital in Kathmandu during 2012 with a case‐fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage‐specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward‐specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM‐1 containing lineage in 2011 would have alerted the high‐dependency ward staff to intervene. We argue that some form of real‐time genetic characterisation, alongside clade‐specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high‐ and low‐income settings.

Exposure to per- and polyfluoroalkyl substances (PFAS) in drinking water is widely recognized as a public health concern. Decision-makers who are responsible for managing PFAS drinking water risks lack the tools to acquire the information they need. In response to this need, we provide a detailed description of a Kentucky dataset that allows decision-makers to visualize potential hot-spot areas and evaluate drinking water systems that may be susceptible to PFAS contamination. The dataset includes information extracted from publicly available sources to create five different maps in ArcGIS Online and highlights potential sources of PFAS contamination in the environment in relation to drinking water systems. As datasets of PFAS drinking water sampling continue to grow as part of evolving regulatory requirements, we used this Kentucky dataset as an example to promote the reuse of this dataset and others like it. We incorporated the FAIR (Findable, Accessible, Interoperable, and Reusable) principles by creating a Figshare item that includes all data and associated metadata with these five ArcGIS maps. [ABSTRACT FROM AUTHOR]

We present a draft Minimum Information About Geospatial Information System (MIAGIS) standard for facilitating public deposition of geospatial information system (GIS) datasets that follows the FAIR (Findable, Accessible, Interoperable and Reusable) principles. The draft MIAGIS standard includes a deposition directory structure and a minimum javascript object notation (JSON) metadata formatted file that is designed to capture critical metadata describing GIS layers and maps as well as their sources of data and methods of generation. The associated miagis Python package facilitates the creation of this MIAGIS metadata file and directly supports metadata extraction from both Esri JSON and GEOJSON GIS data formats plus options for extraction from user-specified JSON formats. We also demonstrate their use in crafting two example depositions of ArcGIS generated maps. We hope this draft MIAGIS standard along with the supporting miagis Python package will assist in establishing a GIS standards group that will develop the draft into a full standard for the wider GIS community as well as a future public repository for GIS datasets. [ABSTRACT FROM AUTHOR]

Abstract Managing trade‐offs through gene regulation is believed to confer resilience to a microbial community in a fluctuating resource environment. To investigate this hypothesis, we imposed a fluctuating environment that required the sulfate‐reducer Desulfovibrio vulgaris to undergo repeated ecologically relevant shifts between retaining metabolic independence (active capacity for sulfate respiration) and becoming metabolically specialized to a mutualistic association with the hydrogen‐consuming Methanococcus maripaludis. Strikingly, the microbial community became progressively less proficient at restoring the environmentally relevant physiological state after each perturbation and most cultures collapsed within 3–7 shifts. Counterintuitively, the collapse phenomenon was prevented by a single regulatory mutation. We have characterized the mechanism for collapse by conducting RNA‐seq analysis, proteomics, microcalorimetry, and single‐cell transcriptome analysis. We demonstrate that the collapse was caused by conditional gene regulation, which drove precipitous decline in intracellular abundance of essential transcripts and proteins, imposing greater energetic burden of regulation to restore function in a fluctuating environment.

Background: The production of monoclonal antibodies for immunoglobulin detection is not cost-effective, while polyclonal antibody production depends on laboratory animals, raising concerns on animal welfare. The widespread use of immunoglobulins in the pharmaceutical industry and the increasing number and variety of new antibodies entering the market require new detection and purification strategies. The Tripartite motif-containing protein 21 is a soluble intracellular immunoglobulin G receptor that binds to the constant region of immunoglobulin G from various species with high affinity. We hypothesized that using this protein as an antibody-binding module to create immunoglobulin detection probes will improve the portfolio of antibody affinity ligands for diagnostic or therapeutic purposes. Results: We created a chimeric protein containing a mutated form of the C-terminal domain of mouse Tripartite motif-containing protein 21 linked to streptavidin to detect immunoglobulin G from various species of mammals. The protein is produced by heterologous expression and consists of an improved molecular tool, expanding the portfolio of antibody-affinity ligands for immunoassays. We also demonstrate that this affinity ligand may be used for purification purposes since imidazole elution of antibodies can be achieved instead of acidic elution conditions of current antibody purification methods. Conclusion: Data reported here provides an additional and superior alternative to the use of secondary antibodies, expanding the portfolio of antibodies affinity ligands for detection and purification purposes. [ABSTRACT FROM AUTHOR]

The risk of significant Kirkendall voiding within the intermetallic bond between a conventional solder joint and an electroplated Cu pad is relatively low and directly related to the presence of certain impurities in the latter. However, while the Cu–Sn reaction has been thoroughly studied so far, there is very limited understanding of the impact of space confinement on the Cu/solder interface dynamics. While no voiding has been found in micro joints on high-purity Cu, the propensity for voiding in the Cu3Sn is higher in such joints than in Ball Grid Array scale (macro) joints for a given quality of electroplated Cu. Systematic trends are also somewhat different. In general, the intermetallic compound growth rate varies with interactions between solder volume to pad area ratio, solder composition, pad finish, initial assembly process parameters, subsequent heat treatments, and specifics of the further thermomechanical history. Notably, when the solder is thin enough, the Cu3Sn growth rate is much higher than for thicker configurations and this is what leads to a substantial increase of the risk of severe voiding in micro joints. A mechanistic understanding leads to strategies for electroplating of Cu with low voiding propensity for use in micro solder joints. [ABSTRACT FROM AUTHOR]

Background: Unilateral lower limb swelling has wide differential diagnoses with varying treatment plans, requiring an early and accurate diagnosis. Doppler ultrasound offers an extensive examination of the vascular system providing a platform for diagnosis and avoidance of unnecessary invasive procedures. Thus, it becomes pertinent to ensure that all the sonographic information required for the accurate diagnosis of a swollen lower limb is documented and critically analyzed in our setting, hence this study. Results: The records of a total of 151 patients with acute unilateral lower limb swelling were retrieved, females constituted the majority (51.7%). The overall mean age was 58.70 ± 16.71 years. Statistical significance was specified at p ≤ 0.05 for this study. The males were on the average 1.86 years younger than the female, but this difference was not statistically significant (p = 0.495). Patients older than 60 years constituted the majority 72 (47.7%) followed by the 40–60-year age category 61 (40.4%), and the left lower limb was affected more often 82 (54.3%). Multiple inguinal lymphadenopathy 82 (35.7%) and edema with thickened skin and subcutaneous layers 67 (29.1%) were the two most recurrent ultrasound features. There was no significant association between the sonographic features and the diagnoses made for acute unilateral lower limb swelling, except for the feature of edema with thickened skin and subcutaneous layers (p = 0.004) and the diagnosis of cellulitis (p = 0.047) that increased significantly with age. Conclusion: Multiple inguinal lymphadenopathy and edema of the skin and subcutaneous layers were the most recurrent ultrasound features with cellulitis as the main diagnosis for acute unilateral lower limb swelling in our setting. Edema with thickened skin and subcutaneous layers and cellulitis both increased significantly with age. Sonographers, sonologists, and radiologists must be on the look-out for these in their practices. [ABSTRACT FROM AUTHOR]

Polar metals, commonly defined by the coexistence of polar crystal structure and metallicity, are thought to be scarce because the long-range electrostatic fields favoring the polar structure are expected to be fully screened by the conduction electrons of a metal. Moreover, reducing from three to two dimensions, it remains an open question whether a polar metal can exist. Here we report on the realization of a room temperature two-dimensional polar metal of the B-site type in tri-color (tri-layer) superlattices BaTiO3/SrTiO3/LaTiO3. A combination of atomic resolution scanning transmission electron microscopy with electron energy-loss spectroscopy, optical second harmonic generation, electrical transport, and firstprinciples calculations have revealed the microscopic mechanisms of periodic electric polarization, charge distribution, and orbital symmetry. Our results provide a route to creating all-oxide artificial non-centrosymmetric quasi-two-dimensional metals with exotic quantum states including coexisting ferroelectric, ferromagnetic, and superconducting phases. [ABSTRACT FROM AUTHOR]

Background: A national project investigated seniors' perceptions of the influences upon their quality of life. The seven participating cities were Montreal, Quebec City, Ottawa, Toronto, Regina, Vancouver and Whitehorse. The project focussed on policy decisions affecting the quality of life of seniors. It was a participatory study in which seniors controlled the direction and shape of the project in each city.Methods: Focus groups and individual interviews with seniors and stakeholders. Data analysis used qualitative methods to see the world through the eyes of participants. Each project was committed to hearing the voices of seniors and their views on which issues were affecting the quality of their lives.Results: Across the seven cities, seniors highlighted access to information, health care, housing, income security, safety and security, social contacts and networks, and transportation as key issues that affect the quality of life of seniors in Canada.Conclusions: The findings affirm the value of participatory activities that involve seniors working with other sectors as a productive policy-informing approach. The Seniors' Quality of Life projects demonstrate the conceptual power of the determinants of health perspective to understand seniors' quality of life issues. While seniors considered health care to be a continuing concern, they also recognized socio-economic issues as significantly affecting the quality of their lives. [ABSTRACT FROM AUTHOR]

Objective:This research examined the proposition that the direct costs of care were no different in an open-bay (OPBY) as compared with a single-family room (SFR) neonatal intensive care (NICU) environment.Study Design:This was a sequential cohort study.Result:General linear models were implemented using clinical and cost data for all neonates admitted to the two cohorts studied. Costs were adjusted to year 2007 U.S. dollars. Models were constructed for the unadjusted regression and subsequently by adding demographic variables, treatment variables, length of respiratory support and length of stay. With the exception of the last, none were found to achieve significance. The full model had R2=0.799 with P=0.0095 and predicted direct costs of care less in the SFR NICU.Conclusion:For the time, location and administrative practices in place, this study demonstrates that care can be provided in the SFR NICU at no additional cost as compared with OPBY NICU. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10−5, odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10−6). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations. [ABSTRACT FROM AUTHOR]

Background/Objectives:Evidence from animal and in vitro models suggest a role of probiotic bacteria in improving glycaemic control and delaying the onset of type 2 diabetes. However, the evidence from controlled trials in humans is limited. The objective was to determine if the probiotic bacteria L. acidophilus La5 and B. animalis subsp lactis Bb12, supplemented in a whole food (yoghurt) or isolated (capsules) form, can improve biomarkers of glycaemic control.Subjects/methods:Following a 3-week washout period, 156 overweight men and women over 55 years (mean age: 67±8 years; mean body mass index (31±4 kg/m2) were randomized to a 6-week double-blinded parallel study. The four intervention groups were: (A) probiotic yoghurt plus probiotic capsules; (B) probiotic yoghurt plus placebo capsules; (C) control milk plus probiotic capsules; and (D) control milk plus placebo capsules. Outcome measurements, including fasting glucose, insulin, glycated haemoglobin and Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR), were performed at baseline and week 6.Results:Relative to the milk-control group, probiotic yoghurt resulted in a significantly higher HOMA-IR (0.32±0.15, P=0.038), but did not have a significant effect on the other three measures of glycaemic control (P>0.05). Relative to placebo capsules, probiotic capsules resulted in a significantly higher fasting glucose (0.15±0.07 mmol/l, P=0.037), with no significant effect on the other three measures of glycaemic control (P>0.05). Further analyses did not identify other variables as contributing to these adverse findings.Conclusions:Data from this study does not support the hypothesis that L. acidophilus La5 and B. animalis subsp lactis Bb12, either in isolated form or as part of a whole food, benefit short-term glycaemic control. Indeed, there is weak data for an adverse effect of these strains on glucose homoeostasis. [ABSTRACT FROM AUTHOR]

Background:A 15-country study of nuclear workers reported significantly increased radiation-related risks of all cancers excluding leukaemia, with Canadian data a major factor behind the pooled results. We analysed mortality (1956-1994) in the updated Canadian cohort and provided revised risk estimates.Methods:Employment records were searched to verify and revise exposure data and to restore missing socioeconomic status. Excess relative risks per sievert (ERR/Sv) of recorded radiation dose and 95% confidence intervals (CIs) were estimated using Poisson regression.Results:A significant heterogeneity of the dose-response for solid cancer was identified (P=0.02), with 3088 early (1956-1964) Atomic Energy of Canada Limited (AECL) workers having a significant increase (ERR/Sv=7.87, 95% CI: 1.88, 19.5), and no evidence of radiation risk for 42 228 workers employed by three nuclear power plant companies and post-1964 AECL (ERR/Sv=−1.20, 95% CI: <−1.47, 2.39). Radiation risks of leukaemia were negative in early AECL workers and non-significantly increased in other workers. In analyses with separate terms for tritium and gamma doses, there was no evidence of increased risk from tritium exposure. All workers had mortality lower than the general population.Conclusion:Significantly increased risks for early AECL workers are most likely due to incomplete transfer of AECL dose records to the National Dose Registry. Analyses of the remainder of the Canadian nuclear workers (93.2%) provided no evidence of increased risk, but the risk estimate was compatible with estimates that form the basis of radiation protection standards. Study findings suggest that the revised Canadian cohort, with the exclusion of early AECL workers, would likely have an important effect on the 15-country pooled risk estimate of radiation-related risks of all cancer excluding leukaemia by substantially reducing the size of the point estimate and its significance. [ABSTRACT FROM AUTHOR]

Background:Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded protein response (UPR) and enhance cell death in combination with ER stress inducers.Methods:Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting.Results:Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells.Conclusion:Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug. [ABSTRACT FROM AUTHOR]

Abstract: The assessment of myocardial viability is important in the management of patients with coronary artery disease and left ventricular systolic dysfunction. There are several different imaging modalities currently available for the identification of viable myocardium: dobutamine stress echocardiography, single photon emission computed tomography, delayed-enhancement cardiac magnetic resonance imaging, and F-18 fluorodeoxyglucose positron emission tomography. The goal of viability imaging is to determine the likelihood of recovery of systolic function after revascularization. Positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET) provides information about perfusion as well as myocardial metabolism, requires meticulous patient preparation, and is currently the gold standard imaging modality for the assessment of myocardial viability. Viability imaging for the purposes of predicting which patients will have improvement in left ventricular systolic function is supported under current guidelines, but the results of the recent STICH-viability substudy have created uncertainty about the incremental benefit. This review article will provide a summary of the currently available imaging modalities with an emphasis on FDG-PET and discuss the clinical relevance of viability imaging in light of the STICH-viability substudy. [Copyright &y& Elsevier]

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10−6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate. [ABSTRACT FROM AUTHOR]

Background:Emerging data have revealed a negative association between adiposity and muscle quality (MQ). There is a lack of research to examine this interaction among young, healthy individuals, and to evaluate the contribution of adiposity to adaptation after resistance exercise (RE).Objective:The purpose of this investigation was to examine the influence of subcutaneous adipose tissue (SAT) on muscle function among non-obese individuals before and after RE.Design:Analyses included 634 non-obese (body mass index <30 kg m−2) subjects (253 males, 381 females; age=23.3±5.2 years). SAT and muscle mass (magnetic resonance imaging-derived SAT and biceps muscle volume), isometric and dynamic biceps strength, and MQ (strength/muscle volume), were analyzed at baseline and after 12 weeks of unilateral RE.Results:At baseline, SAT was independently associated with lower MQ for males (β=−0.55; P<0.01) and females (β=−0.45; P<0.01), controlling for body mass and age. Adaptation to RE revealed a significant negative association between SAT and changes for strength capacity (β=−0.13; p=0.03) and MQ (β=−0.14; P<0.01) among males. No attenuation was identified among females. Post-intervention SAT remained a negative predictor of MQ for males and females (β=−0.47; P<0.01).Conclusions:The findings reveal that SAT is a negative predictor of MQ among non-obese, healthy adults, and that after 12 weeks of progressive RE this association was not ameliorated. Data suggest that SAT exerts a weak, negative influence on the adaptive response to strength and MQ among males. [ABSTRACT FROM AUTHOR]

Student web 2.0 authoring in higher education involves a number of challenges and opportunities for assessment and academic integrity. In this article we describe an Australian project that is investigating how lecturers are using web 2.0 activities in university assessment tasks. In the first stage of the project we documented current web 2.0 assessment practices by conducting a survey and interviews with lecturers who teach in different discipline areas across Australia. Initial findings from this stage of the project are presented here, with a focus on using examples from the interviews to illustrate the opportunities and challenges that web 2.0 affordances introduce for learning, teaching, and assessment in higher education. Student authoring in web 2.0 environments can be quite different from traditional academic writing tasks. Using web 2.0 technologies, students can publish their work to an open audience, use different communication styles and texts, draw on their unique personal identity and experiences, co-create content with other students, and manage their content outside the confines of the university. Each of these affordances provides opportunities for enhancing students' learning in higher education, while simultaneously imposing new ways of thinking about scholarly writing and assessment that can be challenging for both students and staff. [ABSTRACT FROM AUTHOR]

Schizophrenia is associated with structural brain abnormalities, but the timing of onset and course of these changes remains unclear. Longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive brain volume decreases in patients around and after the onset of illness, although considerable discrepancies exist regarding which brain regions are affected. The anatomical pattern of these progressive changes in schizophrenia is largely unknown. In this study, MRI scans were acquired repeatedly from 16 schizophrenia patients approximately 2 years apart following their first episode of illness, and also from 14 age-matched healthy subjects. Cortical Pattern Matching, in combination with Structural Image Evaluation, using Normalisation, of Atrophy, was applied to compare the rates of cortical surface contraction between patients and controls. Surface contraction in the dorsal surfaces of the frontal lobe was significantly greater in patients with first-episode schizophrenia (FESZ) compared with healthy controls. Overall, brain surface contraction in patients and healthy controls showed similar anatomical patterns, with that of the former group exaggerated in magnitude across the entire brain surface. That the pattern of structural change in the early course of schizophrenia corresponds so closely to that associated with normal development is consistent with the hypothesis that a schizophrenia-related factor interacts with normal adolescent brain developmental processes in the pathophysiology of schizophrenia. The exaggerated progressive changes seen in patients with schizophrenia may reflect an increased rate of synaptic pruning, resulting in excessive loss of neuronal connectivity, as predicted by the late neurodevelopmental hypothesis of the illness. [ABSTRACT FROM AUTHOR]

We previously reported that susceptibility to childhood B cell precursor ALL (BCP ALL) is associated with HLA-DPB1 alleles having glutamic acid (E) rather than lysine (K) in the P4 antigenic peptide-binding pocket. Clustering ∼90% of DPB1 alleles into DPB69E (DP2, 6, 8) and DPB69K (DP1, 3, 4) supertypes revealed that DP2 and DP8 are associated with BCP ALL, but DP6 is also associated with non-BCP leukaemia. Here, we report that only one of seven alleles with the DP6 supertype (DPB1*0601) is associated with childhood leukaemia (leukaemia vs controls: odds ratio, 95% confidence interval [OR, CI]: 4.6, 2.0–10.4; corrected P=0.019), but not with childhood solid tumours or lymphomas. DPB1*0601 is also significantly associated with leukaemia subtypes, including BCP ALL, Pro-B ALL, T-ALL and AML. DPB1*0601 is significantly over-transmitted (76.9%) from parents to children with BCP ALL (OR; CI: 4.7; 1.01–22.2). Sequencing the coding region of DPB1*0601 revealed an exon 1–4 haplotype [T-DEAV-KIL-RVI] shared with DPB1*0301 and 0901, but no evidence of germline mutations in childhood leukaemia. These results suggest that the DPβ0601 molecule may be functionally involved in childhood leukaemia. Analysis of peptide binding and T-cell activation by DPβ0601-peptide complexes should help determine its role in childhood leukaemia causation.Leukemia (2009) 23, 863–869; doi:10.1038/leu.2008.374; published online 15 January 2009 [ABSTRACT FROM AUTHOR]

Bee colonies were dosed with chloramphenicol (CAP) 1.0?g per hive (single dose in sucrose solution). Samples of honey were then collected at intervals over a 48-week period and samples of royal jelly, beeswax, honeybees and brood collected at intervals over a 12?week period. The mean concentration of CAP in the honey at 7?days after dosing was 26??g/g, declining to 1.0??g/g at 332?days. Application of the shook swarm procedure resulted in a mean concentration of CAP in honey of 26??g/g at 7?days, declining to 0.1??g/g at 332?days. The mean concentration of CAP in non-honey samples was in the range of 0.5 to 6.8??g/g, and 0.2 to 3.3??g/g at 7?days and 56?days, respectively. These results indicate that use of CAP can be detected up to 332?days after dosing even if the shook swarm procedure is used in an attempt to clean the hives. There was no evidence of any significant formation of bound CAP-glucose conjugates in honey. [ABSTRACT FROM AUTHOR]

Background:Adiponectin is an abundantly expressed adipocyte-specific protein, whose level is decreased in obesity, and which appears to be a key participant in developing inflammation, insulin resistance and metabolic syndrome (MetS). We examined whether the relationship between adiponectin and inflammatory markers, insulin resistance and MetS was independent of obesity.Methods and results:The study was performed in 1094 men and women, aged 27–77 years, from a representative community population. We measured serum inflammatory markers, homoeostasis model assessment of insulin resistance (HOMA-IR) and prevalent MetS using National Cholesterol Education Program ATPIII criteria. Sex- and age-adjusted plasma adiponectin concentration was inversely correlated with body mass index (BMI), waist–hip ratio, diastolic blood pressure, triglycerides, glucose and fasting insulin, and positively correlated with HDL cholesterol (all P<0.005). Log plasma adiponectin was a significant negative correlate of the levels of C-reactive protein, interleukin-6, interleukin-18, fibrinogen and white cell count independent of level of obesity. Log plasma adiponectin was also an inverse associate of log HOMA-IR (P<0.001) independent of obesity. Subjects in the top compared to bottom sex-specific plasma adiponectin quartile had a multivariate-adjusted odds ratio (OR) of 0.21 (95% CI, 0.11–0.42; P<0.001) for prevalent MetS, and the association was independent of age, sex, BMI, log insulin and log intereukin-18 levels.Conclusion:Our findings suggest that higher circulating adiponectin levels may mitigate against adipose-related inflammation, insulin resistance and MetS as much in lean as obese persons. At any rate circulating adiponectin level is a strong risk marker for MetS, which is independent of measures of adiposity, insulin resistance and inflammatory markers.International Journal of Obesity (2008) 32, 772–779; doi:10.1038/sj.ijo.0803793; published online 5 February 2008 [ABSTRACT FROM AUTHOR]

Bee colonies were dosed with tylosin tartrate 1.1 g per hive (single dose in sucrose solution) and samples of honey were then collected at intervals over a 20-week period. The samples were analysed for tylosin A and desmycosin (tylosin B) using LC-MS/MS. The mean concentration of tylosin A in the honey (pooled results) 3 days after dosing was 17??g/g, declining to 0.9??g/g after 140 days. The mean concentration of desmycosin was 2.3 ?g/g, 3 days after dosing declining to 1.1??g/g after 140 days. The shook swarm procedure was investigated and resulted in a tylosin A concentration in brood honey of 10??g/g, 3 days after dosing declining to 0.02??g/g, 140 days after dosing. A corresponding decrease in the mean concentrations of desmycosin in brood honey, 1.1??g/g, 3 days after dosing to 0.03??g/g, 140 days after dosing also was observed. Tylosin A depletes to desmycosin in honey and can still be detected 238 days after dosing. Thus a more accurate residue definition is the sum of tylosin A and desmycosin. [ABSTRACT FROM AUTHOR]