To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Correct diagnosis of cause of death is necessary to suggest the most effective management interventions to reduce perinatal lamb mortality. Haemorrhage on the surface of the brain has been used as a field diagnostic tool to allocate lambs to a cause of death category, but the usefulness of this method was unclear. This study aimed to evaluate whether gross pathology was related to neuronal death and whether haemorrhage of the central nervous system (CNS) was distinct between differing causes of death, enabling indicators to be used in field diagnoses. Lambs dying from natural causes (n = 64) and from euthanasia (n = 7) underwent postmortem examination, then the brain and spinal cord were extracted and examined histologically. Histological changes consistent with neuronal death were not detected in any lamb. Haemorrhage of the meninges and/or parenchyma of the CNS occurred in all lambs. The age of the haemorrhage indicated that it occurred near the time of death in most lambs. Dilation of blood vessels varied in severity but appeared to be unrelated to causal diagnosis, severity of subcutaneous oedema, breathing or milk status. Moderate or severe dilation of blood vessels and haemorrhage of the CNS did not occur in all lambs with alternative clear indicators of dystocia and occurred in all death classifications, so it could not be used as diagnostic indicators for classification of cause of death. Dilation and haemorrhage were unrelated to neuronal damage and may have been artefactual. In conclusion, haemorrhage of the CNS was not indicative of neuronal damage and could not be used to distinguish between lambs with clear indicators of differing causes of death, so it is not recommended as a field diagnostic tool.
Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.
Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.
Urine collection methodologies were developed within home settings.
Different cohorts of free-living volunteers.
Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.
This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
This article examines the institutionalization of online consultation, a prominent instrument of governance reform in contemporary China in which government organizations make public draft laws and regulations and solicit input from interested parties prior to finalizing decisions. The article specifically analyses the extent to which online consultation is a durable governance reform that enhances transparency and participation in policymaking. The analysis focuses on the Ministry of Commerce (MOC) and Guangzhou Municipal Government (GMG), leading organizations in the implementation of online consultation. Through the analysis of original datasets consisting of hundreds of policies proposed by the MOC and GMG and thousands of comments submitted in response to these drafts, the article demonstrates that online consultation has institutionalized government transparency but has not consistently enhanced public participation. Although online consultation has the potential to transform policymaking, the evidence suggests that strong confidence in this possibility is not warranted.
Introduction: Improved access to HIV testing would benefit the one in six Canadians living with undiagnosed HIV, and potentially reduce transmission. Emergency departments may be the first or only point of contact with the healthcare system for people exposed to HIV; however, HIV testing remains inaccessible in many EDs in Canada. Methods: We used a grounded theory approach to characterize the experiences and context of HIV testing in Canadian EDs. We conducted semi-structured phone interviews with ED and public health practitioners from a purposive sample of urban, rural, academic, and community ED catchment areas. Thematic analysis was performed through iterative readings by two authors. Results were triangulated through consultation with public health and HIV experts. Results: Data were obtained from 16 ED physicians and 8 public health practitioners. HIV tests were infrequently performed in the EDs of our sample. Informants from higher incidence regions believed that greater availability of HIV tests in the ED would benefit the populations they serve. In half of the sample, rapid HIV tests were available. However, indications for testing were most often occupational or known high-risk exposure. Notably, two urban EDs in British Columbia screened all patients who otherwise needed blood tests (opt-out), but had shifted to opt-in testing at the time of this study. Consent practices and perceived requirements varied widely between sites; this confused or frustrated physicians. Most EDs were unable to offer a test result to patients during their visit as results were not available until days to weeks later. Commonly, the ordering physician was responsible for communicating results. Some EDs had an assigned physician managing all results on a given day while others relied on public health units for follow-up. All EDs reported access to public health clinics for ongoing care. Barriers to offering a test in the ED included time required for consent, discomfort with pre-test counselling, delay in results availability and unclear processes for follow-up. Conclusion: We describe substantial regional and within-site variation in HIV testing practices across a diverse sample of EDs across Canada. These findings highlight disparities in access to HIV testing and warrant a national discussion on best practices for testing in EDs with an emphasis on reducing barriers for high-risk populations and addressing unmet needs.
Innovation Concept: Research training programs for students, especially in emergency medicine (EM), may be difficult to initiate due to lack of protected time, resources, and mentors (Chang Y, Ramnanan CJ. Academic Medicine 2015). We developed a ten-week summer program for medical students aimed at cultivating research skills through mentorship, clinical enrichment, and immersion in EM research culture through shadowing and project support. Methods: Five second year Ontario medical students were recruited to participate in the Summer Training and Research in Emergency Medicine (STAR-EM) program at University Health Network, Toronto, from June - Aug, 2019. Program design followed review of existing summer research programs and literature regarding challenges to EM research (McRae, Perry, Brehaut et al. CJEM 2018). The program had broad emergency physician (EP) engagement, with five EP research project mentors, and over ten EPs delivering academic sessions. Curriculum development was collaborative and iterative. All projects were approved by the hospital Research Ethics Board (REB). Curriculum, Tool or Material: Each weekly academic morning comprised small group teaching (topics including research methodology, manuscript preparation, health equity, quality improvement, and wellness), followed by EP-led group progress review of each student's project. Each student spent one half day per week in the emergency department (ED), shadowing an EP and identifying patients for recruitment for ongoing mentor-initiated ED research projects. Remaining time was spent on independent student project work. Presentation to faculty and program evaluation occurred in week 10. Scholarly output included one abstract submitted for publication per student. Program evaluation by students reflected a uniform impression that course material and mentorship were each excellent (100%, n = 5). Interest in pursuing academic EM as a career was identified by all students. Faculty researchers rated the program as very effective (80%, n = 4) or somewhat effective (20%, n = 1) in terms of enhancing productivity and scholarly output. Conclusion: The STAR-EM program provides a transferable model for other academic departments seeking to foster the development of future clinician investigators and enhance ED research culture. Program challenges included delays in REB approval for student projects and engaging recalcitrant staff to participate in research.
Introduction: Acute bloody diarrhea obligates rapid and accurate diagnostic evaluation; few studies have described such cohorts of children. Methods: We conducted a planned secondary analysis employing the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) acute gastroenteritis study cohort to describe the characteristics of children with acute bloody diarrhea, compared to a cohort of children without hematochezia. Children <18 years of age presenting to 2 pediatric tertiary care emergency departments (EDs) in Alberta, with ≥3 episodes of diarrhea and/or vomiting in the preceding 24 hours and <7 days of symptoms were consecutively recruited. Stools were tested for 17 viruses, bacteria and parasites. Primary outcomes were clinical characteristics and pathogens identified. Secondary outcomes included interventions and resource utilization. Results: Of 2257 children enrolled between October 2015 and August 2018, hematochezia before or at the index ED visit was reported in 122 (5.4%). Compared to children with nonbloody diarrhea, children with hematochezia had longer illness duration [59.5 vs. 41.5 hrs, difference 10.6, 95% CI 3.5, 19.9], more diarrheal episodes in a 24-hour period [8 vs. 5, difference 3, 95% CI 2, 4], and less vomiting [55.7% vs. 91.1%; difference -35.3%; 95% CI -44.7, -26.3]. They received more intravenous fluids [32.0% vs. 18.3%; difference 13.7%, 95% CI 5.5, 23.0], underwent non-study stool testing [53.7% vs. 4.8%; difference 49.0%, 95% CI 39.6, 58.0], experienced longer ED visits [4.1 vs. 3.3 hours, difference 0.9, 95% CI 0.3, 1.0] and were more likely to have repeat healthcare visits within 14 days [54.8% vs. 34.2%; difference 20.6%, 95% CI 10.8, 30.1]. A bacterial enteric pathogen was found in 31.9% of children with hematochezia versus 6.6% without bloody diarrhea (difference 25.4%, 95% CI 17.2, 34.7). In children with hematochezia, the most commonly detected bacteria were Salmonella spp. (N = 15), Shiga toxin-producing E. coli (N = 9), Campylobacter spp. (N = 7), and Shigella spp. (N = 5). Viruses were detected in 32.8% of children with bloody diarrhea, most commonly adenovirus (N = 15), norovirus (N = 14), sapovirus (N = 8) and rotavirus (N = 7). Conclusion: Children with hematochezia differed clinically from those without hematochezia and required more healthcare resources. While bacterial etiologies are common, several viruses were also detected.
The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2 = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2 = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.
The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.
The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.
In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.
Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).
Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
The stiffness of conjugated polymers should lead to chain alignment near buried interfaces, even if the polymer film is nominally amorphous. Although simulations predict that this alignment layer is approximately 1.5 times the persistence length, chain alignment at buried interfaces of amorphous polymers has not been experimentally measured. Using Mueller matrix spectroscopy, the optical response of regiorandom poly(3-hexylthiophene-2,5-diyl) (P3HT) was modeled in order to extract the aligned layer thickness. By approximating the optical properties of the aligned layer as that of regioregular P3HT, the data can be effectively modeled. When the film is thicker than 150 nm, optical properties are best described with a 4-nm aligned layer, which is quantitatively consistent with previous predictions.
Uranium–35 wt.% zirconium (U–35 wt.% Zr) alloy was annealed for 1 h and 24 h at 650 °C and characterized to understand the early-stage microstructure evolution. Dendritic microstructure with fine (∼300 nm in length) α-U precipitates clustered between dendrite branches were observed in the 1-h annealed sample. After 24-h annealing at 650 °C, the α-U precipitates coarsened, and the dendritic microstructure disappeared because of microstructure homogenization. Furthermore, microchemical homogenization observed with energy-dispersive X-ray spectroscopy analysis suggests that α-U precipitates are approaching thermodynamic equilibrium in the 24-h annealed sample. The findings from this study have potential impacts on the manufacturing and computer modeling of metallic nuclear fuel.
The coronal heating problem is a long-standing perplexing issue. In this study, 13 solar activity indexes are used to investigate their phase relation with the sunspot number (SSN). Only three of them are found to statistically significantly lag the SSN (large-scale magnetic activity) by about one solar rotation period; the three indexes are total solar irradiance (TSI), the modified coronal index, and the solar wind velocity; the former two indexes may represent the long-term variation of energy quantity of the heated photosphere and corona, respectively. The Mount Wilson Sunspot Index (MWSI) and the Magnetic Plage Strength Index (MPSI), which reflect the large- and small-scale magnetic field activities, respectively, are also utilised to investigate their phase relations with the three indexes. The three indexes are found to be much more intimately related to MPSI than to MWSI, and MWSI statistically significantly leads TSI by about one rotation period. The heated corona is found to pulse perfectly in step with the small-scale magnetic activity rather than the large-scale magnetic activity; furthermore, combined with observations, our statistical evidence should thus attribute coronal heating firmly to small-scale magnetic activity phenomena, such as spicules, micro-flares, nano-flares, and others. The photosphere and the corona are synchronously heated, which should seemingly prefer magnetic reconnection heating to wave heating. In the long term, such a coronal heating way is inferred effective. Statistically, it is also small-scale magnetic activity phenomena that produce TSI enhancement. Coronal heating and solar wind acceleration are found to be synchronous, as standard models require.
To examine the relationship between the therapeutic effect of intratympanic methylprednisolone perfusion and histone acetylation in refractory sudden sensorineural hearing loss.
Thirty-four refractory sudden sensorineural hearing loss patients were enrolled and treated with intratympanic methylprednisolone perfusion. Pure tone average, acetylated histone H3, acetylated histone H4 and histone deacetylase 2 (HDAC2) were measured in peripheral blood mononuclear cells before and after intratympanic methylprednisolone perfusion. Sixteen healthy volunteers were recruited to obtain normal reference values.
Pure tone average in sudden sensorineural hearing loss patients improved from 84.14 ± 13.54 dB to 73.56 ± 18.45 dB after intratympanic methylprednisolone perfusion. Up-regulations in HDAC2 protein level, and down-regulations in histone H3 and H4 acetylation were observed in the intratympanic methylprednisolone perfusion sensitive group (pure tone average gain of 15 dB or more), while no significant changes were observed in the intratympanic methylprednisolone perfusion insensitive group (pure tone average gain of less than 15 dB).
Intratympanic methylprednisolone perfusion can improve hearing in a considerable number of refractory sudden sensorineural hearing loss patients. The therapeutic effect is closely related to reduced histone acetylation.
Staphylococcus aureus has been recognised as one of the important zoonotic pathogens. However, knowledge about the epidemiology and genetic characteristics of S. aureus in rabbits was limited. The aim of this study was to determine the characteristics of 281 S. aureus isolated from dead rabbits of nine rabbit farms in Fujian Province, China. All the isolates were characterised by multi-locus sequencing typing, detection of virulence factors and antimicrobial susceptibility test. The results showed that the 281 isolates were grouped into two sequence types, ST121 (13.52%, 38/281) and ST398 (86.48%, 243/281). Surprisingly, the ST121 strains were only recovered from the lung samples from one of the nine rabbit farms studied. In the 281 isolates, the virulence genes of nuc, hla, hlb, clfA, clfB and fnbpA were positive, whereas the sea, seb, tsst, eta and etb genes were negative. Notably, the 38 ST121 isolates carried the pvl gene. All the 281 isolates were methicillin-susceptible S. aureus, and the isolates were susceptible to most of the used antibiotics, except for streptomycin, kanamycin, azithromycin and penicillin, and the resistance rates of which were 23.84%, 19.57%, 16.01% and 11.03%, respectively. This study first described the epidemiology and characteristics of S. aureus in rabbits in Fujian Province, which will help in tracking the evolution of epidemic strains and preventing the rabbit–human transmission events.
While assessing the environmental impact of nuclear power plants, researchers have focused their attention on radiocarbon (14C) owing to its high mobility in the environment and important radiological impact on human beings. The 10 MW high-temperature gas-cooled reactor (HTR-10) is the first pebble-bed gas-cooled test reactor in China that adopted helium as primary coolant and graphite spheres containing tristructural-isotropic (TRISO) coated particles as fuel elements. A series of experiments on the 14C source terms in HTR-10 was conducted: (1) measurement of the specific activity and distribution of typical nuclides in the irradiated graphite spheres from the core, (2) measurement of the activity concentration of 14C in the primary coolant, and (3) measurement of the amount of 14C discharged in the effluent from the stack. All experimental data on 14C available for HTR-10 were summarized and analyzed using theoretical calculations. A sensitivity study on the total porosity, open porosity, and percentage of closed pores that became open after irradiating the matrix graphite was performed to illustrate their effects on the activity concentration of 14C in the primary coolant and activity amount of 14C in various deduction routes.