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Experimental studies suggest that abnormal levels of calcium, magnesium, and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994-1998. Cases of pancreatic cancer (n150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n459) were randomly selected from the general population and frequency matched to cases by age, sex, and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of calcium (936 vs. 1026 mg/day) and dietary intake of magnesium (315 vs. 331 mg/day) and phosphorus (1350 vs. 1402 mg/day) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of calcium, magnesium, and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of calcium, magnesium, and phosphorus were significantly associated with the risk of pancreatic cancer.
Striking an appropriate balance in the intellectual property system has been the subject of a perennial scholarly and policy debate. Article 7 of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) states explicitly that ‘[t]he protection and enforcement of intellectual property rights should contribute to … a balance of rights and obligations’. The preamble of the WIPO Copyright Treaty (WCT) also recognises ‘the need to maintain a balance between the rights of authors and the larger public interest, particularly education, research and access to information’.2
Understanding the impact of the COVID-19 pandemic on paediatric non-COVID-19-related care, as well as patient and caregiver concerns and stressors, is critical for informing healthcare delivery. It was hypothesised that high care disruptions and psychological stress would be observed among paediatric and adult CHD patients in the early phase of the pandemic.
A cross-sectional, international, electronic survey study was completed. Eligible participants included parents of children with acquired or CHD, adults with CHD, or caregivers of adults with CHD.
A total of 1220 participants from 25 countries completed the survey from 16 April to 4 May, 2020. Cardiac care disruption was significant with 38% reporting delays in pre-pandemic scheduled cardiac surgeries and 46% experiencing postponed cardiac clinic visits. The majority of respondents (75%) endorsed moderate to high concern about the patient with heart disease becoming ill from COVID-19. Worry about returning for in-person care was significantly greater than worry of harm to patient due to postponed care. Clinically significant psychological stress was high across the sample including children (50%), adults with CHD (42%), and caregivers (42%).
The early phase of the COVID-19 pandemic contributed to considerable disruptions in cardiac care for patients with paediatric and adult CHD. COVID-19-related fears are notable with potential to impact willingness to return to in-person care. Psychological stress is also very high necessitating intervention. Further study of the impact of delays in care on clinical outcomes is warranted.
To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled nursing facility (SNF), and the strategies that controlled transmission.
Design, Setting, and Participants:
Cohort study during March 22–May 4, 2020 of all staff and residents at a 780-bed SNF in San Francisco, California.
Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPS) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2; whole genome sequencing (WGS) characterized viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact to a confirmed case; restricting movements between units; implementing surgical face masking facility-wide; and recommended PPE (isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.
Of 725 staff and residents tested through targeted testing and serial PPS, twenty-one (3%) were SARS-CoV-2-positive; sixteen (76%) staff and 5 (24%) residents. Fifteen (71%) were linked to a single unit. Targeted testing identified 17 (81%) cases; PPS identified 4 (19%). Most (71%) cases were identified prior to IPC intervention. WGS was performed on SARS-CoV-2 isolates from four staff and four residents; five were of Santa Clara County lineage and the three others were distinct lineages.
Early implementation of targeted testing, serial PPS, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
Biological materials represent a major source of inspiration to engineer protein-based polymers that can replicate the properties of living systems. Combined with our ability to control the molecular structure of proteins at the single amino acid level, this results in a vast array of attractive possibilities for materials science, an interest that is undeniably related to simplified procedures in gene synthesis, cloning, and biotechnological production. In parallel, it has been increasingly appreciated that living organisms exploit liquid–liquid phase separation (LLPS) to fabricate extracellular structures. In this article, we discuss the central role of protein LLPS in the fabrication of selected biological structures, including biological adhesives and hard biomolecular composites, and how physicochemical lessons from these systems are being replicated in synthetic analogs. Recent translational applications of protein LLPS are highlighted, notably aqueous-resistant adhesives, stimuli-responsive therapeutics carriers, and matrix materials for green structural composites.
Contemporary data on temporal trends in acute stroke incidence, specific to stroke type and age, are lacking. We sought to evaluate temporal trends in incidence of ischemic stroke and intracerebral hemorrhage over 15 years in a large population.
We used linked administrative data to identify all emergency department visits and hospital admissions for first-ever ischemic stroke or intracerebral hemorrhage in Ontario, Canada from 2003–2017. We evaluated annual age-/sex-standardized incidence per 100,000 person-years for ischemic stroke and intracerebral hemorrhage across the study period. We used negative binomial regression to determine incidence rate ratios for each year compared to 2003, with assessment of modification by age, sex, or stroke type.
Our cohort had 163,574 people with stroke (88% ischemic stroke). For ischemic stroke and intracerebral hemorrhage combined, age-/sex-standardized incidence decreased between 2003 and 2011 (standardized rate 109.4 to 85.8 per 100,000; 22%), then increased until 2017 (standardized rate 96.8 per 100,000; 13%). The pattern of change was similar for ischemic stroke and intracerebral hemorrhage, and for men and women, but was modified by age. For those aged 60 and above, adjusted incidence rate ratios decreased from 2003 to 2011 then subsequently increased, whereas for those aged <60 years incidence rate ratios increased throughout the entire study time period, particularly after 2011.
Acute stroke incidence decreased from 2003 to 2011 but subsequently increased until 2017. Among those aged <60, incidence increased continuously from 2003 to 2017 but especially after 2011. The underlying reasons for these changes should be determined.
There are available data on in vivo studies of monotherapy of zoonotic cutaneous leishmaniasis with some antibacterial drugs (doxycycline) and their comparison with meglumine antimoniate (glucantime). We used golden Syrian hamsters as a laboratory model. Experimental groups were formed, each of which was treated with one of the tested drugs. Infection of animals was carried out with Leishmania major promastigotes. We selected highly virulent strains of L. major culture isolated from human ulcers or rodents. Meglumine antimoniate monotherapy and doxycycline monotherapy are quite effective and do not differ by the 30th day of their use in such indicators as the average degree of local damage and the average number of Leishmania in the lesions. The main differences were recorded in terms of average body weight gain and average clinical recovery in favour of doxycycline. Leishmania in the lesion on the 60th day were completely absent in treatment with doxycycline. The experiment proved the effectiveness of doxycycline monotherapy: Leishmania in the lesions were absolutely absent by the end of the treatment.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth.
The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years.
Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other.
Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.
The magnetic resonance imaging (MRI) appearance of the brain and spinal cord in humans with neuroangiostrongyliasis (NA) due to Angiostrongylus cantonensis infection has been well reported. Equivalent studies in animals are lacking. This case series describes clinical and MRI findings in 11 dogs with presumptively or definitively diagnosed NA. MRI of the brain and/or spinal cord was performed using high-field (1.5 T) or low-field (0.25 T) scanners using various combinations of transverse, sagittal, dorsal and three-dimensional (3D) T1-weighted (T1W), transverse, sagittal and dorsal T2-weighted (T2W), T2W fluid-attenuated inversion recovery (FLAIR) and T2*-weighted (T2*W) gradient echo (GRE), dorsal T2W short tau inversion recovery (STIR) and post-gadolinium transverse, sagittal, dorsal and 3D T1W and transverse T2W FLAIR sequences. In 4/6 cases where the brain was imaged, changes consistent with diffuse meningoencephalitis were observed. Evidence of meningeal involvement was evident even when not clinically apparent. The spinal cord was imaged in 9 dogs, with evidence of meningitis and myelitis detected in regions consistent with the observed neuroanatomical localization. Pathognomonic changes of neural larva migrans, as described in some human patients with NA, were not detected. NA should be considered in the differential diagnosis of dogs with MRI evidence of focal or diffuse meningitis, myelitis and/or encephalitis, especially in areas where A. cantonensis is endemic. If not precluded by imaging findings suggestive of brain herniation, cerebrospinal fluid (CSF) collection for cytology, fluid analysis, real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) testing should be considered mandatory in such cases after the MRI studies.
In order to elucidate the physical connection between the propulsive performance and the unsteadiness of jet flow, the transient development of the impulse and thrust of laminar starting jets with finite fluid discharged is investigated numerically for cases with different velocity programmes and jet stroke ratios. The simulation quantitatively demonstrates that the impulse and thrust generated are highly sensitive to the jet kinematics and its near-wake dynamics. The momentum flux contribution to the jet impulse is found to be significant and is associated closely with the jet kinematics. On the other hand, although the over pressure effect at the jet initiation stage has been identified previously as the main reason for the enhanced propulsive performance of the starting jet, the current results indicate that its contribution is in fact weakened by the negative local pressure, induced by the formation of the leading vortex ring as well as jet development during the deceleration stage. Contrary to the effects of the leading vortex ring, the stopping vortex formed near the nozzle exit plane during the jet deceleration stage is found to contribute positively to the pressure impulse production, albeit it is relatively small. By augmenting the over pressure effect and mitigating the negative-pressure effect, the cases with the fast acceleration and slow deceleration velocity programme is capable of producing the maximum pressure impulse, leading to additional impulse production over what would be expected from the jet momentum flux alone.
Introduced over a century ago, oil palms are currently Johor's most significant agricultural offering. Over one-third of Johor's entire landmass is planted with oil palms. Thirty per cent of these lands are farmed by independent smallholders, nearly twice the national average (MPOB n.d.-a; MAMPU n.d.). Further downstream, Johor's millers produced one-sixth of Malaysia's crude palm oil in 2018, worth nearly RM7 billion in revenue (MPOB n.d.-b). The territory hosts numerous downstream players pumping out refined palm oil, margarine, specialty fats, oleochemicals, and biodiesel. Johor's two major ports—Pasir Gudang and Tanjung Pelepas—anchor these production clusters, while also exporting RM15.5 billion of vegetable (mostly palm) oil products in 2017—an impressive 28 per cent of Malaysia's world-leading output (DOSM n.d.). Much of this global prominence stems from Johor's long history as an agricultural powerhouse, its forays into resource-based industrialization, and its relative success in becoming a trade hub for edible oils and chemical derivatives.
This essay will survey the oil palm's increasingly heavy presence within Johor's landscape, commerce, and political economy, grounding discussions in broader global and historical contexts where necessary. The paper's next section outlines the oil palm's importance to world trade, the crop's social and environmental complications in Southeast Asia, and the significance of independent smallholder farming arrangements. We then present a brief history of Johor's multilayered oil palm farm sector since its inception. A third section tracks the oil palm's journey through the value chain, mapping out the millers, crushers, refiners, merchants and equipment manufacturers that have consolidated Johor's status as an attractive locale for commodity processing. Having outlined the main commercial players involved, we then turn towards the more political dimensions of Johor's oil palm sector: the electoral significance of Johor's Federal Land Development Authority (FELDA) settler communities, other government-linked entities involved in oil palms, and land control issues, the latter especially dependent on close ties with Johor's state government. Land use concerns also connect with our final section, which looks at how urbanization, landowners and sustainability requirements are influencing the oil palm's future in Johor.
The principal aim of this study was to optimize the diagnosis of canine neuroangiostrongyliasis (NA). In total, 92 cases were seen between 2010 and 2020. Dogs were aged from 7 weeks to 14 years (median 5 months), with 73/90 (81%) less than 6 months and 1.7 times as many males as females. The disease became more common over the study period. Most cases (86%) were seen between March and July. Cerebrospinal fluid (CSF) was obtained from the cisterna magna in 77 dogs, the lumbar cistern in f5, and both sites in 3. Nucleated cell counts for 84 specimens ranged from 1 to 146 150 cells μL−1 (median 4500). Percentage eosinophils varied from 0 to 98% (median 83%). When both cisternal and lumbar CSF were collected, inflammation was more severe caudally. Seventy-three CSF specimens were subjected to enzyme-linked immunosorbent assay (ELISA) testing for antibodies against A. cantonensis; 61 (84%) tested positive, titres ranging from <100 to ⩾12 800 (median 1600). Sixty-one CSF specimens were subjected to real-time quantitative polymerase chain reaction (qPCR) testing using a new protocol targeting a bioinformatically-informed repetitive genetic target; 53/61 samples (87%) tested positive, CT values ranging from 23.4 to 39.5 (median 30.0). For 57 dogs, it was possible to compare CSF ELISA serology and qPCR. ELISA and qPCR were both positive in 40 dogs, in 5 dogs the ELISA was positive while the qPCR was negative, in 9 dogs the qPCR was positive but the ELISA was negative, while in 3 dogs both the ELISA and qPCR were negative. NA is an emerging infectious disease of dogs in Sydney, Australia.
Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’.
In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated.
We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network.
These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
In nonlinear dynamics, there are three classic routes to chaos, namely the period-doubling route, the Ruelle–Takens–Newhouse route and the intermittency route. The first two routes have previously been observed in self-excited thermoacoustic systems, but the third has not. In this experimental study, we present evidence of the intermittency route to chaos in the self-excited regime of a prototypical thermoacoustic system – a laminar flame-driven Rijke tube. We identify the intermittency to be of type II from the Pomeau–Manneville scenario through an analysis of (i) the probability distribution of the quiescent epochs between successive bursts of chaos, (ii) the first return map, and (iii) the recurrence plot. By establishing the last of the three classic routes to chaos, this study strengthens the universality of how strange attractors arise in self-excited thermoacoustic systems, paving the way for the application of generic suppression strategies based on chaos control.
We investigate the phased evolution and variation of the South Asian monsoon and resulting weathering intensity and physical erosion in the Himalaya–Karakoram Mountains since late Pliocene time (c. 3.4 Ma) using a comprehensive approach. Neodymium and strontium isotopic compositions and single-grain zircon U–Pb age spectra reveal the sources of the deposits in the east Arabian Sea, and show a combination of sources from the Himalaya and the Karakoram–Kohistan–Ladakh Mountains, with sediments from the Indian Peninsula such as the Deccan Traps or Craton. We interpret shifts in the sediment sources to have been forced by sea-level changes that correlate with South Asian monsoon rainfall variation since late Pliocene time. We collected 908 samples from the International Ocean Discovery Program Hole U1456A, which was drilled in the east Arabian Sea. Time series of hematite content and grain size of the sediments were examined downcore. We found South Asian monsoon precipitation and weathering intensity experienced three phases from late Pliocene time. Lower monsoon precipitation, with a lower variability and strong weathering intensity, occurred during 3.4–2.4 Ma; an increased and more variable South Asian monsoon rainfall, along with strengthened but fluctuating weathering intensity, occurred at 1.8–1.1 Ma; and a reduced rainfall with lower South Asian monsoon precipitation variability and moderate weathering intensity marked the period 1.1–0.1 Ma. Maximum entropy spectral analysis and wavelet transform show that there were orbital-dominated cycles of periods c. 100 and c. 41 ka in these proxy-based time series. We propose that the monsoon, sea level, global temperature and insolation together forced the weathering and erosion in SW Asia.
Fluid motion has two well-known fundamental processes: the vector transverse process characterized by vorticity, and the scalar longitudinal process consisting of a sound mode and an entropy mode, characterized by dilatation and thermodynamic variables. The existing theories for the sound mode involve the multi-variable issue and its associated difficulty of source identification. In this paper, we define the source of sound inside the fluid by the objective causality inherent in dynamic equations relevant to a longitudinal process, which naturally favours the material time-rate operator
rather than the local time-rate operator
, and describes the sound mode by inhomogeneous advective wave equations. The sources of sound physical production inside the fluid are then examined at two levels. For the conventional formulation in terms of thermodynamic variables at the first level, we show that the universal kinematic source can be condensed to a scalar invariant of the surface deformation tensor. Further, in the formulation in terms of dilatation at the second level, we find that the sound mode in viscous and heat-conducting flow has sources from rich nonlinear couplings of vorticity, entropy and surface deformation, which cannot be disclosed at the first level. Preliminary numerical demonstration of the theoretical findings is made for two typical compressible flows, i.e. the interaction of two corotating Gaussian vortices and the unsteady type IV shock/shock interaction. The results obtained in this study provide a new theoretical basis for, and physical insight into, understanding various nonlinear longitudinal processes and the interactions therein.
Many writings on the changing nature of work portray the employee–organization relationship as a casualty of the modern workplace. This chapter reviews social exchange models of the employee–organization relationship as captured in organizational support and psychological contract theories. We explore the evidence of the extent to which the employee–organization relationship has changed as a result of changes in employment practices over the past several decades. Our analysis considers both overall trends in the employee–organization relationship as well as specific issues tied to temporary and part-time work, independent contractors, tripartite employment relationships, job insecurity, job hopping, and income inequality. The evidence suggests that while certain employment practices threaten the quality of the employee–organization relationship, social exchange models provide useful and relevant frameworks through which to understand the nature of these changes and employees’ reactions to them.