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 email@example.com
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.
Knowledge of the crop-weed interference on weed biology along with yield penalties can be used for the development of integrated weed management (IWM) tactics. Nevertheless, little is known about the beneficial effects of soybean density, an important aspect of IWM, on late Palmer amaranth (Amaranthus palmeri S. Watson) establishment time. Two field experiments were conducted in 2014 and 2015 to investigate how various soybean [Glycine max (L.) Merr.]densities with A. palmeri establishment timings in weeks after crop emergence (WAE) affect height, biomass and seed production of the weed but also crop yield in drill-seeded soybean. Soybean density had a significant impact on dry weight and seed production of A. palmeri that established within the first two weeks of crop emergence, but not for establishment timings of the weed four weeks and later in relation to crop emergence. Differential performance of A. palmeri gender was observed regarding greater biomass production of female than male plants under crop presence merits further investigation. Grain yield reductions were recorded at earlier A. palmeri establishment timings (i.e. 0 and 1 WAE) compared to 8 WAE establishment timing in 2014 and 2015. High soybean densities resulted in greater soybean yields compared to low soybean density, but no grain yield benefits were observed between medium and high soybean densities. Crop budget analysis revealed the benefits of moderate seeding rate (i.e. 250, 000 seeds ha-1) increases in comparison to lower (i.e. 125,000 seeds ha-1) or high (i.e. 400,000 seeds ha-1) on crop revenue, net income returns and breakeven price. Earlier A. palmeri establishment timings (i.e. 0, 1 and 2 WAE) resulted in lower crop revenue and net income returns compared to later establishment timings of the weed.
Dual energy X-ray absorptiometry (DEXA) is an imaging modality that has been used to predict the computed tomography (CT)-determined carcass composition of multiple species, including sheep and pigs, with minimal inaccuracies, using medical grade DEXA scanners. An online DEXA scanner in an Australian abattoir has shown that a high level of precision can be achieved when predicting lamb carcass composition in real time. This study investigated the accuracy of that same online DEXA when predicting fat and lean percentages as determined by CT over a wide range of phenotypic and genotypic variables across 454 lambs over 6 kill groups and contrasted these results against the current Australian industry standard of grade-rule (GR) measurements to grade carcasses. Lamb carcasses were DEXA scanned and then CT scanned to determine CT Fat % and CT Lean %. All phenotypic traits and genotypic information, including Australian Sheep Breeding Values, were recorded for each carcass. Residuals of the DEXA predicted CT Fat % and Lean %, and the actual CT Fat % and Lean % were calculated and tested against all phenotypic and genotypic variables. Excellent overall precision was recorded when predicting CT Fat % (R2 = 0.91, RMSE = 1.19%). Small biases present for sire breed, sire type, dam breed, hot carcass weight and c-site eye muscle area could be explained by a regression paradox; however, biases among kill group (−0.73% to 1.01% for CT Fat %, −1.48% to 0.76% for CT Lean %) and the Merino sire type (0.36% for CT Fat %, −0.73% for CT Lean %) could not be explained by this effect. Over the large range of phenotypic and genotypic variation, there was excellent precision when predicting CT Fat % and CT Lean % by an online DEXA, with only minor biases, showing superiority to the existing Australian standard of GR measurements.
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.
Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.
Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.
Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.
A growing number of political activists and scholars defend the idea of state-based or political-institutional civil disobedience: they locate civil disobedience's agency in state rather than civil society–based actors. Diverging from older ideas of civil disobedience as directed against government, the concept of institutional disobedience raises tough questions its exponents have not yet fully answered. Civil disobedience has usually referred to politically motivated lawbreaking that is morally conscientious, nonviolent, and demonstrates basic respect for law. Because of the modern state's normatively ambivalent traits (e.g., its monopoly on legitimate coercion), political-institutional disobedience is incompatible with minimally acceptable interpretations of civil disobedience's core components. Political-institutional civil disobedience's advocates mischaracterize what they in fact are proposing, namely, disobedience to the law by individual state officials. Such offiical disobedience poses challenges distinct from and probably greater than civil society–based disobedience.
Lumateperone (lumateperone tosylate, ITI-007) is an investigational drug for the treatment of schizophrenia, bipolar depression, and other disorders. Lumateperone has a unique mechanism of action that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This may provide advantages in the treatment of the broad symptoms associated with schizophrenia, including negative and depression symptoms. In 2 previous placebo-controlled trials in patients with acute schizophrenia, lumateperone 42mg (ITI-007 60mg) demonstrated statistically significant improvement in the Positive and Negative Syndrome Scale (PANSS) Total score compared with placebo. In these studies, lumateperone was well tolerated with a safety profile similar to placebo. This open-label long-term study evaluated the safety and effectiveness of lumateperone 42mg in patients with schizophrenia and stable symptoms.
Patients with stable schizophrenia were treated for up to 1 year with lumateperone 42mg. Safety assessments included adverse events (AEs), body weight, laboratory parameters, and extrapyramidal symptoms (EPS)/motor symptom assessments. Efficacy analyses included evaluation of changes in PANSS Total score and in depression symptoms, as measured by the Calgary Depression Scale for Schizophrenia (CDSS).
In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42mg; at the time of this interim analysis, 107 patients had completed 1 year of treatment. Only 4 TEAEs occurred in ≥5% of patients (weight decrease, dry mouth, headache and diarrhea); the majority of AEs were mild or moderate in intensity. Most metabolic parameters and mean prolactin levels decreased from SOC baseline, as did mean body weight and BMI. Based on AE reporting and EPS/motor symptom scales, lumateperone treatment was associated with minimal EPS risk. Lumateperone 42mg treatment was associated with significant reductions in PANSS Total score from baseline, with continuing PANSS improvement throughout the study. In patients with moderate-to-severe depression symptoms at baseline (CDSS>5), mean CDSS scores decreased from 7.4 (baseline) to 3.1 (Day 300); 60% of patients met CDSS response criteria (50% improvement from baseline) by Day 75 and this response rate was maintained through day 300. Similar magnitude of CDSS improvement was seen regardless of concurrent antidepressant therapy.
In long-term treatment, lumateperone was associated with minimal metabolic, EPS, and cardiovascular safety issues relative to current SOC antipsychotic therapy. Lumateperone improved schizophrenia symptoms with continued long-term treatment. In patients with moderate-to-severe depression symptoms at baseline, lumateperone treatment was associated with marked improvement in CDSS scores. These data are consistent with and extend data previously reported in placebo-controlled studies in patients with acute schizophrenia treated with lumateperone.
Supported by funding from Intra-Cellular Therapies, Inc.
Lumateperone (ITI-007) is in late-phase clinical development for schizophrenia. Lumateperone has a unique mechanism of action that modulates serotonin, dopamine, and glutamate neurotransmission. This pooled analysis of lumateperone in 3 randomized, double-blind, placebo-controlled studies was conducted to evaluate the safety and tolerability of lumateperone 42mg (ITI-007 60mg).
Data were pooled from the 3 controlled late-phase studies of lumateperone 42mg in patients with acute exacerbation of schizophrenia. Safety assessments of all patients who received at least one dose of any treatment included treatment-emergent adverse events (TEAEs), changes in laboratory parameters, extrapyramidal symptoms (EPS), and vital signs.
The safety population comprised 1,073 patients (placebo [n=412], lumateperone 42mg [n=406], risperidone [n=255]). TEAEs that occurred in the lumateperone 42mg group at a rate of ≥5% and twice placebo were somnolence/sedation (24.1% vs 10.0%) and dry mouth (5.9% vs 2.2%). Rates of discontinuation due to TEAEs with lumateperone 42mg (0.5%) were similar to placebo (0.5%) and lower than risperidone (4.7%). Mean change in weight and rates of EPS-related TEAEs were less for lumateperone 42mg and placebo patients than risperidone patients. Mean change from baseline in metabolic parameters were similar or smaller for lumateperone 42mg vs placebo. Mean changes were notably higher in risperidone patients vs lumateperone 42mg and placebo for glucose, cholesterol, triglycerides, and prolactin.
In this pooled analysis, lumateperone 42mg showed good tolerability with potential benefits over risperidone for metabolic, prolactin, and EPS risks. The only TEAE that occurred in >10% of lumateperone patients was somnolence/sedation, which was impacted by morning administration; in subsequent studies that administered lumateperone in the evening, somnolence/sedation rates were markedly reduced. These results suggest that lumateperone 42mg may be a promising new treatment for schizophrenia.
Supported by funding from Intra-Cellular Therapies, Inc.
This study investigated subjective memory complaints in older adults and the roles of setting, response bias, and personality.
Cognitively normal older adults from two settings completed questionnaires measuring memory complaints, response bias, and personality.
(A) Neuroimaging study with community-based recruitment and (B) academic memory clinic.
Cognitively normal older adults who (A) volunteer for research (N = 92) or (B) self-referred to a memory clinic (N = 20).
Neuropsychological evaluation and adjudication of normal cognitive status were done by the neuroimaging study or memory clinic. This study administered self-reports of subjective memory complaints, response bias, five-factor personality, and depressive symptoms. Primary group differences were examined with secondary sensitivity analyses to control for sex, age, and education differences.
There was no significant difference in over-reporting response bias between study settings. Under-reporting response bias was higher in volunteers. Cognitive complaints were associated with response bias for two cognitive complaint measures. Neuroticism was positively associated with over-reporting in evaluation-seekers and negatively associated with under-reporting in volunteers. The relationship was reversed for Extraversion. Under-reporting bias was positively correlated with Agreeableness and Conscientiousness in volunteers.
Evaluation-seekers do not show bias toward over-reporting symptoms compared to volunteers. Under-reporting response bias may be important to consider when screening for memory impairment in non-help-seeking settings. The Memory Functioning Questionnaire was less sensitive to reporting biases. Over-reporting may be a facet of higher Neuroticism. Findings help elucidate psychological influences on self-perceived cognitive decline and help seeking in aging and may inform different strategies for assessment by setting.
This paper considers the significant role of cross-sectional geometry on resistance in co-axial pipe flows. We consider an axially flowing viscous fluid in between two long and thin elliptical coaxial cylinders, one inside the other. The outer cylinder is stationary, while the inner cylinder (rod) is free to move. The rod poses a resistance to the axial flow, while the viscous fluid poses a resistance to any motion of the rod. We show that the equations for flow in the axial direction – driven by a prescribed flux – and for flow within the cross-section of the domain – driven by the motion of the rod – decouple in the asymptotic limit of small cylinder aspect ratio into axial Poiseuille flow and transverse Stokes flow, respectively. The objective of this paper is to calculate numerically the axial and cross-sectional resistances and to determine their dependence on cross-sectional geometry – i.e. rod position and the ellipticities of the rod and bounding cylinder. We characterise axial resistance, first for three reduced parameter spaces that have not been fully analysed in the literature: (i) a circle in an ellipse, (ii) an ellipse in a circle and (iii) an ellipse in an ellipse of equal eccentricity and orientation, before extending our geometric parameter space to determine the overall optimal geometry to minimise axial flow resistance for fixed cross-sectional area. Cross-sectional resistance is characterised via coefficients in a Stokes resistance matrix and we highlight the interdependent effects of cross-sectional ellipticity and boundary interactions.
Atom probe tomography (APT) is used to quantify atomic-scale elemental and isotopic compositional variations within a very small volume of material (typically <0.01 µm3). The small analytical volume ideally contains specific compositional or microstructural targets that can be placed within the context of the previously characterized surface in order to facilitate a correct interpretation of APT data. In this regard, careful targeting and preparation are paramount to ensure that the desired target, which is often smaller than 100 nm, is optimally located within the APT specimen. Needle-shaped specimens required for atom probe analysis are commonly prepared using a focused ion beam scanning electron microscope (FIB-SEM). Here, we utilize FIB-SEM-based time-of-flight secondary ion mass spectrometry (ToF-SIMS) to illustrate a novel approach to targeting <100 nm compositional and isotopic variations that can be used for targeting regions of interest for subsequent lift-out and APT analysis. We present a new method for high-spatial resolution targeting of small features that involves using FIB-SEM-based electron deposition of platinum “buttons” prior to standard lift-out and sharpening procedures for atom probe specimen manufacture. In combination, FIB-ToF-SIMS analysis and application of the “button” method ensure that even the smallest APT targets can be successfully captured in extracted needles.
Older adults often have atypical presentation of illness and are particularly vulnerable to influenza and its sequelae, making the validity of influenza case definitions particularly relevant. We sought to assess the performance of influenza-like illness (ILI) and severe acute respiratory illness (SARI) criteria in hospitalized older adults.
Prospective cohort study.
The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network undertakes active surveillance for influenza among hospitalized adults.
Data were pooled from 3 influenza seasons: 2011/12, 2012/13, and 2013/14. The ILI and SARI criteria were defined clinically, and influenza was laboratory confirmed. Frailty was measured using a validated frailty index.
Of 11,379 adult inpatients (7,254 aged ≥65 years), 4,942 (2,948 aged ≥65 years) had laboratory-confirmed influenza. Their median age was 72 years (interquartile range [IQR], 58–82) and 52.6% were women. The sensitivity of ILI criteria was 51.1% (95% confidence interval [CI], 49.6–52.6) for younger adults versus 44.6% (95% CI, 43.6–45.8) for older adults. SARI criteria were met by 64.1% (95% CI, 62.7–65.6) of younger adults versus 57.1% (95% CI, 55.9–58.2) of older adults with laboratory-confirmed influenza. Patients with influenza who were prefrail or frail were less likely to meet ILI and SARI case definitions.
A substantial proportion of older adults, particularly those who are frail, are missed by standard ILI and SARI case definitions. Surveillance using these case definitions is biased toward identifying younger cases, and does not capture the true burden of influenza. Because of the substantial fraction of cases missed, surveillance definitions should not be used to guide diagnosis and clinical management of influenza.
The objectives of this study were to obtain patient evaluations of the content, structure, and delivery modality of Meaning-Centered Pain Coping Skills Training (MCPC), a novel psychosocial intervention for patients with advanced cancer and pain. MCPC aims to help patients connect with valued sources of meaning in their lives (e.g., family relationships), while providing training in evidence-based cognitive and behavioral skills (e.g., guided imagery) to reduce pain.
Semi-structured interviews were conducted with 12 patients with stage IV solid tumor cancers and persistent pain. Transcripts were analyzed using methods from applied thematic analysis.
When evaluating MCPC's educational information and skills training descriptions, participants described ways in which this content resonated with their experience. Many coped with their pain and poor prognosis by relying on frameworks that provided them with a sense of meaning, often involving their personally held religious or spiritual beliefs. They also expressed a need for learning ways to cope with pain in addition to taking medication. A few participants offered helpful suggestions for refining MCPC's content, such as addressing common co-occurring symptoms of sleep disturbance and fatigue. Concerning MCPC's structure and delivery modality, most participants preferred that sessions include their family caregiver and described remote delivery (i.e., telephone or videoconference) as being more feasible than attending in-person sessions.
Significance of results
Participants were interested in an intervention that concurrently focuses on learning pain coping skills and enhancing a sense of meaning. Using remote delivery modalities may reduce access barriers (e.g., travel) that would otherwise prevent many patients from utilizing psychosocial services.
To compare the microbicidal activity of low-temperature sterilization technologies (vaporized hydrogen peroxide [VHP], ethylene oxide [ETO], and hydrogen peroxide gas plasma [HPGP]) to steam sterilization in the presence of salt and serum to simulate inadequate precleaning.
Test carriers were inoculated with Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, vancomycin-resistant Enterococcus, Mycobacterium terrae, Bacillus atrophaeus spores, Geobacillus stearothermophilus spores, or Clostridiodes difficile spores in the presence of salt and serum and then subjected to 4 sterilization technologies: steam, ETO, VHP and HPGP.
Steam, ETO, and HPGP sterilization techniques were capable of inactivating the test organisms on stainless steel carriers with a failure rate of 0% (0 of 220), 1.9% (6 of 310), and 1.9% (5 of 270), respectively. The failure rate for VHP was 76.3% (206 of 270).
Steam sterilization is the most effective and had the largest margin of safety, followed by ETO and HPGP, but VHP showed much less efficacy.
We present the analysis of global sympagic primary production (PP) from 300 years of pre-industrial and historical simulations of the E3SMv1.1-BGC model. The model includes a novel, eight-element sea ice biogeochemical component, MPAS-Seaice zbgc, which is resolved in three spatial dimensions and uses a vertical transport scheme based on internal brine dynamics. Modeled ice algal chlorophyll-a concentrations and column-integrated values are broadly consistent with observations, though chl-a profile fractions indicate that upper ice communities of the Southern Ocean are underestimated. Simulations of polar integrated sea ice PP support the lower bound in published estimates for both polar regions with mean Arctic values of 7.5 and 15.5 TgC/a in the Southern Ocean. However, comparisons of the polar climate state with observations, using a maximal bound for ice algal growth rates, suggest that the Arctic lower bound is a significant underestimation driven by biases in ocean surface nitrate, and that correction of these biases supports as much as 60.7 TgC/a of net Arctic PP. Simulated Southern Ocean sympagic PP is predominantly light-limited, and regional patterns, particularly in the coastal high production band, are found to be negatively correlated with snow thickness.
Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.
Homeless and precariously housed individuals experience a high burden of comorbid illnesses, and excess mortality. Cross-sectional studies report a high rate of cognitive impairment. Long-term trajectories have not been well investigated in this group.
To longitudinally assess risks for premature and/or accelerated cognitive ageing, and the relationship with early mortality in homeless and precariously housed people.
This is a 9-year community-based study of 375 homeless and precariously housed individuals from Vancouver, Canada. Annual cognitive testing assessed verbal learning and memory, and inhibitory control. Linear mixed-effects models examined associations between clinical risk factors (traumatic brain injury, psychotic disorders, viral exposure, alcohol dependence) and cognitive change over 9 years. Cox regression models examined the association between cognition and mortality.
Traumatic brain injury and alcohol dependence were associated with decline in verbal memory. Inhibitory control declined, independent of risk factors and to a greater extent in those who died during the study. Better inhibitory control was associated with a 6.6% lower risk of mortality at study entry, with a 0.3% greater effect for each year of life. For each one-point increase in the Charlson Comorbidity Index score at study entry, the risk of mortality was 9.9% higher, and was consistent across age. Adjusting for comorbidities, inhibitory control remained a significant predictor of mortality.
Findings raise the possibility of a premature onset, and accelerated trajectory, of cognitive ageing in this group of homeless and precariously housed people. Traumatic brain injury, alcohol dependence and cognition could be treatment priorities.