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.
In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
In the light of Chile’s comprehensive new restriction on unhealthy food marketing, we analyse food advertising on Chilean television prior to the first and final phases of implementation of the restriction.
Content analysis of marketing strategies of 6976 advertisements, based on products’ nutritional quality. Statistical analysis of total and child audience reached using television ratings data.
Advertising from television aired between 06.00 and 00.00 hours during two random composite weeks across April–May 2016 from the four broadcast and four cable channels with the largest youth audiences.
Food ads represented 16 % of all advertising; 34 % of food ads featured a product high in energy, saturated fats, sugars and/or salt (HEFSS), as defined by the initial regulation. HEFSS ads were seen by more children and contained more child-directed marketing strategies than ads without HEFSS foods. If HEFSS advertising was restricted only in programmes where 20 % are children aged 4–12 years, 31 % of children’s and 8 % of the general audience’s HEFSS advertising exposure would be reduced. The newest 06.00–22.00 hours restriction captures 80 % of all audience exposure.
HEFSS advertising was seen by a large proportion of children before Chile’s regulation. Chile’s first implementation based on audience composition should reduce a third of this exposure and its second restriction across the television day should eliminate most of the exposure. The current study is a crucial first step in evaluating how Chile’s regulation efforts will impact children’s diets and obesity prevalence.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Reports in the literature of treatment with recombinant tissue plasminogen activator following cardiac surgery are limited. We reviewed our experience to provide a case series of the therapeutic use of tissue plasminogen activator for the treatment of venous thrombosis in children after cardiac surgery. The data describe the morbidity, mortality, and clinical outcomes of tissue plasminogen activator administration for treatment of venous thrombosis in children following cardiac surgery.
The study was designed as a retrospective case series.
The study was carried out in a 25-bed cardiac intensive care unit in an academic, free-standing paediatric hospital.
All children who received tissue plasminogen activator for venous thrombosis within 60 days of cardiac surgery, a total of 13 patients, were included.
Data was collected, collated, and analysed as a part of the interventions of this study.
Measurements and main results
Patients treated with tissue plasminogen activator were principally young infants (median 0.2, IQR 0.07–0.58 years) who had recently (22, IQR 12.5–27.3 days) undergone cardiac surgery. Hospital mortality was high in this patient group (38%), but there was no mortality attributable to tissue plasminogen activator administration, occurring within <72 hours. There was one major haemorrhagic complication that may be attributable to tissue plasminogen activator. Complete or partial resolution of venous thrombosis was confirmed using imaging in 10 of 13 patients (77%), and tissue plasminogen activator administration was associated with resolution of chylous drainage, with no drainage through chest tubes, at 10 days after tissue plasminogen activator treatment in seven of nine patients who had upper-compartment venous thrombosis-associated chylothorax.
On the basis of our experience with administration of tissue plasminogen activator in children after cardiac surgery, tissue plasminogen activator is both safe and effective for resolution of venous thrombosis in this high-risk population.
Chromium doped II-VI semiconductors (such as ZnSe and ZnS) feature broad mid-IR emission in the 2-3 μm spectral range due to intershell transitions of the Cr2+ ions. These materials show much promise for development of a tunable, electrically-pumped, mid-IR laser source. For integration into a mid-IR active multilayered structure, the ternary alloy ZnSxSe1-x is an attractive waveguiding material due to its lattice-matching ability and lower index of refraction with respect to the Cr2+:ZnSe active material. Epitaxial growth of each layer is desired to achieve the electronic and optical properties necessary for successful integration into a lasing device, so a study was conducted on the effects of sulfur content and growth temperature on the crystal quality of the resulting thin films. Several films of ZnSxSe1-x were deposited by pulsed laser deposition (PLD) using a 248 nm KrF excimer laser source at varying growth temperatures and with various compositional parameters onto (100) GaAs substrates. The samples were analyzed via x-ray diffraction (XRD) and energy dispersive x-rays (EDX) to investigate the crystal quality and elemental content of the films for device integration. Film-substrate epitaxy was achieved and upper bounds to the defect density were calculated for several regimes of compositional parameter and growth temperature. From all samples produced, the lowest defect density of 2.2 x 1010 cm-2 was observed for the x=0.06 film grown at 450°C, while the lowest lattice mismatch between the substrate and epilayer of 0.059% was observed for the x=0.02 film grown at 450°C.
Due to rising pressure to appear egalitarian, subtle discrimination pervades today's workplace. Although its ambiguous nature may make it seem innocuous on the surface, an abundance of empirical evidence suggests subtle discrimination undermines employee and organizational functioning, perhaps even more so than its overt counterpart. In the following article, we argue for a multidimensional and continuous, rather than categorical, framework for discrimination. In doing so, we propose that there exist several related but distinct continuums on which instances of discrimination vary, including subtlety, formality, and intentionality. Next, we argue for organizational scholarship to migrate toward a more developmental, dynamic perspective of subtle discrimination in order to build a more comprehensive understanding of its antecedents, underlying mechanisms, and outcomes. We further contend that everyone plays a part in the process of subtle discrimination at work and, as a result, bears some responsibility in addressing and remediating it. We conclude with a brief overview of research on subtle discrimination in the workplace from each of four stakeholder perspectives—targets, perpetrators, bystanders, and allies—and review promising strategies that can be implemented by each of these stakeholders to remediate subtle discrimination in the workplace.
This paper examines heterogeneity in blockholder monitoring across investor types. We document which blockholder types (e.g., mutual funds, hedge funds) are more likely to be associated with active monitoring and show that firms targeted by such blockholders are more likely to increase the equity portion of chief executive officer (CEO) pay. Further, using market-wide and exogenous shocks to liquidity to identify differences in efficacy across blockholder types, we observe greater operating-performance improvements in actively monitored firms when passive monitoring is less effective, suggesting causal impact. We propose differences in compensation arrangements across blockholder types as a mechanism underlying blockholders’ heterogeneous role.
After neary 20 years since their discovery by Kosovichev and Zharkova, the mechanics of the release of seismic transients into the solar interior from some flares remain a mystery. Seismically emissive flares invariably show the signatures of intense chromosphere heating consistent with pressure variations sufficient to drive seismic transients commensurate with helioseismic observations—under certain conditions. Magnetic observations show the signatures of apparent magnetic changes, suggesting Lorentz-force transients that could likewise drive seismic transients—similarly subject to certain conditions. But, the diagnostic signatures of both of these prospective drivers are apparent over vast regions from which no significant seismic emission emanates. What distinguishes the source regions of transient seismic emission from the much vaster regions that show the signatures of both transient heating and magnetic variations but are acoustically unproductive? Observations of acoustically active flares in He II 304 Å by the Atomospheric Imaging Assembly (AIA) aboard the Solar Dynamics Observatory (SDO) offer a promising new resource with which to address this question.
Accurate data on the incidence of West Nile virus (WNV) disease are important for directing public health education and control activities. The objective of this project was to assess the underdiagnosis of WNV neuroinvasive disease through laboratory testing of patients with suspected viral meningitis or encephalitis at selected hospitals serving WNV-endemic regions in three states. Of the 279 patients with cerebrospinal fluid (CSF) specimens tested for WNV immunoglobulin M (IgM) antibodies, 258 (92%) were negative, 19 (7%) were positive, and two (1%) had equivocal results. Overall, 63% (12/19) of patients with WNV IgM-positive CSF had WNV IgM testing ordered by their attending physician. Seven (37%) cases would not have been identified as probable WNV infections without the further testing conducted through this project. These findings indicate that over a third of WNV infections in patients with clinically compatible neurological illness might be undiagnosed due to either lack of testing or inappropriate testing, leading to substantial underestimates of WNV neuroinvasive disease burden. Efforts should be made to educate healthcare providers and laboratorians about the local epidemiology of arboviral diseases and the optimal tests to be used in different clinical situations.
A systematic investigation of unstable steady-state solutions of the Darcy–Oberbeck–Boussinesq equations at large values of the Rayleigh number
is performed to gain insight into two-dimensional porous medium convection in domains of varying aspect ratio
. The steady convective states are shown to transport less heat than the statistically steady ‘turbulent’ flow realised at the same parameter values: the Nusselt number
for turbulent porous medium convection, while
for the maximum heat-transporting steady solutions. A key finding is that the lateral scale of the heat-flux-maximising solutions shrinks roughly as
, reminiscent of the decrease of the mean inter-plume spacing observed in turbulent porous medium convection as the thermal forcing is increased. A spatial Floquet analysis is performed to investigate the linear stability of the fully nonlinear steady convective states, extending a recent study by Hewitt et al. (J. Fluid Mech., vol. 737, 2013, pp. 205–231) by treating a base convective state, and secondary stability modes, that satisfy appropriate boundary conditions along plane parallel walls. As in that study, a bulk instability mode is found for sufficiently small-aspect-ratio base states. However, the growth rate of this bulk mode is shown to be significantly reduced by the presence of the walls. Beyond a certain critical
-dependent aspect ratio, the base state is most strongly unstable to a secondary mode that is localised near the heated and cooled walls. Direct numerical simulations, strategically initialised to investigate the fully nonlinear evolution of the most dangerous secondary instability modes, suggest that the (long time) mean inter-plume spacing in statistically steady porous medium convection results from a balance between the competing effects of these two types of instability.
Fossils of Columbian mammoths (Mammuthus columbi) and pygmy mammoths (Mammuthus exilis) have been reported from Channel Islands National Park, California. Most date to the last glacial period (Marine Isotope Stage [MIS] 2), but a tusk of M. exilis (or immature M. columbi) was found in the lowest marine terrace of Santa Rosa Island. Uranium-series dating of corals yielded ages from 83.8 ± 0.6 ka to 78.6 ± 0.5 ka, correlating the terrace with MIS 5.1, a time of relatively high sea level. Mammoths likely immigrated to the islands by swimming during the glacial periods MIS 6 (~ 150 ka) or MIS 8 (~ 250 ka), when sea level was low and the island–mainland distance was minimal, as during MIS 2. Earliest mammoth immigration to the islands likely occurred late enough in the Quaternary that uplift of the islands and the mainland decreased the swimming distance to a range that could be accomplished by mammoths. Results challenge the hypothesis that climate change, vegetation change, and decreased land area from sea-level rise were the causes of mammoth extinction at the Pleistocene/Holocene boundary on the Channel Islands. Pre-MIS 2 mammoth populations would have experienced similar or even more dramatic changes at the MIS 6/5.5 transition.
To examine the acceptability and feasibility of using smartphone technology to assess beverage intake and evaluate whether the feasibility of smartphone use is greater among key sub-populations.
An acceptability and feasibility study of recording the video dietary record, the acceptability of the ecological momentary assessment (EMA), wearing smartphones and whether the videos helped participants recall intake after a cross-over validation study.
Rural and urban area in Shanghai, China.
Healthy adults (n 110) aged 20–40 years old.
Most participants reported that the phone was acceptable in most aspects, including that videos were easy to use (70 %), helped with recalls (77 %), EMA reminders helped them record intake (75 %) and apps were easy to understand (85 %). However, 49 % of the participants reported that they had trouble remembering to take videos of the beverages before consumption or 46 % felt embarrassed taking videos in front of others. Moreover, 72 % reported that the EMA reminders affected their consumption. When assessing overall acceptability of using smartphones, 72 % of the participants were favourable responders. There were no statistically significant differences in overall acceptability for overweight v. normal-weight participants or for rural v. urban residents. However, we did find that the overall acceptability was higher for males (81 %) than females (61 %, P=0·017).
Our study did not find smartphone technology helped with dietary assessments in a Chinese population. However, simpler approaches, such as using photographs instead of videos, may be more feasible for enhancing 24 h dietary recalls.
Legislative changes during the 1960s–1970s granted user rights over wildlife to landowners in southern Africa, resulting in a shift from livestock farming to wildlife-based land uses. Few comprehensive assessments of such land uses on private land in southern Africa have been conducted and the associated benefits are not always acknowledged by politicians. Nonetheless, wildlife-based land uses are growing in prevalence on private land. In Namibia wildlife-based land use occurs over c. 287,000 km2. Employment is positively related to income from ecotourism and negatively related to income from livestock. While 87% of meat from livestock is exported ≥ 95% of venison from wildlife-based land uses remains within the country, contributing to food security. Wildlife populations are increasing with expansion of wildlife-based land uses, and private farms contain 21–33 times more wildlife than in protected areas. Because of the popularity of wildlife-based land uses among younger farmers, increasing tourist arrivals and projected impacts of climate change on livestock production, the economic output of wildlife-based land uses will probably soon exceed that of livestock. However, existing policies favour livestock production and are prejudiced against wildlife-based land uses by prohibiting reintroductions of buffalo Syncerus caffer, a key species for tourism and safari hunting, and through subsidies that artificially inflate the profitability of livestock production. Returns from wildlife-based land uses are also limited by the failure to reintroduce other charismatic species, failure to develop fully-integrated conservancies and to integrate black farmers sufficiently.
Accurate data on West Nile virus (WNV) cases help guide public health education and control activities, and impact regional WNV blood product screening procedures. During an outbreak of WNV disease in Arizona, records from patients with meningitis or encephalitis were reviewed to determine the proportion tested for WNV. Of 60 patients identified with meningitis or encephalitis, 24 (40%) were tested for WNV. Only 12 (28%) of 43 patients aged <50 years were tested for WNV compared to 12 (71%) of 17 patients aged ⩾50 years (P<0·01). Patients with clinical signs of weakness or paralysis, elevated CSF protein, admitted to an inpatient facility, or discharged to a rehabilitation facility were also more likely to have WNV testing performed. The lack of testing in younger age groups and in those with less severe disease probably resulted in substantial underestimates of WNV neuroinvasive disease burden.
In South Africa there are efforts to manage reintroduced subpopulations of the Vulnerable cheetah Acinonyx jubatus in small reserves (10–1,000 km2) as a managed metapopulation. We estimated areas required to support cheetahs given varying prey densities, prey profiles and presence/absence of competing predators. A recent population and habitat viability assessment indicated that 20 subpopulations of 10 cheetahs or 10 subpopulations of 15 cheetahs are required to retain 90% of the heterozygosity of free-ranging cheetahs and to overcome stochastic events in the absence or presence of lions Panthera leo, respectively. We estimate that 203 ± SE 42 km2 (range 48–466 km2) is required to support 10 cheetahs in the absence of lions, whereas 703 ± SE 311 km2 (166–2,806 km2) is required to support 15 cheetahs given equal numbers of lions, and 2,424 ± SE 890 km2 (727–3,739 km2) given equal numbers of leopards Panthera pardus, spotted hyaenas Crocuta crocuta, wild dogs Lycaon pictus and lions. Existing subpopulations of cheetahs generally occur at densities higher than our mean predicted densities but usually within the range of predicted densities. The large area requirements of cheetahs have implications for the development of the managed metapopulation. Sourcing reintroduction sites of the sizes required to support recommended subpopulation sizes will be difficult. Consequently, innovative measures to increase the carrying capacity of reserves for cheetahs and/or to enlarge reserves will be required. Managers may be forced to stock cheetahs close to or beyond the carrying capacity of their reserves. Consequently, careful management of reintroduced subpopulations will be required to prevent declines in prey populations.