To save 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 saving content to .
To save 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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
Until recently, the influence of basal liquid water on the evolution of buried glaciers in Mars' mid latitudes was assumed to be negligible because the latter stages of Mars' Amazonian period (3 Ga to present) have long been thought to have been similarly cold and dry to today. Recent identifications of several landforms interpreted as eskers associated with these young (100s Ma) glaciers calls this assumption into doubt. They indicate basal melting (at least locally and transiently) of their parent glaciers. Although rare, they demonstrate a more complex mid-to-late Amazonian environment than was previously understood. Here, we discuss several open questions posed by the existence of glacier-linked eskers on Mars, including on their global-scale abundance and distribution, the drivers and dynamics of melting and drainage, and the fate of meltwater upon reaching the ice margin. Such questions provide rich opportunities for collaboration between the Mars and Earth cryosphere research communities.
According to Aristotle, the goal of anyone who is not simply stupid or slavish is to live a worthwhile life.1 There are, no doubt, people who have no goal at all beyond the moment’s pleasure or release from pain. There may be people incapable of reaching any reasoned decision about what to do, and acting on it.2 But anyone who asks how she should live implicitly agrees that her goal is to live well, to live a life that she can think worth living. That goal, eudaimonia, is something that is sought for its own sake, and for nothing else. Anyone who asks herself how she should live can answer that she should live well. The answer, admittedly, needs further comment. Aristotle went on to suggest that ‘living well’ amounted to living in accordance with virtue, or if there is more than one virtue, in accordance with the best and most complete. Eudaimonia, happiness, is virtuous activity over a whole life. To live a worthwhile life we must acquire and practice habits of doing the right thing, for the right reason. Equivalently, we must do what a virtuous person would, and in the way she would, for the sake of to kalon, or beauty.
Adverse drug reactions (ADRs) are associated with increased morbidity, mortality, and resource utilization. Drug interactions (DDIs) are among the most common causes of ADRs, and estimates have cited that up to 22% of patients take interacting medications. DDIs are often due to the propensity for agents to induce or inhibit enzymes responsible for the metabolism of concomitantly administered drugs. However, this phenomenon is further complicated by genetic variants of such enzymes. The aim of this study is to quantify and describe potential drug-drug, drug-gene, and drug-drug-gene interactions in a community-based patient population.
A regional pharmacy with retail outlets in Arkansas provided deidentified prescription data from March 2020 for 4761 individuals. Drug-drug and drug-drug-gene interactions were assessed utilizing the logic incorporated into GenMedPro, a commercially available digital gene-drug interaction software program that incorporates variants of 9 pharmacokinetic (PK) and 2 pharmacodynamic (PD) genes to evaluate DDIs and drug-gene interactions. The data were first assessed for composite drug-drug interaction risk, and each individual was stratified to a risk category using the logic incorporated in GenMedPro. To calculate the frequency of potential drug-gene interactions, genotypes were imputed and allocated to the cohort according to each gene’s frequency in the general population. Potential genotypes were randomly allocated to the population 100 times in a Monte Carlo simulation. Potential drug-drug, gene-drug, or gene-drug-drug interaction risk was characterized as minor, moderate, or major.
Based on prescription data only, the probability of a DDI of any impact (mild, moderate, or major) was 26% [95% CI: 0.248-0.272] in the population. This probability increased to 49.6% [95% CI: 0.484-0.507] when simulated genetic polymorphisms were additionally assessed. When assessing only major impact interactions, there was a 7.8% [95% CI: 0.070-0.085] probability of drug-drug interactions and 10.1% [95% CI: 0.095-0.108] probability with the addition of genetic contributions. The probability of drug-drug-gene interactions of any impact was correlated with the number of prescribed medications, with an approximate probability of 77%, 85%, and 94% in patients prescribed 5, 6, or 7+ medications, respectively. When stratified by specific drug class, antidepressants (19.5%), antiemetics (21.4%), analgesics (16%), antipsychotics (15.6%), and antiparasitics (49.7%) had the highest probability of major drug-drug-gene interaction.
In a community-based population of outpatients, the probability of drug-drug interaction risk increases when genetic polymorphisms are attributed to the population. These data suggest that pharmacogenetic testing may be useful in predicting drug interactions, drug-gene interactions, and severity of interactions when proactively evaluating patient medication profiles.
Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED).
We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm.
Emergency department of a university teaching hospital.
Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a ‘high-risk’ area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area.
Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34–92) for FebriDx-negative patients and 203 minutes (IQR, 142–255) for FebriDx-positive patients (difference of −134 minutes; 95% CI, −144 to −122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%–97%).
FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2–positive patients.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.
The southern pine beetle, Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae), is among the most destructive bark beetle pests of pines (Pinaceae) of the southeast and mid-Atlantic United States of America, Mexico, and Central America. Numerous volatile compounds can stimulate or reduce attraction of the beetle, but efforts to incorporate these into effective, practical technologies for pest management have yielded mixed results. Attractants have been incorporated into lures used in monitoring traps that are employed operationally to forecast outbreaks and detect emerging populations. The attraction inhibitor, verbenone, shows efficacy for suppressing southern pine beetle infestations but has not yet been adopted operationally. No effective semiochemical tree protectant has been developed for the beetle. We discuss complexities in the chemical ecology of the beetle that likely have impeded research and development of semiochemical management tools, and we describe basic science gaps that may hinder further progress if not addressed. We also report some supporting, original experimental data indicating (1) that a verbenone device can inhibit the beetle’s response to sources of attractant in a radius of at least several metres, (2) similar olfactory responses by the beetle to both enantiomers of verbenone, and (3) that pheromone background can cause conflicting results in semiochemical field tests.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
A naturally occurring hematitic iron oxide/layer-silicate complex has been found in red mottled patches of a deeply weathered granite in north-east Scotland. X-ray diffraction shows a basal spacing of 36 Å—also observable by high resolution electron microscopy—which expands to 40 Å with glycerol and contracts to 33·5 Å on heating. Selected area electron diffraction reveals a composite hematite/layer-silicate pattern with the a-axis of hematite parallel to the b-axis of the silicate. The IR spectrum of the complex clearly shows the contribution made by each of the components. The silicate, with bands due to OH stretching at 3602 cm−1, OH deformation at 855 cm−1, and Si-O stretching at 1085, 1035, 540 and 471 cm−1 resembles ferruginous pyrophyllite, while the hematite, with a perpendicular band at 647 cm−1, in-plane bands at 519, 438, 400, 302 and 227 cm−1 and a characteristic pattern of relative band intensities, is similar to a platy form of soil hematite. Electron microprobe analysis of individual particles gives the complex an (Fe + Al): Si ratio of 6:1, which is consistent with a structure made up of twelve octahedral sheets terminated on both sides by a silicate sheet. It seems likely that the complex developed from a siliceous ferrihydrite which became progressively more organized with geological time.
Austinite belongs to the adelite mineral group of calcium and lead arsenates, and has the conichalcite/descloizite type of crystal structure. The crystal structure of nearly pure austinite, CaZn(AsO4)OH, was redetermined (R = 0.014) and the absolute configuration identified. The space group P212121 and cell parameters a 7.5092(8), b 9.0438(9), c 5.9343(8) Å match previous data. Zinc octahedra share edges to form chains parallel to c. Arsenic tetrahedra share vertices with the Zn octahedra to generate a compact framework. Calcium square antiprisms share edges to make chains parallel to a that occupy the channels in the zinc-arsenic framework.
Philosophical pagans in late antiquity charged Christians with believing ‘without evidence’, but were themselves accused of arbitrariness in their initial choice of philosophical school. Stoics and Platonists in particular adopted a form of cosmic religion that Christians criticized on rationalistic as well as sectarian grounds. The other charge levelled against Christians was that they had abandoned ancestral creeds in arrogant disregard of an earlier consensus, and of the world as pagans themselves conceived it. A clearer understanding of the dispute can be gained from a comparison of Heracles and Christ as divinized ‘sons of God’. The hope on both sides was that we might become, or somehow join with, God. Both sought an escape from the image of a pointless, heartless universe – an image that even moderns find difficult to accept and live by. The notion that pagans and Christians had of God, and of the divine life we might hope to share, was almost identical – up to the point, at least, where both philosophical and common pagans conceived God as Pheidias had depicted him (the crowned Master), and Christians rather as the Crucified, ‘risen against the world’.