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The invention of silicon drift detectors has resulted in an unprecedented improvement in detection efficiency for energy-dispersive X-ray (EDX) spectroscopy in the scanning transmission electron microscope. The result is numerous beautiful atomic-scale maps, which provide insights into the internal structure of a variety of materials. However, the task still remains to understand exactly where the X-ray signal comes from and how accurately it can be quantified. Unfortunately, when crystals are aligned with a low-order zone axis parallel to the incident beam direction, as is necessary for atomic-resolution imaging, the electron beam channels. When the beam becomes localized in this way, the relationship between the concentration of a particular element and its spectroscopic X-ray signal is generally nonlinear. Here, we discuss the combined effect of both spatial integration and sample tilt for ameliorating the effects of channeling and improving the accuracy of EDX quantification. Both simulations and experimental results will be presented for a perovskite-based oxide interface. We examine how the scattering and spreading of the electron beam can lead to erroneous interpretation of interface compositions, and what approaches can be made to improve our understanding of the underlying atomic structure.
We examined whether Research Domain Criteria (RDoC)-informed measures of prenatal stress predicted newborn neurobehavior and whether these effects differed by newborn sex. Multilevel, prenatal markers of prenatal stress were obtained from 162 pregnant women. Markers of the Negative Valence System included physiological functioning (respiratory sinus arrhythmia [RSA] and electrodermal [EDA] reactivity to a speech task, hair cortisol), self-reported stress (state anxiety, pregnancy-specific anxiety, daily stress, childhood trauma, economic hardship, and family resources), and interviewer-rated stress (episodic stress, chronic stress). Markers of the Arousal/Regulatory System included physiological functioning (baseline RSA, RSA, and EDA responses to infant cries) and self-reported affect intensity, urgency, emotion regulation strategies, and dispositional mindfulness. Newborns’ arousal and attention were assessed via the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Path analyses showed that high maternal episodic and daily stress, low economic hardship, few emotion regulation strategies, and high baseline RSA predicted female newborns’ low attention; maternal mindfulness predicted female newborns’ high arousal. As for male newborns, high episodic stress predicted low arousal, and high pregnancy-specific anxiety predicted high attention. Findings suggest that RDoC-informed markers of prenatal stress could aid detection of variance in newborn neurobehavioral outcomes within hours after birth. Implications for intergenerational transmission of risk for psychopathology are discussed.
Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
Platinum-based chemotherapy drugs are associated with substantial ototoxicity. The hearing of children treated with these drugs should be closely monitored.
A questionnaire was sent out to the 19 audiology departments associated with national paediatric cancer specialist centres in the UK looking at current practice in ototoxicity monitoring.
Responses were received from 17 of 19 centres (89 per cent). All offered some form of audiometric monitoring service. Extended high-frequency testing (9–20 kHz) was only utilised by 7 services (29 per cent). A majority of respondents were reluctant to consider self-test devices in paediatric ototoxicity monitoring (n = 9; 53 per cent). Provision of long-term audiological follow up is sporadic with only 4 (23 per cent) respondents keeping all children with normal hearing under review once treatment is completed.
While some good practice in paediatric ototoxicity was identified, opportunities exist to improve clinical practice and protocols, promote multidisciplinary team working and to utilise technologies such as extended high frequency and self-test audiometry.
With the exception of near-occlusion, CEA is of overall benefit for selected patients with recent symptomatic carotid stenosis =50% (NASCET method), provided surgical stroke/death risk is low. The benefit is greater with greater stenosis, men, the elderly (aged =75y), most recent ischaemic event within 2w, irregular plaque surface, and impaired cerebral perfusion reserve. Patients with recent symptomatic carotid territory ischaemic events should be screened by Doppler ultrasonography, MRA, or CTA, confirming substantial stenosis with a second non-invasive investigation. Catheter angiography may be required to confirm uncertain results. The surgical peri-operative stroke and death rate (7% in RCTs) is higher in women, hypertension, peripheral arterial disease, and occlusion of the contralateral ICA or ipsilateral ECA. The experience of the surgeon and hospital are crucial, and audited peri-operative complication rates should be publically available. Carotid stenting is less invasive than CEA and causes fewer local complications (cranial neuropathy and neck haematoma), but carries a higher procedural risk of stroke. Stenting should be considered in younger patients, or those at increased risk from CEA. While stenting is of high risk for intracranial vertebral artery stenosis, risk is low for extracranial stenosis and should be considered for recurrent symptoms despite optimal medical therapy.
Intracerebral haemorrhage and subarachnoid haemorrhage are associated with considerable morbidity and mortality. Too often the focus is on acute treatment after a haemorrhage has occurred, instead of primary and secondary prevention. Medical therapies to control hypertension, achieve tobacco abstinence, and avoid excessive alcohol consumption can confer broad reductions in haemorrhage risk across pathophysiological subtypes. Judicious restriction of antiplatelet and anticoagulant therapies to only those individuals and those intensities for which they are indicated also can substantially reduce haemorrhagic stroke frequency. Specific endovascular and surgical therapies, judiciously employed, will further reduce risk of first or recurrent haemorrhage from structural vascular anomalies, including arteriovenous malformation, cavernous malformations, and saccular aneurysms. For unruptured intracranial aneurysms, features that favour consideration of preventive occlusion include include younger patient age, prior subarachnoid haemorrhage from a different aneurysm, familial intracranial aneurysms, large aneurysm size, irregular shape, basilar or vertebral artery location, and aneurysm growth on serial imaging. Among individuals who are technical candidates for either coiling or clipping, endovascular coiling is associated with a reduction in procedural morbidity and mortality but has a higher risk of recurrence.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
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.
Before his incoherent response to the COVID-19 pandemic, the focus of President Trump's health policy agenda was the elimination of the Patient Protection and Affordable Care Act (ACA), which he has called a ‘disaster’. The attacks on the ACA included proposals to repeal the law through the legislative process, to erode it through a series of executive actions, and to ask the courts to declare it unconstitutional. Despite these ongoing challenges, the ACA remains largely intact as the U.S. heads into the 2020 election. The longer term fate of the law, however, is uncertain and the outcome of the 2020 election is likely to have a dramatic effect on the direction of health policy in the U.S.
Gender is a highly salient and important social group that shapes how children interact with others and how they are treated by others. In this Element, we offer an overview and review of the research on gender development in childhood from a developmental science perspective. We first define gender and the related concepts of sex and gender identity. Second, we discuss how variations in cultural context shape gender development around the world and how variations within gender groups add to the complexity of gender identity development. Third, we discuss major theoretical perspectives in developmental science for studying child gender. Fourth, we examine differences and similarities between girls and boys using the latest meta-analytic evidence. Fifth, we discuss the development of gender, gender identity, and gender socialization throughout infancy, early childhood, and middle childhood. We conclude with a discussion of future directions for the study of gender development in childhood.
The medical savings account model of health insurance in the United States combines a high-deductible health insurance plan‹ A high-deductible health plan is an insurance plan under which the beneficiary is responsible for a substantial amount of expense (the deductible) before the insurer begins paying benefits. US federal law as of 2015 requires a deductible of at least US$1300 for single coverage and US$2600 for family coverage for health saving account-qualified high-deductible health plans ().› with a dedicated savings account used to pay expenses incurred below the deductible. Savings in the plan can roll over from one year to the next and, after some predefined period during which they are dedicated to health spending, can be used for non-health-related expenses.‹ Use of savings for non-health expenses before this predefined period (age 65 under current law), incurs a tax and 20% penalty.› In principle, this model combines the incentives for frugal use of health services that exist in high-deductible health insurance with assurance that the funds required in the event of true medical need will be available.
Life can be a tale of woe so people contrive arrangements that insulate them from the consequences of some familiar feared mishaps. Insurance – a small present payment in promise of larger compensation in the event of future losses – is one such arrangement. Insurance contracts recompense policy-holders for, for instance, loss of or damage to their home in a fire or their car in an accident, or the death of a benefactor who took out life insurance. People may also buy insurance that will cover some (maybe most) of their medical costs if they or members of their family fall ill and need care.
Insights into the dynamics of electrochemical processes are critically needed to improve our fundamental understanding of electron, charge, and mass transfer mechanisms and reaction kinetics that influence a broad range of applications, from the functionality of electrical energy-storage and conversion devices (e.g., batteries, fuel cells, and supercapacitors), to materials degradation issues (e.g., corrosion and oxidation), and materials synthesis (e.g., electrodeposition). To unravel these processes, in situ electrochemical scanning/transmission electron microscopy (ec-S/TEM) was developed to permit detailed site-specific characterization of evolving electrochemical processes that occur at electrode–electrolyte interfaces in their native electrolyte environment, in real time and at high-spatial resolution. This approach utilizes “closed-form” microfabricated electrochemical cells that couple the capability for quantitative electrochemical measurements with high spatial and temporal resolution imaging, spectroscopy, and diffraction. In this article, we review the state-of-the-art instrumentation for in situ ec-S/TEM and how this approach has resulted in new observations of electrochemical processes.
Glyphosate is an important component of herbicide programs in orchard crops in California. It can be applied alone or in tank-mix combinations under the crop rows or to the entire field and often is used multiple times each year. There has been speculation about the potential impacts of repeated use of glyphosate in perennial crop systems, because of uptake from shallow root systems or indirectly because of effects on nutrient availability in soil. To address these concerns, research was conducted from 2013 to 2020 on key orchard crops to evaluate tree response to glyphosate regimens. Almond, cherry, and prune were evaluated in separate experiments. In each crop, the experimental design was a factorial arrangement of two soil types, four glyphosate rates (0, 1.1, 2.2, and 4.4 kg ae ha−1, applied three times annually), and two post-glyphosate application irrigation treatments. In the first 2 yr of the study, there was no clear impact of the glyphosate regimens on shikimate accumulation or leaf chlorophyll content, which suggested no direct effect on the crop. In the seventh year of the study, after six consecutive years of glyphosate application to the orchard floors, there were no negative impacts of glyphosate application on leaf nutrient concentration or on cumulative trunk growth in any of the three orchard crops. Lack of a negative growth impact even at the highest treatment rate, which included 18 applications of glyphosate totaling nearly 80 kg ae ha−1 glyphosate over the course of the experiment suggest there is not likely a significant risk to tree health of judicious use of the herbicide in these production systems. Given the economic importance of orchard crops in California, and grower and industry concerns about pesticides generally and specifically about glyphosate, these findings are timely contributions to weed management concerns in perennial specialty crops.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.