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Maternal obesity may affect foetal programming representing a risk for adult mental health. Oxidative stress and inflammation associated with maternal obesity can alter the maturation of neuronal circuits affecting behaviour and mood.
We investigated the emotional phenotype of male and female mouse offspring born from a high-fat diet (HFD) fed dams. We also tested the efficacy of N-acetyl-cysteine (NAC – an antioxidant) in preventing the negative effects of HFD. We focused on adolescence, an age of main vulnerability for the onset of psychopathology.
Female C57BL/6N mice were fed HFD for 13 weeks and, after 5 weeks, were also exposed to NAC (1 g/kg b.w.) via drinking water, until delivery. The neurodevelopment of offspring was assessed through the homing test. Emotionality was assessed in 35-45-day-old adolescent mice through elevated-plus-maze (EPM) and social interaction tests (SIT). Transcriptomic analysis of hippocampal tissue were performed to identify mechanisms of action of both HFD and NAC.
NAC was effective in moderating body weight gain in HFD-fed dams. Neither HFD or NAC affected offspring development. Regardless of sex, prenatal HFD reduced exploration and decreased sociability, in EPM and SIT respectively. Prenatal HFD decreased hippocampal levels of BDNF in female offspring. Prenatal NAC administration prevented social anxiety and restored BDNF levels in the HFD group.
Data indicate long-term effects of maternal obesity on dams’ weight, offspring’s behaviour and hippocampal BDNF levels. These effects may be mediated by changes in oxidative stress as NAC was effective as a preventive agent. ERANET-NEURON-JTC 2018 (Mental Disorders) Project “EMBED”.
IFRS 17 Insurance Contracts is a new accounting standard currently expected to come into force on 1 January 2023. It supersedes IFRS 4 Insurance Contracts. IFRS 17 establishes key principles that entities must apply in all aspects of the accounting of insurance contracts. In doing so, the Standard aims to increase the usefulness, comparability, transparency and quality of financial statements.
A fundamental concept introduced by IFRS 17 is the contractual service margin (CSM). This represents the unearned profit that an entity expects to earn as it provides services. However, as a principles-based standard, IFRS 17 results in entities having to apply significant judgement when determining the inputs, assumptions and techniques it uses to determine the CSM at each reporting period.
In general, the Standard resolves broad categories of mismatches which arise under IFRS 4. Notable examples include mismatches between assets recorded at current market value and liabilities calculated using fixed discount rates as well as inconsistencies in the timing of profit recognition over the duration of an insurance contract. However, there are requirements of IFRS 17 that may create economic or accounting mismatches of its own. For example, new mismatches could arise between the measurement of underlying contracts and the corresponding reinsurance held. Additionally, mismatches can still arise between the measurement of liabilities and the assets that support the liabilities.
This paper explores the technical, operational and commercial issues that arise across these and other areas focusing on the CSM. As a standard that is still very much in its infancy, and for which wider consensus on topics is yet to be achieved, this paper aims to provide readers with a deeper understanding of the issues and opportunities that accompany it.
This review collates the published reports that focus on microbial and viral illnesses that can be transmitted by breast milk, donor milk and powdered infant formula (PIF). In this context, we attempt to define a risk framework encompassing those hazards, exposure scenarios, vulnerability and protective factors.
A literature search was performed for reported cases of morbidity and mortality associated with different infant feeding modes.
Exclusive breast-feeding is the recommended for infant feeding under 6 months, or failing that, provision of donated human milk. However, the use of PIF remains high despite its intrinsic and extrinsic risk of microbial contamination, as well as the potential for adverse physiological effects, including infant gut dysbiosis.
Viable pathogen transmission via breast-feeding or donor milk (pasteurised and unpasteurised) is rare. However, transmission of HIV and human T-cell lymphotropic virus-1 is a concern for breast-feeding mothers, particularly for mothers undertaking a mixed feeding mode (PIF and breast-feeding). In PIF, intrinsic and extrinsic microbial contamination, such as Cronobacter and Salmonella, remain significant identifiable causes of infant morbidity and mortality.
Disease transmission through breast-feeding or donor human milk is rare, most likely owing to its complex intrinsically protective composition of human milk and protection of the infant gut lining. Contamination of PIF and the morbidity associated with this is likely underappreciated in terms of community risk. A better system of safe donor milk sharing that also establishes security of supply for non-hospitalised healthy infants in need of breast milk would reduce the reliance on PIF.
Although the science of team science is no longer a new field, the measurement of team science and its standardization remain in relatively early stages of development. To describe the current state of team science assessment, we conducted an integrative review of measures of research collaboration quality and outcomes.
Collaboration measures were identified using both a literature review based on specific keywords and an environmental scan. Raters abstracted details about the measures using a standard tool. Measures related to collaborations with clinical care, education, and program delivery were excluded from this review.
We identified 44 measures of research collaboration quality, which included 35 measures with reliability and some form of statistical validity reported. Most scales focused on group dynamics. We identified 89 measures of research collaboration outcomes; 16 had reliability and 15 had a validity statistic. Outcome measures often only included simple counts of products; publications rarely defined how counts were delimited, obtained, or assessed for reliability. Most measures were tested in only one venue.
Although models of collaboration have been developed, in general, strong, reliable, and valid measurements of such collaborations have not been conducted or accepted into practice. This limitation makes it difficult to compare the characteristics and impacts of research teams across studies or to identify the most important areas for intervention. To advance the science of team science, we provide recommendations regarding the development and psychometric testing of measures of collaboration quality and outcomes that can be replicated and broadly applied across studies.
Polar subglacial hydrologic systems have garnered much interest since the recognition of Lake Vostok in 1996. In Antarctica, these environments are hydrologically diverse, including isolated lakes of different sizes, river–lake flow-through systems, “swamps” and groundwater (Siegert 2016). The refreezing of subglacial meltwater is also an important process beneath a large portion of the East Antarctic Ice Sheet (Bell et al. 2011). As subglacial water refreezes it exsolves salts, potentially leaving behind saline and hypersaline brines. Brines thought to derive from this cryoconcentration process have been observed in the northern polar permafrost regions and in the McMurdo Dry Valleys (MDVs) region of Antarctica. Additionally, sediments in the Victoria Land Basin have diagenetic signatures produced by brine movement dating from 3–11 m.y.a, suggesting hypersaline brines have existed in the McMurdo region since at least this time (Staudigel et al. 2018).
We sought to address the prior limitations of symptom checker accuracy by analysing the diagnostic and triage feasibility of online symptom checkers using a consecutive series of real-life emergency department (ED) patient encounters, and addressing a complex patient population – those with hepatitis C or HIV. We aimed to study the diagnostic and triage accuracy of these symptom checkers in relation to an emergency room physician-determined diagnosis. An ED retrospective analysis was performed on 8363 consecutive adult patients. Eligible patients included: 90 HIV, 67 hepatitis C, 11 both HIV and hepatitis C. Five online symptom checkers were utilised for diagnosis (Mayo Clinic, WebMD, Symptomate, Symcat, Isabel), three with triage capabilities. Symptom checker output was compared with ED physician-determined diagnosis data in regards to diagnostic accuracy and differential diagnosis listing, along with triage advice. All symptom checkers, whether for combined HIV and hepatitis C, HIV alone or hepatitis C alone had poor diagnostic accuracy in regards to Top1 (<20%), Top3 (<35%), Top10 (<40%), Listed at All (<45%). Significant variations existed for each individual symptom checker, as some appeared more accurate for listing the diagnosis in the top of the differential, vs. others more apt to list the diagnosis at all. In regards to ED triage data, a significantly higher percentage of hepatitis C patients (59.7%; 40/67) were found to have an initial diagnosis with emergent criteria than HIV patients (35.6%; 32/90). Symptom checker diagnostic capabilities are quite inferior to physician diagnostic capabilities. Complex patients such as those with HIV or hepatitis C may carry a more specific differential diagnosis, warranting symptom checkers to have diagnostic algorithms accounting for such complexity. Symptom checkers carry the potential for real-time epidemiologic monitoring of patient symptoms, as symptom entries and subsequent symptom checker diagnosis could allow health officials a means to track illnesses in specific patient populations and geographic regions. In order to do this, accurate and reliable symptom checkers are warranted.
Although food from grazed animals is increasingly sought by consumers because of perceived animal welfare advantages, grazing systems provide the farmer and the animal with unique challenges. The system is dependent almost daily on the climate for feed supply, with the importation of large amounts of feed from off farm, and associated labour and mechanisation costs, sometimes reducing economic viability. Furthermore, the cow may have to walk long distances and be able to harvest feed efficiently in a highly competitive environment because of the need for high levels of pasture utilisation. She must, also, be: (1) highly fertile, with a requirement for pregnancy within ~80 days post-calving; (2) ‘easy care’, because of the need for the management of large herds with limited labour; (3) able to walk long distances; and (4) robust to changes in feed supply and quality, so that short-term nutritional insults do not unduly influence her production and reproduction cycles. These are very different and are in addition to demands placed on cows in housed systems offered pre-made mixed rations. Furthermore, additional demands in environmental sustainability and animal welfare, in conjunction with the need for greater system-level biological efficiency (i.e. ‘sustainable intensification’), will add to the ‘robustness’ requirements of cows in the future. Increasingly, there is evidence that certain genotypes of cows perform better or worse in grazing systems, indicating a genotype×environment interaction. This has led to the development of tailored breeding objectives within countries for important heritable traits to maximise the profitability and sustainability of their production system. To date, these breeding objectives have focussed on the more easily measured traits and those of highest relative economic importance. In the future, there will be greater emphasis on more difficult to measure traits that are important to the quality of life of the animal in each production system and to reduce the system’s environmental footprint.
Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research (CSER) Consortium. The authors then negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death.
A range of precision farming technologies are used commercially for variable rate applications of nitrogen (N) for cereals, yet these usually adjust N rates from a pre-set value, rather than predicting economically optimal N requirements on an absolute basis. This paper reports chessboard experiments set up to examine variation in N requirements, and to develop and test systems for its prediction, and to assess its predictability. Results showed very substantial variability in fertiliser N requirements within fields, typically >150 kg ha−1, and large variation in optimal yields, typically >2 t ha−1. Despite this, calculated increases in yield and gross margin with N requirements perfectly matched across fields were surprisingly modest (compared to the uniform average rate). Implications are discussed, including the causes of the large remaining variation in grain yield, after N limitations were removed.
To characterize the multiple dimensions and benefits of the Mediterranean diet as a sustainable diet, in order to revitalize this intangible food heritage at the country level; and to develop a multidimensional framework – the Med Diet 4.0 – in which four sustainability benefits of the Mediterranean diet are presented in parallel: major health and nutrition benefits, low environmental impacts and richness in biodiversity, high sociocultural food values, and positive local economic returns.
A narrative review was applied at the country level to highlight the multiple sustainable benefits of the Mediterranean diet into a single multidimensional framework: the Med Diet 4.0.
We included studies published in English in peer-reviewed journals that contained data on the characterization of sustainable diets and of the Mediterranean diet. The methodological framework approach was finalized through a series of meetings, workshops and conferences where the framework was presented, discussed and ultimately refined.
The Med Diet 4.0 provides a conceptual multidimensional framework to characterize the Mediterranean diet as a sustainable diet model, by applying principles of sustainability to the Mediterranean diet.
By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.
Thornicroft's giraffe Giraffa camelopardalis thornicrofti is limited in distribution to a single population resident in the Luangwa Valley, Zambia. During 1973−2003 regular counts were recorded along the Luangwa River in the core section of the subspecies’ range. In 2013 we conducted a count in the same region for comparison with the earlier survey results. During the 30-year period 1973−2003 the giraffe index (no. of individuals per km surveyed) was relatively stable, with an increase in 1994 and 1995 coinciding with an influx of giraffes to the west bank following an exceptionally reduced flow of the Luangwa River. The mean giraffe index during this period was 0.51 km−1, whereas the 2013 count yielded an index of 0.44 km−1. Given the limited range of the Thornicroft's giraffe, we estimate that the population comprises c. 500–600 individuals.
A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7–27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29–23·4) and 5·65 (95% CI 1·09–29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.
The debate about how to manage individual research results and incidental findings in genetic and genomic research has focused primarily on what information, if any, to offer back to research participants. However, increasing controversy surrounds the question of whether researchers have any responsibility to offer a participant’s results (defined here to include both individual research results and incidental findings) to the participant’s relatives, including after the participant’s death. This question arises in multiple contexts, including when researchers discover a result with potentially important health implications for genetic relatives, when a participant’s relatives ask a researcher whether any research results about the participant have implications for their own health or reproductive planning, when a participant’s relative asks whether any of the participant’s results have implications for a child’s health, and when the participant is deceased and the participant’s relatives seek information about the participant’s genetic results in order to address their own health or reproductive concerns.
In vitro fertilization (IVF) using donated oocytes has proven to be an effective treatment option for many prospective parents struggling with infertility, and the usage of donated oocytes in assisted reproduction has increased markedly since the technique was first successfully used in 1984. Data published by the Centers for Disease Control and Prevention (CDC) on the use of assisted reproductive technologies (ARTs) in the United States indicate that approximately 12% of all ART cycles in the country now use donated oocytes. The increased use of oocyte donation in the United States has prompted discussion regarding risks associated with the process and how best to ensure the safety of oocyte donors.
Physical risks associated with oocyte donation include bleeding, infection, ovarian hyperstimulation syndrome and a potential, although unconfirmed, increased risk of developing various forms of cancer, such as uterine, colon, breast, ovarian, and endometrial cancers.
Small changes in the availability of liquid water can have profound effects on the water levels, aqueous chemistry and biogeochemical dynamics of the closed-basin, perennially ice-covered lakes of the McMurdo Dry Valleys, Antarctica. We have compiled the published and unpublished data on dissolved gas, tritium and chlorofluorocarbons (CFCs) for Lake Fryxell and Lake Hoare to determine the effects of a high meltwater year (2001–02 summer) on the lakes. The dissolved gas, tritium and CFC data indicate that the pulse of freshwater that flowed onto the surfaces of the lakes did not mix extensively with the upper water column. At the bottom of Lake Hoare, the measurable CFC and lower dissolved gas values suggest that the recent meltwater may have mixed with bottom waters. The probable mechanism for this transportation is weak density currents with c. 0.1–1.5% surface water being transported downwards in Lake Hoare. This deep water input, while not constant, may have a significant effect on the chemistry of the bottom waters in Lake Hoare over time. In Lake Fryxell, the tritium and CFC data indicate that the recent meltwater did not significantly affect the bottom water chemistry; therefore, weak density currents may not be present in Lake Fryxell.
Genetic selection for milking speed is feasible. The existence of a correlation structure between milking speed and milk yield, however, necessitates a selection strategy to increase milking speed with no repercussion on genetic merit for milk yield. Residual milking duration (RMD) and residual milking duration including somatic cell score (RMDS), defined as the residuals from a regression model of milking duration on milk yield or milk yield plus somatic cell score (SCS) have been advocated. The objective of this study was to undertake a first ever genetic analysis of these novel traits. Data on electronically recorded milking duration and other milking characteristics from 235 005 test-day records on 74 608 cows in 1075 Irish dairy herds were available. Variance components for the milking characteristic traits were estimated using animal linear mixed models and covariances with other performance traits, including udder-related type traits, were estimated using sire models. The heritability of milking duration, RMD and RMDS was 0.20, 0.22 and 0.18, respectively. There were little differences in the heritability of RMD or RMDS when defined using genetic regression. The genetic standard deviation of RMDS defined on the phenotypic or genetic level was 36.8 s and 37.6 s, respectively, clearly indicating considerable exploitable genetic variation in milking duration independent of both milk yield and SCS. The genetic correlation between phenotypically derived RMDS and milk yield was favourable (−0.43), but RMDS was unfavourably genetically correlated with SCS (−0.30); the genetic correlations with both traits when RMDS was defined at a genetic level were zero. RMDS defined at the phenotypic level was negatively (i.e. unfavourable) genetically correlated (−0.35; s.e. = 0.15) with mastitis; however, when defined using genetic regression, shorter RMDS was not associated with greater expected incidence of mastitis. RMDS, defined at the genetic level, is a useful heritable trait with ample genetic variation for inclusion in a national breeding strategy without influencing genetic gain in either milk yield or udder health.
There is ongoing debate surrounding the roles of surgery and adjuvant radiotherapy in the management of primary and recurrent Merkel cell carcinoma of the head and neck. This study assessed the influence of local excision, margin status, adjuvant radiotherapy and chemotherapy on locoregional recurrence and survival.
A retrospective review of 54 consecutive cases of head and neck Merkel cell carcinoma at a single institution.
Median disease-specific survival time was 120 months. Forty-four per cent of patients developed locoregional recurrence. Combined treatment with surgery and locoregional radiotherapy improved disease-specific survival. Radiotherapy was associated with longer time to recurrence and regional recurrence. Irradiation of the regional nodes improved regional control, irrespective of clinical status. Margin-negative excision was not associated with improved local control. Combined modality treatment of recurrent disease resulted in a four-fold improvement of local control, but small numbers prevented this trend from reaching statistical significance.
Surgical excision of the primary disease and clinically involved regional nodes, plus adjuvant radiotherapy to the surgical bed and regional nodes are recommended for all patients with Merkel cell carcinoma of the head and neck, irrespective of clinical status. Recurrent disease should be aggressively treated with combined modality treatment.
Approximately 10% of all babies worldwide are born preterm, and preterm birth is the leading cause of perinatal mortality in developed countries. Although preterm birth is associated with adverse short- and long-term health outcomes, it is not yet clear whether this relationship is causal. Rather, there is evidence that reduced foetal growth, preterm birth and the long-term health effects of both of these may all arise from a suboptimal intrauterine environment. Further, most infants born preterm also experience suboptimal postnatal growth, with potential adverse effects on long-term health and development. A number of interventions are used widely in the neonatal period to optimise postnatal growth and development. These commonly include supplementation with macronutrients and/or micronutrients, all of which have potential short-term risks and benefits for the preterm infant, whereas the long-term health consequences are largely unknown. Importantly, more rapid postnatal growth trajectory (and the interventions required to achieve this) may result in improved neurological outcomes at the expense of increased cardiovascular risk in later life.
There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.