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.
The perinatal period is a vulnerable time for the development of psychopathology, particularly mood and anxiety disorders. In the study of maternal anxiety, important questions remain regarding the association between maternal anxiety symptoms and subsequent child outcomes. This study examined the association between depressive and anxiety symptoms, namely social anxiety, panic, and agoraphobia disorder symptoms during the perinatal period and maternal perception of child behavior, specifically different facets of development and temperament. Participants (N = 104) were recruited during pregnancy from a community sample. Participants completed clinician-administered and self-report measures of depressive and anxiety symptoms during the third trimester of pregnancy and at 16 months postpartum; child behavior and temperament outcomes were assessed at 16 months postpartum. Child development areas included gross and fine motor skills, language and problem-solving abilities, and personal/social skills. Child temperament domains included surgency, negative affectivity, and effortful control. Hierarchical multiple regression analyses demonstrated that elevated prenatal social anxiety symptoms significantly predicted more negative maternal report of child behavior across most measured domains. Elevated prenatal social anxiety and panic symptoms predicted more negative maternal report of child effortful control. Depressive and agoraphobia symptoms were not significant predictors of child outcomes. Elevated anxiety symptoms appear to have a distinct association with maternal report of child development and temperament. Considering the relative influence of anxiety symptoms, particularly social anxiety, on maternal report of child behavior and temperament can help to identify potential difficulties early on in mother–child interactions as well as inform interventions for women and their families.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Introduction: Prehospital field trauma triage (FTT) standards were reviewed and revised in 2014 based on the recommendations of the Centers for Disease Control and Prevention. The FTT standard allows a hospital bypass and direct transport, within 30 min, to a lead trauma hospital (LTH). Our objectives were to assess the impact of the newly introduced prehospital FTT standard and to describe the emergency department (ED) management and outcomes of patients that had bypassed closer hospitals. Methods: We conducted a 12-month multi-centred health record review of paramedic and ED records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness (physiologic), step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as urgent that met FTT standard, regardless of transport time. We developed and piloted a data collection tool and obtained consensus on all definitions. The primary outcome was the rate of appropriate triage to a LTH which was defined as: ISS ≥12, admitted to intensive care unit (ICU), non-orthopedic surgery, or death. We have reported descriptive statistics. Results: 570 patients were included: mean age 48.8, male 68.9%, falls 29.6%, motor vehicle collisions 20.2%, stab wounds 10.5%, transported to a LTH 76.5% (n = 436). 72.2% (n = 315) of patients transported to a LTH had bypassed a closer hospital and 126/306 (41.2%) of those were determined to be an appropriate triage to LTH (9 patients had missing outcomes). ED management included: CT head/cervical spine 69.9%, ultrasound 53.6%, xray 51.6%, intubation 15.0%, sedation 11.1%, tranexamic acid 9.8%, blood transfusion 8.2%, fracture reduction 6.9%, tube thoracostomy 5.9%. Outcomes included: ISS ≥ 12 32.7%, admitted to ICU 15.0%, non-orthopedic surgery 11.1%, death 8.8%. Others included: admission to hospital 57.5%, mean LOS 12.8 days, orthopedic surgery 16.3% and discharged from ED 37.3%. Conclusion: Despite a high number of admissions, the majority of trauma patients bypassed to a LTH were considered over-triaged, with a low number of ED procedures and non-orthopedic surgeries. Continued work is needed to appropriately identify patients requiring transport to a LTH.
Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.
It has been hypothesized that the first five years after first episode of psychosis constitutes a critical period in with opportunities for ameliorating the course of illness. Based on this rationale, specialized assertive early intervention services were developed. We wanted to investigate the evidence basis for such interventions.
The evidence for the effectiveness of specialized assertive early intervention services is mainly based on one large randomized clinical trial, the OPUS trial, but it is supported by the findings in smaller trials such as the Lambeth Early Onset (LEO) trial, the Croydon Outreach and Assertive Support Team COAST trial and the Norwegian site of Optimal Treatment (OTP) trial. There are positive effects on psychotic and negative symptoms, on substance abuse and user satisfaction, but the clinical effects are not sustainable when patients are transferred back to standard treatment. However the positive effects on service use and ability to live independently seem to be durable.
Implementation of specialized assertive early intervention services is recommended, but the evidence basis needs to be strengthened through replication in large high quality trials. Recommendation regarding the duration of treatment must await results of ongoing trials comparing two years of intervention with extended treatment periods.
Introduction: Trauma and injury play a significant role in the population's burden of disease. Limited research exists evaluating the role of trauma bypass protocols. The objective of this study was to assess the impact and effectiveness of a newly introduced prehospital field trauma triage (FTT) standard, allowing paramedics to bypass a closer hospital and directly transport to a trauma centre (TC) provided transport times were within 30 minutes. Methods: We conducted a 12-month multi-centred health record review of paramedic call reports and emergency department health records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness, step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as an urgent transport to hospital, that met one of the 4 steps of the FTT standard and would allow for a bypass consideration. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions. The primary outcome was the rate of appropriate triage to a TC, defined as any of the following: injury severity score ≥12, admitted to an intensive care unit, underwent non-orthopedic operation, or death. We report descriptive and univariate analysis where appropriate. Results: 570 adult patients were included with the following characteristics: mean age 48.8, male 68.9%, attended by Advanced Care Paramedic 71.8%, mechanisms of injury: MVC 20.2%, falls 29.6%, stab wounds 10.5%, median initial GCS 14, mean initial BP 132, prehospital fluid administered 26.8%, prehospital intubation 3.5%, transported to a TC 74.6%. Of those transported to a TC, 308 (72.5%) had bypassed a closer hospital prior to TC arrival. Of those that bypassed a closer hospital, 136 (44.2%) were determined to be “appropriate triage to TC”. Bypassed patients more often met the step 1 or step 2 of the standard (186, 66.9%) compared to the step 3 or step 4 (122, 39.6%). An appropriate triage to TC occurred in 104 (55.9%) patients who had met step 1 or 2 and 32 (26.2%) patients meeting step 3 or 4 of the FTT standard. Conclusion: The FTT standard can identify patients who should be bypassed and transported to a TC. However, this is at a cost of potentially burdening the system with poor sensitivity. More work is needed to develop a FTT standard that will assist paramedics in appropriately identifying patients who require a trauma centre.
Introduction: Early recognition of sepsis can improve patient outcomes yet recognition by paramedics is poor and research evaluating the use of prehospital screening tools is limited. Our objective was to evaluate the predictive validity of the Regional Paramedic Program for Eastern Ontario (RPPEO) prehospital sepsis notification tool to identify patients with sepsis and to describe and compare the characteristics of patients with an emergency department (ED) diagnosis of sepsis that are transported by paramedics. The RPPEO prehospital sepsis notification tool is comprised of 3 criteria: current infection, fever &/or history of fever and 2 or more signs of hypoperfusion (eg. SBP<90, HR 100, RR24, altered LOA). Methods: We performed a review of ambulance call records and in-hospital records over two 5-month periods between November 2014 February 2016. We enrolled a convenience sample of patients, assessed by primary and advanced care paramedics (ACPs), with a documented history of fever &/or documented fever of 38.3°C (101°F) that were transported to hospital. In-hospital management and outcomes were obtained and descriptive, t-tests, and chi-square analyses performed where appropriate. The RPPEO prehospital sepsis notification tool was compared to an ED diagnosis of sepsis. The predictive validity of the RPPEO tool was calculated (sensitivity, specificity, NPV, PPV). Results: 236 adult patients met the inclusion criteria with the following characteristics: mean age 65.2 yrs [range 18-101], male 48.7%, history of sepsis 2.1%, on antibiotics 23.3%, lowest mean systolic BP 125.9, treated by ACP 58.9%, prehospital temperature documented 32.6%. 34 (14.4%) had an ED diagnosis of sepsis. Patients with an ED diagnosis of sepsis, compared to those that did not, had a lower prehospital systolic BP (114.9 vs 127.8, p=0.003) and were more likely to have a prehospital shock index >1 (50.0% vs 21.4%, p=0.001). 44 (18.6%) patients met the RPPEO sepsis notification tool and of these, 27.3% (12/44) had an ED diagnosis of sepsis. We calculated the following predictive values of the RPPEO tool: sensitivity 35.3%, specificity 84.2%, NPV 88.5%, PPV 27.3%. Conclusion: The RPPEO prehospital sepsis notification tool demonstrated modest diagnostic accuracy. Further research is needed to improve accuracy and evaluate the impact on patient outcomes.
Segregation of polydisperse granular materials occurs in many natural and industrial settings, but general theoretical modelling approaches with predictive power have been lacking. Here we describe a model capable of accurately predicting segregation for both discrete and continuous particle size distributions based on a generalized expression for the percolation velocity. The predictions of the model depend on the kinematics of the flow and other physical parameters such as the diffusion coefficient and the percolation length scale, quantities that can be determined directly from experiment, simulation or theory and that are not arbitrarily adjustable. The model is applied to heap and chute flow, and the resulting predictions are consistent with experimentally validated discrete element method (DEM) simulations. Several different continuous particle size distributions are considered to demonstrate the broad applicability of the approach.
Expert judgement has been used since the actuarial profession was founded. In the past, there has often been a lack of transparency regarding the use of expert judgement, even though those judgements could have a very significant impact on the outputs of calculations and the decisions made by organisations. The lack of transparency has a number of dimensions, including the nature of the underlying judgements, as well as the process used to derive those judgements. This paper aims to provide a practical framework regarding expert judgement processes, and how those processes may be validated. It includes a worked example illustrating how the process could be used for setting a particular assumption. It concludes with some suggested tools for use within expert judgement. Although primarily focussed on the insurance sector, the proposed process framework could be applied more widely without the need for significant changes.
Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.
Repeated epidemiological surveys show no decline in depression although uptake of treatments has grown. Universal depression prevention interventions are effective in schools but untested rigorously in adulthood. Selective prevention programmes have poor uptake. Universal interventions may be more acceptable during routine healthcare contacts for example antenatally. One study within routine postnatal healthcare suggested risk of postnatal depression could be reduced in non-depressed women from 11% to 8% by giving health visitors psychological intervention training. Feasibility and effectiveness in other settings, most notably antenatally, is unknown.
We conducted an external pilot study using a cluster trial design consisting of recruitment and enhanced psychological training of randomly selected clusters of community midwives (CMWs), recruitment of pregnant women of all levels of risk of depression, collection of baseline and outcome data prior to childbirth, allowing time for women ‘at increased risk’ to complete CMW-provided psychological support sessions.
Seventy-nine percent of eligible women approached agreed to take part. Two hundred and ninety-eight women in eight clusters participated and 186 termed ‘at low risk’ for depression, based on an Edinburgh Perinatal Depression Scale (EPDS) score of <12 at 12 weeks gestation, provided baseline and outcome data at 34 weeks gestation. All trial protocol procedures were shown to be feasible. Antenatal effect sizes in women ‘at low risk’ were similar to those previously demonstrated postnatally. Qualitative work confirmed the acceptability of the approach to CMWs and intervention group women.
A fully powered trial testing universal prevention of depression in pregnancy is feasible, acceptable and worth undertaking.
We investigated an outbreak of 396 Salmonella enterica serotype I 4,5,12:i:- infections to determine the source. After 7 weeks of extensive hypothesis-generation interviews, no refined hypothesis was formed. Nevertheless, a case-control study was initiated. Subsequently, an iterative hypothesis-generation approach used by a single interviewing team identified brand A not-ready-to-eat frozen pot pies as a likely vehicle. The case-control study, modified to assess this new hypothesis, along with product testing indicated that the turkey variety of pot pies was responsible. Review of product labels identified inconsistent language regarding preparation, and the cooking instructions included undefined microwave wattage categories. Surveys found that most patients did not follow the product's cooking instructions and did not know their oven's wattage. The manufacturer voluntarily recalled pot pies and improved the product's cooking instructions. This investigation highlights the value of careful hypothesis-generation and the risks posed by frozen not-ready-to-eat microwavable foods.
Atherosclerosis is the underlying cause of cardiovascular disease and stroke. Endothelial cell dysfunctions are early events in atherosclerosis, resulting in the recruitment of circulating monocytes. The immune system can elicit an inflammatory response toward the atherosclerotic lesion, thereby accelerating lesion growth. Risk factors for atherosclerosis include hypertension, smoking, stress perception or low birth weight. As prenatal stress challenge decreases the birth weight and affects the offspring's postnatal immune response, we aimed to investigate whether prenatal stress contributes to the development of atherosclerosis in mice. Syngenic pregnant apolipoprotein E-deficient (apoE−/−) dams were exposed to sound stress on gestation days 12.5 and 14.5. The presence and size of atherosclerotic plaques in the offspring at the age of 15 weeks was evaluated by histomorphology, accompanied by flow cytometric analysis of the frequency and phenotype of monocytes/macrophages and regulatory T (Treg) cells in the blood. Further, cytokine secretion of peripheral blood lymphocytes was analyzed. In response to prenatal stress challenge, an increased frequency of large atherosclerotic plaques was detectable in apoE−/− offspring, which was particularly profound in females. Prenatal stress also resulted in alterations of the offspring's immune response, such as a decreased frequency of Treg cells in blood, alterations of macrophage populations in blood and an increased secretion of inflammatory cytokines. We provide novel evidence that prenatally stressed adult offspring show an increased severity of atherosclerosis. As Treg cells are key players in dampening inflammation, the observed increase in atherosclerosis may be due to the lack of Treg cell frequency. Future interdisciplinary research is urgently required to understand the developmental origin of prenatal stress-induced atherosclerosis. The availability of our model may facilitate and foster such research endeavors.
Under- and over-nutrition during gestation may influence fetal hypothalamic development resulting in individuals predisposed to adverse health effects. This study examined fetuses from obese and control ewes to determine whether dam obesity alters hypothalamic expression of fetal appetite regulatory genes. A second objective was to contrast the expression of appetite regulatory genes in ewes that become the most obese to those that remained in moderate body condition on the same energy-rich diet. Multiparous, western white-faced ewes were weighed and individually fed 100% (control) or 150% (obese) of National Research Council requirements from day 60 before mating until day 75 of gestation. At day 75 of gestation, fetuses were collected and weighed. Hypothalamic tissue from fetal lambs and dams was collected and frozen for mRNA extraction. Dam obesity (P ⩾ 0.16), fetal sex (P ⩾ 0.44) or their interaction (P ⩾ 0.42) did not affect the relative expression of fetal hypothalamic regulators of appetite, including neuropeptide Y, agouti-related protein, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript and receptors for leptin. Maternal obesity at day 75 of gestation in ewes did not affect developmental mechanisms responsible for the expression of fetal appetite regulatory genes and would not be expected to predispose offspring to adult-onset obesity through disrupted appetite regulation at this developmental time point. In the ewe, appetite regulatory genes did not differ (P > 0.20) with ewe adiposity; however, expression of estrogen receptor α, but not β (P = 0.37), in the medial basal hypothalamus was greater (P = 0.04) in obese than in control ewes.
Human genomic structural variation (SV) is significant factor in genome complexity, and thus has substantial implications to the cause, development and progression of genetic diseases. These SVs, ranging in size of 1kbp-1Mbp, are challenging to assess with current technologies. As such, we have developed a commercial system (nanoAnalyzer® 1000) for the rapid linear analysis of genomes at single-molecule level.
The core of our system is a nanofluidic chip consisting of an array of channels with a diameter less than 100 nm, nanofabricated on the surface of a silicon substrate. Thousands of unamplified genomic DNA molecules of 100’s kbps to several Mbps can be isolated and linearly streamed into the array for analysis in a parallel fashion. Fluorescently labeled sequence-specific signatures can then be identified and aligned to reference patterns at high resolution with custom software. This automated, multi-color imaging platform will enable a wide range of applications, such as accurate sequencing assembly, discovering genome structural variations, and uncovering epigenomic content. Nanochannel arrays promise to substantially lower the barriers of entry for single-molecule DNA analysis for scientists and clinicians, greatly impacting the advancement of molecular diagnostics, personalized medicine, and biomedical research.