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Introduction: Optimizing naloxone dosing in the context of increasing fentanyl and ultra-potent opioid (UPO) prevalence is an important consideration for emergency health care providers. The goal of this systematic review was to evaluate the association between initial and cumulative naloxone doses on effective reversal and adverse events in undifferentiated and fentanyl/UPO overdoses. Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings from July to October 2018 and back to 1972. Our search included pertinent indexing terms for UPOs. We included interventional and observational studies reporting on naloxone administration for opioid toxicity reversal in people ≥12 years old. Additionally, we accessed non-traditional evidence sources (case reports and series) given this rapidly changing field. We conducted inclusion screens, data extraction and quality assessments in duplicate. We summarized study characteristics and where reported, analyzed number of patients with clinical response. Response was defined as not receiving further naloxone doses and remaining alive. Results: We included 174 studies (108 case reports and series, 55 observational, 9 interventional) with 26,660 subjects (median age 35.1; 74.2% male). We observed lower response among patients exposed to fentanyl/UPO versus heroin for initial naloxone doses ≤0.4mg (56.8% versus 80.2%) and > 0.4mg (27.0% versus 82.1%). Mean cumulative doses were higher for fentanyl/UPO (2.10 mg, SD 1.80 mg) versus heroin (1.48 mg, SD 1.68 mg) overdoses. In North American studies the median cumulative dose used was higher for fentanyl/UPO versus heroin overdoses. A dose-response curve for fentanyl/UPO studies showed marked variability in doses among responders, indicating heterogeneity. Adverse events reporting was inconsistent; 10% of subjects experienced withdrawal based on studies in which they were reported. Conclusion: This is the first systematic review to summarize proportion of patients with clinical response by naloxone dose provided. While variable reporting, study quality, heterogeneity, and our outcome definitions limit the conclusions we can draw, it appears that higher initial doses and in some cases, higher cumulative naloxone doses were used and may be necessary to reverse toxicity due to fentanyl/UPO compared to other opioids. High-quality prospective studies assessing effectiveness and safety are needed.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.
Decades of fetal programming research indicates that we may be able to map the origins of many physical, psychological, and medical variations and morbidities before the birth of the child. While great strides have been made in identifying associations between prenatal insults, such as undernutrition or psychosocial stress, and negative developmental outcomes, far less is known about how adaptive responses to adversity regulate the developing phenotype to match stressful conditions. As the application of epigenetic methods to human behavior has exploded in the last decade, research has begun to shed light on the role of epigenetic mechanisms in explaining how prenatal conditions shape later susceptibilities to mental and physical health problems. In this review, we describe and attempt to integrate two dominant fetal programming models: the cumulative stress model (a disease-focused approach) and the match–mismatch model (an evolutionary–developmental approach). In conjunction with biological sensitivity to context theory, we employ these two models to generate new hypotheses regarding epigenetic mechanisms through which prenatal and postnatal experiences program child stress reactivity and, in turn, promote development of adaptive versus maladaptive phenotypic outcomes. We conclude by outlining priority questions and future directions for the fetal programming field.
Prenatal exposure to maternal mood disturbances shapes children's cognitive development reflected in the critical construct of executive functions (EFs). Little is known, however, about underlying mechanisms. By examining cortisol responses in both everyday and lab challenge settings, we tested whether the child/offspring hypothalamic–pituitary–adrenal axis mediates effects of prenatal maternal mood on child EFs at age 6. In 107 Canadian children born to women with a wide range of anxious and depressive symptoms during pregnancy, we found that in boys but not girls, depressed and/or anxious prenatal maternal mood is associated with heightened diurnal cortisol levels in everyday settings, as well as heightened cortisol reactivity to a lab challenge and that this heightened reactivity was associated with poorer EFs. Among boys we also observed that cortisol reactivity but not diurnal cortisol mediated the association between depressed and/or anxious prenatal maternal mood and EFs. Depressed and/or anxious prenatal maternal mood was related to child EFs for both girls and boys. To our knowledge, this is the first study to demonstrate a mediating role for child stress regulation in the association between prenatal maternal stress-related mood disturbances and child EFs, providing evidence of a mechanism contributing to fetal programming of cognition.
Currently policies enabling cattle herds to regain Official Tuberculosis Free (OTF) status after a bovine tuberculosis (bTB) herd incident vary between individual parts of the British Isles from requiring only one negative single comparative intradermal tuberculin test (SCITT) herd test when bTB infection is not confirmed to needing two consecutively negative SCITT herd tests after disclosure of two or more reactors, irrespective of bTB confirmation. This study used Kaplan–Meier curves and univariable and multivariable Cox Proportional Hazard models to evaluate the effect of the number of SCITT reactors and bTB confirmation on the risk of future bTB herd incident utilising data extracted from the national animal health database in Northern Ireland. Based on multivariable analyses the risk of a future bTB herd incident was positively associated with the number of SCITT reactors identified during the incident period (hazard ratio = 1.861 in incidents >5 SCITT reactors compared to incidents with only one SCITT reactor; P < 0.001), but not with bTB confirmation. These findings suggest that the probability of residual bTB infection in a herd increases with an increasing number of SCITT reactors disclosed during a bTB herd incident. It was concluded that bTB herd incidents with multiple SCITT reactors should be subjected to stricter control measures irrespective of bTB infection confirmation status.
Background: Acromegaly is associated with significant morbidity. The purpose of this study was to establish characteristics and outcomes of patients treated for acromegaly at The Ottawa Hospital, to compare our results with published reports from other centers and to identify opportunities to improve patient care. Methods: A retrospective chart review of patients surgically and medically treated for acromegaly between January 1, 2007 and December 31, 2016 was completed. Demographic information, biochemical data, presenting features, disease comorbidities, treatment interventions, and were collected. Results: Fifty-one patients were identified using CCI/ICD-10 codes and IGF-1 levels. Similar to other centers, the majority of patients had a macroadenoma (78.4% vs 11.8%) with a high percentage invading the cavernous sinus (57.5%). While surgical intervention was performed in 90% of patients, only 23.3% of patient achieved surgical cure (IGF-1 normalization within reference range). Approximately 30% of patients were controlled with adjuvant medical therapy while more than 40 % had elevated IGF-1 levels at last follow-up. Radiotherapy was less commonly used. Conclusions: Despite a multi-modal treatment approach for acromegaly, outcomes are variable. This study highlights the need for further research to better understand factors associated with surgical cure, response to medical therapy and the role of radiotherapy.
Objectives: Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: <30 weeks/<1250 grams) and term born controls during late childhood. Additionally, early risk factors (neonatal brain abnormalities, medical complications, and sex) were examined in relationship to goal setting outcomes within the VP group. Methods: Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQ<70. Within the VP group, regression models were performed to examine the relationship between brain abnormalities, medical complications, and sex, on goal setting scores. Results: The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13. Conclusions: Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018, 24, 372–381)
Determination of the proportion of bovine tuberculosis (bTB) breakdowns attributed to a herd purchasing infected animals has not been previously quantified using data from the Animal and Public Health Information System (APHIS) database in Northern Ireland. We used a case–control study design to account for the infection process occurring in the disclosing bTB breakdown herds. Cases (N = 6926) were cattle moving to a future confirmed bTB breakdown where they would disclose as a confirmed bTB reactor or a Lesion at Routine Slaughter (LRS). Controls (N = 303 499) were cattle moving to a future confirmed bTB breakdown where they did not become a bTB reactor or LRS. Our study showed that the cattle leaving herds which disclosed bTB within 450 days had an increased odds of becoming a confirmed bTB reactor or LRS compared with the cattle which left herds that remained free for 450 days (odds ratio (OR) = 2·09: 95% CI 1·96–2·22). Of the 12 060 confirmed bTB breakdowns included in our study (2007–2015 inclusive), 31% (95% CI 29·8–31·5) contained a confirmed bTB reactor(s) or LRS(s) at the disclosing test which entered the herd within the previous 450 days. After controlling for the infection process occurring in the disclosing bTB breakdown herd, our study showed that 6·4% (95% CI 5·9–6·8) of bTB breakdowns in Northern Ireland were directly attributable to the movement of infected animals.
Objectives: Studies suggest that impairments in some of the same domains of cognition occur in different neuropsychiatric conditions, including those known to share genetic liability. Yet, direct, multi-disorder cognitive comparisons are limited, and it remains unclear whether overlapping deficits are due to comorbidity. We aimed to extend the literature by examining cognition across different neuropsychiatric conditions and addressing comorbidity. Methods: Subjects were 486 youth consecutively referred for neuropsychiatric evaluation and enrolled in the Longitudinal Study of Genetic Influences on Cognition. First, we assessed general ability, reaction time variability (RTV), and aspects of executive functions (EFs) in youth with non-comorbid forms of attention-deficit/hyperactivity disorder (ADHD), mood disorders and autism spectrum disorder (ASD), as well as in youth with psychosis. Second, we determined the impact of comorbid ADHD on cognition in youth with ASD and mood disorders. Results: For EFs (working memory, inhibition, and shifting/ flexibility), we observed weaknesses in all diagnostic groups when participants’ own ability was the referent. Decrements were subtle in relation to published normative data. For RTV, weaknesses emerged in youth with ADHD and mood disorders, but trend-level results could not rule out decrements in other conditions. Comorbidity with ADHD did not impact the pattern of weaknesses for youth with ASD or mood disorders but increased the magnitude of the decrement in those with mood disorders. Conclusions: Youth with ADHD, mood disorders, ASD, and psychosis show EF weaknesses that are not due to comorbidity. Whether such cognitive difficulties reflect genetic liability shared among these conditions requires further study. (JINS, 2018, 24, 91–103)
We examine time series of the transition region spectral line O v 629 Å, observed with the Coronal Diagnostic Spectrometer (CDS) onboard the SoHO spacecraft. Primarily we were looking for intensity and velocity oscillations in polar plumes, however by chance we detected a giant macro-spicule at the limb and were able to follow its dynamical structure. We have reported the dynamics of the giant macro-spicule in Banerjee et al. (2000a) and have also reported the existence of long period oscillations in the polar plumes as observed in the O v 629 Å line in Banerjee et al. (2000a,b). In this short contribution we revisit one of these dataset, namely s16834r01 to test the reliability of the observed periods. The statistical significance of the oscillations is estimated by using a randomisation method. Our analysis re-confirms the presence of compressional waves with periods of 20-25 minutes.
The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity.
To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity.
An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses.
Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26–1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14–1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively.
The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.
A heuristic greedy algorithm is developed for efficiently tiling spatially dense redshift surveys. In its first application to the Galaxy and MassAssembly (GAMA) redshift survey we find it rapidly improves the spatial uniformity of our data, and naturally corrects for any spatial bias introduced by the 2dF multi-object spectrograph. We make conservative predictions for the final state of the GAMA redshift survey after our final allocation of time, and can be confident that even if worse than typical weather affects our observations, all of our main survey requirements will be met.
The objectives of the present study were to determine the effects of nitrogen (N) application rate, harvest date and maize cultivar on the yield, quality and the subsequent conservation characteristics of whole-crop, cob and stover silages. The experiment was organized in a spilt-plot design, with harvest date (15 September, 6 October and 27 October) as the main plot, and a three (maize cultivars: Tassilo, Andante and KXA 7211)×two (N application rate: 33 and 168 kg N/ha) factorial arrangement of treatments as the sub-plot, within three replicate blocks, and was conducted at Grange, Dunsany, Co. Meath, Ireland in 2009. The three harvest dates represented early, normal and late harvests, respectively, for a midland site in Ireland. Of the three maize cultivars selected, cvars Tassilo and Andante represent conventional cultivars sown by commercial livestock farmers in Ireland, while cvar KXA 7211 is categorized as a high biomass cultivar. No effect of N application rate was observed on the dry matter (DM) yield, nutritive value or ensiling characteristics of maize whole-crop or cob. Whole-crop and stover harvested on the later date had a lower digestible DM (DDM) content and the silages underwent a more restricted fermentation, compared to silages produced from herbage harvested on earlier dates. Cob silages produced from crops harvested on 15 September had lower DDM content and higher DM loss during ensiling than later harvest dates. Despite higher whole-crop DM yields, the later maturing cultivar KXA 7211 did not improve the DM yields of cob and also resulted in increased DM losses from the ensilage of cob, when compared with the other cultivars. In addition to the DM yield and nutritive value of forage maize at harvest, the subsequent fermentation profile during ensilage influences the optimum choice of cultivar and date for crop harvest in a maize silage production system.
Polydimethylsiloxane [PDMS]-modified SiO2-TiO2, glasses have been prepared via the sol-gel route. Polymer compositions varied between 17 and 67 wt% PDMS, using PDMS of molecular weights 1,700 and 36,000. Also varied was the Si/Ti ratio for a given polymer content and the nature of the Ti alkoxide.A general synthetic procedure was found which made optically clear samples. Dense monolithic structures were obtained at room temperature for all compositions. The room temperature densification is attributed to relaxation and flow in the sample due to the presence of the polymer. The effects on properties of the overall composition and molecular weight of the polymer are reported, and implications in terms of structural models are considered.
We have been developing a low energy Ne atom scattering system combined with a time-of-flight spectrometer for insulator surface structural analysis. Insulator surface structure is difficult to study because of charging effects during electron or ion beam bombardment. Structural analyses of insulator surfaces are very important in fundamental research as well as technology fields. In our system, charged ion beams of 2 keV-Ne+ are converted into neutral beams by charge exchange with the same element gas after the primary beam passes through a chopper. Other features of this system are pulsed beams, time-of-flight measurements, and a micochannel plate (MCP) detector is coaxially mounted along the primary beam. This is a home made equipment. We will show the detection systems, as well.