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OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
The objective of this study was to prospectively validate the “Brief Developmental Assessment”, which is a new early recognition tool for neurodevelopmental abnormalities in children with heart disease that was developed for use by cardiac teams.
This was a prospective validation study among a representative sample of 960 pre-school children with heart disease from three United Kingdom tertiary cardiac centres who were analysed grouped into five separate age bands.
The “Brief Developmental Assessment” was successfully validated in the older four age bands, but not in the youngest representing infants under the age of 4 months, as pre-set validation thresholds were met – lower 95% confidence limit for the correlation coefficient above 0.75 – in terms of agreement of scores between two raters and with an external measure the “Mullen Scales of Early Learning”. On the basis of American Association of Pediatrics Guidelines, which state that the sensitivity and specificity of a developmental screening tool should fall between 70 and 80%, “Brief Developmental Assessment” outcome of Red meets this threshold for detection of Mullen scores >2 standard deviations below the mean.
The “Brief Developmental Assessment” may be used to improve the quality of assessment of children with heart disease. This will require a training package for users and a guide to action for abnormal results. Further research is needed to determine how best to deploy the “Brief Developmental Assessment” at different time points in children with heart disease and to determine the management strategy in infants younger than 4 months old.
Intellectual ability may be an endophenotypic marker for bipolar disorder.
Within a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood.
We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 years and lifetime manic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n=1881 individuals). An ordinary least squares linear regression model was used, with normal childhood IQ (range 90–109) as the referent group. We adjusted analyses for confounding factors, including gender, ethnicity, handedness, maternal social class at recruitment, maternal age, maternal history of depression and maternal education.
There was a positive association between IQ at age 8 years and lifetime manic features at age 22–23 years (Pearson's correlation coefficient 0.159 (95% CI 0.120–0.198), P>0.001). Individuals in the lowest decile of manic features had a mean full-scale IQ (FSIQ) which was almost 10 points lower than those in the highest decile of manic features: mean FSIQ 100.71 (95% CI 98.74–102.6) v. 110.14 (95% CI 107.79–112.50), P>0.001. The association between IQ and manic features was present for FSIQ, VIQ and for PIQ but was strongest for VIQ.
A higher childhood IQ score, and high VIQ in particular, may represent a marker of risk for the later development of bipolar disorder. This finding has implications for understanding of how liability to bipolar disorder may have been selected through generations. It will also inform future genetic studies at the interface of intelligence, creativity and bipolar disorder and is relevant to the developmental trajectory of bipolar disorder. It may also improve approaches to earlier detection and treatment of bipolar disorder in adolescents and young adults.
The Amount of Freedom enjoyed by individuals varies widely in countries around the world. In the Americas it is a matter of particular concern because of a common history of colonialism. This concern is complicated by ideological and scholarly disagreements about just what constitutes freedom. Such impediments notwithstanding, the subject holds broad public interest and frequently is the basis for comparing governments although not always in an informed manner.
The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
This paper examines the attempt of British missionaries on Madagascar to use medicine and the mission hospital as a way to convert the Malagasy people during the latter half of the nineteenth century. In their attempt to educate the Malagasy about the benefits of Western civilization, which was often defined through science as well as Christianity, missionaries were challenged by Malagasy culture and the local environment. To counter the ability of the Malagasy to challenge Western methods through their cultural beliefs and healing practices and so convert the Malagasy to Western ways, British missionaries had to carve out a space isolated from the Malagasy environment. Medicine, particularly the mission hospital, offered a space to champion Western science and Christianity. In their attempt to bring civilization to Madagascar, missionaries directly tied together science and Christianity while domesticating the space of the hospital.
Background: Cerebral venous thrombosis is a rare cause of stroke, with a number of well-defined risk factors. However, there exist few studies that describe trends in the prognosis of this disease over time. Methods: A retrospective study was performed on patients diagnosed with cerebral venous thrombosis at the University of Alberta Hospital during two time periods: 1988-1998 (21 patients) and 1999-2009 (40 patients). Signs and symptoms, risk factors, imaging findings, etiologies, treatment modalities, and status at discharge were examined. Results: Headache, nausea and vomiting, focal motor deficit, and seizure were the most common signs and symptoms, and active hormonal contraception was the most commonly identified risk factor between the two cohorts. Hematoma and hyperdense sinuses were the most commonly identified CT findings between groups. Thrombophilia and the use of hormonal contraception were the most frequently identified etiologies between the two cohorts. Treatment was similar, with the majority of patients in both cohorts receiving unfractionated heparin as first-line therapy. Patients in the 1999-2009 cohort were significantly less likely to have a severe deficit or be dead at discharge (odds ratio [OR]=0.178; 95% confidence interval [CI95%]=0.051, 0.625) and were more likely to have a favorable modified Rankin Scale score of 0 or 1 at discharge (OR=7.98; CI95%=1.79, 35.71). Conclusions: Our data indicate a reduction in severe residual symptoms at discharge and improved functional status at discharge for patients presenting with cerebral venous thrombosis from 1999 to 2009, as compared with 1988-1998.
Ice velocities observed in 2005/06 at three GPS stations along the Sermeq Avannarleq flowline, West Greenland, are used to characterize an observed annual velocity cycle. We attempt to reproduce this annual ice velocity cycle using a 1-D ice-flow model with longitudinal stresses coupled to a 1-D hydrology model that governs an empirical basal sliding rule. Seasonal basal sliding velocity is parameterized as a perturbation of prescribed winter sliding velocity that is proportional to the rate of change of glacier water storage. The coupled model reproduces the broad features of the annual basal sliding cycle observed along this flowline, namely a summer speed-up event followed by a fall slowdown event. We also evaluate the hypothesis that the observed annual velocity cycle is due to the annual calving cycle at the terminus. We demonstrate that the ice acceleration due to a catastrophic calving event takes an order of magnitude longer to reach CU/ETH (‘Swiss’) Camp (46 km upstream of the terminus) than is observed. The seasonal acceleration observed at Swiss Camp is therefore unlikely to be the result of velocity perturbations propagated upstream via longitudinal coupling. Instead we interpret this velocity cycle to reflect the local history of glacier water balance.
We apply a novel one-dimensional glacier hydrology model that calculates hydraulic head to the tidewater-terminating Sermeq Avannarleq flowline of the Greenland ice sheet. Within a plausible parameter space, the model achieves a quasi-steady-state annual cycle in which hydraulic head oscillates close to flotation throughout the ablation zone. Flotation is briefly achieved during the summer melt season along a ∼17 km stretch of the ∼50 km of flowline within the ablation zone. Beneath the majority of the flowline, subglacial conduit storage ‘closes’ (i.e. obtains minimum radius) during the winter and ‘opens’ (i.e. obtains maximum radius) during the summer. Along certain stretches of the flowline, the model predicts that subglacial conduit storage remains open throughout the year. A calculated mean glacier water residence time of ∼2.2 years implies that significant amounts of water are stored in the glacier throughout the year. We interpret this residence time as being indicative of the timescale over which the glacier hydrologic system is capable of adjusting to external surface meltwater forcings. Based on in situ ice velocity observations, we suggest that the summer speed-up event generally corresponds to conditions of increasing hydraulic head during inefficient subglacial drainage. Conversely, the slowdown during fall generally corresponds to conditions of decreasing hydraulic head during efficient subglacial drainage.
Neogene deposits of the northern Dominican Republic contain a diverse fossil assemblage that is especially rich in corals and mollusks. To see if faunal change was concordant or discordant within and among taxa and decipher factors controlling distributions, we compared distributions of coral communities, the gastropod families Strombidae and Marginellidae, and the bivalve family Corbulidae. We also incorporated published ranges for the Cardiidae (Vokes, 1989), Cancellariidae (Jung and Petit, 1990), and the columbellid genus Strombina (Jung, 1986).
First and last appearances of individual mollusk species were diachronous among sections. Within the sections, however, first and last appearances of mollusk species tended to coincide. Concordance of species ranges could be caused by unconformities or faults, be an artifact of sampling, or indicate similar responses by species to environmental changes. Neither stratigraphic gaps nor faults appear to correspond to concordant first or last appearances. Although the absence of mollusk taxa generally corresponds to less intense sampling, sampling intensity is highly correlated with the presence of macrofossils and therefore, taxa absence is probably real. First and last appearances do coincide with paleoenvironmental changes such as rapid deepening, introduction of marine conditions, increased intensity of erosional bottom currents, and changes from reefal to sand flat facies.
Comparisons among taxa also helped elucidate other distributions patterns. For instance, comparing coral communities to strombid ranges showed that strombid diversity increased in grass flats (inhabited by free living corals) and reefal deposits, indicating similar ecologic preferences to many modern strombid species. Using the coral fauna to distinguish a grass flat community from other shallow marine facies also helped explain corbulid abundances as environmentally induced, with lower numbers in grass flat deposits.
Simultaneous comparison of species distributions within diverse taxa can help explain the nature of species occurrences. For several mollusk taxa from the Neogene of the Dominican Republic, the general correspondence in distribution patterns across taxa indicates that paleoenvironmental conditions were controlling species distributions.
Hypertension following primary coarctation repair affects up to a third of subjects. A number of studies suggest that future hypertension risk is reduced if primary repair is performed at a younger age.
The objective of this study was to evaluate the risk of future medical treatment for hypertension depending on age of primary coarctation repair.
This study was carried out at a tertiary paediatric cardiology referral centre. Retrospective database evaluation of children aged <16 years undergoing primary surgical coarctation repair between October, 2005 and October, 2014 was carried out. Patients with complex heart diseases were excluded. The following age groups were considered: neonate (⩽28 days), infant (>28 days and ⩽12 months), and children (>12 months). Main outcome measure is the need for long-term anti-hypertensive medication. The risk for re-coarctation was also evaluated.
A total of 87 patients were analysed: 60 neonates, 17 infants, 10 children. Among them, 6.7% neonates, 29.4% infants, and 40% children required long-term anti-hypertensive medications. Group differences were statistically significant (p=0.004). After adjustment for type of repair, the risk of long-term anti-hypertensive therapy was 4.5 (95% confidence interval 1.2–16.9, p=0.025) and 10.5 times (95% confidence interval 2.6–42.3, p=0.001) higher if primary repair was carried out in infancy and childhood, respectively, compared with neonates. Among all, 13 patients developed re-coarctation: 21.7% in the neonatal group, 5.9% in the infant group, and 20% in the child group. We could not demonstrate a significant difference between these proportions or calculate a reliable risk for developing re-coarctation.
Risk of medical treatment for hypertension was lowest when primary repair was carried out during the neonatal period, rising 10-fold if first operated on as a child. Knowing the likelihood of hypertension development depending on age of primary repair is useful for long-term surveillance and counselling.
In any society a loss of confidence in the capacity of contemporary institutions and leadership to deal with current problems creates anxieties and feelings of loss of control. A classical reaction to such stress is efforts to return to earlier, presumably simpler, institutional forms and lifestyles, thereby regaining control and the lost sense of purpose and direction. Today in the Northeast, as in much of the nation, many people are alarmed by the recent disturbances and shocks to the American way of life: the energy shortage, the threat of nuclear disaster, high unemployment and prices, faltering state and local finances, and a recurring credibility gap at all levels of government. The perceived inability of institutional forms to deal with these concerns has fostered a re-examination of individual, local and regional goals and a rediscovery of more traditional values based on self-reliance. One manifestation of this phenomenon is the promotion in the region by some professionals and laymen alike of a policy of self-sufficiency in agricultural production.
During the summer of 1993, a field program was conducted to collect several shallow firn cores from two locations in the southern region of the Greenland ice sheet. Stratigraphic evidence of melt from these cores was used for comparison with satellite-derived indications of melt.
The shallow firn cores were examined for stratigraphic evidence of past melt events and were sampled for oxygen-isotope analysis to delineate the annual accumulation layers in the snowpack. The relative intensity of each year’s summer melt episode was compared to the corresponding melt frequency derived from microwave emissions. This comparison demonstrates that a linkage between the stratigraphic record and microwave data can be established. Both data sets indicate that there was less melt during the late 1970s and early 1980s than during the late 1980s, in general agreement with climate observations.
A simple microwave-emission model is used to simulate 37 GHz brightness temperatures associated with snowpack-melt conditions for locations across the Greenland ice sheet. The simulated values are utilized as threshold values and compared to daily, gridded SMMR and SSM/I passive-microwave data, in order to reveal regions experiencing melt. The spatial extent of the area classified as melting is examined on a daily, monthly and seasonal (May-August) basis for 1979–91. The typical seasonal cycle of melt coverage shows melt beginning in late April, a rapid increase in the melting area from mid-May to mid-July, a rapid decrease in melt extent from late July through mid-August, and cessation of melt in late September. Seasonal averages of the daily melt extents demonstrate an apparent increase in melt coverage over the 13 year period of approximately 3.8% annually (significant at the 95% confidence interval). This increase is dominated by statistically significant positive trends in melt coverage during July and August in the west and southwest of the ice sheet. We find that a linear correlation between microwave-derived melt extent and a surface measure of ablation rate is significant in June and July but not August, so caution must be exercised in using the microwave-derived melt extents in August. Nevertheless, knowledge of the variability of snowpack melt on the Greenland ice sheet as derived from microwave data should prove useful in detecting climate change in the Arctic and examining the impact of climate change on the ice sheet.
Passive microwave-brightness temperatures over the Greenland ice sheet are examined during the melt season in order to develop a technique for determining surface-melt occurrences. Time series of Special Sensor Microwave/ Imager (SSM/I) data are examined for three locations on the ice sheet, two of which are known to experience melt. These two sites demonstrate a rapid increase in brightness temperatures in late spring to early summer, a prolonged period of elevated brightness temperatures during the summer, and a rapid decrease in brightness temperatures during late summer. This increase in brightness temperatures is associated with surface snow melting. An objective technique is developed to extract melt occurrences from the brightness-temperature time series. Of the two sites with summer melt, the site at the lower elevation had a longer period between the initial and final melt days and had more total days classified as melt during 1988 and 1989. The technique is then applied to the entire Greenland ice sheet for the first major surface-melt event of 1989. The melt-zone signal is mapped from late May to early June to demonstrate the advance and subsequent retreat of one “melt wave”. The use of such a technique to determine melt duration and extent for multiple years may provide an indication of climate change.
Establishes Shakespeare's plays as some of the period's most speculative political literature. Shakespeare's Fugitive Politics makes the case that Shakespeare's plays reveal there is always something more terrifying to the king than rebellion. The book seeks to move beyond the presumption that political evolution leads ineluctably away from autocracy and aristocracy toward republicanism and popular sovereignty. Instead, it argues for affirmative politics in Shakespeare – the process of transforming scenes of negative affect into political resistance. Shakespeare's Fugitive Politics makes the case that Shakespeare's affirmative politics appears not in his dialectical opposition to sovereignty, absolutism, or tyranny; nor is his affirmative politics an inchoate form of republicanism on its way to becoming politically viable. Instead, this study claims that it is in the place of dissensus that the expression of the eventful condition of affirmative politics takes place – a fugitive expression that the sovereign order always wishes to shut down. Key FeaturesPromotes a new understanding of 'fugitive democracy'Establishes the presence of a form of alternative politics in early modern drama, articulated through the contours of theories of sovereigntyExplores how the parameters of contemporary radical politics take shape in major Shakespeare plays, including Coriolanus, King John, Henry V, Titus Andronicus, The Winter's Tale and Julius Caesar