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 email@example.com
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.
Children who have been adopted internationally commonly experience institutional care and other forms of adversity prior to adoption that can alter the functioning of the hypothalamic–pituitary–adrenal (HPA) axis. In particular, internationally adopted children tend to have blunted diurnal declines compared to children raised in their birth families. The Attachment and Biobehavioral Catch-Up (ABC) intervention was developed to enhance young children's biological and behavioral regulation by promoting sensitive parenting. The current study used a randomized controlled trial to assess whether ABC improved the diurnal functioning of the HPA axis among 85 children who had been adopted internationally when they were between the ages of 4 and 33 months (M = 16.12). Prior to the intervention, there were no significant differences in diurnal cortisol production between children whose parents were randomly assigned to receive ABC and children whose parents were randomly assigned to receive a control intervention. After the intervention, children whose parents had received the ABC intervention exhibited steeper declines in cortisol levels throughout the day than children whose parents had received the control intervention. These results indicate that the ABC intervention is effective in enhancing a healthy pattern of diurnal HPA axis regulation for young children who have been adopted internationally.
The purpose of this study was to examine how exposure to the armed conflict and the tsunami, perceived availability of resources, and perceived helpfulness of religious practices would predict depression, anxiety, posttraumatic stress, and psychosocial functioning in a multi-ethnic sample of Sri Lankan youth. A sample of Tamil (174), Sinhalese (332), and Muslim (215) children (girls=391) between 12 and 19 years (mean age =14.4, sd =1.9), completed a survey including demographic questions and items assessing exposure to the conflict and the tsunami, the perceived availability of resources, and perceived helpfulness of religious practices. Scales assessing depression, anxiety, posttraumatic stress, and psychosocial functioning were also completed. Four hierarchical multiple regression analyses were conducted with exposure to the conflict and tsunami, perceived availability of resources, and perceived helpfulness of religious beliefs as predictors, and with depression, anxiety, posttraumatic stress and psychosocial functioning as outcomes. The results revealed that exposure to the armed conflict significantly predicted posttraumatic stress (R2 =.03, F [1,494] = 12.77, p< .001), while exposure to the tsunami predicted anxiety (R2 =.03, F [2,506] = 7.8, p< .001), and perceived availability of resources predicted depression (R2=.09, F [4,499] = 11.83, p< .001) and psychosocial functioning (R2=.098, F [4,506] = 13.67, p< .001). The results suggest that exposure to traumatic events should not be assumed to be the only or even the most important variable when considering the overall psychological and psychosocial functioning of children in developing countries and traditional cultures. Implications for interventions, policy, and future research are discussed.
There has been increasing interest in the association between childhood trauma and psychosis. Proposals for potential mechanisms involved include affective dysregulation and appraisals of threat, yet few large-scale clinical studies exist in affective psychosis.
We hypothesise that within bipolar disorder (BD), childhood events will show a significant association with psychosis, and in particular with symptoms driven by dysregulation of mood or with a persecutory content.
2019 participants were recruited as part of our programme of research into the genetic and non-genetic determinants of BD (www.bdrn.org). Data on lifetime ever presence of psychosis and specific psychotic symptoms were determined by detailed structured interview with case note review. Childhood events were recorded after self-report questionnaire and case note information.
There was no relationship between childhood events, or childhood abuse, and psychosis per se. Childhood events were not associated with increased risk of persecutory or other delusions. Significant associations were found between childhood abuse and auditory hallucinations, strongest between sexual abuse and mood congruent or abusive voices. These relationships remain significant after controlling for lifetime ever cannabis misuse.
Within affective disorder, the relationship between childhood events and psychosis appears to be relatively symptom-specific. It is possible that the pathways leading to psychotic symptoms differ, with delusions and non-hallucinatory symptoms being influenced less by childhood or early environmental experience.
1. Upthegrove R, Chard C, Jones, L, Gordon –Smith K, Forty L, Jones I and Craddock N. Adverse Childhood Events and Psychosis in Bipolar Affective Disorder. BJPsych In press BJP/2014/152611
Phobic Postural Vertigo (PPV) is the 3rd most common cause for vertigo, characterized by the combination of a dizziness and subjective disturbance of balance in the absence of objective findings during routine Neurological evaluation. In most cases the clinical presentation is indistinguishable from agoraphobia. Despite this, most clinical data does not support direct correlation between anxiety disorder and PPV.
In this case series 10 patients who suffer from PPV went through psychiatry interview after a neurologist check up has been made to confirm the diagnosis of PPV. ACQ, BCQ and HDRS were filled for all patients.
According to this preliminary case series evidence for anxiety/somatization disorder were evident in 50% (5/10) before the development of PPV while in 30% (3/10) anxiety symptoms appeared in parallel or sequential to the development of PPV. In 20% (2/10), no signs for anxiety symptoms detected during evaluation.
The results of this case series suggest that PPV is a heterogeneous diagnosis that in part includes patient with previous anxiety/somatization disorder and patient in which vertigo is the presenting sign of anxiety disorder.
Farther research is needed in order to farther characterize PPV patients and promote suitable interventions.
The spatial distribution of basal water critically impacts the evolution of ice sheets. Current estimates of basal water distribution beneath the Greenland Ice Sheet (GrIS) contain large uncertainties due to poorly constrained boundary conditions, primarily from geothermal heat flux (GHF). The existing GHF models often contradict each other and implementing them in numerical ice-sheet models cannot reproduce the measured temperatures at ice core locations. Here we utilize two datasets of radar-detected basal water in Greenland to constrain the GHF at regions with a thawed bed. Using the three-dimensional ice-sheet model SICOPOLIS, we iteratively adjust the GHF to find the minimum GHF required to reach the bed to the pressure melting point, GHFpmp, at locations of radar-detected basal water. We identify parts of the central-east, south and northwest Greenland with significantly high GHFpmp. Conversely, we find that the majority of low-elevation regions of west Greenland and parts of northeast have very low GHFpmp. We compare the estimated constraints with the available GHF models for Greenland and show that GHF models often do not honor the estimated constraints. Our results highlight the need for community effort to reconcile the discrepancies between radar data, GHF models, and ice core information.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague–Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (<1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.
In the occurrence of dicamba drift, it is not well understood what measurements from soybean plants would correlate with damage to soybean offspring; therefore, possible relationships are of great interest. Sixteen drift trials were established in 2014 and 2015 at the Northeast Research and Extension Center in Keiser, AR. A single 8-m-wide by 30- or 60-m-long pass with a high-clearance sprayer was made in each soybean field, resulting in a dicamba drift event. Seeds were collected from plants in each drift trial and planted in the field in 2015 and 2016. Data were subjected to correlation analysis to determine pairwise associations among parent and offspring observations. Auxin-like symptomology in offspring consistent with dicamba, primarily as leaf cupping, appeared in plots at the unifoliate and first trifoliate stages. Auxin-like symptoms were more prevalent in offspring collected from plants from later reproductive stages as opposed to early reproductive stages. The highest correlation coefficients occurred when parent plants were treated at the R5 growth stage. Parent mature pod malformation was correlated with offspring emergence (r=−0.37, P=0.0082), vigor (r=−0.57, P ≤ 0.0001), injury (r=0.93, P ≤ 0.0001), and percent of plants injured (r=0.92, P ≤ 0.0001). This research documents that soybean damaged from dicamba drift during the R1 to R6 growth stages can negatively affect offspring and that occurrence of pod malformation after dicamba drift at the R5 growth stage may be indicative of injury to the offspring.
It is well established that dicamba can cause severe injury to soybean that is not resistant to dicamba. Dicamba-resistant (DR) cotton became available in 2015, followed by DR soybean in 2016; in late 2016 came the release of new dicamba formulations approved for topical use in cotton and soybeans. Until this approval, use of dicamba was limited to primarily corn, small grains, range and pasture, and eco-fallow acres. Hence, studies were conducted in 2015 and 2016 to examine off-target movement of two dicamba formulations using non-DR soybean as a bio-indicator. Diglycolamine (DGA) and N,N-Bis(3-aminopropyl)methylamine (BAPMA) dicamba were applied simultaneously at 560 g ae ha–1 in the center of two side-by-side 8-ha fields to vegetative glufosinate-resistant soybean. On the same day, a rate response experiment was established encompassing nine different dicamba rates of each formulation. Results from the rate response experiment indicate that soybean is equally sensitive to DGA and BAPMA dicamba. In 2015, a rain event occurring 6 to 8 h after application of the large drift trial probably limited off-target movement by incorporating some of the herbicide into the soil. As a result, secondary drift was less in 2015 than in 2016. However, minimal secondary injury (<5%) occurred 12 m farther into DGA dicamba plots in 2015. In 2016, secondary movement was decreased by 72 m when BAPMA dicamba was used compared to DGA dicamba. Appreciable secondary movement of both DGA and BAPMA dicamba is possible following in-crop applications of either formulated product to soybean in early to mid-summer. Additionally, the risk for secondary movement of BAPMA dicamba is slightly less than for DGA dicamba.
Soybean with resistance to dicamba (DR soybean) and glyphosate and cotton with resistance to glyphosate, glufosinate, and dicamba were recently commercialized in the United States and have been readily adopted. To evaluate results of over-the-top application of dicamba in DR crops, field studies were designed to examine off-target movement using proposed sprayer setup recommendations. Association analysis and nonlinear regression techniques were used to examine the effects of 26 field-scale drift trials conducted in 2014 and 2015 during soybean reproductive development (R1 through R6). The greatest predictors (injury, height reduction) of soybean yield reduction generally occurred and had steeper relationships after drift events at the R1 growth stage than at later stages. Using non-DR soybean as an indicator, dicamba was documented to move as much as 152 m from the application area (distance to 5% injury). Instances of height reduction (5%) differed among growth stages, with the greatest distance occurring at R1 (83.4 m). Soybean yield reduction was erratic, with the greatest distance to 5% loss in yield occurring at 42.8 m after an R1 drift event. Overall, the data suggest flowering-stage soybean is more sensitive than later reproductive soybean to injury, height reductions, and yield loss. Average and maximum wind speeds did not account for the injury documented from dicamba, and it is hypothesized that other meteorological variables also play a notable role in dicamba off-target movement as well as growing conditions following exposure. With concerns surrounding off-target movement of dicamba, proper stewardship of this new technology will be key to its longevity.
Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.
It is well established that soybean that does not contain the dicamba-resistant (DR) trait is highly sensitive to off-target exposure to dicamba. However, there is limited information on the effect of low doses of dicamba plus glyphosate mixtures on dicamba-sensitive soybean—a mixture likely to be used on a vast acreage of dicamba/glyphosate-resistant soybean. The objective of this research was to examine leaf and pod malformation, along with height and yield effects, when dicamba, glyphosate, or a mixture of the two was applied to soybean sensitive to both dicamba and glyphosate at sublethal doses. Field applications were made at three growth stages (R1, R3, and R5) at multiple locations. Two glyphosate rates (1/64 and 1/256 of the labeled rate of 870 g ae ha−1) and two dicamba rates (1/64 and 1/256 of the labeled rate of 560 g ae ha−1) were used. Adding glyphosate to dicamba increased leaf malformation by 6% more than dicamba alone when applied at the R1 soybean growth stage. After R3 applications, pod malformation was 10% greater in treatments containing dicamba and glyphosate than dicamba alone. Applications at R5 showed minimal leaf and pod malformation. Seed from field trials was planted in the greenhouse to evaluate the offspring. The number of offspring plants showing dicamba-like symptomology was not increased with the addition of glyphosate to dicamba. Overall, injury to offspring was similar in dicamba alone and dicamba plus glyphosate treatments; however, the number of plants injured increased when parent plants were exposed to sublethal doses of dicamba at R3 and R5 compared with R1 growth-stage exposure. Vigor was reduced in dicamba-containing treatments, but not glyphosate-alone treatments. Glyphosate addition to dicamba had no effect on vigor of soybean offspring. Although there is increased injury to parent plants when glyphosate is added to dicamba, this research demonstrates that glyphosate does not contribute to the negative effects of dicamba on soybean offspring.
Evidence from animal models indicates that exposure to an obesogenic or hyperglycemic intrauterine environment adversely impacts offspring kidney development and renal function. However, evidence from human studies has not been evaluated systematically. Therefore, the aim of this systematic review was to synthesize current research in humans that has examined the relationship between gestational obesity and/or diabetes and offspring kidney structure and function. Systematic electronic database searches were conducted of five relevant databases (CINAHL, Cochrane, EMBASE, MEDLINE and Scopus). Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles screened by two independent reviewers generated nine eligible papers for inclusion. Six studies were assessed as being of ‘neutral’ quality, two of ‘negative’ and one ‘positive’ quality. Observational studies suggest that offspring exposed to a hyperglycemic intrauterine environment are more likely to display markers of renal dysfunction and are at higher risk of end-stage renal disease. There was limited and inconsistent evidence for a link between exposure to an obesogenic intrauterine environment and offspring renal outcomes. Offspring renal outcome measures across studies were diverse, with a large variation in offspring age at follow-up, limiting comparability across studies. The collective current body of evidence suggests that intrauterine exposure to maternal obesity and/or diabetes adversely impacts renal programming in offspring, with an increased risk of kidney disease in adulthood. Further high-quality, longitudinal, prospective cohort studies that measure indicators of offspring renal development and function, including fetal kidney volume and albuminuria, at standardized follow-up time points, are warranted.
The thermal state at the bed of a large ice sheet is a critical boundary condition governing its future evolution. Radar surveys provide an opportunity for direct but remote observation of the ice-sheet bed, and therefore offer a means of constraining numerical ice-sheet models at the ice–bed interface. Here we have processed results of radar surveys of the Greenland Ice Sheet undertaken by the Program for Arctic Regional Climate Assessment (PARCA) between 1999 and 2003, to explore this opportunity. We consider the robustness of the measurements in the context of uncertain dielectric losses in the ice sheet, concluding that the observed radar signal characteristics reflect the character of the bed itself rather than that of uncertain englacial absorption. However, the identification of thaw is restricted to areas where subglacial water has sufficient depth to influence the radar reflection. We derive a map of inferred areas of subglacial thaw, and compare our results with other studies predicting regions with temperate bed. We show that in many areas the radar inferences of ponded water lie within areas predicted to be thawed by modelling and radiostratigraphy. There is clear disagreement in certain areas, suggesting the presence of high geothermal flux anomalies.
Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science—sponsored Clinical and Translational Science Award (CTSA) program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA program and other National Institutes of Health (NIH) Institutes and Centers that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN’s mission is to execute high-quality trials in a quick, cost-efficient manner. The TIN awardees are composed of 3 Trial Innovation Centers, the Recruitment Innovation Center, and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) Institutional Review Board system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH Institutes and Centers across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN-related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.
Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
After describing a newly assembled dataset consisting of almost 9,000 local appropriations made by the U.S. Congress between 1789 and 1882, we test competing accounts of the politics surrounding them before offering a more nuanced, historically contingent view of the emergence of the pork barrel. We demonstrate that for most of this historical period—despite contemporary accusations of crass electoral motives—the pattern of appropriations is largely inconsistent with accounts of distributive politics grounded in a logic of legislative credit-claiming. Instead, support for appropriations in the House mapped cleanly onto the partisan/ideological structure of Congress for most of this period, and only in the 1870s produced the universalistic coalitions commonly associated with pork-barrel spending. We trace this shift to two historical factors: the emergence of a solid Democratic South, and growth in the fraction of appropriations funding recurrent expenditures on extant projects rather than new starts.