What we talk about when we talk about colors.

Names for colors vary widely across languages, but color categories are remarkably consistent. Shared mechanisms of color perception help explain consistent partitions of visible light into discrete color vocabularies. But the mappings from colors to words are not identical across languages, which may reflect communicative needs-how often speakers must refer to objects of different color. Here we quantify the communicative needs of colors in 130 different languages by developing an inference algorithm for this problem. We find that communicative needs are not uniform: Some regions of color space exhibit 30-fold greater demand for communication than other regions. The regions of greatest demand correlate with the colors of salient objects, including ripe fruits in primate diets. Our analysis also reveals a hidden diversity in the communicative needs of colors across different languages, which is partly explained by differences in geographic location and the local biogeography of linguistic communities. Accounting for language-specific, nonuniform communicative needs improves predictions for how a language maps colors to words, and how these mappings vary across languages. Our account closes an important gap in the compression theory of color naming, while opening directions to study cross-cultural variation in the need to communicate different colors and its impact on the cultural evolution of color categories.

Barriers to Home Haemodialysis.

INTRODUCTION: Significant variation exists in the prevalence of home haemodialysis (HHD) among UK renal centres. Our centre has a HHD prevalence of 2%, and we aimed to study how many patients who chose HHD as their preferred mode of renal replacement therapy (RRT) went on to receive this treatment and the barriers to starting this treatment. METHODS: A retrospective single-centre analysis of electronic medical records for all patients who chose HHD at the time of RRT education was performed, and data were collected on patient demographics, comorbidity, frailty, RRT events, and barriers to HHD. RESULTS: 116 patients chose HHD as their preferred mode of RRT between 2006 and 2018. Of these patients, 93 required RRT, but only 28 patients ever received HHD. No statistical difference was identified between those patients who only received unit haemodialysis (UHD) and those who went onto receive HHD with respect to age, gender, comorbidity, frailty, and socioeconomic deprivation. Patient choice, change in clinical condition, transplantation, home environment, vascular access problems, and training delays were identified as reasons patients did not start HHD. No documented reason could be found in 9 patients with a breakdown of communication between clinics and peripheral dialysis units attributed as a significant contributor in some of these patients. Of the 26 patients who started HHD after UHD, 19 did so within 1 year of starting UHD. CONCLUSION: Most patients who choose HHD do not receive HHD. Many patients never start HHD because of potentially reversible barriers including inadequate communication among clinicians about patient choices, patients changing their minds once in a dialysis unit, and inadequate timely training support.

Risk factors for perianeurysmal vasogenic oedema (pavo) following embolization therapy: literature review.

Perianeurysmal vasogenic oedema (PAVO) is a rare complication associated post-embolisation of intracranial aneurysms. The prevalence, risk factors predisposing to susceptibility, and pathologic mechanisms underlying this process are not clearly understood. Since this complication may be associated with poor clinical outcomes, the authors designed this study to describe possible risk factors, underlying mechanisms, and management of PAVO through published case reports. Developing a priori protocol according to PRISMA guidelines, we searched MEDLINE/PubMed, Embase and Web of Science to identify case studies and reports of adult patients with intracranial aneurysms who developed perianeurysmal oedema following coil embolization therapy. Data extracted from these studies included patient demographics, aneurysm characteristics, coil type, PAVO characteristics, treatment, and outcomes. Quality was assessed using a standardized tool. 21 eligible studies of acceptable quality were identified, comprising 40 unique cases from 9 countries. The mean patient age was 56.4 years and 25 (62.5%) were female. Aneurysm size ranged from 6 to 30 mm, with a mean size of 15.2 mm; only 6 (15%) of cases were giant intracranial aneurysm (≥ 25 mm). The more frequent locations of intracranial aneurysms associated with PAVO were the ICA (50%) and posterior circulation (32.5%), with 7.5% and 10% of cases occurring in MCA and anterior circulation, respectively. 16 cases (40%) were treated with bare platinum coils, and 14 (35%) with a combination of BPCs and bioactive coils; in 10 cases (25%), the coil type was not mentioned. PAVO presented between 0 days and 8 years of coil embolization, with 23 (57.5% cases) presenting symptomatically in relation to brain region affected. Management strategies for PAVO included conservative, steroids, re-embolization, clipping, stenting, parent artery occlusion either as monotherapy or as combination therapy. Of reported studies, 26 treated cases (65%) resolved, with 8 (20%) remaining stable, and 4 (10%) deteriorating. PAVO can be associated with small or large intracranial aneurysms, bare and bioactive platinum coils, and all regions of the intracranial circulation. The understanding of the risk factors of this complication lies in the underlying mechanisms, which will ultimately guide appropriate patient follow-up and subsequent optimal management.

Evaluating growth trends of residual sporadic vestibular schwannomas: a systematic review and meta-analysis.

BACKGROUND: Gross total resection remains the gold-standard approach for vestibular schwannomas (VS) when surgery is indicated. In select cases, incomplete resection (IR) becomes a desired alternative to preserve the facial nerve function and the patient's quality of life. While a lot of earlier studies described incompletely resected sporadic VSs as dormant, more recent studies reported a higher growth rate following IR, therefore an evaluation of the residual VS growth rates could have important implications for the follow-up treatment protocols and provide relevant information for neurosurgeons, neuro-otologists, neuropathologists, and radiologists. Although prognostic factors predicting preoperative VS growth have been previously investigated, these factors have not been investigated following IR. Our review aims to examine the growth rate of residual sporadic VS following IR and to examine variables associated with the regrowth of residual VS. METHODS: The review was conducted in accordance with the PRISMA guidelines. Six databases (MEDLINE (Ovid), Embase (Ovid), CINAHL Plus (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform and UK Clinical Trials Gateway (WHO ICTRP) were searched. Full-text articles analysing growth rates in at least ten patients who had residual VS after IR were assessed. We conducted a meta-analysis using a random-effects model via RevMan. RESULTS: 14 studies totalling 849 patients were included in the analysis. The mean planimetric growth rate was 1.57 mm/year (range 0.16-3.81 mm/year). The mean volumetric growth rate was 281.725 mm3/year (range 17.9-530.0 mm3/year). Age, sex, pre-operative tumour size/volume, cystic tumour sub-type, MIB-1 index, and intracanalicular tumour location were not associated with residual growth. Residual tumour size/volume was statistically significant to growth (OR = 0.65, 95% CI 0.47-0.90, p = 0.01). Radiological re-growth occurred in an average of 26.6% of cases (range 0-54.5%). CONCLUSION: From our analysis, only the residual tumour volume/size was associated with residual VS growth. Therefore, close postoperative surveillance for the first year, followed by an annual MRI scan for at least 5 years, and subsequently extended interval surveillance remains of utmost importance to monitor disease progression and provide timely surgical and adjuvant interventions. Our study shows that future work should be aimed at molecular and histological characteristics of residual VSs to aid prognostic understanding of growth.

Assessing the efficacy of coproduction to better understand the barriers to achieving sustainability in NHS chronic kidney services and create alternate pathways.

CONTEXT: Too many people living with chronic kidney disease are opting for and starting on hospital-based dialysis compared to a home-based kidney replacement therapy. Dialysis services are becoming financially unsustainable. OBJECTIVE: This study aimed to assess the efficacy of coproductive research in chronic kidney disease service improvement to achieve greater sustainability. DESIGN: A 2-year coproductive service improvement study was conducted with multiple stakeholders with the specific intention of maximizing engagement with the national health kidney services, patients and public. SETTING AND PARTICIPANTS: A national health kidney service (3 health boards, 18 dialysis units), patients and families (n = 50), multidisciplinary teams including doctors, nurses, psychologists, social workers, and so forth (n = 68), kidney charities, independent dialysis service providers and wider social services were part of this study. FINDINGS: Coproductive research identified underutilized resources (e.g., patients on home dialysis and social services) and their potential, highlighted unmet social care needs for patients and families and informed service redesign. Education packages were reimagined to support the home dialysis agenda including opportunities for wider service input. The impacts of one size fits all approaches to dialysis on specialist workforce skills were made clearer and also professional, patient and public perceptions of key sustainability policies. DISCUSSION AND CONCLUSIONS: Patient and key stakeholders mapped out new ways to link services to create more sustainable models of kidney health and social care. Maintaining principles of knowledge coproduction could help achieve financial sustainability and move towards more prudent adult chronic kidney disease services. PATIENT OR PUBLIC CONTRIBUTION: Involved in developing research questions, study design, management and conduct, interpretation of evidence and dissemination.

Cavernous sinus haemangioma: systematic review and pooled analysis relating to a rare skull base pathology.

Cavernous sinus haemangiomas (CSHs) are rare malformations of the microcirculation arising from the cavernous sinus. A systematic review and pooled data analysis of the associated clinical features, diagnostic modalities, management, and outcomes for CSHs was done. In total, 68 articles (338 cases) were eligible for analysis based on our selection criteria. The primary outcome measures were the occurrence of (i) and (ii) symptom resolution/improvement. Categorical outcome variables were assessed by binary logistic regression at 5% significance level. With headaches (39.9%) and diplopia (36.5%) as the most common presenting symptoms reported, dynamic contrast-enhanced MRI was the most commonly used diagnostic modality and was the most definitive pre-treatment imaging modality for diagnosing CSH with a sensitivity of 89.5%. The majority of CSHs were managed with radiosurgery (47.9% of cases), 37.9% by surgical resection alone, and 14.2% by a combination of both. Compared to patients that were treated with surgical resection only, those treated solely with radiosurgery had a 100% decrease in the odds of developing post-treatment complications (adjusted OR: 0.00, 95% CI: 0.00-0.002, p < 0.001), with a 5.03 times greater odds of symptom resolution/improvement (adjusted OR: 5.03, 95% CI: 1.89-13.4, p = 0.001). Patients that underwent combined therapy had a 79% reduction in risk of developing post-treatment complications (adjusted OR: 0.21, 95% CI: 0.06-0.68, p = 0.01), with no statistically significant difference in the odds of symptom resolution/improvement, compared to those that had surgery only. In conclusion, radiosurgery offered the best outcomes with regards to symptom resolution/improvement and post-treatment complications in patients with CSH.

Lifetime Stressor Exposure and Psychophysiological Reactivity and Habituation to Repeated Acute Social Stressors.

This study addressed whether lifetime stressor exposure was associated with psychophysiological reactivity and habituation to a novel laboratory-based stressor. Eighty-six participants (Mage = 23.31 years, SD = 4.94) reported their exposure to lifetime non-sport and sport-specific stressors before completing two consecutive trials of the Trier Social Stress Test, while cardiovascular (i.e., heart rate) and endocrine (i.e., salivary cortisol) data were recorded. Exposure to a moderate number of lifetime non-sport and sport-specific stressors was associated with adaptive cardiovascular reactivity, whereas very low or very high stressor exposure was related to maladaptive reactivity. Moreover, experiencing a very low number of lifetime non-sport (but not sport-specific) stressors was associated with poorer habituation. In contrast, lifetime stressor severity was unrelated to cardiovascular reactivity. Finally, greater lifetime non-sport and sport-specific stressor counts were associated with blunted cortisol reactivity and poorer habituation. These results suggest that lifetime stressor exposure may influence sport performers' acute stress responses.

Improvement in air quality and its impact on land surface temperature in major urban areas across India during the first lockdown of the pandemic.

The SARS CoV-2 (COVID-19) pandemic and the enforced lockdown have reduced the use of surface and air transportation. This study investigates the impact of the lockdown restrictions in India on atmospheric composition, using Sentinel-5Ps retrievals of tropospheric NO2 concentration and ground-station measurements of NO2 and PM2.5 between March-May in 2019 and 2020. Detailed analysis of the changes to atmospheric composition are carried out over six major urban areas (i.e. Delhi, Mumbai, Kolkata, Chennai, Bangalore, and Hyderabad) by comparing Moderate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth (AOD) and land surface temperature (LST) measurements in the lockdown year 2020 and pre-lockdown (2015-2019). Satellite-based data showed that NO2 concentration reduced by 18% (Kolkata), 29% (Hyderabad), 32-34% (Chennai, Mumbai, and Bangalore), and 43% (Delhi). Surface-based concentrations of NO2, PM2.5, and AOD also substantially dropped by 32-74%, 10-42%, and 8-34%, respectively over these major cities during the lockdown period and co-located with the intensity of anthropogenic activity. Only a smaller fraction of the reduction of pollutants was associated with meteorological variability. A substantial negative anomaly was found for LST both in the day (-0.16 °C to -1 °C) and night (-0.63 °C to -2.1 °C) across select all cities, which was also consistent with air temperature measurements. The decreases in LST could be associated with a reduction in pollutants, greenhouse gases and water vapor content. Improvement in air quality with lower urban temperatures due to lockdown may be a temporary effect, but it provides a crucial connection among human activities, air pollution, aerosols, radiative flux, and temperature. The lockdown for a shorter-period showed a significant improvement in environmental quality and provides a strong evidence base for larger scale policy implementation to improve air quality.

Radiological surveillance of small unruptured intracranial aneurysms: a systematic review, meta-analysis, and meta-regression of 8428 aneurysms.

With the widespread use of imaging techniques, the possibility that an asymptomatic unruptured intracranial aneurysm (UIA) is detected has increased significantly. There is no established consensus regarding follow-up, duration, and frequency of such imaging surveillance. The objectives of this study include assessing the growth rate and rupture risk of small (less than 7mm) UIAs, identifying associated risk factors and providing an aneurysm surveillance protocol in appropriately selected patients. Systematic searches of Medline, Embase, and Cochrane Central were undertaken from database inception to March 2020 for published studies reporting the growth and rupture risks of small UIAs. Twenty-one studies reporting 8428 small UIAs were included in our meta-analysis. The pooled mean age was 61 years (95% CI: 55-67). The mean follow-up period for growth and rupture ranged from 11 to 108 months, with the pooled mean follow-up period across 14 studies being 42 months (95% CI: 33-51). Pooled overall growth rate was 6.0% (95% CI: 3.8-8.7). Pooled growth rates for aneurysms < 5mm and < 3 mm were 5.2% (95% CI: 3.0-7.9) and 0.8% (95% CI: 0.0-6.1), respectively. Pooled overall rupture rate was 0.4% (95% CI: 0.2-0.7). From the meta-regression analysis, having multiple aneurysms, smoking, hypertension, and personal history of SAH did not significantly predict growth, and a personal history of SAH, smoking, hypertension, and multiple aneurysms were not statistically significant predictors of rupture. Our findings suggest that small UIAs have low growth and rupture rates and very small UIAs have little or no risk for rupture. In the setting of incidental small UIAs, patients with multiple and/or posterior circulation aneurysms require more regular radiological monitoring.

A dynamic model of bovine tuberculosis spread and control in Great Britain.

Bovine tuberculosis (TB) is one of the most complex, persistent and controversial problems facing the British cattle industry, costing the country an estimated £100 million per year. The low sensitivity of the standard diagnostic test leads to considerable ambiguity in determining the main transmission routes of infection, which exacerbates the continuing scientific debate. In turn this uncertainty fuels the fierce public and political disputes on the necessity of controlling badgers to limit the spread of infection. Here we present a dynamic stochastic spatial model for bovine TB in Great Britain that combines within-farm and between-farm transmission. At the farm scale the model incorporates stochastic transmission of infection, maintenance of infection in the environment and a testing protocol that mimics historical government policy. Between-farm transmission has a short-range environmental component and is explicitly driven by movements of individual cattle between farms, as recorded in the Cattle Tracing System. The resultant model replicates the observed annual increase of infection over time as well as the spread of infection into new areas. Given that our model is mechanistic, it can ascribe transmission pathways to each new case; the majority of newly detected cases involve several transmission routes with moving infected cattle, reinfection from an environmental reservoir and poor sensitivity of the diagnostic test all having substantive roles. This underpins our findings on the implications of control measures. Very few of the control options tested have the potential to reverse the observed annual increase, with only intensive strategies such as whole-herd culling or additional national testing proving highly effective, whereas controls focused on a single transmission route are unlikely to be highly effective.

Who do we discharge from renal clinic and what does it mean for primary care?

BACKGROUND: It is unclear whether discharging patients from renal clinic to primary care is safe. AIM: To determine the characteristics, primary care monitoring and renal outcomes of patients discharged from renal clinic. DESIGN AND SETTING: A retrospective study of 2236 adults discharged from a tertiary renal clinic between 2013-2018. METHOD: Patient demographics, primary renal disease, laboratory results and timeline dates were collected from the renal IT system. Timing of blood tests, renal progression, needing dialysis and patient survival were analysed. Reasons for discharge and cause of disease progression were reviewed in patients developing new estimated glomerular filtration rate <20 ml/min/1.73 m2. RESULTS: Patients were older (median age 75; interquartile range 63-84) with non-progressive, seemingly non-proteinuric renal disease. Median time to repeat blood test post-discharge was 75 days with 90% tested within 12 months. Sixty-six percent saw an improvement in kidney function post-discharge and only 13% had a decline of >10 ml/min/1.73 m2. Only 132 patients (6%) developed new advanced chronic kidney disease (estimated glomerular filtration rate < 20 ml/min/1.73 m2) of whom 40% were palliative, 36% had developed acute kidney injury and 23% discharged for failing to attend clinic. One hundred and thirty-four patients (6%) were referred back to nephrology and eight started dialysis of whom six were discharged for failure to attend clinic. CONCLUSION: Most discharged patients are low risk of progressive renal disease and need infrequent monitoring. Non-adherent patients discharged for failing to attend appear to be at risk of poor outcomes and new strategies are needed to better support this population.

A model for the evolution of prokaryotic DNA restriction-modification systems based upon the structural malleability of Type I restriction-modification enzymes.

Restriction Modification (RM) systems prevent the invasion of foreign genetic material into bacterial cells by restriction and protect the host's genetic material by methylation. They are therefore important in maintaining the integrity of the host genome. RM systems are currently classified into four types (I to IV) on the basis of differences in composition, target recognition, cofactors and the manner in which they cleave DNA. Comparing the structures of the different types, similarities can be observed suggesting an evolutionary link between these different types. This work describes the 'deconstruction' of a large Type I RM enzyme into forms structurally similar to smaller Type II RM enzymes in an effort to elucidate the pathway taken by Nature to form these different RM enzymes. Based upon the ability to engineer new enzymes from the Type I 'scaffold', an evolutionary pathway and the evolutionary pressures required to move along the pathway from Type I RM systems to Type II RM systems are proposed. Experiments to test the evolutionary model are discussed.

Structure and operation of the DNA-translocating type I DNA restriction enzymes.

Type I DNA restriction/modification (RM) enzymes are molecular machines found in the majority of bacterial species. Their early discovery paved the way for the development of genetic engineering. They control (restrict) the influx of foreign DNA via horizontal gene transfer into the bacterium while maintaining sequence-specific methylation (modification) of host DNA. The endonuclease reaction of these enzymes on unmethylated DNA is preceded by bidirectional translocation of thousands of base pairs of DNA toward the enzyme. We present the structures of two type I RM enzymes, EcoKI and EcoR124I, derived using electron microscopy (EM), small-angle scattering (neutron and X-ray), and detailed molecular modeling. DNA binding triggers a large contraction of the open form of the enzyme to a compact form. The path followed by DNA through the complexes is revealed by using a DNA mimic anti-restriction protein. The structures reveal an evolutionary link between type I RM enzymes and type II RM enzymes.

International intercomparison on internal dose assessment (ICIDOSE 2017).

Internal dose assessment intercomparison exercises are useful tools: to verify the performance of an internal dosimetry service; to promote the harmonisation of dose assessments; and to identify weaknesses where further improvements are necessary. However, no such international intercomparisons have been performed for more than ten years. In the period May 2014-May 2016, the 'Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides' were developed on the initiative of the European Commission, and later published within the EC Radiation Protection series, as RP188. In 2017 the Working Group 'Internal Dosimetry' of the European Radiation Dosimetry Group (EURADOS) organised a new intercomparison action, named ICIDOSE 2017, with the main aim of testing the practical applicability of these technical recommendations (RP188). Four case studies were proposed to participants: an artificially created case of inhalation of 60Co to simulate a simple special monitoring case; a real case of inhalation of 125I, with simple routine monitoring; a real and more complex case of incorporation of 234+235+238U, featuring both confirmatory and special monitoring; and a complex real case of an accidental incorporation of 241Am, including multiple administrations of diethylenetriamine pentaacetic acid (DTPA). Results were received from 66 participants from 26 countries; these were compared to reference or recommended solutions, developed for each case based on the application of RP188. In cases 1, 2 and 4 only a small number of results were identified as outliers, with the spread of all the results, expressed as the geometric standard deviation (GSD) of the values, assessed as 1.07, 1.04 and 1.43, respectively. This observed spread of the submitted results was improved from those obtained from similar cases in previous intercomparison exercises, showing that the availability of RP188 contributes to the harmonisation of the internal dose assessment process. There was a much wider spread of results for the uranium case: this case was characterised by an absence of any prior knowledge of the exposure scenario, and participants assumed a range of different exposure pathways and patterns.

DNA target recognition domains in the Type I restriction and modification systems of Staphylococcus aureus.

Staphylococcus aureus displays a clonal population structure in which horizontal gene transfer between different lineages is extremely rare. This is due, in part, to the presence of a Type I DNA restriction-modification (RM) system given the generic name of Sau1, which maintains different patterns of methylation on specific target sequences on the genomes of different lineages. We have determined the target sequences recognized by the Sau1 Type I RM systems present in a wide range of the most prevalent S. aureus lineages and assigned the sequences recognized to particular target recognition domains within the RM enzymes. We used a range of biochemical assays on purified enzymes and single molecule real-time sequencing on genomic DNA to determine these target sequences and their patterns of methylation. Knowledge of the main target sequences for Sau1 will facilitate the synthesis of new vectors for transformation of the most prevalent lineages of this 'untransformable' bacterium.

Unconventional Human T Cells Accumulate at the Site of Infection in Response to Microbial Ligands and Induce Local Tissue Remodeling.

The antimicrobial responsiveness and function of unconventional human T cells are poorly understood, with only limited access to relevant specimens from sites of infection. Peritonitis is a common and serious complication in individuals with end-stage kidney disease receiving peritoneal dialysis. By analyzing local and systemic immune responses in peritoneal dialysis patients presenting with acute bacterial peritonitis and monitoring individuals before and during defined infectious episodes, our data show that Vγ9/Vδ2(+) γδ T cells and mucosal-associated invariant T cells accumulate at the site of infection with organisms producing (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and vitamin B2, respectively. Such unconventional human T cells are major producers of IFN-γ and TNF-α in response to these ligands that are shared by many microbial pathogens and affect the cells lining the peritoneal cavity by triggering local inflammation and inducing tissue remodeling with consequences for peritoneal membrane integrity. Our data uncover a crucial role for Vγ9/Vδ2 T cells and mucosal-associated invariant T cells in bacterial infection and suggest that they represent a useful predictive marker for important clinical outcomes, which may inform future stratification and patient management. These findings are likely to be applicable to other acute infections where local activation of unconventional T cells contributes to the antimicrobial inflammatory response.

The evolutionary pathway from a biologically inactive polypeptide sequence to a folded, active structural mimic of DNA.

The protein Ocr (overcome classical restriction) from bacteriophage T7 acts as a mimic of DNA and inhibits all Type I restriction/modification (RM) enzymes. Ocr is a homodimer of 116 amino acids and adopts an elongated structure that resembles the shape of a bent 24 bp DNA molecule. Each monomer includes 34 acidic residues and only six basic residues. We have delineated the mimicry of Ocr by focusing on the electrostatic contribution of its negatively charged amino acids using directed evolution of a synthetic form of Ocr, termed pocr, in which all of the 34 acidic residues were substituted for a neutral amino acid. In vivo analyses confirmed that pocr did not display any antirestriction activity. Here, we have subjected the gene encoding pocr to several rounds of directed evolution in which codons for the corresponding acidic residues found in Ocr were specifically re-introduced. An in vivo selection assay was used to detect antirestriction activity after each round of mutation. Our results demonstrate the variation in importance of the acidic residues in regions of Ocr corresponding to different parts of the DNA target which it is mimicking and for the avoidance of deleterious effects on the growth of the host.

The effects of dexamphetamine on the resting-state electroencephalogram and functional connectivity.

The catecholamines-dopamine and noradrenaline-play important roles in directing and guiding behavior. Disorders of these systems, particularly within the dopamine system, are associated with several severe and chronically disabling psychiatric and neurological disorders. We used the recently published group independent components analysis (ICA) procedure outlined by Chen et al. (2013) to present the first pharmaco-EEG ICA analysis of the resting-state EEG in healthy participants administered 0.45 mg/kg dexamphetamine. Twenty-eight healthy participants between 18 and 41 were recruited. Bayesian nested-domain models that explicitly account for spatial and functional relationships were used to contrast placebo and dexamphetamine on component spectral power and several connectivity metrics. Dexamphetamine led to reductions across delta, theta, and alpha spectral power bands that were predominantly localized to Frontal and Central regions. Beta 1 and beta 2 power were reduced by dexamphetamine at Frontal ICs, while beta 2 and gamma power was enhanced by dexamphetamine in posterior regions, including the parietal, occipital-temporal, and occipital regions. Power-power coupling under dexamphetamine was similar for both states, resembling the eyes open condition under placebo. However, orthogonalized measures of power coupling and phase coupling did not show the same effect of dexamphetamine as power-power coupling. We discuss the alterations of low- and high-frequency EEG power in response to dexamphetamine within the context of disorders of dopamine regulation, in particular schizophrenia, as well as in the context of a recently hypothesized association between low-frequency power and aspects of anhedonia. Hum Brain Mapp 37:570-588, 2016. © 2015 Wiley Periodicals, Inc.

Probing the excited state relaxation dynamics of pyrimidine nucleosides in chloroform solution.

Ultrafast transient electronic and vibrational absorption spectroscopy (TEAS and TVAS) of 2'-deoxy-cytidine (dC) and 2'-deoxy-thymidine (dT) dissolved in chloroform examines their excited-state dynamics and the recovery of ground electronic state molecules following absorption of ultraviolet light. The chloroform serves as a weakly interacting solvent, allowing comparisons to be drawn with prior experimental studies of the photodynamics of these nucleosides in the gas phase and in polar solvents such as water. The pyrimidine base nucleosides have some propensity to dimerize in aprotic solvents, but the monomer photochemistry can be resolved clearly and is the focus of this study. UV absorption at a wavelength of 260 nm excites a 1ππ* ← S0 transition, but prompt crossing of a significant fraction (50% in dC, 17% in dT) of the 1ππ* population into a nearby 1nπ* state is too fast for the experiments to resolve. The remaining flux on the 1ππ* state leaves the vertical Franck-Condon region and encounters a conical intersection with the ground electronic state of ethylenic twist character. In dC, the 1ππ* state decays to the ground state with a time constant of 1.1 ± 0.1 ps. The lifetime of the 1nπ* state is much longer in the canonical forms of both molecules: recovery of the ground state population from these states occurs with time constants of 18.6 ± 1.1 ps in amino-oxo dC and ∼114 ps in dT, indicating potential energy barriers to the 1nπ*/S0 conical intersections. The small fraction of the imino-oxo tautomer of dC present in solution has a longer-lived 1nπ* state with a lifetime for ground state recovery of 193 ± 55 ps. No evidence is found for photo-induced tautomerization of amino-oxo dC to the imino-oxo form, or for population of low lying triplet states of this nucleoside. In contrast, ∼8% of the UV-excited dT molecules access the long-lived T1 (3ππ*) state through the 1nπ* state. The primary influence of the solvent appears to be the degree to which it destabilizes the states of 1nπ* character, with consequences for the lifetimes of these states as well as the triplet state yields.

Assessing delivery practices of mothers over time and over space in Uganda, 2003-2012.

BACKGROUND: It is well known that safe delivery in a health facility reduces the risks of maternal and infant mortality resulting from perinatal complications. What is less understood are the factors associated with safe delivery practices. We investigate factors influencing health facility delivery practices while adjusting for multiple other factors simultaneously, spatial heterogeneity, and trends over time. METHODS: We fitted a logistic regression model to Lot Quality Assurance Sampling (LQAS) data from Uganda in a framework that considered individual-level covariates, geographical features, and variations over five time points. We accounted for all two-covariate interactions and all three-covariate interactions for which two of the covariates already had a significant interaction, were able to quantify uncertainty in outputs using computationally intensive cluster bootstrap methods, and displayed outputs using a geographical information system. Finally, we investigated what information could be predicted about districts at future time-points, before the next LQAS survey is carried out. To do this, we applied the model to project a confidence interval for the district level coverage of health facility delivery at future time points, by using the lower and upper end values of known demographics to construct a confidence range for the prediction and define priority groups. RESULTS: We show that ease of access, maternal age and education are strongly associated with delivery in a health facility; after accounting for this, there remains a significant trend towards greater uptake over time. We use this model together with known demographics to formulate a nascent early warning system that identifies candidate districts expected to have low prevalence of facility-based delivery in the immediate future. CONCLUSIONS: Our results support the hypothesis that increased development, particularly related to education and access to health facilities, will act to increase facility-based deliveries, a factor associated with reducing perinatal associated mortality. We provide a statistical method for using inexpensive and routinely collected monitoring and evaluation data to answer complex epidemiology and public health questions in a resource-poor setting. We produced a model based on this data that explained the spatial distribution of facility-based delivery in Uganda. Finally, we used this model to make a prediction about the future priority of districts that was validated by monitoring and evaluation data collected in the next year.