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Previous studies showed that replacing conventional flattened beams (FF) with flattening filter-free (FFF) beams improves the therapeutic ratio in lung stereotactic body radiation therapy (SBRT), but these findings could have been impacted by dose calculation uncertainties caused by the heterogeneity of the thoracic anatomy and by respiratory motion, which were particularly high for target coverage. In this study, we minimised such uncertainties by calculating doses using high-spatial-resolution Monte Carlo and four-dimensional computed tomography (4DCT) images. We aimed to evaluate more reliably the benefits of using FFF beams for lung SBRT.
Materials and methods:
For a cohort of 15 patients with early-stage lung cancer that we investigated in a previous treatment planning study, we recalculated dose distributions with Monte Carlo using 4DCT images. This included 15 FF and 15 FFF treatment plans.
Compared to Monte Carlo, the treatment planning system (TPS) over-predicted doses in low-dose regions of the planning target volume (PTV). For most patients, replacing FF beams with FFF beams improved target coverage, tumour control, and uncomplicated tumour control probabilities.
Monte Carlo tends to reveal deficiencies in target coverage compared to coverage predicted by the TPS. Our data support previously reported benefits of using FFF beams for lung SBRT.
The aim of this study was to investigate the extent to which lung stereotactic body radiotherapy (SBRT) treatment plans can be improved by replacing conventional flattening filter (FF) beams with flattening filter-free (FFF) beams.
Materials and methods:
We selected 15 patients who had received SBRT with conventional 6-MV photon beams for early-stage lung cancer. We imported the patients’ treatment plans into the Eclipse 13·6 treatment planning system, in which we configured the AAA dose calculation model using representative beam data for a TrueBeam accelerator operated in 6-MV FFF mode. We then created new treatment plans by replacing the conventional FF beams in the original plans with FFF beams.
The FFF plans had better target coverage than the original FF plans did. For the planning target volume, FFF plans significantly improved the D98, D95, D90, homogeneity index and uncomplicated tumour control probability. In most cases, the doses to organs at risk were lower in FFF plans. FFF plans significantly reduced the mean lung dose, V10, V20, V30, and normal tissue complication probability for the total lung and improved the dosimetric indices for the ipsilateral lung. For most patients, FFF beams achieved lower maximum doses to the oesophagus, heart and the spinal cord, and a lower chest wall V30.
Compared with FF beams, FFF beams achieved lower doses to organs at risk, especially the lung, without compromising tumour coverage; in fact, FFF beams improved coverage in most cases. Thus, replacing FF beams with FFF beams can achieve a better therapeutic ratio.
While negative affect reliably predicts binge eating, it is unknown how this association may decrease or ‘de-couple’ during treatment for binge eating disorder (BED), whether such change is greater in treatments targeting emotion regulation, or how such change predicts outcome. This study utilized multi-wave ecological momentary assessment (EMA) to assess changes in the momentary association between negative affect and subsequent binge-eating symptoms during Integrative Cognitive Affective Therapy (ICAT-BED) and Cognitive Behavior Therapy Guided Self-Help (CBTgsh). It was predicted that there would be stronger de-coupling effects in ICAT-BED compared to CBTgsh given the focus on emotion regulation skills in ICAT-BED and that greater de-coupling would predict outcomes.
Adults with BED were randomized to ICAT-BED or CBTgsh and completed 1-week EMA protocols and the Eating Disorder Examination (EDE) at pre-treatment, end-of-treatment, and 6-month follow-up (final N = 78). De-coupling was operationalized as a change in momentary associations between negative affect and binge-eating symptoms from pre-treatment to end-of-treatment.
There was a significant de-coupling effect at follow-up but not end-of-treatment, and de-coupling did not differ between ICAT-BED and CBTgsh. Less de-coupling was associated with higher end-of-treatment EDE global scores at end-of-treatment and higher binge frequency at follow-up.
Both ICAT-BED and CBTgsh were associated with de-coupling of momentary negative affect and binge-eating symptoms, which in turn relate to cognitive and behavioral treatment outcomes. Future research is warranted to identify differential mechanisms of change across ICAT-BED and CBTgsh. Results also highlight the importance of developing momentary interventions to more effectively de-couple negative affect and binge eating.
Metabolic syndrome induced by atypical antipsychotics is more prevalence in schizophrenic patients. Much less is known regarding paliperidone ER. The objective of this study was to compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. Eighty hospitalized patients with schizophrenia (DSM-) were randomly assigned to treatment with paliperidone ER or olanzapine for 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density level (HDL) cholesterol, low density level (LDL) cholesterol and prolactin. And we also evaluate the body mass index (BMI), homeostasis insulin resistance (HOMA-IR) and homeostasis β-cell function (HOMA-B). 33 patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine completed the entire 12-week treatment. Within-group overall analysis showed that the fasting measures were increased in weight, BMI, waist circumferences, hip circumferences, subcutaneous fat, cholesterol, triglyceride and prolactin for two groups, and fasting glucose, LDL and HOMA-B were increased for olanzapine group. There was significantly difference in serum prolactin between paliperidone ER and olanzapine group. And there was a trend for HOMA-B to increase in olanzapine group over 12 weeks compared to paliperidone ER group. However, there were no overall differential drug effects over 12 weeks on the fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride and HOMA-IR. The study further reinforces the necessity of regular monitoring the metabolic parameters in schizophrenic patients with atypical antipsychotics including paliperidone ER.
Developing empirically sound measures for social cognition is a key step in improving the factors that contribute to deficits in social functioning in schizophrenia. Investigating the psychometric properties and acceptability of social cognitive instruments may contribute to identification of a reliable and valid instrument for schizophrenia patients.
To investigate the psychometric properties and acceptability of a dynamic social cognition scale (DSCB) compared to three common social cognition instruments in schizophrenia.
41 patients with schizophrenia were evaluated to assess acceptability, internal consistency and validity of five social cognition measures: DSCB, Emotion Recognition-40 (ER-40), Facial Emotion Identification Task (FEIT), Tone Matching Task and MSCEIT. Multiple linear regressions were conducted to identify variables which perform well as social cognition determinants.
The DSCB and FEIT showed good acceptability, evidenced by shorter administration time, completion and patient preference for the DSCB. Good levels of internal consistency were found for the DSCB (α = 0.851), ER-40 (α = 0.803), and FEIT (α = 0.782). Confirmatory Factor Analysis indicated sufficient to good model fit. The DSCB and the ER-40 demonstrated a good model fit. The correlations for the DSCB were significant for the ER-40 (r = 0.512) and FEIT (r = 0.500).
Findings suggest that DSCB is the preferred instrument to evaluate social cognition, due to its dynamic nature and short administration time. Further research is needed to develop and improve these measurements. Additionally, the DSCB, FEIT and ER-40 show adequate to good reliability and validity.
Recent imaging studies have shown that brain morphology and neural activity during sexual arousal differ between homosexual and heterosexual men. Whether the structural and task-related functional differences also exist in the resting state is unknown. The purpose of the study is to characterize the association of homosexual preference with measures of regional homogeneity and functional connectivity in the resting state. Participants were 26 homosexual men and 26 age-matched heterosexual men. The sexual orientation of every participant was evaluated using the Kinsey Scale. We first assessed group differences in regional homogeneity and then, taking the identified differences as seed regions, we compared groups in measures of functional connectivity from those seeds. The behavioral significances of the differences in regional homogeneity and functional connectivity were assessed by examining their associations with scores on the Kinsey Scale. Homosexual participants showed significantly reduced regional homogeneity in the left inferior occipital gyrus, right middle occipital gyrus, right superior occipital gyrus, left cuneus, right precuneus, and increased regional homogeneity in the rectal gyrus, bilateral midbrain, and left temporal lobe. Regional homogeneity correlated positively with Kinsey scores in the left inferior occipital gyrus. The homosexual group also showed reduced functional connectivity in left middle temporal gyrus, left supra-marginal gyrus and right cuneus. In addition, the connection between the left inferior occipital gyrus and right thalamus in the homosexual group was correlated positively with Kinsey scores. This differences in homogeneity and fucntional connectivity may contribute to a better understanding of the neural basis of male sexual orientation.
Psychiatric disorders, including eating disorders (EDs), have clinical outcomes that range widely in severity and chronicity. The ability to predict such outcomes is extremely limited. Machine-learning (ML) approaches that model complexity may optimize the prediction of multifaceted psychiatric behaviors. However, the investigations of many psychiatric concerns have not capitalized on ML to improve prognosis. This study conducted the first comparison of an ML approach (elastic net regularized logistic regression) to traditional regression to longitudinally predict ED outcomes.
Females with heterogeneous ED diagnoses completed demographic and psychiatric assessments at baseline (n = 415) and Year 1 (n = 320) and 2 (n = 277) follow-ups. Elastic net and traditional logistic regression models comprising the same baseline variables were compared in ability to longitudinally predict ED diagnosis, binge eating, compensatory behavior, and underweight BMI at Years 1 and 2.
Elastic net models had higher accuracy for all outcomes at Years 1 and 2 [average Area Under the Receiving Operating Characteristics Curve (AUC) = 0.78] compared to logistic regression (average AUC = 0.67). Model performance did not deteriorate when the most important predictor was removed or an alternative ML algorithm (random forests) was applied. Baseline ED (e.g. diagnosis), psychiatric (e.g. hospitalization), and demographic (e.g. ethnicity) characteristics emerged as important predictors in exploratory predictor importance analyses.
ML algorithms can enhance the prediction of ED symptoms for 2 years and may identify important risk markers. The superior accuracy of ML for predicting complex outcomes suggests that these approaches may ultimately aid in advancing precision medicine for serious psychiatric disorders.
Acifluorfen is a nonsystemic PPO-inhibiting herbicide commonly used for POST Palmer amaranth control in soybean, peanut, and rice across the southern United States. Concerns have been raised regarding herbicide selection pressure and particle drift, increasing the need for application practices that optimize herbicide efficacy while mitigating spray drift. Field research was conducted in 2016, 2017, and 2018 in Mississippi and Nebraska to evaluate the influence of a range of spray droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)], using acifluorfen to create a novel Palmer amaranth management recommendation using pulse width modulation (PWM) technology. A pooled site-year generalized additive model (GAM) analysis suggested that 150-μm (Fine) droplets should be used to obtain the greatest Palmer amaranth control and dry biomass reduction. Nevertheless, GAM models indicated that only 7.2% of the variability observed in Palmer amaranth control was due to differences in spray droplet size. Therefore, location-specific GAM analyses were performed to account for geographical differences to increase the accuracy of prediction models. GAM models suggested that 250-μm (Medium) droplets optimize acifluorfen efficacy on Palmer amaranth in Dundee, MS, and 310-μm (Medium) droplets could sustain 90% of maximum weed control. Specific models for Beaver City, NE, indicated that 150-μm (Fine) droplets provide maximum Palmer amaranth control, and 340-μm (Medium) droplets could maintain 90% of greatest weed control. For Robinsonville, MS, optimal Palmer amaranth control could be obtained with 370-μm (Coarse) droplets, and 90% maximum control could be sustained with 680 μm (Ultra Coarse) droplets. Differences in optimal droplet size across location could be a result of convoluted interactions between droplet size, weather conditions, population density, plant morphology, and soil fertility levels. Future research should adopt a holistic approach to identify and investigate the influence of environmental and application parameters to optimize droplet size recommendations.
Herbicide applications performed with pulse width modulation (PWM) sprayers to deliver specific spray droplet sizes could maintain product efficacy, minimize potential off-target movement, and increase flexibility in field operations. Given the continuous expansion of herbicide-resistant Palmer amaranth populations across the southern and midwestern United States, efficacious and cost-effective means of application are needed to maximize Palmer amaranth control. Experiments were conducted in two locations in Mississippi (2016, 2017, and 2018) and one location in Nebraska (2016 and 2017) for a total of 7 site-years. The objective of this study was to evaluate the influence of a range of spray droplet sizes [150 (Fine) to 900 μm (Ultra Coarse)] on lactofen and acifluorfen efficacy for Palmer amaranth control. The results of this research indicated that spray droplet size did not influence lactofen efficacy on Palmer amaranth. Palmer amaranth control and percent dry-biomass reduction remained consistent with lactofen applied within the aforementioned droplet size range. Therefore, larger spray droplets should be used as part of a drift mitigation approach. In contrast, acifluorfen application with 300-μm (Medium) spray droplets provided the greatest Palmer amaranth control. Although percent biomass reduction was numerically greater with 300-μm (Medium) droplets, results did not differ with respect to spray droplet size, possibly as a result of initial plant injury, causing weight loss, followed by regrowth. Overall, 900-μm (Ultra Coarse) droplets could be used effectively without compromising lactofen efficacy on Palmer amaranth, and 300-μm (Medium) droplets should be used to achieve maximum Palmer amaranth control with acifluorfen.
The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets.
Using a large case–control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status.
Over and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD.
Results indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT).
Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership.
Five classes, namely rapid responder (7–17%), steep linear responder (14–22%), gradual responder (30–34%), non-responder (27–33%), and symptom exacerbation (7–13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT.
Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36−47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28–0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.
Exotic annual grasses such as medusahead [Taeniatherum caput-medusae (L.) Nevski] and downy brome (Bromus tectorum L.) dominate millions of hectares of grasslands in the western United States. Applying picloram, aminopyralid, and other growth regulator herbicides at late growth stages reduces seed production of most exotic annual grasses. In this study, we applied aminopyralid to T. caput-medusae to determine how reducing seed production in the current growing season influenced cover in the subsequent growing season. At eight annual grassland sites, we applied aminopyralid at 55, 123, and 245 g ae ha−1 in spring just before T. caput-medusae heading. The two higher rates were also applied pre-emergence (PRE) in fall to allow comparisons with this previously tested timing. When applied in spring during the roughly 10-d period between the flag leaf and inflorescence first becoming visible, just 55 g ae ha−1 of aminopyralid greatly limited seed production and subsequently reduced T. caput-medusae cover to nearly zero. Fall aminopyralid applications were less effective against T. caput-medusae, even at a rate of 245 g ae ha−1. The growing season of application, fall treatments, but not spring treatments, sometimes reduced cover of desirable winter annual forage grasses. The growing season after application, both spring and fall treatments tended to increase forage grasses, though spring treatments generally caused larger increases. Compared with other herbicide treatment options, preheading aminopyralid treatments are a relatively inexpensive, effective approach for controlling T. caput-medusae and increasing forage production.
Habits are behavioral routines that are automatic and frequent, relatively independent of any desired outcome, and have potent antecedent cues. Among individuals with anorexia nervosa (AN), behaviors that promote the starved state appear habitual, and this is the foundation of a recent neurobiological model of AN. In this proof-of-concept study, we tested the habit model of AN by examining the impact of an intervention focused on antecedent cues for eating disorder routines.
The primary intervention target was habit strength; we also measured clinical impact via eating disorder psychopathology and actual eating. Twenty-two hospitalized patients with AN were randomly assigned to 12 sessions of either Supportive Psychotherapy or a behavioral intervention aimed at cues for maladaptive behavioral routines, Regulating Emotions and Changing Habits (REaCH).
Covarying for baseline, REaCH was associated with a significantly lower Self-Report Habit Index (SRHI) score and significantly lower Eating Disorder Examination-Questionnaire (EDE-Q) global score at the end-of-treatment. The end-of-treatment effect size for SRHI was d = 1.28, for EDE-Q was d = 0.81, and for caloric intake was d = 1.16.
REaCH changed habit strength of maladaptive routines more than an active control therapy, and targeting habit strength yielded improvement in clinically meaningful measures. These findings support a habit-based model of AN, and suggest habit strength as a mechanism-based target for intervention.
The re-emergence of debates on the decolonisation of knowledge has revived interest in the National Question, which began over a century ago and remains unresolved. Tensions that were suppressed and hidden in the past are now being openly debated. Despite this, the goal of one united nation living prosperously under a constitutional democracy remains elusive. This edited volume examines the way in which various strands of left thought have addressed the National Question, especially during the apartheid years, and goes on to discuss its relevance for South Africa today and in the future. Instead of imposing a particular understanding of the National Question, the editors identified a number of political traditions and allowed contributors the freedom to define the question as they believed appropriate – in other words, to explain what they thought was the Unresolved National Question. This has resulted in a rich tapestry of interweaving perceptions. The volume is structured in two parts. The first examines four foundational traditions: Marxism-Leninism (the Colonialism of a Special Type thesis); the Congress tradition; the Trotskyist tradition; and Africanism. The second part explores the various shifts in the debate from the 1960s onwards, and includes chapters on Afrikaner nationalism, ethnic issues, black consciousness, feminism, workerism and constitutionalism. The editors hope that by revisiting the debates not popularly known among the scholarly mainstream, this volume will become a catalyst for an enriched debate on our identity and our future.