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Pelvic internal organs change in volume and position during radiotherapy. This may compromise the efficacy of treatment or worsen its toxicity. There may be limitations to fully correcting these changes using online image guidance; therefore, effective and consistent patient preparation and positioning remain important. This review aims to provide an overview of the extent of pelvic organ motion and strategies to manage this motion.
Methods and Materials:
Given the breadth of this topic, a systematic review was not undertaken. Instead, existing systematic reviews and individual high-quality studies addressing strategies to manage pelvic organ motion have been discussed. Suggested levels of evidence and grades of recommendation for each strategy have been applied.
Various strategies to manage rectal changes have been investigated including diet and laxatives, enemas and rectal emptying tubes and rectal displacement with endorectal balloons (ERBs) and rectal spacers. Bladder-filling protocols and bladder ultrasound have been used to try to standardise bladder volume. Positioning the patient supine, using a full bladder and positioning prone with or without a belly board, has been examined in an attempt to reduce the volume of irradiated small bowel. Some randomised trials have been performed, with evidence to support the use of ERBs, rectal spacers, bladder-filling protocols and the supine over prone position in prostate radiotherapy. However, there was a lack of consistent high-quality evidence that would be applicable to different disease sites within the pelvis. Many studies included small numbers of patients were non-randomised, used less conformal radiotherapy techniques or did not report clinical outcomes such as toxicity.
There is uncertainty as to the clinical benefit of many of the commonly adopted interventions to minimise pelvic organ motion. Given this and the limitations in online image guidance compensation, further investigation of adaptive radiotherapy strategies is required.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
OBJECTIVES/SPECIFIC AIMS: In the first aim, we will evaluate the proportion of highly HIV-susceptible memory CD4+ T cells present in the rectal mucosa, based on the proliferation status and expression of the HIV susceptibility markers, CCR5 and α4β7, between HIV-negative adolescent MSM and adult MSM engaging in RAI. The second aim will assess differences between the two study groups in the ratio of Th17 cells (CD4+ IL17+) to Treg cells (CD4+ FoxP3+ CD25+) in the rectal mucosa as a determinant of mucosal inflammation. Finally, in the third aim, we will utilize ex vivo rectal biopsy explant challenge experiments to examine whether HIV target cell availability and the Th17/Treg ratio influence rectal mucosal HIV susceptibility. METHODS/STUDY POPULATION: Rectal biopsy specimens are being collected from healthy, HIV-negative men that comprise the two study groups: 40 adolescent MSM 18-21 years of age who have engaged in RAI at least once previously in their lifetime and 40 adult MSM ≥35 years of age who have engaged in RAI for the previous 5 consecutive years with a minimum of 12 episodes annually. To identify CD4+ subsets of interest for aims 1 and 2, rectal mucosal mononuclear cells are isolated and phenotyped with CD45, CD3, CD4, CD45RA, CCR7, CD69, CCR5, α4β7, Ki67, FOXP3, and CD25 antibodies. To identify the Th17 cell subtype, the cells are stimulated with PMA/Ionamycin and stained with an antibody specific to IL-17A. Using cross-sectional analyses, we will compare the frequencies of mucosal CD4+ T cells that express certain phenotypic characteristics and evaluate differences in the Th17/Treg ratio between adolescent and adult MSM. For aim 3, rectal biopsy specimens are inoculated with HIV virus and the culture supernatant is assayed for p24 concentration on days 3, 7, 10 14, and 18. Longitudinal analyses will be performed to detect differences in p24 concentration at each time point and assess associations with mucosal target cell availability and with the Th17/Treg ratio. RESULTS/ANTICIPATED RESULTS: We hypothesize that younger age will be associated with enhanced memory CD4+ T cell proliferation and increased expression of HIV susceptibility markers (CCR5 and/or α4β7). In addition, we expect that the rectal mucosa of adolescent MSM will demonstrate a higher Th17/Treg ratio as compared to adult MSM, which could facilitate HIV transmission. It is also anticipated that rectal mucosal immune phenotypes characterized by increased HIV target cell availability and high Th17/Treg ratios will be associated with enhanced mucosal HIV susceptibility in the explant challenge model. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a paucity of information regarding the mechanisms of rectal HIV transmission, and no studies to date investigate the immunologic effects of aging on transmission in the rectal mucosa. The results from this study will provide important information regarding age-related differences in the immune cell composition of the rectal mucosa as a critical step in better understanding immunologic factors that influence rectal HIV transmission.
The Community Assessment of Psychic Experiences (CAPE) is a 42-item self-report questionnaire that has been developed and validated to measure the dimensions of psychosis in the general population. The CAPE has a three-factor structure with dimensions of positive, negative and depression. Assessing the cross-national equivalence of a questionnaire is an essential prerequisite before pooling data from different countries. In this study, our aim was to investigate the measurement invariance of the CAPE across different countries.
Data were drawn from the European Union Gene-Environment Interaction (EU-GEI) study. Participants (incident cases of psychotic disorder, controls and siblings of cases) were recruited in Brazil, France, Italy, the Netherlands, Spain and UK. To analyse the measurement invariance across these samples, we tested configural invariance (i.e. identical structures of the factors), metric invariance (i.e. equivalence of the factor loadings) and scalar invariance (i.e. equivalence of the thresholds) of the three CAPE dimensions using multigroup categorical confirmatory factor analysis methods.
The configural invariance model fits well, providing evidence for identical factorial structure across countries. In comparison with the configural model invariance, the fit indices were very similar in the metric and scalar invariance models, indicating that factor loadings and thresholds did not differ across the six countries.
We found that, across six countries, the CAPE showed equivalent factorial structure, factor loadings and thresholds. Thus, differences observed in scores between individuals from different countries should be considered as reflecting different levels of psychosis.
For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between ‘soil health’, ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed.
Parameters from in vitro gas production techniques could have potential as predictors of dry-matter intake (DMI) and digestibility. Fermentation is usually carried out under conditions where nitrogen (N) is not limiting. Therefore where N supply is a constraint to intake and digestibility, prediction equations may be inaccurate. This study compared the use of N-free and N-rich media in an in vitro fermentation method (Theodorou et al., 1994) and studied the relationships between in vitro and in vivo parameters obtained using both media.
Objectives: To evaluate prospective and retrospective memory abilities in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans with and without a self-reported history of blast-related mild traumatic brain injury (mTBI). Methods: Sixty-one OEF/OIF/OND Veterans, including Veterans with a self-reported history of blast-related mTBI (mTBI group; n=42) and Veterans without a self-reported history of TBI (control group; n=19) completed the Memory for Intentions Test, a measure of prospective memory (PM), and two measures of retrospective memory (RM), the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. Results: Veterans in the mTBI group exhibited significantly lower PM performance than the control group, but the groups did not differ in their performance on RM measures. Further analysis revealed that Veterans in the mTBI group with current PTSD (mTBI/PTSD+) demonstrated significantly lower performance on the PM measure than Veterans in the control group. PM performance by Veterans in the mTBI group without current PTSD (mTBI/PTSD-) was intermediate between the mTBI/PTSD+ and control groups, and results for the mTBI/PTSD- group were not significantly different from either of the other two groups. Conclusions: Results suggest that PM performance may be a sensitive marker of cognitive dysfunction among OEF/OIF/OND Veterans with a history of self-reported blast-related mTBI and comorbid PTSD. Reduced PM may account, in part, for complaints of cognitive difficulties in this Veteran cohort, even years post-injury. (JINS, 2018, 24, 324–334)
Violence against women and girls (VAWG) is an urgent global health problem. Root causes for VAWG include the individual- and family-level factors of alcohol abuse, mental health problems, violence exposure, and related adverse experiences. Few studies in low- and middle-income countries (LMIC) have assessed the effectiveness of psychological interventions for reducing VAWG. This randomized controlled trial, part of the What Works to Prevent Violence Against Women and Girls consortium, examines the effectiveness of a common elements treatment approach (CETA) for reducing VAWG and comorbid alcohol abuse among families in Zambia.
Study participants are families consisting of three persons: an adult woman, her male husband or partner, and one of her children aged 8–17 (if available). Eligibility criteria include experience of moderate-to-severe intimate partner violence by the woman and hazardous alcohol use by her male partner. Family units are randomized to receive CETA or treatment as usual. The primary outcome is VAWG as measured by the Severity of Violence Against Women Scale, assessed along with secondary outcomes at 24 months post-baseline. Interim assessments are also conducted at 4–5 months (following CETA completion) and 12 months post-baseline.
This ongoing trial is one of the first in sub-Saharan Africa to evaluate the use of an evidence-based common elements approach for reducing VAWG by targeting a range of individual- and family-level factors, including alcohol abuse. Results of this trial will inform policy on what interventions work to prevent VAWG in LMIC with local perspectives on scale up and wider implementation.
Bakaninbreen in Svalbard and Trapridge Glacier in Yukon Territory, Canada, are two prominent examples of surging glaciers which are thought to be controlled by their thermal regime. Both glaciers have developed large bulges which have propagated forward as travelling wave fronts, and which are thought to divide relatively stagnant downstream cold-based ice from faster-moving warm-based upstream ice. Additionally, both glaciers are underlain by a wet, metres thick layer of deforming till. We develop a simple model for the cyclic surging behaviour of these glaciers, which interrelates the motion of the ice and till through a description of the subglacial hydrology. We find that oscillations (surges) can occur if the subglacial hydrological transmissivity is sufficiently low and the till layer is sufficiently thin, and we suggest that these oscillations are associated with the development and propagation of a travelling wave front down the glacier. We therefore interpret the travelling wave fronts on both Trapridge Glacier and Bakaninbreen as manifestations of surges. In addition, we find that the violence of the surge in the model is associated with the resistance to ice flow offered by undulations in the bed, and the efficiency with which occasional hydrological events can release water accumulated at the glacier sole.
Acoustic sub-bottom profiler surveys on the northeast Antarctic Peninsula shelf indicate that parts of the seabed are underlain by an acoustically transparent layer that is thin on the inner shelf and becomes thicker and more extensive towards the outer shelf. Sedimentological and geophysical data are combined to construct a bed model where streaming ice flow, by both deformation and basal sliding, took place within cross-shelf troughs. The model suggests only limited deformation contributed to fast flow on the inner shelf, i.e. in the onset zone of ice streaming, where the bed was predominantly underlain by a stiff till. Thus, fast ice flow in this area might have been by basal sliding, with deformation confined to discontinuous patches of soft till <40 cm thick. Towards the middle and outer shelf, extensive, thick sequences of soft till suggest a change in the dominant subglacial process towards widespread deformation. This downstream change from basal sliding to subglacial deformation is manifest in the transition from stiff-till dominance to soft-till dominance, while a downstream increase in ice flow velocity is evident from the complex geomorphic imprint on the inner shelf evolving to the more restricted set of bedforms on the outer shelf.
Alzheimer’s disease (AD) has long been recognized as a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common “atypical” clinical presentations, including syndromes dominated by visual, aphasic, “frontal,” or apraxic symptoms. Our knowledge of atypical clinical phenotypes of AD comes from clinicopathologic studies, but with the growing use of in vivo molecular biomarkers of amyloid and tau pathology, we are beginning to recognize that these syndromes may not be as rare as once thought. When a clinician is evaluating a patient whose clinical phenotype is dominated by progressive aphasia, complex visual impairment, or other neuropsychiatric symptoms with relative sparing of memory, the differential diagnosis may be broader and a confident diagnosis of an atypical form of AD may require the use of molecular biomarkers. Despite the evolving sophistication in our diagnostic tools, and the acknowledgment of atypical AD syndromes in the 2011 revised diagnostic criteria for AD, the assessment of such patients still poses substantial challenges. We use a case-based approach to review the clinical and imaging phenotypes of a series of patients with typical and atypical AD, and discuss our current approach to their evaluation. One day, we hope that regardless of whether a patient exhibits typical or atypical symptoms of AD pathology, we will be able to identify the condition at a prodromal phase and institute a combination of symptomatic and disease-modifying therapies to support cognitive processes, function, and behavior, and slow or halt progression to dementia.
The archaeological site of Al-Ashoosh is a third-millennium BC settlement
located in the Rub al-Khali Desert (or Empty Quarter), 70km south of Dubai
in the United Arab Emirates (UAE) (Figure 1). This site provides an
excellent example of the type of occupation of the inland deserts of the
Oman peninsula during the period following the Holocene Climatic Optimum.
Between November 2015 and May 2016, the Dubai Municipality and the Sanisera
Archaeology Institute conducted excavations at the site of Al-Ashoosh. This
site was discovered during two seasons of survey in 2002–2003. This survey
work, undertaken by the Dubai Municipality and the Department of Antiquities
of Jordan, identified 33 archaeological sites ranging in date from
prehistory to the late Islamic period. In 2006–2007, more-detailed
archaeological investigations of the area of Al-Ashoosh were conducted,
including survey, excavation and geological sampling (Casana et
al. 2009; Herrmann 2012; Contreras & Carcacer 2016).
To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid levels are associated with episodes of self-harm or depression over a 10-year period.
We included 40 individuals who self-harmed and 40 controls. Episodes of self-harm and depression were ascertained and levels of depression, impulsivity, suicidal ideation and plasma lipid levels measured at baseline and at 10-year follow-up.
Further episode(s) of self-harm occurred in 26% of cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm episodes. Baseline eicosapentaenoic acid levels were modestly correlated with suicidal ideation at follow-up and dihomo-γ-linolenic acid and arachidonic acid were modestly correlated with motor impulsivity at follow-up in cases.
Despite significant negative correlations at baseline between plasma lipids, n-3 PUFAs and psychopathology, these levels were not predictive of clinical outcome over a 10-year period. Further research however is required due to the relatively low sample size and the risk of selection bias due to loss to follow-up in this study.
Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.
This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.
Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).
For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.
Groundnuts are an important crop for Ugandan smallholders because they are high in protein, resupply nutrients to the soil, and are a storable source of wealth once dried. Adoption of virus-resistant seeds that increase yield and reduce yield variance may improve household food security, but the complex relationship is an empirical question. This article considers the effect of improved groundnut seed on smallholder food security in eastern Uganda. Results indicate that adopters have significantly higher household food security after controlling for observed and unobserved household heterogeneity. The food consumption score index increases more than 15 points with improved seed adoption.
Background: Planning for neurology training necessitated a reflection on the experience of graduates. We explored practice characteristics, and training experience of recent graduates. Methods: Graduates from 2010-2014 completed a survey. Results: Response rate was 37% of 211. 56% were female. 91% were adult neurologists. 65% practiced in an outpatient setting. 63% worked in academics. 85% completed subspecialty training (median 1 year). 36% work 3 days a week or less. 82% took general call (median 1 night weekly). Role preparation was considered very good or excellent for most; however poor or fair ratings were 17% in advocacy and 8% in leadership. Training feedback was at least “good” for 87%. Burnout a few times a week or more was noted by 5% (6% during residency, particularly PGY1 and 5). 64% felt overly burdened by paperwork. Although most felt training was adequate, it was poor or fair at preparing for practice management (85%) and personal balance (55%). Most conditions were under-observed in training environment. Many noted a need for more independent practice development and community neurology. Conclusions: Although our training was found to be very good, some identified needs included advocacy training, and more training in general neurology in the longitudinal outpatient/community settings.
Centaurus A (NGC 5128) is a giant early-type galaxy containing the nearest radio-bright AGN. The high-angular resolution Chandra images of Cen A reveal multi-scale X-ray structures with unprecedented detail and clarity. We present results from our study of X-ray structures surrounding the Cen A nuclear region, including the discovery of giant arc-like structures, extending to about 8 kpc in the direction perpendicular to the jet. We compare the X-ray structures with observations in other wavelengths and discuss their implication for a global understanding of the morphology of Cen A.
We describe preliminary results from our study of multi-scale structures in Centaurus A (NGC 5128) obtained using the Chandra X-ray Observatory HRC-I observations. The high-angular resolution Chandra images reveal X-ray multi-scale structures in this object with unprecedented detail and clarity. The region surrounding the Cen A nucleus, believed to be associated with a supermassive black hole, shows structures on arcsecond scales clearly resolved from the central source.
We present preliminary results from a number of deep radio polarization surveys being made of the Magellanic Clouds at 2.3 GHz, 4.75 GHz and 8.55 GHz. Extended and linearly polarized radio emission has been found at 2.3 and 4.75 GHz from both the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC). However, as the analysis of these data is not yet complete we present only some of the 4.75 GHz results at this time.