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Oral treatment (targeted or chemotherapy) for cancer is being increasingly used. While fatigue is a known side effect of intravenous chemotherapy, the rate of fatigue and the impact of fatigue on other patient-reported outcomes are not well described.
At Massachusetts General Hospital Cancer Center, 180 adult patients prescribed oral targeted or chemotherapy for various malignancies enrolled in a randomized controlled trial of adherence and symptom management. Patients completed baseline self-reported measures of fatigue (Brief Fatigue Inventory; BFI), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale; HADS), and quality of life, including subscales for physical, social, emotional, and functional well-being ([QOL] Functional Assessment of Cancer Therapy — General; FACT-G). We examined clinically relevant fatigue using a validated cut-off score for moderate-severe fatigue (BFI global fatigue ≥4) and tested the associations with anxiety symptoms, depressive symptoms, and QOL with independent samples t-tests.
At baseline, 45 of 180 participants (25.0%) reported moderate-severe fatigue. Fatigued patients experienced more anxiety symptoms (mean diff. 3.73, P < 0.001), more depressive symptoms (mean diff. 4.14, P < 0.001), and worse QOL on the total FACT-G score (mean diff. −19.58, P < 0.001) and all subscales of the FACT-G compared to patients without moderate-severe fatigue.
Significance of results
One in four patients on oral treatment for cancer experienced clinically relevant fatigue that is associated with greater anxiety and depressive symptoms and worse QOL.
TwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King’s College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several ‘omic’ technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the ‘TwinsUK’ resource with the scientific community — interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.
Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up.
Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models.
Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups.
These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.
Attention impairment is an under-investigated feature and diagnostic criterion of Major Depressive Disorder (MDD) that is associated with poorer outcomes. Despite increasing knowledge regarding mechanisms of attention in healthy adults, we lack a detailed characterization of attention impairments and their neural signatures in MDD.
Here, we focus on selective attention and advance a deep multi-modal characterization of these impairments in MDD, using data acquired from n = 1008 patients and n = 336 age- and sex-matched healthy controls. Selective attention impairments were operationalized and anchored in a behavioral performance measure, assessed within a battery of cognitive tests. We sought to establish the accompanying neural signature using independent measures of functional magnetic resonance imaging (15% of the sample) and electroencephalographic recordings of oscillatory neural activity.
Greater impairment on the behavioral measure of selective attention was associated with intrinsic hypo-connectivity of the fronto-parietal attention network. Not only was this relationship specific to the fronto-parietal network unlike other large-scale networks; this hypo-connectivity was also specific to selective attention performance unlike other measures of cognition. Selective attention impairment was also associated with lower posterior alpha (8–13 Hz) power at rest and was related to more severe negative bias (frequent misidentifications of neutral faces as sad and lingering attention on sad faces), relevant to clinical features of negative attributions and brooding. Selective attention impairments were independent of overall depression severity and of worrying or sleep problems.
These results provide a foundation for the clinical translational development of objective markers and targeted therapeutics for attention impairment in MDD.
We describe the design and deployment of GREENBURST, a commensal Fast Radio Burst (FRB) search system at the Green Bank Telescope. GREENBURST uses the dedicated L-band receiver tap to search over the 960–1 920 MHz frequency range for pulses with dispersion measures out to
. Due to its unique design, GREENBURST is capable of conducting searches for FRBs when the L-band receiver is not being used for scheduled observing. This makes it a sensitive single pixel detector capable of reaching deeper in the radio sky. While single pulses from Galactic pulsars and rotating radio transients will be detectable in our observations, and will form part of the database we archive, the primary goal is to detect and study FRBs. Based on recent determinations of the all-sky rate, we predict that the system will detect approximately one FRB for every 2–3 months of continuous operation. The high sensitivity of GREENBURST means that it will also be able to probe the slope of the FRB fluence distribution, which is currently uncertain in this observing band.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
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.
To sustainably improve cleaning of high-touch surfaces (HTSs) in acute-care hospitals using a multimodal approach to education, reduction of barriers to cleaning, and culture change for environmental services workers.
The study was conducted in 2 academic acute-care hospitals, 2 community hospitals, and an academic pediatric and women’s hospital.
Frontline environmental services workers.
A 5-module educational program, using principles of adult learning theory, was developed and presented to environmental services workers. Audience response system (ARS), videos, demonstrations, role playing, and graphics were used to illustrate concepts of and the rationale for infection prevention strategies. Topics included hand hygiene, isolation precautions, personal protective equipment (PPE), cleaning protocols, and strategies to overcome barriers. Program evaluation included ARS questions, written evaluations, and objective assessments of occupied patient room cleaning. Changes in hospital-onset C. difficile infection (CDI) and methicillin-resistant S. aureus (MRSA) bacteremia were evaluated.
On average, 357 environmental service workers participated in each module. Most (93%) rated the presentations as ‘excellent’ or ‘very good’ and agreed that they were useful (95%), reported that they were more comfortable donning/doffing PPE (91%) and performing hand hygiene (96%) and better understood the importance of disinfecting HTSs (96%) after the program. The frequency of cleaning individual HTSs in occupied rooms increased from 26% to 62% (P < .001) following the intervention. Improvement was sustained 1-year post intervention (P < .001). A significant decrease in CDI was associated with the program.
A novel program that addressed environmental services workers’ knowledge gaps, challenges, and barriers was well received and appeared to result in learning, behavior change, and sustained improvements in cleaning.
The warm, equable, and ice-free early Eocene Epoch permits investigation of ecosystem function and macro-ecological patterns during a very different climate regime than exists today. It also provides insight into what the future may entail, as anthropogenic CO2 release drives Earth toward a comparable hothouse condition. Studying plant–insect herbivore food webs during hothouse intervals is warranted, because these account for the majority of nonmicrobial terrestrial biodiversity. Here, we report new plant and insect herbivore damage census data from two floodplain sites in the Wind River Basin of central Wyoming, one in the Aycross Formation (50–48.25 Ma) at the basin edge (WRE) and the second in the Wind River Formation in the interior of the basin (WRI). The WRI site is in stratigraphic proximity to a volcanic ash that is newly dated to 52.416 ± 0.016/0.028/0.063 (2σ). We compare the Wind River Basin assemblages to published data from a 52.65 Ma floodplain flora in the neighboring Bighorn (BH) Basin and find that only 5.6% of plant taxa occur at all three sites and approximately 10% occur in both basins. The dissimilar floras support distinct suites of insect herbivores, as recorded by leaf damage. The relatively low-diversity BH flora has the highest diversity of insect damage, contrary to hypotheses that insect herbivore diversity tracks floral diversity. The distinctiveness of the WRE flora is likely due to its younger age and cooler reconstructed paleotemperature, but these factors are nearly identical for the WRI and BH floras. Site-specific microenvironmental factors that cannot be measured easily in deep time may account for these differences. Alternatively, the Owl Creek Mountains between the two basins may have provided a formidable barrier to the thermophilic organisms that inhabited the basin interiors, supporting Janzen's hypothesis that mountain passes appear higher in tropical environments.
Precise radiocarbon (14C) dating of sedimentary sequences is important for developing robust chronologies of environmental change, but sampling of suitable components can be challenging in highly dynamic landscapes. Here we investigate radiocarbon determinations of different peat size fractions from six peat sites, representing a range of geomorphological contexts on the South Atlantic subantarctic islands of the Falklands and South Georgia. To investigate the most suitable fraction for dating, 112 measurements were obtained from three components within selected horizons: a fine fraction <0.2 mm, a coarse fraction >0.2 mm, and bulk material. We find site selection is critical, with locations surrounded by high-ground and/or relatively slowly accumulating sites more susceptible to the translocation of older carbon. Importantly, in locations with reduced potential for redeposition of material, our results show that there is no significant or systematic difference between ages derived from bulk material, fine or coarse (plant macrofossil) material, providing confidence in the resulting age model. Crucially, in areas comprising complex terrain with extreme relief, we recommend dating macrofossils or bulk carbon rather than a fine fraction, or employing comprehensive dating of multiple sedimentary fractions to determine the most reliable fraction(s) for developing a robust chronological framework.
Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala–ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.
Current techniques for measuring the dry matter intake (DMI) of grazing lactating beef cows are invasive, time consuming and expensive making them impractical for use on commercial farms. This study was undertaken to explore the potential to develop and validate a model to predict DMI of grazing lactating beef cows, which could be applied in a commercial farm setting, using non-invasive animal measurements. The calibration dataset used to develop the model was comprised of 94 measurements recorded on 106 beef or beef–dairy crossbred cows (maternal origin). The potential of body measurements, linear type scoring, grazing behaviour and thermal imaging to predict DMI in combination with known biologically plausible adjustment variables and energy sinks was investigated. Multivariable regression models were constructed for each independent variable using SAS PROC REG and contained milk yield, BW, parity, calving day and maternal origin (dairy or beef). Of the 94 variables tested, 32 showed an association with DMI (P < 0.25) upon multivariable analysis. These variables were incorporated into a backwards linear regression model using SAS PROC REG. Variables were retained in this model if P < 0.05. Five variables; width at pins, full body depth, ruminating mastications, central ligament and rump width score, were retained in the model in addition to milk yield, BW, parity, calving day and maternal origin. The inclusion of these variables in the model increased the predictability of DMI by 0.23 (R2 = 0.68) when compared to a model containing milk yield, BW, parity, calving day and maternal origin only. This model was applied to data recorded on an independent dataset; a herd of 60 lactating beef cows two years after the calibration study. The R2 for the validation was 0.59. Estimates of DMI are required for measuring feed efficiency. While acknowledging challenges in applicability, the findings suggest a model such as that developed in this study may be used as a tool to more easily and less invasively estimate DMI on large populations of commercial beef cows, and therefore measure feed efficiency.
We present an account of why we decided to retract a paper. We discovered a lack of adherence to conventional trials registration, execution, interpretation and reporting, and consequently, with the authors, needed to correct the scientific record. We set out our responses in general to strengthen research integrity.
Declaration of interest
K.S.B. is Editor-in-Chief of the British Journal of Psychiatry. W.L., K.R.K. and S.M.L. are members of the senior editorial committee and the research integrity committee for the journal. In the past three years, S.M.L. has received research support from Janssen and Lundbeck, and personal support from Janssen, Otsuka and Sunovion.
Proactive integrated weed management (IWM) is critically needed in no-till production to reduce the intensity of selection pressure for herbicide-resistant weeds. Reducing the density of emerged weed populations and the number of larger individuals within the population at the time of herbicide application are two practical management objectives when integrating cover crops as a complementary tactic in herbicide-based production systems. We examined the following demographic questions related to the effects of alternative cover-cropping tactics following small grain harvest on preplant, burndown management of horseweed (Erigeron canadensis L.) in no-till commodity-grain production: (1) Do cover crops differentially affect E. canadensis density and size inequality at the time of herbicide exposure? (2) Which cover crop response traits are drivers of E. canadensis suppression at time of herbicide exposure? Interannual variation in growing conditions (study year) and intra-annual variation in soil fertility (low vs. high nitrogen) were the primary drivers of cover crop response traits and significantly affected E. canadensis density at the time of herbicide exposure. In comparison to the fallow control, cover crop treatments reduced E. canadensis density 52% to 86% at the time of a preplant, burndown application. Cereal rye (Secale cereale L.) alone or in combination with forage radish (Raphanus sativus L.) provided the most consistent E. canadensis suppression. Fall and spring cover crop biomass production was negatively correlated with E. canadensis density at the preplant burndown application timing. Our results also show that winter-hardy cover crops reduce the size inequality of E. canadensis populations at the time of herbicide exposure by reducing the number of large individuals within the population. Finally, we advocate for advancement in our understanding of complementarity between cover crop– and herbicide-based management tactics in no-till systems to facilitate development of proactive, herbicide-resistant management strategies.
We present a workflow to track icebergs in proglacial fjords using oblique time-lapse photos and the Lucas-Kanade optical flow algorithm. We employ the workflow at LeConte Bay, Alaska, where we ran five time-lapse cameras between April 2016 and September 2017, capturing more than 400 000 photos at frame rates of 0.5–4.0 min−1. Hourly to daily average velocity fields in map coordinates illustrate dynamic currents in the bay, with dominant downfjord velocities (exceeding 0.5 m s−1 intermittently) and several eddies. Comparisons with simultaneous Acoustic Doppler Current Profiler (ADCP) measurements yield best agreement for the uppermost ADCP levels (~ 12 m and above), in line with prevalent small icebergs that trace near-surface currents. Tracking results from multiple cameras compare favorably, although cameras with lower frame rates (0.5 min−1) tend to underestimate high flow speeds. Tests to determine requisite temporal and spatial image resolution confirm the importance of high image frame rates, while spatial resolution is of secondary importance. Application of our procedure to other fjords will be successful if iceberg concentrations are high enough and if the camera frame rates are sufficiently rapid (at least 1 min−1 for conditions similar to LeConte Bay).
Surgery for CHD has been slow to develop in parts of the former Soviet Union. The impact of an 8-year surgical assistance programme between an emerging centre and a multi-disciplinary international team that comprised healthcare professionals from developed cardiac programmes is analysed and presented.
Material and methods
The international paediatric assistance programme included five main components – intermittent clinical visits to the site annually, medical education, biomedical engineering support, nurse empowerment, and team-based practice development. Data were analysed from visiting teams and local databases before and since commencement of assistance in 2007 (era A: 2000–2007; era B: 2008–2015). The following variables were compared between periods: annual case volume, operative mortality, case complexity based on Risk Adjustment for Congenital Heart Surgery (RACHS-1), and RACHS-adjusted standardised mortality ratio.
A total of 154 RACHS-classifiable operations were performed during era A, with a mean annual case volume by local surgeons of 19.3 at 95% confidence interval 14.3–24.2, with an operative mortality of 4.6% and a standardised mortality ratio of 2.1. In era B, surgical volume increased to a mean of 103.1 annual cases (95% confidence interval 69.1–137.2, p<0.0001). There was a non-significant (p=0.84) increase in operative mortality (5.7%), but a decrease in standardised mortality ratio (1.2) owing to an increase in case complexity. In era B, the proportion of local surgeon-led surgeries during visits from the international team increased from 0% (0/27) in 2008 to 98% (58/59) in the final year of analysis.
The model of assistance described in this report led to improved adjusted mortality, increased case volume, complexity, and independent operating skills.
Migrant youths endure many challenges. Such challenges can be stressful and lead to psychological difficulties. We investigated the relationship between migration, psychopathology and stressful events in children and adolescents. We hypothesised that migrant youths would show higher levels of psychopathology and more stressful life events than non-migrant youths.
Using the Child cohort (Cohort ‘98) of the ‘Growing up in Ireland’ study we investigated psychopathology, as measured by the Strengths and Difficulties questionnaire (SDQ) at age 9 and 13 and stressful life events in migrant and non-migrant youths.
There was no significant difference between the proportion of migrant and non-migrant youths reporting psychopathology in childhood (p>0.05) or adolescence (p>0.05). Analysis of the SDQ subscales revealed that a significantly greater proportion of migrant youths had hyperactivity problems in childhood (p = 0.04) but a greater proportion of non-migrant youths had emotional problems in early adolescence (p = 0.04). We found that migrant youths experienced significantly more stressful life events than their non-migrant counterparts (p<0.01), however, once ‘Moving house/country‘ was removed as a stressor, there was no difference between the groups (p>0.27).
Contrary to our hypothesis, we observed that there were few differences between migrant and non-migrant youths in the levels of psychopathology. Migrant youths experienced a greater number of stressful life events, however, this was attributable to stressors relating to moving. An increased understanding of the factors promoting resilience, as demonstrated by the migrant youths, could aid health professionals and policy makers to effectively tailor interventions for mental health promotion.
Wearable devices such as a wrist actigraph may have a potential to objectively estimate patients’ functioning and may supplement performance status (PS). This proof-of-concept study aimed to evaluate whether actigraphy data are significantly associated with patients’ functioning and are predictive of their survival in patients with metastatic non-small cell lung cancer.
We collected actigraphy data for a three-day period in ambulatory patients with stage IV non-small cell lung cancer. We computed correlations between actigraphy data (specifically, proportion of time spent immobile while awake) and clinician-rated PS, subjective report of physical activities, quality of life (the Functional Assessment of Cancer Therapy – Trial Outcome Index), and survival.
Actigraphy data (the proportion of time awake spent immobile) were significantly correlated with Functional Assessment of Cancer Therapy – Trial Outcome Index (r = −0.53, p < 0.001) and with the Eastern Cooperative Oncology Group PS (ECOG PS) (r = 0.37, p < 0.001). The proportion of time awake spent immobile was significantly associated with worse survival. For each 10% increase in this measure, the hazard ratio (HR) was 1.48 (95% confidence interval [CI95%] = 1.06, 2.06) for overall mortality, and odds ratio was 2.99 (CI95% = 1.27, 7.05) for six-month mortality. ECOG PS was also associated with worse survival (HR = 2.80, CI95% = 1.34, 5.86). Among patients with ECOG PS 0-1, the percentage of time awake spent immobile was significantly associated with worse survival, HR = 1.93 (CI95% = 1.10, 3.42), whereas ECOG PS did not predict survival.
Significance of Results
Actigraphy may have potential to predict important clinical outcomes, such as quality of life and survival, and may serve to supplement PS. Further validation study is warranted.
To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition.
In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15–28 weeks) and third trimester (28–39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes.
Women were recruited from twelve US sites (2009–2013).
Non-obese women with singleton pregnancies (n 2334).
A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (−0·57 to −0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (−0·05 to 0·06 mm per week).
The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.