Eight years after the Institute of Medicine recommended survivorship care plans (SCPs) for all cancer survivors, this study systematically reviewed the evidence for their use.
Studies evaluating ...outcomes after implementation of SCPs for cancer survivors were identified by searching databases (MEDLINE, EMBASE and Cochrane). Data were extracted and summarised.
Ten prospective studies (2286 survivors) met inclusion criteria (5 randomised controlled trials (RCTs)). Study populations included survivors of breast, gynaecological, colorectal and childhood cancer. Several models of SCP were evaluated (paper based/on-line, oncologist/nurse/primary-care physician-delivered and different templates). No significant effect of SCPs was found on survivor distress, satisfaction with care, cancer-care coordination or oncological outcomes in RCTs. Breast cancer survivors with SCPs were better able to correctly identify the clinician responsible for their follow-up care. One study suggested a positive impact on reducing unmet needs. Levels of survivor satisfaction with, and self-reported understanding of, their SCP were very high. Feasibility was raised by health professionals as a significant barrier, as SCPs took 1-4 h of their time to develop.
Emerging evidence shows very few measurable benefits of SCPs. Survivors reported high levels of satisfaction with SCPs. Resource issues were identified as a significant barrier to implementation.
While being overweight or obese in adolescence may have detrimental effects on academic attainment, the evidence base is limited by reliance on cross-sectional studies with small sample sizes, ...failure to take account of confounders and lack of consideration of potential mediators. The present study aimed to address these limitations and examine longitudinal associations between obesity in adolescence and academic attainment.
Associations between weight status at 11 years old and academic attainment assessed by national tests at 11, 13 and 16 years were examined in the Avon Longitudinal Study of Parents and Children. Healthy weight was defined as body mass index (BMI) Z-score <1.04; overweight as BMI Z-score 1.04-1.63; obesity as BMI Z-score ⩾1.64.
Data from 5966 participants with objectively measured weight status were examined: 71.4% were healthy weight (1935 males; 2325 females), 13.3% overweight (372 males; 420 females) and 15.3% obese (448 males; 466 females).
Girls obese at 11 years had lower academic attainment at 11, 13 and 16 years compared with those of a healthy weight, even after controlling for a wide range of confounders. Associations between obesity and academic attainment were less clear in boys. The potential mediating effects of depressive symptoms, intelligence quotient (IQ) and age of menarche in girls were explored, but when confounders were included, there was no strong evidence for mediation.
For girls, obesity in adolescence has a detrimental impact on academic attainment 5 years later. Mental health, IQ and age of menarche did not mediate this relationship, suggesting that further work is required to understand the underlying mechanisms. Parents, education and public health policy makers should consider the wide reaching detrimental impact of obesity on educational outcomes in this age group.
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy ...number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10
), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10
) and 1.68 (P=2.18 × 10
), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10
) for all patients and 3.19 (P=1.23 × 10
) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10
), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.
Objective To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth.Design Secondary analysis of data from the Millennium ...Cohort Study (MCS).Setting Longitudinal study of infants born in the United Kingdom between 2000 and 2002.Participants 18 818 infants participated in the MCS. Effects of gestational age at birth on health outcomes at 3 (n=14 273) and 5 years (n=14 056) of age were analysed.Main outcome measures Growth, hospital admissions, longstanding illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating of their children’s health.Results Measures of general health, hospital admissions, and longstanding illness showed a gradient of increasing risk of poorer outcome with decreasing gestation, suggesting a “dose-response” effect of prematurity. The greatest contribution to disease burden at 3 and 5 years was in children born late/moderate preterm or early term. Population attributable fractions for having at least three hospital admissions between 9 months and 5 years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to 6.5%) for children born very preterm (<32 weeks). Similarly, 2.7% (1.1% to 4.3%), 5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at 5 years were attributed to very preterm birth, moderate/late preterm birth, and early term birth.Conclusions These results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies. Additional research should quantify how much of the effect is due to maternal/fetal complications rather than prematurity itself. Irrespective of the reason for preterm birth, large numbers of these babies present a greater burden on public health services than very preterm babies.
The Integrated Science Investigation of the Sun (ISIS) is a complete science investigation on the Solar Probe Plus (SPP) mission, which flies to within nine solar radii of the Sun’s surface. ISIS ...comprises a two-instrument suite to measure energetic particles over a very broad energy range, as well as coordinated management, science operations, data processing, and scientific analysis. Together, ISIS observations allow us to explore the mechanisms of energetic particles dynamics, including their: (1) Origins—defining the seed populations and physical conditions necessary for energetic particle acceleration; (2) Acceleration—determining the roles of shocks, reconnection, waves, and turbulence in accelerating energetic particles; and (3) Transport—revealing how energetic particles propagate from the corona out into the heliosphere. The two ISIS Energetic Particle Instruments measure lower (EPI-Lo) and higher (EPI-Hi) energy particles. EPI-Lo measures ions and ion composition from ∼20 keV/nucleon–15 MeV total energy and electrons from ∼25–1000 keV. EPI-Hi measures ions from ∼1–200 MeV/nucleon and electrons from ∼0.5–6 MeV. EPI-Lo comprises 80 tiny apertures with fields-of-view (FOVs) that sample over nearly a complete hemisphere, while EPI-Hi combines three telescopes that together provide five large-FOV apertures. ISIS observes continuously inside of 0.25 AU with a high data collection rate and burst data (EPI-Lo) coordinated with the rest of the SPP payload; outside of 0.25 AU, ISIS runs in low-rate science mode whenever feasible to capture as complete a record as possible of the solar energetic particle environment and provide calibration and continuity for measurements closer in to the Sun. The ISIS Science Operations Center plans and executes commanding, receives and analyzes all ISIS data, and coordinates science observations and analyses with the rest of the SPP science investigations. Together, ISIS’ unique observations on SPP will enable the discovery, untangling, and understanding of the important physical processes that govern energetic particles in the innermost regions of our heliosphere, for the first time. This paper summarizes the ISIS investigation at the time of the SPP mission Preliminary Design Review in January 2014.
We present a time‐of‐flight mass spectrometer design for the measurement of ions in the ~30 keV to 10 MeV range for protons (up to ~40 MeV and ~150 MeV for He and heavy ions, respectively) and ~30 ...keV to 1 MeV range for electrons, covering half of the sky with 80 apertures. The instrument, known as the “Mushroom,” owing to its shape, solves the field of view problem for magnetospheric and heliospheric missions that employ three‐axis stabilized spacecraft, yet still require extended angular coverage; the Mushroom is also compatible with a spinning spacecraft. The most important new feature of the Mushroom is the method through which uncomplicated electrostatic optics and clean position sensing combine to permit many apertures to fit into a compact, low‐mass sensor head (or wedge), several of which (ideally eight) compose a full instrument. Most of the sensor head's volume is an empty, equipotential region, resulting in the modest 250 g mass of each 10‐aperture wedge. The Mushroom is capable of separating ion species across most of its energy range and angular field of view. For example, separation of the neighboring 3He and 4He isotopes is excellent; the full width at half maximum mass resolution has been measured to be 0.24 amu to 0.32 amu, respectively. Converting this to a Gaussian width σm in mass m, this represents a σm/m mass resolution better than 0.04. This separation is highly desirable for the flight program for which the first Mushroom was built, the Solar Probe Plus mission. More generally, we estimate the mass resolution to be σm/m ≈ 0.1, but this is energy, mass, and angularly dependent. We also discuss the solid‐state detector stack capability, which extends the energy range of protons and helium, with composition, to ~100 MeV.
Key Points
Anisotropy, pitch angle distributions, and large field of view are important for energetic ion and electron science
The “Mushroom” instrument has been developed by JHU/APL to provide needed large FOV and angular resolution
The first Mushroom, EPI‐Lo, part of the ISʘIS investigation on Solar Probe Plus, has achieved excellent composition and spatial separation
Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional ...antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.
Toxoplasma gondii, an obligate intracellular parasite of the phylum Apicomplexa, can cause severe disease in humans with an immature or suppressed immune system. The outcome of Toxoplasma infection ...is highly dependent on the strain type, as are many of its in vitro growth properties. Here we use genetic crosses between type II and III lines to show that strain-specific differences in the modulation of host cell transcription are mediated by a putative protein kinase, ROP16. Upon invasion by the parasite, this polymorphic protein is released from the apical organelles known as rhoptries and injected into the host cell, where it ultimately affects the activation of signal transducer and activator of transcription (STAT) signalling pathways and consequent downstream effects on a key host cytokine, interleukin (IL)-12. Our findings provide a new mechanism for how an intracellular eukaryotic pathogen can interact with its host and reveal important differences in how different Toxoplasma lineages have evolved to exploit this interaction.
Randomized controlled trials (RCT) are required to test relationships between physical activity and cognition in children, but these must be informed by exploratory studies. This study aimed to ...inform future RCT by: conducting practical utility and reliability studies to identify appropriate cognitive outcome measures; piloting an RCT of a 10 week physical education (PE) intervention which involved 2 hours per week of aerobically intense PE compared to 2 hours of standard PE (control).
64 healthy children (mean age 6.2 yrs SD 0.3; 33 boys) recruited from 6 primary schools. Outcome measures were the Cambridge Neuropsychological Test Battery (CANTAB), the Attention Network Test (ANT), the Cognitive Assessment System (CAS) and the short form of the Connor's Parent Rating Scale (CPRS:S). Physical activity was measured habitually and during PE sessions using the Actigraph accelerometer.
Test- retest intraclass correlations from CANTAB Spatial Span (r 0.51) and Spatial Working Memory Errors (0.59) and ANT Reaction Time (0.37) and ANT Accuracy (0.60) were significant, but low. Physical activity was significantly higher during intervention vs. control PE sessions (p < 0.0001). There were no significant differences between intervention and control group changes in CAS scores. Differences between intervention and control groups favoring the intervention were observed for CANTAB Spatial Span, CANTAB Spatial Working Memory Errors, and ANT Accuracy.
The present study has identified practical and age-appropriate cognitive and behavioral outcome measures for future RCT, and identified that schools are willing to increase PE time.
ISRCTN70853932 (http://www.controlled-trials.com).
Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. ...The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.
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