Multi-GeV Electron Acceleration in Wakefields Strongly Driven by Oversized Laser Spots.

Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250 TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies E_{max}>2.5 GeV, in fields exceeding 500 GV m^{-1}, with more than 80 pC of charge at energies E>1 GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.

Rovibrational analysis of AlCO3, OAlO2, and HOAlO2 for possible atmospheric detection.

The lack of observational data for the AlO molecule in the mesosphere/lower thermosphere may be due to ablated aluminum reacting quickly to form other species. Previously proposed reaction pathways show that aluminum could be ablated in the atmosphere from meteoritic activity, but there currently exist very limited spectroscopic data on the intermediates in these reactions, limiting the possible detection of said molecules. As such, rovibrational spectroscopic data are computed herein using quartic force field methodology at four different levels of theory for the neutral intermediates AlCO3, OAlO2, and HOAlO2. Each molecule exhibits multiple vibrational modes with large vibrational transition intensities. For instance, the C-O stretch (ν1) in AlCO3 has a harmonic intensity of 536 km mol-1, the Al-O stretch (ν2) in OAlO2 has an intensity of 678 km mol-1, and the out-of-plane torsion (ν9) in HOAlO2 has an intensity of 158 km mol-1. All three molecules have exceptionally large dipole moments of 6.27, 4.21, and 5.04 D, respectively. These properties indicate that all three molecules are good candidates for potential atmospheric observation utilizing vibrational and/or rotational spectroscopic techniques.

Spectroscopy and Photochemistry of OAlNO and Implications for New Metal Chemistry in the Atmosphere.

A new aluminum-bearing species, OAlNO, which has the potential to impact the chemistry of the Earth's upper atmosphere, is characterized via high-level, ab initio, spectroscopic methods. Meteor-ablated aluminum atoms are quickly oxidized to aluminum oxide (AlO) in the mesosphere and lower thermosphere (MLT), where a steady-state layer of AlO then builds up. Concurrent formation of nitric oxide (NO) in the same region of the atmosphere will lead to the bimolecular formation of the OAlNO molecule. Molecular orbital analysis provides fundamental insights into the chemical bonding and energetic arrangement of the triplet (1 3A″) ground state and singlet (1 1A') excited-state species of OAlNO. Additionally, unpaired electrons on the terminal oxygen atom of triplet (1 3A″) OAlNO cause it to be reactive to atmospheric species, potentially impacting climate science and high-altitude chemistry. The triplet (1 3A″) ground-state species exhibits a large permanent dipole moment useful for rotational spectroscopic detection; however, similar rotational constants to the singlet (1 1A') excited-state species will hamper differentiation in a spectrum. Strong infrared intensities will assist in detection and discrimination of the different spin states and isomers. Repulsive electronic excited states of OAlNO will lead to photolysis of the Al-N bond and formation of various electronic states of AlO + NO through nonadiabatic pathways. Reaction through the OAlNO intermediate represents a means for the production of electronically excited AlO, leading to new chemistry in the atmosphere. Excitation to higher-lying electronic states will lead to fluorescence with a minor Stokes shift, useful for laboratory investigation. Such physical properties of this molecule will allow for new, unexplored chemical pathways in the MLT to be considered.

Fifty Years of Fungicide Development, Deployment, and Future Use.

Plant disease management has not significantly changed in the past 50 years, even as great strides have been made in the understanding of fungal biology and the etiology of plant disease. Issues of climate change, supply chain failures, war, political instability, and exotic invasives have created even more serious implications for world food and fiber security, and the stability of managed ecosystems, underscoring the urgency for reducing plant disease-related losses. Fungicides serve as the primary example of successful, widespread technology transfer, playing a central role in crop protection, reducing losses to both yield and postharvest spoilage. The crop protection industry has continued to improve upon previous fungicide chemistries, replacing active ingredients lost to resistance and newly understood environmental and human health risks, under an increasingly stricter regulatory environment. Despite decades of advances, plant disease management continues to be a constant challenge that will require an integrated approach, and fungicides will continue to be an essential part of this effort.

Effective communications on invasive alien species: Identifying communication needs of Swedish domestic garden owners.

Invasive alien species threaten biodiversity with domestic gardens acting as a major pathway for the introduction of alien species. Even though the Nordic region is not currently a hotspot for biological invasions, the number of invasions in the Nordic area has been predicted to increase due to climate change. Given a time lag between introduction and invasion, many non-invasive horticultural alien species already introduced into gardens may become invasive in the future. This study aimed to identify the communication needs of Swedish garden owners regarding their management of invasive alien species. A survey among domestic garden owners, informed by topic specialists and local area experts, and interviews with garden owners were conducted in three different bio-climatic areas in a latitudinal gradient across Sweden. The questions targeted invasive alien species and their relations to biodiversity loss and climate change, as well as measures taken to control these species. Analysing the survey data collected in relation to measures taken to control invasive species, Bayesian Additive Regression Tree (BART) modelling was used to identify geographically varying communication needs of the domestic garden owners. In all study areas, the garden owners' measures taken to control invasive alien species were correlated with their strength of beliefs in having experienced local biodiversity loss. A majority of the garden owners were, moreover, uncertain about the impact of climate change on the invasiveness of alien species. In addition, the garden owners' capacity for identifying invasive alien species was often in need of improvement, in particular with respect to the species Impatiens glandulifera, Reynoutria japonica and Rosa rugosa. The results suggest that the evidence-based guidelines for effective communications we developed, have the potential to help communicators meet the local communication needs of garden owners across Sweden, in relation to the management of invasive alien garden species.

Distinct Regionalization Patterns of Cortical Morphology are Associated with Cognitive Performance Across Different Domains.

Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.

Lack of impact of radiologic septal measurements upon patient symptoms and performance of septoplasty during endoscopic sinus surgery.

BACKGROUND: Recent literature suggests that concurrent septoplasty during endoscopic sinus surgery (ESS) improves patient outcomes, however, the underlying indications for performing concurrent septoplasty are unknown. The objective of this study was to investigate the relationship between objective radiologic measures of nasal septal deviation with preoperative patient symptomatology and measures of CRS disease severity. We also sought to understand the association of objective radiologic measurements with surgeon performance of concurrent septoplasty during ESS. METHODOLOGY: Seventy-four patients with CRS undergoing ESS were prospectively enrolled. Angles of septal deviation, intranasal areas and volumes were assessed on preoperative computed tomography (CT) scans and correlated with a robust battery of patient reported outcomes measures (PROMs), objective measures of CRS severity including olfaction scores, radiologic and endoscopic staging, and performance of septoplasty. RESULTS: Intranasal areas and volumes demonstrated only weak linear associations with patient-reported nasal congestion, however, angles of septal deviation alone did not correlate with congestion or any other PROM measure. Meanwhile, radiologic septal-related measurements did not correlate with objective measures of CRS disease severity or the performance of a concurrent septoplasty. CONCLUSIONS: Though prior studies demonstrate improved patient outcomes in the setting of concurrent septoplasty during ESS, this study failed to establish an association between preoperative radiologic septal-related measurements and patient symptomatology or surgeon decision to perform septoplasty. Although objective factors to identify patients most likely to benefit from concurrent septoplasty remain unidentified, the potential improvement of surgical recommendations and patient outcomes makes this an important area of continued investigation.

Tunable Plasma-Based Energy Dechirper.

A tunable plasma-based energy dechirper has been developed at FLASHForward to remove the correlated energy spread of a 681 MeV electron bunch. Through the interaction of the bunch with wakefields excited in plasma the projected energy spread was reduced from a FWHM of 1.31% to 0.33% without reducing the stability of the incoming beam. The experimental results for variable plasma density are in good agreement with analytic predictions and three-dimensional simulations. The proof-of-principle dechirping strength of 1.8 GeV/mm/m significantly exceeds those demonstrated for competing state-of-the-art techniques and may be key to future plasma wakefield-based free-electron lasers and high energy physics facilities, where large intrinsic chirps need to be removed.

MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer.

Background: MSR1 repeats are a 36-38 bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV). Patients and methods: Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer. Results: MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1 and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P = 4.80 × 10-7) and ion channel activity (P = 2.7 × 10-4). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9 and 11 copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P = 0.004; P = 0.03). In the white British population, the minor allele conferred an increased risk of 1.21-3.51 times for all non-familial disease, or 1.7-5.3 times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27-1.56; P =0.009). Conclusions: MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.

Observation of Laser Power Amplification in a Self-Injecting Laser Wakefield Accelerator.

We report on the depletion and power amplification of the driving laser pulse in a strongly driven laser wakefield accelerator. Simultaneous measurement of the transmitted pulse energy and temporal shape indicate an increase in peak power from 187±11 TW to a maximum of 318±12 TW after 13 mm of propagation in a plasma density of 0.9×10^{18} cm^{-3}. The power amplification is correlated with the injection and acceleration of electrons in the nonlinear wakefield. This process is modeled by including a localized redshift and subsequent group delay dispersion at the laser pulse front.

Individuals with filaggrin-related eczema and asthma have increased long-term medication and hospital admission costs.

BACKGROUND: Eczema and asthma are chronic diseases with onset usually before the age of 5 years. More than 50% of individuals with eczema will develop asthma and/or other allergic diseases. Several loss-of-function mutations in filaggrin (FLG) have been identified in patients with eczema. However, the association of FLG with healthcare use is unknown. OBJECTIVES: To determine whether FLG mutations are associated with increased prescribing for eczema and asthma and whether increased prescribing is associated with increased healthcare costs. METHODS: A secondary analysis of BREATHE, a cross-sectional study of gene-environment associations with asthma severity, was undertaken. BREATHE data was collected for 1100 participants with asthma, in Tayside and Fife, Scotland during the period 2003-2005. Through collaboration with the Health Informatics Centre in Dundee, BREATHE was linked to accident and emergency, community prescribing and Scottish morbidity records. The data linkage allowed longitudinal exploration of associations between genetic variation and prescribing. RESULTS: An association was found between FLG mutations and increased prescribing for mild and moderate eczema, asthma-reliever medicine and asthma exacerbations. A strong association was found between FLG mutations and prescribing of emollients [incidence rate ratio (IRR) 2·19, 95% confidence interval (CI) 1·36-3·52], treatment for severe eczema (IRR 2·18, 95% CI 1·22-3·91) and a combination of a long-acting ß2 -agonist and corticosteroids (IRR 3·29, 95% CI 1·68-6·43). CONCLUSIONS: The presence of FLG mutations in this cohort is associated with increased prescribing for eczema and asthma. Randomized controlled trials are required to determine if these individuals could benefit from management strategies to reduce morbidity and treatment costs.

Rovibrational Considerations for the Monomers and Dimers of Magnesium Hydride and Magnesium Fluoride.

Magnesium is an understudied chemical element that is quite useful in materials science and may be an essential astrochemical building block for grain formation in proto-planetary disks. This work provides quantum chemical prediction for the vibrational and rovibrational spectra of the structurally similar magnesium hydride and magnesium fluoride monomers and dimers. Magnesium fluoride is commonly utilized in infrared-observing windows and is a known terrestrial mineral, sellaite. Magnesium hydride is likely to exist in various astrophysical environments. Comparison of the anharmonic quantum chemical spectral data computed in this work to known gas phase values for MgH2 is excellent with the computed 1584.1 cm-1 antisymmetric Mg-H stretch less than 5 cm-1 below experiment for example. The condensed phase vibrational attributions of the dimer, however, are less comparable with the present results potentially indicating that some of the previous assignments may need to be revisited. The magnesium fluoride monomer and dimer have no previous vibrational experimental results reported, and the work here should be solid predictions as to their spectral features for comparison either to laboratory work or potentially even to interstellar observations.

Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI.

BACKGROUND/OBJECTIVES: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum. SUBJECTS/METHODS: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry. RESULTS: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010). CONCLUSIONS: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.

Revised Functional Capacity Index as a predictor of outcome following injury.

BACKGROUND: Assessment of functional outcomes in survivors of severe injury is an identified priority for trauma systems. The predictive Functional Capacity Index (pFCI) within the 2008 Abbreviated Injury Scale dictionary (pFCI08) offers a widely available tool for predicting functional outcomes without requiring long-term follow-up. This study aimed to assess the 12-month functional outcome predictions of pFCI08 in a major trauma population, and to test the assumptions made by its developers to ensure population homogeneity. METHODS: Patients with major trauma from Victoria, Australia, were followed up using routine telephone interviews. Assessment of survivors 12 months after injury included the Glasgow Outcome Scale - Extended (GOS-E). κ scores were used to measure agreement between pFCI08 and assessed GOS-E scores. RESULTS: Of 20 098 patients with severe injury, 12 417 had both pFCI08 and GOS-E scoring available at 12 months. The quadratic weighted κ score across this population was 0·170; this increased to 0·244 in the subgroup of 1939 patients who met all pFCI assumptions. However, expanding the age range used in this group did not significantly affect κ scores until patients over the age of 70 years were included. DISCUSSION: The pFCI08 has only a slight agreement with outcomes following major trauma. However, the age limits in the pFCI development assumptions are unnecessarily restrictive. The pFCI08 may be able to contribute to future systems predicting functional outcomes following severe injury, but is likely to explain only a small proportion of the variability in patient outcomes.

A genome-wide association study suggests that MAPK14 is associated with diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcers (DFUs) are a devastating complication of diabetes. OBJECTIVES: To identify genetic contributors to the development of DFUs in the presence of peripheral neuropathy in a Scottish cohort with diabetes using a genome-wide association study. METHODS: A genome-wide association approach was applied. A case was defined as a person with diabetes (type 1 or type 2) who had ever had a foot ulcer (current or previous) in at least one foot, as well as a positive monofilament test result (i.e. evidence of peripheral neuropathy) recorded in their longitudinal e-health records. A control was defined as an individual with diabetes (type 1 or type 2) who has never been recorded as having a foot ulcer in either foot but who had a positive monofilament test result recorded in either foot in their longitudinal e-health records. RESULTS: There were 699 DFU cases and 2695 controls in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. The single-nucleotide polymorphism rs80028505 (Chr6p21·31) in MAPK14 reached genome-wide significance with a lowest P-value of 2·45 × 10-8 . The narrow-sense heritability of this phenotype is 0·06. CONCLUSIONS: We suggest that MAPK14 is associated with DFUs.

HLA-Cw6-positive patients with psoriasis show improved response to methotrexate treatment.

It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type 1) psoriasis have increased severity and reduced age of onset of psoriasis. However, not much is known about any differential response of this genetic subgroup to various treatments. We set out to determine if there was any genetic association of the HLA-Cw6 allele with the first-line systemic treatment commonly used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland was recruited through a novel generic consenting process (GoShare); they were extensively phenotyped and analysed for an association of their HLA-Cw6 genotype status with treatment outcomes. HLA-Cw6+ patients showed notably improved response to methotrexate (P = 0.05), and further analysis demonstrated an even greater response in a subcohort of the HLA-Cw6+ patients, who did not have concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited fewer treatment-limiting adverse events. In addition to these findings, the methodology and primary clinical outcome phenotype, which we validate here, will greatly facilitate replication of the present results in independent cohorts.

A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

Risk of Injury According to Attention Deficit Hyperactivity Disorder, Comorbid Mental Illness, and Medication Therapy.

INTRODUCTION: We identify the risk of selected types of injuries among patients with ADHD or ADHD and comorbid mental illness. We also assess whether selected medications used by patients with ADHD increase the risk of comorbid mental illness or influence the association between ADHD and injury. METHODS: A retrospective cohort study design was conducted using medical claims data from the Deseret Mutual Benefit Administrators (DMBA). ADHD diagnosis, injury, medication, and demographic data were extracted from claims files during 2001-2013. Rate ratios were adjusted for age, sex, and calendar year. RESULTS: Patients with ADHD were 7.9 (95% CI 7.6-8.2) times more likely to have psychosis, 5.5 (3.9-7.8) times more likely to have alcohol- or drug-induced psychosis, and 6.0 (5.9-6.2) times more likely to have neurotic or personality disorder. Therapy with amphetamine was positively associated with neurotic or personality disorder (rate ratio=1.08, 1.02-1.15); methylphenidate was negatively associated with neurotic or personality disorder (0.90, 0.84-0.97); and atomoxetine was positively associated with psychosis (1.33, 1.21-1.46), alcohol- or drug-induced psychosis (2.38, 1.04-5.43), and neurotic or personality disorder (2.38, 1.04-5.43). ADHD was associated with an increased risk of injury, with ADHD and comorbid mental illness having a stronger increased risk of injury. Psychostimulants ameliorated the increased risk of injury for patients with ADHD. CONCLUSION: Patients with ADHD have an increased risk of injury, significantly more so for those with ADHD and comorbid mental illness. Psychostimulants can lower the risk of injury among patients with ADHD.

ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults.

BACKGROUND: The clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS. METHODS: We performed a meta-analysis of three cohort studies: Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory effects (n = 357, age: 4-12 years, the Netherlands), BREATHE (n = 820, age: 3-22 years, UK) and Paediatric Asthma Gene Environment Study (n = 391, age: 2-16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signalling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the Childhood Asthma Management Programme (clinical trial, n = 172, age: 5-12 years, USA), the Genes- environment and Mixture in Latino Americans II- study (n = 745, age: 8-21, USA) and the Pharmacogenetics of adrenal suppression cohort (n = 391, age: 5-18, UK) to test the robustness of the findings. Finally, all results were meta-analysed. RESULTS: Two SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year; OR = 1.22 (P = 0.013) and OR = 1.22 (P = 0.0017), respectively. CONCLUSION AND CLINICAL RELEVANCE: A novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signalling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.

The effectiveness of exercise for the prevention and treatment of antenatal depression: systematic review with meta-analysis.

BACKGROUND: Antenatal depression can have harmful consequences for the mother and fetus. Exercise may be a useful intervention to prevent and treat antenatal depression. OBJECTIVES: This systematic review aims to establish whether there is sufficient evidence to conclude that exercise is an effective intervention for preventing and treating antenatal depression. SEARCH STRATEGY: Searches using electronic databases from MEDLINE, Cochrane Library, CINAHL, EMBASE, AMED and PsycINFO were performed. SELECTION CRITERIA: Randomised controlled trials (RCT) that compared any type of exercise intervention with any comparator in pregnant women were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Meta-analysis was performed calculating standardised mean differences (SMD). MAIN RESULTS: Six trials (seven comparisons) were eligible for inclusion. Meta-analysis showed a significant reduction in depression scores (SMD -0.46, 95% CI -0.87 to -0.05, P = 0.03, I(2) = 68%) for exercise interventions relative to comparator groups. The test for subgroup differences in women who were non-depressed (one trial) (SMD -0.74, 95%CI -1.22 to -0.27, P = 0.002) and depressed (five trials) (SMD -0.41, 95% CI -0.88 to 0.07, P = 0.09) at baseline was not significant (P = 0.32). The test for subgroup differences between aerobic (one trial) and non-aerobic exercise (five trials) was also nonsignificant (P = 0.32). AUTHORS' CONCLUSIONS: We found some evidence that exercise may be effective in treating depression during pregnancy but this conclusion is based on a small number of low-moderate quality trials with significant heterogeneity and wide confidence intervals.