Aim
To systematically review the association between breastfeeding and childhood allergic disease.
Methods
Predetermined inclusion/exclusion criteria identified 89 articles from PubMed, CINAHL and ...EMBASE databases. Meta‐analyses performed for categories of breastfeeding and allergic outcomes. Meta‐regression explored heterogeneity.
Results
More vs. less breastfeeding (duration) was associated with reduced risk of asthma for children (5–18 years), particularly in medium‐/low‐income countries and with reduced risk of allergic rhinitis ≤5 years, but this estimate had high heterogeneity and low quality. Exclusive breastfeeding for 3–4 months was associated with reduced risk of eczema ≤2 years (estimate principally from cross‐sectional studies of low methodological quality). No association found between breastfeeding and food allergy (estimate had high heterogeneity and low quality). Meta‐regression found differences between study outcomes may be attributable to length of breastfeeding recall, study design, country income and date of study inception. Some of the protective effect of breastfeeding for asthma may be related to recall bias in studies of lesser methodological quality.
Conclusion
There is some evidence that breastfeeding is protective for asthma (5–18 years). There is weaker evidence for a protective effect for eczema ≤2 years and allergic rhinitis ≤5 years of age, with greater protection for asthma and eczema in low‐income countries.
Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds—urging the quest for predictive biomarkers. We hypothesize ...that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response.
In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients.
The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P<0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P=0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P<0.001), resulting in a 1-year survival difference of 24% (P=0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy.
These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.
Quantitative saccadic testing is a non-invasive method of evaluating the neural networks involved in the control of eye movements. The aim of this study is to provide a standardized and reproducible ...protocol for infrared oculography measurements of eye movements and analysis, which can be applied for various diseases in a multicenter setting.
Development of a protocol to Demonstrate Eye Movement Networks with Saccades (DEMoNS) using infrared oculography. Automated analysis methods were used to calculate parameters describing the characteristics of the saccadic eye movements. The two measurements of the subjects were compared with descriptive and reproducibility statistics.
Infrared oculography measurements of all subjects were performed using the DEMoNS protocol and various saccadic parameters were calculated automatically from 28 subjects. Saccadic parameters such as: peak velocity, latency and saccade pair ratios showed excellent reproducibility (intra-class correlation coefficients > 0.9). Parameters describing performance of more complex tasks showed moderate to good reproducibility (intra-class correlation coefficients 0.63-0.78).
This study provides a standardized and transparent protocol for measuring and analyzing saccadic eye movements in a multicenter setting. The DEMoNS protocol details outcome measures for treatment trial which are of excellent reproducibility. The DEMoNS protocol can be applied to the study of saccadic eye movements in various neurodegenerative and motor diseases.
Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based ...chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.
•Platinum-based chemotherapy remains the most active treatment for ovarian cancer.•Platinum should not be withheld after response to last platinum and a treatment-free interval of <6 months.•We propose to move beyond the definition of platinum resistance to a therapy-oriented definition of platinum eligibility.•Platinum-non-eligible ovarian cancer patients are those with progression on or immediately after their last platinum.
Nonlinear graphene plasmonics Ooi, Kelvin J. A.; Tan, Dawn T. H.
Proceedings of the Royal Society. A, Mathematical, physical, and engineering sciences,
10/2017, Letnik:
473, Številka:
2206
Journal Article
Recenzirano
Odprti dostop
The rapid development of graphene has opened up exciting new fields in graphene plasmonics and nonlinear optics. Graphene's unique two-dimensional band structure provides extraordinary linear and ...nonlinear optical properties, which have led to extreme optical confinement in graphene plasmonics and ultrahigh nonlinear optical coefficients, respectively. The synergy between graphene's linear and nonlinear optical properties gave rise to nonlinear graphene plasmonics, which greatly augments graphene-based nonlinear device performance beyond a billion-fold. This nascent field of research will eventually find far-reaching revolutionary technological applications that require device miniaturization, low power consumption and a broad range of operating wavelengths approaching the far-infrared, such as optical computing, medical instrumentation and security applications.
Summary
Food allergy is a growing clinical and public health problem world‐wide. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, but it is yet to be ...determined whether environmental factors might act in interaction with genetic risk. That is to say, are environmental factors more likely to affect those genetically at risk? Family history is a strong risk factor for the development of food allergy as it co‐aggregates with other atopic diseases and as such genetic factors do play an important role in food allergy risk. However, significant interest has now turned to the role of epigenetic modifications of the genome as the major mediator of gene–environment interaction. The consideration of the role of epigenetics in food allergy is likely to provide an insight into aetiological and biological disease mechanisms. This paper discusses the current state of knowledge regarding genetic and environmental risk factors for food allergy, and considers the potential for furthering our understanding of food allergy aetiology by examining the role of epigenetic variation.
Cite this as: T. H.‐T. Tan, J. A. Ellis, R. Saffery and K. J. Allen, Clinical & Experimental Allergy, 2012 (42) 20–29.
East-Southeast Asia is currently one of the fastest urbanizing regions in the world, with countries such as China climbing from 20 to 50% urbanized in just a few decades. By 2050, these countries are ...projected to add 1 billion people, with 90% of that growth occurring in cities. This population shift parallels an equally astounding amount of built-up land expansion. However, spatially-and temporally-detailed information on regional-scale changes in urban land or population distribution do not exist; previous efforts have been either sample-based, focused on one country, or drawn conclusions from datasets with substantial temporal spatial mismatch and variability in urban definitions. Using consistent methodology, satellite imagery and census data for >1000 agglomerations in the East-Southeast Asian region, we show that urban land increased >22% between 2000 and 2010 (from 155 000 to 189 000 km2), an amount equivalent to the area of Taiwan, while urban populations climbed >31% (from 738 to 969 million). Although urban land expanded at unprecedented rates, urban populations grew more rapidly, resulting in increasing densities for the majority of urban agglomerations, including those in both more developed (Japan, South Korea) and industrializing nations (China, Vietnam, Indonesia). This result contrasts previous sample-based studies, which conclude that cities are universally declining in density. The patterns and rates of change uncovered by these datasets provide a unique record of the massive urban transition currently underway in East-Southeast Asia that is impacting local-regional climate, pollution levels, water quality availability, arable land, as well as the livelihoods and vulnerability of populations in the region.
No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors ...associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.
The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.
2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 25·5% of 1965) and 1 year (232 28·9% of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 95% CI 0·46–0·99), obesity (0·50 0·34–0·74) and invasive mechanical ventilation (0·42 0·23–0·76). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 IQR 0·74–1·00), at 5 months (0·74 0·64–0·88) to 1 year (0·75 0·62–0·88), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.
The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.
UK Research and Innovation and National Institute for Health Research.
Clot extent, location, and collateral integrity are important determinants of outcome in acute stroke. We hypothesized that a novel clot burden score (CBS) and collateral score (CS) are important ...determinants of clinical and radiologic outcomes and serve as useful additional stroke outcome predictors.
One hundred twenty-one patients with anterior circulation infarct presenting within 3 hours of stroke onset were reviewed. The Spearman correlation was performed to assess the correlation between CBS and CS and clinical and radiologic outcome measures. Patients were dichotomized by using a 90-day modified Rankin scale (mRS) score. Uni- and multivariate logistic regression models were used to assess variables predicting favorable clinical and radiologic outcomes. Receiver operating characteristic and intraclass correlation coefficient (ICC) analyses were performed. Diagnostic performance of a CBS threshold of >6 was assessed.
There were 85 patients (mean age, 70 +/- 14.5 years). Patients with higher CBS and CS demonstrated smaller pretreatment perfusion defects and final infarct volume and better clinical outcome (all, P < .01). CBS (P = .009) and recanalization (P = .015) independently predicted favorable outcome. A CBS >6 predicted good clinical outcome with an area under the curve of 0.75 (95% confidence interval CI, 0.65-0.84; P = .0001), sensitivity of 73.0 (95% CI, 55.9-86.2), and specificity of 64.6 (95% CI, 49.5-77.8). The recanalization rate with intravenous recombinant tissue plasminogen activator was higher in patients with CBS >6 (P = .04; odds ratio, 3.2; 95% CI, 1.1-9.4). The ICC was 0.97 (95% CI, 0.95-0.98) and 0.87 (95% CI, 0.80-0.91) for CBS and CS, respectively.
CBS and CS are useful additional markers predicting clinical and radiologic outcomes.
Dysregulation of Axl and its ligand growth arrest-specific 6 is implicated in the pathogenesis of several human cancers. In this study, we have used RNAi and monoclonal antibodies to assess further ...the oncogenic potential of Axl. Here we show that Axl knockdown reduces growth of lung and breast cancer xenograft tumors. Inhibition of Axl expression attenuates breast cancer cell migration and inhibits metastasis to the lung in an orthotopic model, providing the first in vivo evidence that links Axl directly to cancer metastasis. Axl knockdown in endothelial cells impaired tube formation and this effect was additive with anti-vascular endothelial growth factor (VEGF). Further analysis demonstrated that Axl regulates endothelial cell functions by modulation of signaling through angiopoietin/Tie2 and Dickkopf (DKK3) pathways. We have developed and characterized Axl monoclonal antibodies that attenuate non-small cell lung carcinoma xenograft growth by downregulation of receptor expression, reducing tumor cell proliferation and inducing apoptosis. Our data demonstrate that Axl plays multiple roles in tumorigenesis and that therapeutic antibodies against Axl may block Axl functions not only in malignant tumor cells but also in the tumor stroma. The additive effect of Axl inhibition with anti-VEGF suggests that blocking Axl function could be an effective approach for enhancing antiangiogenic therapy.
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