The CHARA Array is a six 1 m telescope optical/IR interferometric array located on Mount Wilson, California, designed and built by the Center for High Angular Resolution Astronomy of Georgia State ...University. In this paper we describe the main elements of the Array hardware and software control systems, as well as the data reduction methods currently being used. Our plans for upgrades in the near future are also described.
Recent evidence suggests that suppression of the cellular immune response is often attributable to populations of functionally distinct T cells that act to down-regulate Ag-specific effector T cells. ...Using flow cytometry, we evaluated tumor-infiltrating lymphocytes (TIL) from patients undergoing neurosurgical resection of glioblastoma multiforme (GBM), metastatic lung carcinoma, and meningioma for markers known to be expressed on immunoregulatory T cells. Ex vivo phenotypic characteristics, cellular proliferation, and cytokine expression patterns were compared between T cell subsets found in the PBMC and within TIL from fresh tumor samples. Interestingly, nearly half of all T cells infiltrating GBM specimens were CD56(+) T cells, while much smaller percentages of similar cells were identified within metastatic lung tumors and meningiomas. CD56(+) T cells identified within GBM were not canonical, or "invariant," NKT cells, as they demonstrated diverse TCR expression, a primarily CD4 single-positive phenotype, and lack of CD1d reactivity. The percentage of CD56(+) T cells exhibiting evidence of proliferation within GBM was 3- to 4-fold higher than the proportion of proliferating CD56(-) T cells from these lesions. In addition, direct ex vivo analysis of cytokine expression by TIL from GBM demonstrated significant numbers of IL-4/IL-13 positive cells, cytokines that are integral in the cell-mediated repression of tumor immunity in experimental models. We propose that GBM has a unique capacity to recruit and activate CD4(+)CD56(+) T cells, a population that has not been previously described within human tumors.
Background
Malnutrition is one the greatest global health challenges of our generation, leading to the increased utilisation of healthcare resources, as well as morbidity and mortality. Research has ...primarily been driven by industry, academia and clinical working groups and has had little involvement from patients and carers. The project described in the present study aimed to establish a priority setting partnership allowing patients, carers and healthcare professionals an opportunity to influence the research agenda.
Methods
A national survey was conducted to gather malnutrition uncertainties and identify key issues (i.e. areas within scope where an evidence‐base is lacking) from those with experience of malnutrition. Uncertainties were analysed according to themes. Similar questions were grouped and summary questions were developed. A second survey was conducted and respondents were asked to choose their 10 most important summary questions. A workshop was conducted to finalise the top 10 research priorities from the most frequently indicated uncertainties on the interim survey.
Results
Overall, 1128 uncertainty questions were submitted from 268 people. The interim survey had 71 responses and a list of the top 26 questions was generated for the workshop. There were 26 questions discussed, ranked and agreed by healthcare professionals, carers and patients at the workshop. The top 10 research priorities were then chosen. These included questions on oral nutritional supplements, vulnerable groups, screening, community care, use of body mass index and technology.
Conclusions
The top 10 research priorities in malnutrition and nutritional screening have been identified from a robust process involving patients, carers and healthcare professionals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lifestyle and youthful looks Gunn, D.A.; Dick, J.L.; van Heemst, D. ...
British journal of dermatology (1951),
20/May , Volume:
172, Issue:
5
Journal Article
Peer reviewed
Summary
Background
Lifestyle has been proven to have a dramatic effect on the risk of age‐related diseases. The association of lifestyle and facial ageing has been less well studied.
Objectives
To ...identify lifestyle factors that associate with perceived facial age in white north European men and women.
Methods
Lifestyle, facial wrinkling and perceived facial age were studied in two cross‐sectional studies consisting of 318 Dutch men and 329 women aged 45–75 years who were part of the Leiden Longevity Study, and 162 English women aged 45–75 years who were nonsmokers.
Results
In Dutch men, smoking, having skin that went red in the sun, being outside in the sun most of the summer, sunbed use, wearing false teeth and not flossing teeth were all significantly associated (P < 0·05) with a total 9·3‐year higher perceived facial age in a multivariate model adjusting for chronological age. In Dutch women, smoking, sunbathing, sunbed use, few remaining teeth and a low body mass index (BMI) were associated with a total 10·9‐year higher perceived facial age. In English women, cleaning teeth only once a day, wearing false teeth, irregular skin moisturization and having skin that went red in the sun were associated with a total 9·1‐year higher perceived facial age. Smoking and sunbed use were associated more strongly with wrinkling in women than in men. BMI, sun exposure and skincare were associated predominantly with perceived facial age via wrinkling, whereas oral care was associated via other facial features.
Conclusions
Although associative in nature, these results support the notion that lifestyle factors can have long‐term beneficial effects on youthful looks.
What's already known about this topic?
Smoking, sun exposure and body mass index have been associated with the perceived age of subjects in passport‐type images in a study of north Europeans aged ≥ 70 years.
What does this study add?
Sunbed use and oral care were also found to associate significantly with a higher perceived facial age in 45–75‐year‐old north European men and women.
Significant lifestyle factors accounted for around 10 years of perceived facial age, illustrating the strong relationship between lifestyle and perceived age.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
For medulloblastoma patients, the current therapeutic paradigm of surgery followed by radiation and chemotherapy can lead to long-term remission. However, the sequelae of treatment can be very ...debilitating, particularly in young children. Immunotherapy is an attractive treatment approach to optimize the targeting of tumor cells while sparing the vulnerable surrounding brain that is still developing in children. Understanding the relationship between medulloblastoma and the immune system is critical to develop effective immunologic-based treatment strategies for these patients. This review focuses on current knowledge of tumor immunology and the factors that contribute to the lack of immune system recognition of these tumors. The specificity of tumor antigens present in medulloblastoma is also discussed along with a summary of early clinical immunotherapy results.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Background Very few over‐the‐counter cosmetic ‘anti‐ageing’ products have been subjected to a rigorous double‐blind, vehicle‐controlled trial of efficacy. Previously we have shown that ...application of a cosmetic ‘anti‐ageing’ product to photoaged skin under occlusion for 12 days can stimulate the deposition of fibrillin‐1. This observation infers potential to repair and perhaps clinically improve photoaged skin.
Objective We examined another similar over‐the‐counter cosmetic ‘anti‐ageing’ product using both the patch test assay and a 6‐month double‐blind, randomized controlled trial (RCT), with a further 6‐month open phase to assess clinical efficacy in photoaged skin.
Methods For the patch test, a commercially available test product and its vehicle were applied occluded for 12 days to photoaged forearm skin (n = 10) prior to biopsy and immunohistochemical assessment of fibrillin‐1; all‐trans retinoic acid (RA) was used as a positive control. Sixty photoaged subjects were recruited to the RCT (test product, n = 30 vs. vehicle, n = 30; once daily for 6 months, face and hands) with clinical assessments performed at recruitment and following 1, 3 and 6 months of use. Twenty‐eight volunteers had skin biopsies (dorsal wrist) at baseline and at 6 months treatment for immunohistochemical assessment of fibrillin‐1 (test product, n = 15; vehicle, n = 13). All volunteers received the test product for a further 6 months. Final clinical assessments were performed at the end of this open period.
Results In the 12‐day patch test assay, we observed significant immunohistological deposition of fibrillin‐1 in skin treated with the test product and RA compared with the untreated baseline (P = 0·005 and 0·015, respectively). In the clinical RCT, at 6 months, the test product produced statistically significant improvement in facial wrinkles as compared to baseline assessment (P = 0·013), whereas vehicle‐treated skin was not significantly improved (P = 0·11). After 12 months, there was a significant benefit of the test product over that projected for the vehicle (70% vs. 33% of subjects improving; combined Wilcoxon rank tests, P = 0·026). There was significant deposition of fibrillin‐1 in skin treated for 6 months with the test product (mean ± SE) vehicle 1·84 ± 0·23; test product 2·57 ± 0·19; ancovaP = 0·019).
Conclusions In a double‐blind RCT, an over‐the‐counter cosmetic ‘anti‐ageing’ product resulted in significant clinical improvement in facial wrinkles, which was associated with fibrillin‐1 deposition in treated skin. This study demonstrates that a cosmetic product can produce significant improvement in the appearance of wrinkles and further supports the use of fibrillin‐1 as a robust biomarker for the repair of photoaged dermis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background Insulin‐like growth factor (IGF)‐1 is a growth factor that can influence fibroblast functioning, with effects including the inhibition of collagenases and the induction of ...collagen expression.
Objectives To assess whether serum IGF‐1, IGF‐binding protein (IGFBP)3 and the ratio between IGF‐1 and IGFBP3, as a measure of IGF‐1 bioavailability, are associated with facial ageing and skin wrinkling.
Methods From a random sample comprising 617 subjects from the Leiden Longevity Study, perceived age and skin wrinkling were assessed from facial photographs, and IGF‐1 and IGFBP3 were measured in serum. The associations were assessed using linear regression models, adjusted for chronological age, sex, body mass index, smoking and sun exposure.
Results Across tertiles of the ratio of IGF‐1 to IGFBP3, and after adjusting for all potential confounding factors, the mean perceived age decreased from 60·6 years in the lowest tertile to 59·5 years in the highest (Ptrend = 0·045). Similarly, the mean skin wrinkling grade decreased from 4·8 in the lowest tertile to 4·5 in the highest (Ptrend = 0·011). Adding skin wrinkling as a covariate in the analysis between IGF‐1 and perceived age diminished this association.
Conclusions This study demonstrates that a higher ratio of IGF‐1 to IGFBP3 associates with a lower perceived age, via its association with reduced skin wrinkling. Whether high IGF‐1 levels actually delay the accumulation of skin wrinkling now needs investigating.
What’s already known about this topic?
•
Previous research has indicated that insulin‐like growth factor (IGF)‐1 might be a marker of ageing, as well as a marker for overall health.
•
In vitro experiments have shown that IGF‐1 can induce collagen expression and inhibit the expression of collagenase.
What does this study add?
•
This study showed that high levels of IGF‐1 relative to IGF‐binding protein 3 were associated with a lower perceived age and a lower degree of skin wrinkling.
•
The results suggest that the association with perceived age is mainly driven by skin wrinkling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background With increasing age the immune system shows functional decline. In the skin this is associated with an increased incidence of epidermal malignancies and infections. Epidermal ...Langerhans cells (LCs) act as sentinels of the immune system, recognizing, processing and presenting antigen and inducing T‐cell responses. Previous investigations have demonstrated a reduction in the number of epidermal LCs in elderly subjects. Moreover, the ability of LCs to migrate in response to tumour necrosis factor (TNF)‐α, but not interleukin (IL)‐1β, is significantly impaired in the elderly.
Objectives To characterize further the changes in LC function that are associated with increasing chronological age, we have evaluated age‐related changes in the response of monocyte‐derived LCs (mLCs) to IL‐1β and TNF‐α.
Methods The phenotype and function of mLCs were compared in six young (≤ 30 years) and six aged (≥ 70 years) healthy individuals using a combination of flow cytometry, cytokine and chemokine array, and a Transwell migration assay.
Results Monocytes from aged individuals were able to differentiate into LCs. There were no significant differences in expression of activation markers, or in baseline or inducible cytokine secretion, by mLCs derived from aged or young subjects. Furthermore, migration in response to a chemokine ligand, CCL19, was equivalent in both age groups.
Conclusions These data demonstrate that changes in LC function in the elderly are not associated with changes in systemic dendritic cell phenotype and function. Conditioning of LCs in situ by the epidermal microenvironment is likely to be more important.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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