Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude

Context and purpose There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. Methods IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5–86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. Results To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Conclusions Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose–response relationship and risk characterisation for health outcomes.Peer reviewe

The course of pain drawings during a 10-week treatment period in patients with acute and sub-acute low back pain

BACKGROUND: Pain drawings are widely used as an assessment of patients' subjective pain in low back pain patients being considered for surgery. Less work has been done on primary health care patients. Moreover, the possible correlation between pain drawing modalities and other pain assessment methods, such as pain score and functional variables needs to be described. Thus, the objectives were to describe the course of pain drawings during treatment in primary health care for low back pain patients. METHODS: 160 primary health care outpatients with acute or sub-acute low back pain were studied during 10 weeks of a stay active concept versus manual therapy in addition to the stay active concept. The patients filled out 3 pain drawings each, at baseline and after 5 and 10 weeks of treatment. In addition the patients also reported pain and functional variables during the 3 measurement periods. RESULTS: The proportion of areas marked, the mean number of areas marked (pain drawing score), mean number of modalities used (area score), and the proportion of patients with pain radiation all decreased during the 10-week treatment period. Most of the improvement occurred during the first half of the period. The seven different pain modalities in the pain drawing were correlated to pain and functional variables. In case of no radiation some modalities were associated with more pain and disability than others, a finding that grew stronger over time. For patients with pain radiation, the modality differences were smaller and inconsistent. CONCLUSION: Pain modalities are significantly correlated with pain and functional variables. There is a shift from painful modalities to less painful ones over time

Surface Treatments for Inkjet Printing onto a PTFE-Based Substrate for High Frequency Applications

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the journal Industrial and Engineering Chemistry Research [copyright © American Chemical Society] after peer review and technical editing by the publisher. To access the final edited and published work see: http://pubs.acs.org/doi/abs/10.1021/ie4006639Inkjet printing onto laminates for use in high frequency applications (high frequency laminates) is challenging, due to the substrate surface roughness present after etching away the copper layer(s). This has a detrimental effect on interconnect losses as the frequency increases. In this paper, different surface treatments to reduce the surface roughness of a typical high frequency laminate (RO3006) are investigated. In particular, the importance of matching the substrate surface energy to the ink to achieve a smooth coated layer for the case of a UV cured insulator is demonstrated. This is achievable within the parameters of heating the platen, which is a more flexible approach compared to modifying the ink to improve the ink-substrate interaction. In printing onto the surface modified substrates, the substrate roughness was observed to affect the printed line width significantly. A surface roughness factor was introduced to take into account the phenomenon by modifying the original formula of Smith et al. Lastly, the authors show that the printed line widths are also influenced by the surface tension arising from charges present on the surface modified substrates

Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer–stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes

Persian cats under first opinion veterinary care in the UK:demography, mortality and disorders

Persian cats are a popular cat breed worldwide, and especially in the US, Europe and Asia. This study aimed to describe the demography, common disorders and mortality in Persians under general practice veterinary care in 2013 in the UK. The study population of 285,547 cats overall included 3235 (1.1%) Persians. Mean adult Persian bodyweight was 3.9 kg (SD 0.9) and median age was 7.0 years (IQR 3.3–11.6). At least one disorder was recorded in 2099 (64.9%) Persians. The most common specific disorders were haircoat disorders (411, 12.7%), periodontal disease (365, 11.3%), overgrown nails (234, 7.2%), and ocular discharge (188, 5.8%). The most common disorder groups were dermatological (578, 17.9%), ophthalmological (496, 15.3%) and dental (397, 12.3%). Median longevity was 13.5 years (IQR 9.9–16.0). The most common grouped causes of death were renal disease (102, 23.4%), neoplasia (37, 8.5%) and mass-associated disorder (35, 8.0%). This is the first study to use general practice data to examine the overall health of Persian cats. With haircoat, ocular and dental disorders being the predominant disorders identified, this study highlights the need for increased owner awareness to manage and prevent the typical health problems associated with this breed’s phenotype

Building up the tension between the epithelial and stromal compartment in pancreatic ductal adenocarcinoma

In recent years, pancreatic cancer-associated stroma has been the topic of a number of studies that have proposed stromal components as promising, but still controversial, targets for novel therapeutic strategies. A new study describes how epithelial TGF-β signalling deficiency and consequential STAT3 activation act as key players in modulating the desmoplastic reaction, with implications for both clinical outcome and future drug developmen