To have your citizen science cake and eat it? Delivering research and outreach through Open Air Laboratories (OPAL)

Background: The vast array of citizen science projects which have blossomed over the last decade span a spectrum of objectives from research to outreach. While some focus primarily on the collection of rigorous scientific data and others are positioned towards the public engagement end of the gradient, the majority of initiatives attempt to balance the two. Although meeting multiple aims can be seen as a ‘win–win’ situation, it can also yield significant challenges as allocating resources to one element means that they may be diverted away from the other. Here we analyse one such programme which set out to find an effective equilibrium between these arguably polarised goals. Through the lens of the Open Air Laboratories (OPAL) programme we explore the inherent trade-offs encountered under four indicators derived from an independent citizen science evaluation framework. Assimilating experience from the OPAL network we investigate practical approaches taken to tackle arising tensions. Results: Working backwards from project delivery to design, we found the following elements to be important: ensuring outputs are fit for purpose, developing strong internal and external collaborations, building a sufficiently diverse partnership and considering target audiences. We combine these ‘operational indicators’ with four pre-existing ‘outcome indicators’ to create a model which can be used to shape the planning and delivery of a citizen science project. Conclusions: Our findings suggest that whether the proverb in the title rings true will largely depend on the identification of challenges along the way and the ability to address these conflicts throughout the citizen science projec

An evaluation of the SENTiFIT 270 analyser for quantitation of faecal haemoglobin in the investigation of patients with suspected colorectal cancer.

BACKGROUND: An evaluation of SENTiFIT® 270 (Sentinel Diagnostics, Italy; Sysmex, Spain) analyser for the quantitation of faecal haemoglobin (f-Hb) was performed. METHODS: The analytical imprecision, linearity, carry over and f-Hb stability were determined. Evaluation of the diagnostic accuracy was performed on 487 patients. RESULTS: Within-run and between-run imprecision ranged 1.7%-5.1% and 3.8%-6.2%, respectively. Linearity studies revealed a mean recovery of 101.1% (standard deviation, 6.7%) for all dilutions. No carry over was detected below 7650 μg Hb/g faeces. Decay of f-Hb in refrigerated samples ranged 0.2%-0.5% per day. f-Hb in patients with advanced colorectal neoplasia (ACRN) (colorectal cancer [CRC] plus advanced adenoma [AA]) were significantly higher than from those with a normal colonoscopy. Sensitivity for ACRN at f-Hb cutoffs from 10 to 60 μg Hb/g faeces ranged from 28.9% (95% confidence interval [CI], 21.7%-37.2%) to 46.5% (95% CI, 38.1%-55%), the specificity ranged from 85% (95% CI, 82.3%-87.3%) to 93.2% (95% CI, 91.2%-94.8%), positive predictive values for detecting CRC and AA ranged from 11.6% (95% CI, 7.6%-17.2%) to 20.6% (95% CI, 13.3%-30.3%) and from 34.7% (95% CI, 28.1%-42%) to 42.3% (95% CI, 32.4%-52.7%), respectively, and the negative predictive value for ACRN ranged from 90.2% (95% CI, 87.9%-92.2%) to 88.4% (95% CI, 86%-90.4%). Using two samples per patient sensitivity increased with a slight decrease in specificity. CONCLUSIONS: The analytical and clinical performances of SENTiFIT assay demonstrate a specific and accurate test for detecting ACRN in symptomatic patients and those undergoing surveillance. KEYWORDS: adenoma; analyser evaluation; colorectal cancer; faecal haemoglobin; faecal immunochemical tes

Clinical utility of one versus two faecal immunochemical test samples in the detection of advanced colorectal neoplasia in symptomatic patients

The utility of faecal immunochemical tests (FIT) in assessment of symptomatic patients with lower gastrointestinal symptoms has not been well explored. The aims of this study were to evaluate the diagnostic yield for advanced colorectal neoplasia (ACRN) in symptomatic patients using the first of two FIT samples (FIT/1) and the higher concentration of two FIT samples (FIT/max). METHODS: Samples from two consecutive bowel motions from 208 symptomatic patients who required colonoscopy were analysed using the HM-JACKarc analyser (Kyowa Medex Co., Ltd., Tokyo, Japan). Patients were categorised into two groups: patients with any ACRN and individuals with other diagnoses or normal colonoscopy. RESULTS: Colonoscopy detected ACRN in 29 patients. In these patients, FIT/1 and FIT/max were significantly higher than in patients with low-risk adenoma (p=0.006 and p=0.024), other findings (p=0.002 and p=0.002) and normal colonoscopy (p<0.001 and p<0.001). The areas under the curves (AUC) of FIT/1 and FIT/max were 0.71 and 0.69, respectively. Undetectable FIT/1 rules out 96.6% of ACRN and the specificity was 10.6%. Increasing the FIT/1 cut-off to 10 μg Hb/g faeces, sensitivity and specificity were 34.5% and 87.2%, respectively. Similar results were obtained using FIT/max with 20 μg Hb/g faeces cut-off, providing a sensitivity and specificity of 34.5% and 85.6%, respectively. CONCLUSIONS: Undetectable FIT is a good strategy to rule-out ACRN in symptomatic patients. The diagnostic yield of collecting two samples for FIT can be achieved with one sample, but a lower faecal haemoglobin concentrations (f-Hb) cut-off is required

Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence

Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed after a 5 μM cocaine exposure, whereas no changes in gene expression or in neuronal activity took place at 1 μM cocaine. Changes in gene expression were identified in a total of 756 genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as mitogen-activeated protein kinase (MAPK), CREB, neurotrophin and neuregulin signaling pathways. Some genes displaying altered expression were subsequently targeted with predicted functional single-nucleotide polymorphisms (SNPs) in a case-control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3′-untranslated region of the NFAT5 gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with magnetic resonance imaging, did not correlate with NFAT5 variation. These results suggest that the NFAT5 gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence

Serum 25-hydroxyvitamin D3 levels and vitamin D receptor variants in melanoma patients from the Mediterranean area of Barcelona

BACKGROUND: Serum 25-hydroxyvitamin D3 (Vitamin D) insufficiency and single-nucleotide polymorphisms (SNPs) on its receptor, Vitamin D receptor (VDR), have been reported to be involved in melanoma susceptibility in populations mostly from northern countries. OBJECTIVE: To investigate 25-hydroxyvitamin D3 levels and VDR SNPs in melanoma patients from sunny area of Barcelona, two studies were carried out. The first study evaluated the levels of Vitamin D at time of melanoma diagnosis and the second one analyzed the association between VDR genetic variants and risk of having a high nevus number, the strongest phenotypic risk factor for melanoma. METHODS: The levels of 25-hydroxyvitamin D3 in 81 melanoma patients at diagnosis were measured. In a second group of melanoma patients, including 150 with low and 113 with high nevus number, 11 VDR SNPs were analyzed for their association with nevus number. RESULTS: In the first study, 68% of patients had insufficient levels of 25-hydroxyvitamin D3 (<25 ng/ml). Autumn-winter months and fair phototype were associated with 25-hydroxyvitamin D3 insufficiency; after multivariate analysis, season of sampling remained the only independent predictor of 25-hydroxyvitamin D3 levels. In the second study, VDR variant rs2189480 (P = 0.006) was associated with risk of high nevus number whereas rs2239179 (P = 0.044) and rs7975128 (P = 0.0005) were protective against high nevus number. After Bonferroni adjustment only rs7975128 remained significant. In stratified analysis, SNP rs7975128 was found protective against multiple melanomas (P = 0.021). CONCLUSION: This study showed that even in Barcelona, a sunny Mediterranean area, 25-hydroxyvitamin D3 levels were sub-optimal in the majority of melanoma patients at diagnosis. The involvement of VDR in nevi and, in turn, in melanoma susceptibility has also been suggested. Larger studies are needed to confirm our findings

Parkinson’s disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration

A deeper understanding of early disease mechanisms occurring in Parkinson's disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients' networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases