Investigating Collaborative Data Practices: a Case Study on Artificial Intelligence for Healthcare Research

Developing artificial intelligence (AI) tools for healthcare is a collaborative effort, bringing data scientists, clinicians, patients and other disciplines together. In this paper, we explore the collaborative data practices of research consortia tasked with applying AI tools to understand and manage multiple long-term conditions in the UK. Through an inductive thematic analysis of 13 semi-structured interviews with participants of these consortia, we aimed to understand how collaboration happens based on the tools used, communication processes and settings, as well as the conditions and obstacles for collaborative work. Our findings reveal the adaptation of tools that are used for sharing knowledge and the tailoring of information based on the audience, particularly those from a clinical or patient perspective. Limitations on the ability to do this were also found to be imposed by the use of electronic healthcare records and access to datasets. We identified meetings as the key setting for facilitating exchanges between disciplines and allowing for the blending and creation of knowledge. Finally, we bring to light the conditions needed to facilitate collaboration and discuss how some of the challenges may be navigated in future work.Comment: 17 page

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM 2.5), nitrogen dioxide (NO 2), black carbon (BC), and ozone (O 3), as well as 8 PM 2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM 2.5 (hazard ratio per 5 µg/m 3: 1.25; 95% confidence interval: 1.01-1.55), NO 2 (1.13; 0.95-1.34 per 10 µg/m 3), and BC (1.12; 0.94-1.34 per 0.5 × 10 -5m -1), and a negative association with O 3 (0.74; 0.58-0.94 per 10 µg/m 3). Associations of PM 2.5, NO 2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM 2.5 remained robust when adjusted for NO 2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO 2 or BC attenuated to null. O 3 associations remained negative, but no longer statistically significant in models with PM 2.5. We detected suggestive positive associations with the potassium component of PM 2.5. CONCLUSION: Long-term exposure to PM 2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

Background: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality

Shiga toxin-producing Escherichia coli: detection and isolation from swine feces and wheat grains by PCR and culture methods

Master of ScienceDepartment of Veterinary Biomedical SciencesRaghavendra G. AmachawadiShiga toxin-producing Escherichia coli (STEC) are major foodborne pathogens that cause mild to hemorrhagic colitis, which could lead to a serious complication of renal failure, called hemolytic uremic syndrome, particularly in children. Seven serogroups of STEC, O26, O45, O103, O111, O121, O145, and O157, often called top-7, account for most of the STEC-associated illness in humans in the United States. Two Shiga toxins, Shiga toxin 1 and 2, encoded by stx1 and stx2, respectively, and intimin, a protein that mediates attachment of STEC onto enterocytes, encoded by eae gene, are major virulence factors involved in STEC infections. Cattle are a major reservoir of the ‘top-7’ serogroups, in which STEC colonize the hindgut and are shed in the feces. The feces serve as a major source of food, feed and water contaminations. In addition to cattle, other domestic animals and even wild animals harbor STEC and shed them in the feces. Sources of STEC foodborne illness outbreaks have been traced to food of animal and plant origin. Two studies were conducted to detect and isolate STEC, based on culture- and PCR methods, from swine feces and wheat grains. Swine fecal samples (n=598), collected from ten swine farms with finisher pigs, located in eight states, were enriched with EC broth. The enriched samples were subjected to a three-plex quantitative PCR (qPCR) assay targeting three virulence genes, stx1, stx2, and eae. Samples positive for either of the two Shiga toxin genes were then tested by a multiplex PCR assay targeting top-7 serogroups (O26, O45, O103, O111, O121, O145, and O157) and the O104 serogroup. Also, stx-positive samples were subjected to an eight-plex PCR assay, designed and validated to detect 8 serogroups (O8, O20/O137, O59, O86, O91, O100, O120, and O174) considered to be the top-8 prevalent STEC in swine feces. Samples positive for the top-7 plus O104 serogroups were subjected to a serogroup-specific IMS culture method and plating on selective media for detection and isolation of top-7 serogroups of STEC. Samples positive for stx1 or stx2 gene and negative for the top-7 serogroups were directly plated onto MacConkey and Eosin-Metheylene Blue agar. Putative colonies, up to ten per sample and medium, were picked, pooled and tested for stx genes. If pooled colonies were positive for stx1 or stx2 gene, then each colony in the pool was tested individually to identify stx1 and/or stx2-carrying E. coli. Of the 598 fecal samples tested by qPCR for the three major virulence genes, 155 (25.9%), 389 (65.1%), and 398 (66.6%) samples were positive for stx1, stx2, and eae genes, respectively. Based on the mPCR assay for the top-7 plus O104 serogroups, the three predominant serogroups detected were O26 (10.7%; 64/598), O121 (17.6%; 105/598), and O157 (11.5%; 69/598). The 8-plex PCR assay designed to detect the top-8 serogroups of swine STEC indicated the prevalence of 88.6% of O8 (530/598), 35.5% of O86 (212/598), 24.1% of O174 (144/598), 20.2% of O100 (121/598), 15.6% of O91, 4.3% of O59 (26/598), 4.2% of O120 (25/598), and 3.2% of O20/O137 (19/598). The culture method identified STEC O121 as the dominant top-7 STEC serogroup (3.8%; 23/598). None of the O157 isolates (3.5%; 21/598) carried the stx gene. Isolates that were non top-7 (or O104) were tested by 12 different PCR assays that can detect 130 serogroups to identify the serogroups of STEC. The most prevalent non top-7 STEC serogroups isolated were STEC O8 and STEC O86. In conclusion, our study indicated that the major top-7 STEC was O121, and among the non-top-7 STEC, serogroups of O8 and O86 were the dominant. Interestingly, the O157 serogroup implicated in outbreaks traced to pork products, was shed in the feces, but none of the isolates carried the stx gene. Data on the prevalence and virulence potential of STEC from swine will be useful information to have to evaluate management strategies and mitigate the effects on food borne illnesses in the United States. Wheat grain samples (n=626), collected from different regions of the country and transported to the laboratory, were enriched using two different media, modified Buffered Peptone Water with pyruvate (mBPWp) and Escherichia coli (EC) broth and subjected to a mPCR assay to detect the top-7 serogroups (O26, O45, O103, O111, O121, O145, and O157) and three major virulence genes (stx1, stx2, and eae). Samples positive by PCR for any of the top-7 serogroups and or stx genes were then cultured using serogroup-specific immunomagnetic separation (IMS) and plating on selective media for detection and isolation of top-7 STEC. Based on the mPCR assay, the prevalence of the top-7 serogroups in wheat grain samples, enriched by mBPWp, were 0.2% of O26 (1/626), 0.6% of O45 (4/626), 0.2% of O103 (1/626), and 0.6% of O157 (4/626), and the prevalence of virulence genes were 0.2% of stx1 (1/626), 0.2% of stx2 (1/626), and 0.8% of eae (5/626). The prevalence of top-7 serogroups, enriched in EC broth, were 0.2% of O26 (1/626), 1.9% of O45 (12/626), 0.5% of O103 (3/626), and 1.0% of O157 (6/626), and that of virulence genes were stx1 (0.3%; 2/626), stx2 (1.3%; 8/626), and eae (1.1%; 7/626). The number of wheat grain samples positive for STEC serogroups and or virulence genes, by PCR method (36/626; 5.8%), was higher in samples enriched by EC broth than mBPWp broth (15/626; 2.4%). Based on culture methods, the top-7 serogroups prevalent in wheat grain samples, enriched in mBPWp, were 0.2% of O26 (1/626), 0.5% of O45 (3/626), 0.2% of O103 (1/626), and 0.6% of O157 (4/626), and none of the isolates was positive for any of the three virulence genes. In wheat grain samples enriched in EC broth, the prevalence of the top-7 serogroups were 0.2% of O26 (1/626), 0.8% of O45 (5/626), 0.3% of O103 (2/626), and 0.8% of O157 (5/626), with no detection of virulence genes. The number of wheat grain samples positive for STEC serogroups and or virulence genes, by culture method, was higher in samples enriched by EC broth than mBPWp broth (5/36 and 0/15, respectively). None of the isolates of the top-7 serogroups by either enrichment method was positive for the Shiga toxin genes. A total five isolates that carried the Shiga toxin 2 gene were isolated from wheat grains enriched in EC broth. The five isolates were confirmed as serogroups O8 (0.64%; 4/626) and O130 (0.16%; 1/626) by PCR. Our study shows that wheat grains were contaminated with the top-7 serogroups of E. coli, but none of the isolates carried the Shiga toxin genes. The two stx2-positive serogroups that were isolated, O8 and O130, are not major STEC pathogens and have only been implicated in sporadic diarrheal cases in animals and humans

Restricted exposure of mice to primer pheromones coincident with prolactin surges blocks pregnancy by changing hypothalamic dopamine release

Exposure of recently mated female mice to strange male urine revealed that exposure for 8 h was sufficient to produce pregnancy block providing exposure is for two 4-h periods coincident with prolactin surges. Exposure for 8 h between prolactin surges or one 4-h exposure coincident with either the nocturnal or the diurnal prolactin surge was without effect. When bromocriptine, a dopamine agonist, was given coincident with the nocturnal and diurnal prolactin surges, it was equally effective, but the opiate antagonist (naltrexone) administered in a similar manner was without effect. This result indicates that pheromonal action is through excitation of the tuberoinfundibular neurones rather than by inhibition of beta-endorphin neurones. Further evidence for dopamine involvement in pregnancy block is demonstrated by showing DOPA accumulation in the medio-basal hypothalamus following exposure to male urinary pheromones after dihydroxybenzylhydrazine (DHBH) administration, which blocks the enzyme DOPA-decarboxylase. Taken together, this series of experiments provides convincing evidence for the dopamine inhibition of prolactin release being the final pathway for pheromone action in the context of pregnancy block

Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank

AimThis study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.MethodsBaseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.ResultsAmong the 363 313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01–1.03)], greater deprivation [RHR: 1.02 (1.00–1.03)], hypertension [RHR: 1.14 (1.02–1.27)], and current smoking [RHR: 1.45 (1.27–1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84–0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01–2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00–1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58–4.14)].ConclusionOlder age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women

Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank

Aim: this study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.Methods: baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.Results: among the 363 313 participants (53.5% women), 8 470 experienced MI (29.9% women) and 7 705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].Conclusions: older age, hypertension and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.</p

Long-term airborne dioxin exposure and breast cancer risk in a case-control study nested within the French E3N prospective cohort

International audienceCadmium, due to its estrogen‐like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long‐term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System‐based metric, which included subject's residence‐to‐cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (OR Q5 vs . Q1 = 0.63; 95% CI: 0.41–0.95, p trend = 0.043) and for ER−/PR− breast tumors (OR Q4 vs . Q1 = 0.62; 95% CI: 0.40–0.95, OR Q5 vs . Q1 = 0.68; 95% CI: 0.42–1.07, p trend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

International audienceBackground: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality

Long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in a large pooled European cohort: ELAPSE study.

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10-5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide