CloudASM: an ultra-efficient cloud-based pipeline for mapping allele-specific DNA methylation.

SUMMARY: Methods for quantifying the imbalance in CpG methylation between alleles genome-wide have been described but their algorithmic time complexity is quadratic and their practical use requires painstaking attention to infrastructure choice, implementation and execution. To solve this problem, we developed CloudASM, a scalable, ultra-efficient, turn-key, portable pipeline on Google Cloud Platform (GCP) that uses a novel pipeline manager and GCP's serverless enterprise data warehouse. AVAILABILITY AND IMPLEMENTATION: CloudASM is freely available in the GitHub repository https://github.com/TyckoLab/CloudASM and a sample dataset and its results are also freely available at https://console.cloud.google.com/storage/browser/cloudasm. CONTACT: emmanuel.dumont@hmh-cdi.org.

An Ecological Study Indicates the Importance of Ultraviolet A Protection in Sunscreens.

The use of sunscreens is recommended to limit the impact of sun exposure on the skin. The objective of this study was to examine the relationship between sunscreen sales and melanoma in 4 different countries with diverse sunscreen regulations. Data from publicly avail-able databases were examined for Sweden, England, Australia, and the USA from 1999 to 2018. The association between incidence of melanoma and sunscreen sales was estimated using a generalized estimating equation, and modelling was used to predict melanoma cases. Incidence of melanoma was positively associated with sunscreen sales in England, Australia, and the USA, and negatively associated with sunscreen sales in Sweden. Growth rates in melanoma cases of 0.42%, 16.7%, 19.1% and 12.2% were predicted for Sweden, England, Australia, and the USA, respectively. The differences observed between England, Australia, and the USA, on the one hand, and Sweden, on the other hand, are consistent with the adoption of strong regulations requiring the use of ultraviolet A blocking agents in sunscreens.

The Ultraviolet Index Is Well Estimated by the Terrestrial Irradiance at 310 nm.

Ultraviolet (UV) exposure significantly contributes to non-melanoma skin cancer. In the context of health, UV exposure is the product of time and the UV Index (UVI), a weighted sum of the irradiance I(λ) over all wavelengths from λ = 250 to 400 nm. In our analysis of the United States Environmental Protection Agency's UV-Net database of over 400,000 spectral irradiance measurements taken over several years, we found that the UVI is well estimated by 77 I310. To further understand this result, we applied an optical atmospheric model to generate terrestrial irradiance spectra and found that it applies across a wide range of conditions. An accurate UVI radiometer can be built from a photodiode covered by a bandpass filter centered at 310 nm.

[Experience of an exorcist working with mental health professionals]. / Témoignage d'un exorciste collaborant avec des professionnels de la santé mentale.

A collaboration between mental health professionals and an exorcist service in Lyon is not new in France. It is even recommended by the Church, for the well being of sufferers, as long as each party plays its role in line with their own discipline. This requires open-mindedness on both sides which must be developed and cultivated.

Impact of land-use on PAH transfer in sub-surface water as recorded by CaCO3 concretions in urban underground structures (Paris, France).

In densely populated urban areas, the pressure on water resources is considerable and will tend to intensify over the next decades. Preserving water resources therefore seems fundamental, but many questions remain as to the transfer of contaminants to subsurface waters in these largely sealed areas. Because of their toxicity and persistence in the environment, this work focused on the study of polycyclic aromatic hydrocarbons (PAHs), ubiquitous pollutants mainly produced by human activities. To better understand the main factors leading to the retention or transport of these pollutants in urban environments, vertical transects, from the surface to several meters down, were established on three study sites in or near Paris (France), selected according to an urbanization gradient. Soil samples collected at the surface and urban secondary carbonate deposits (USCD), similar to cave speleothems, sampled underground in quarries and aqueducts were analyzed. As the hydrophobic properties of PAHs favor their sorption onto organic matter, the latter was also studied using organic carbon analysis and UV fluorescence spectroscopy. The USCD located closest to the urbanized surface contained high concentrations of PAHs (76.8 ± 5.3 ng g-1), while the USCD located at greater depth with organic soil on the surface contained the lowest amount of PAHs (2.9 ± 0.4 ng g-1), and no PAHs with log KOC > 5. The results highlight the predominant role played by the presence of organic topsoil at the surface in retaining and storing large amounts of PAHs (1914-2595 ng. gsoil-1), particularly the most hydrophobic ones (i.e. 60% of the 15 PAHs are characterized by a Log KOC >5), which are also the most toxic. The lithology and thickness of the bedrock (between the surface and the USCD) also play an important role in the retention of PAHs, particularly those adsorbed on the particulate phase.

A randomized trial of a wearable UV dosimeter for skin cancer prevention.

Background: Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. Despite guidelines on ultraviolet (UV) avoidance, it remains difficult for people to assess their exposure, as UV is invisible and the onset of UV-induced symptoms is delayed. Methods: In a prospective randomized trial, 97 elderly patients with a history of actinic keratoses (AK) were followed over 6 months. Fifty patients received UV counseling from a dermatologist and a wearable UV dosimeter that provided real-time and cumulative UV exposure. Forty-seven patients received only UV counseling from a dermatologist. Results: Over 75% of participants recorded UV exposure at least once a week during the summer. After 6 months of intervention, when comparing the device group to the control group, we observed a non-significant 20% lower ratio of incidence rates of AKs (95% CI = [-41, 55%], p-value = 0.44) and a significant 95% lower ratio of incidence rates of NMSCs (95% CI = [33, 99.6%], p-value = 0.024). Surveys demonstrated that the control group's score in self-perceived ability to participate in social activities significantly increased by 1.2 (p-value = 0.04), while in the device group, this score non-significantly decreased by 0.9 (p-value = 0.1). We did not observe changes, or between-group differences, in anxiety and depression surveys. Conclusion: This pilot clinical trial has a short duration and a small sample size. However, device adherence and quality of life questionnaires suggest a smartphone-connected wearable UV dosimeter is well accepted by an elderly population. This trial also indicates that a wearable UV dosimeter may be an effective behavioral change tool to reduce NMSC incidence in an elderly population with a prior history of AKs.Clinical trial registration: clinicaltrials.gov, identifier NCT03315286.

Observing the mushroom-to-brush transition for kinesin proteins.

The height of polymers grafted to a surface is predicted to be constant at low densities ("mushroom" regime) and increase with the third root of the polymer surface density at high densities ("brush" regime). This mushroom-to-brush transition is explored with kinesin-1 proteins adhered to a surface at controlled densities. The kinesin height is measured by attaching fluorescently labeled microtubules to the kinesins and determining their elevation using fluorescence interference contrast microscopy. Our measurements are consistent with a mushroom regime and a brush regime and a transition near the theoretically predicted density. The mushroom-to-brush transition may play a role in protein behavior in crowded cellular environments and may be exploited as a signal in intracellular regulation and mechanotransduction.

Fatigue failure and molecular machine design.

Sophisticated molecular machines have evolved in nature, and the first synthetic molecular machines have been demonstrated. With our increasing understanding of individual operating cycles, the question of how operation can be sustained over many cycles comes to the forefront. In the design of macroscale machines, performance and lifetime are opposing goals. Similarly, the natural evolution of biological nanomachines, such as myosin motor proteins, is likely constrained by lifetime requirements. Rather than bond rupture at high forces, bond fatigue under repeated small stresses may limit the mechanical performance of molecular machines. Here, the effect of cyclic stresses using single and double bonds as simple examples are discussed. Additionally, it is demonstrated that an increase in lifetime requires a reduction in mechanical load and that molecular engineering design features, such as polyvalent bonds capable of rebinding, can extend the bond lifetime dramatically. A universal scaling law for the force output of motors is extrapolated to the molecular scale to estimate the design space for molecular machines.

Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs.

BACKGROUND: Mapping of allele-specific DNA methylation (ASM) can be a post-GWAS strategy for localizing regulatory sequence polymorphisms (rSNPs). The advantages of this approach, and the mechanisms underlying ASM in normal and neoplastic cells, remain to be clarified. RESULTS: We perform whole genome methyl-seq on diverse normal cells and tissues and three cancer types. After excluding imprinting, the data pinpoint 15,112 high-confidence ASM differentially methylated regions, of which 1838 contain SNPs in strong linkage disequilibrium or coinciding with GWAS peaks. ASM frequencies are increased in cancers versus matched normal tissues, due to widespread allele-specific hypomethylation and focal allele-specific hypermethylation in poised chromatin. Cancer cells show increased allele switching at ASM loci, but disruptive SNPs in specific classes of CTCF and transcription factor binding motifs are similarly correlated with ASM in cancer and non-cancer. Rare somatic mutations affecting these same motif classes track with de novo ASM. Allele-specific transcription factor binding from ChIP-seq is enriched among ASM loci, but most ASM differentially methylated regions lack such annotations, and some are found in otherwise uninformative "chromatin deserts." CONCLUSIONS: ASM is increased in cancers but occurs by a shared mechanism involving disruptive SNPs in CTCF and transcription factor binding sites in both normal and neoplastic cells. Dense ASM mapping in normal plus cancer samples reveals candidate rSNPs that are difficult to find by other approaches. Together with GWAS data, these rSNPs can nominate specific transcriptional pathways in susceptibility to autoimmune, cardiometabolic, neuropsychiatric, and neoplastic diseases.

Molecular wear of microtubules propelled by surface-adhered kinesins.

Wear is the progressive loss of material from a body caused by contact and relative movement and is a major concern in both engineering and biology. Advances in nanotechnology have allowed the origins of wear processes to be studied at the atomic and molecular scale, but also demand that wear in nanoscale systems can be predicted and controlled. Biomolecular systems can undergo a range of active movements at the nanoscale, which are enabled by the transduction of chemical energy into mechanical work by polymerization processes and motor proteins. The active movements are accompanied by dissipative processes that can be conceptually understood as 'protein friction'. Here, we show that wear also occurs in an in vitro system consisting of microtubules gliding across a surface coated with kinesin-1 motor proteins, and that energetic considerations suggest a molecule-by-molecule removal of tubulin proteins. The rates of removal show a complex dependence on sliding velocity and kinesin density, which, in contrast to the friction behaviour between microtubules and kinesin-8, cannot be explained by simple chemical reaction kinetics.

Three centuries of heavy metal pollution in Paris (France) recorded by urban speleothems.

The first record of urban speleothems used to reconstruct the history of heavy metal pollution of shallow groundwaters is presented. Two speleothems grew during the last 300 years in an underground aqueduct in the north-eastern part of Paris. They display high Pb, Mn V, Cu, Cd and Al concentrations since 1900 due to the urbanization of the site which triggered anthropogenic contamination of the water feeding the speleothems. Surprisingly, these heavy metal concentrations are also high in the oldest part. This early pollution could come from the use of Parisian waste as fertilizers in the orchards and vineyards cultivated above the aqueduct before urbanization. Lead isotopes were measured in these carbonates as well as in lead artifacts from the 17th-18th centuries ((206)Pb/(207)Pb=1.180+/-0.003). The mean (206)Pb/(207)Pb ratio, for one of the speleothems is 1.181+/-0.003 unvarying with time. These lead signatures are close to those of coal and old lead from northern European mines, lower than the natural background signature. It confirms that the high metal concentrations found come from anthropogenic pollution. Conversely, the lead isotopic composition of the second speleothem presents two temporal trends: for the oldest levels, the mean value (1.183+/-0.003) is similar to the first speleothem. For the youngest part, a lower value (1.172+/-0.005) is recorded, evidencing the contribution of a new lead source at the beginning of the industrial revolution. Pb isotopes were also measured in recent samples from a nearby superficial site. The first sample is a recent (AD 1975+/-15 years) deposit ((206)Pb/(207)Pb=1.148+/-0.003), and the second, a thin subactual layer ((206)Pb/(207)Pb=1.181+/-0.002). These data are compatible with the adding of anthropogenic sources (leaded gasoline and industrial lead from Rio Tinto ore).

Clinical and surgical applications of smart glasses.

BACKGROUND: With the increased efforts to adopt health information technology in the healthcare field, many innovative devices have emerged to improve patient care, increase efficiency, and decrease healthcare costs. A recent addition is smart glasses: web-connected glasses that can present data onto the lenses and record images or videos through a front-facing camera. OBJECTIVE: In this article, we review the most salient uses of smart glasses in healthcare, while also denoting their limitations including practical capabilities and patient confidentiality. METHODS: Using keywords including, but not limited to, ``smart glasses'', ``healthcare'', ``evaluation'', ``privacy'', and ``development'', we conducted a search on Ovid-MEDLINE, PubMed, and Google Scholar. A total of 71 studies were included in this review. RESULTS: Smart glasses have been adopted into the healthcare setting with several useful applications including, hands-free photo and video documentation, telemedicine, Electronic Health Record retrieval and input, rapid diagnostic test analysis, education, and live broadcasting. CONCLUSIONS: In order for the device to gain acceptance by medical professionals, smart glasses will need to be tailored to fit the needs of medical and surgical sub-specialties. Future studies will need to qualitatively assess the benefits of smart glasses as an adjunct to the current health information technology infrastructure.

Mobile Phone-Connected Wearable Motion Sensors to Assess Postoperative Mobilization.

BACKGROUND: Early mobilization after surgery reduces the incidence of a wide range of complications. Wearable motion sensors measure movements over time and transmit this data wirelessly, which has the potential to monitor patient recovery and encourages patients to engage in their own rehabilitation. OBJECTIVE: We sought to determine the ability of off-the-shelf activity sensors to remotely monitor patient postoperative mobility. METHODS: Consecutive subjects were recruited under the Department of Neurosurgery at Columbia University. Patients were enrolled during physical therapy sessions. The total number of steps counted by the two blinded researchers was compared to the steps recorded on four activity sensors positioned at different body locations. RESULTS: A total of 148 motion data points were generated. The start time, end time, and duration of each walking session were accurately recorded by the devices and were remotely available for the researchers to analyze. The sensor accuracy was significantly greater when placed over the ankles than over the hips (P<.001). Our multivariate analysis showed that step length was an independent predictor of sensor accuracy. On linear regression, there was a modest positive correlation between increasing step length and increased ankle sensor accuracy (r=.640, r(2)=.397) that reached statistical significance on the multivariate model (P=.03). Increased gait speed also correlated with increased ankle sensor accuracy, although less strongly (r=.444, r(2)=.197). We did not note an effect of unilateral weakness on the accuracy of left- versus right-sided sensors. Accuracy was also affected by several specific measures of a patient's level of physical assistance, for which we generated a model to mathematically adjust for systematic underestimation as well as disease severity. CONCLUSIONS: We provide one of the first assessments of the accuracy and utility of widely available and wirelessly connected activity sensors in a postoperative patient population. Our results show that activity sensors are able to provide invaluable information about a patient's mobility status and can transmit this data wirelessly, although there is a systematic underestimation bias in more debilitated patients.

The quantified patient: a patient participatory culture.

The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient's Quantified Self can be directly monitored and remotely accessed by health care professionals.

Smart wearable body sensors for patient self-assessment and monitoring.

BACKGROUND: Innovations in mobile and electronic healthcare are revolutionizing the involvement of both doctors and patients in the modern healthcare system by extending the capabilities of physiological monitoring devices. Despite significant progress within the monitoring device industry, the widespread integration of this technology into medical practice remains limited. The purpose of this review is to summarize the developments and clinical utility of smart wearable body sensors. METHODS: We reviewed the literature for connected device, sensor, trackers, telemonitoring, wireless technology and real time home tracking devices and their application for clinicians. RESULTS: Smart wearable sensors are effective and reliable for preventative methods in many different facets of medicine such as, cardiopulmonary, vascular, endocrine, neurological function and rehabilitation medicine. These sensors have also been shown to be accurate and useful for perioperative monitoring and rehabilitation medicine. CONCLUSION: Although these devices have been shown to be accurate and have clinical utility, they continue to be underutilized in the healthcare industry. Incorporating smart wearable sensors into routine care of patients could augment physician-patient relationships, increase the autonomy and involvement of patients in regards to their healthcare and will provide for novel remote monitoring techniques which will revolutionize healthcare management and spending.