Germline loss-of-function variants in the base-excision repair gene MBD4 cause a Mendelian recessive syndrome of adenomatous colorectal polyposis and acute myeloid leukaemia

Inherited defects in base-excision repair (BER) predispose to adenomatous polyposis and colorectal cancer (CRC), yet our understanding of this important DNA repair pathway remains incomplete. By combining detailed clinical, histological and molecular profiling, we reveal biallelic germline loss-of-function (LOF) variants in the BER gene MBD4 to predispose to adenomatous polyposis and -uniquely amongst CRC predisposition syndromes- to myeloid neoplasms. Neoplasms from MBD4-deficient patients almost exclusively accumulate somatic CpG>TpG mutations, resembling mutational signature SBS1. MBD4-deficient adenomas harbour mutations in known CRC driver genes, although AMER1 mutations were more common and KRAS mutations less frequent. We did not find an increased risk for colorectal tumours in individuals with a monoallelic MBD4 LOF variant. We suggest that this condition should be termed MBD4-associated neoplasia syndrome (MANS) and that MBD4 is included in testing for the genetic diagnosis of polyposis and/or early-onset AM

A Smart Service Platform for Cost Efficient Cardiac Health Monitoring

Aim: In this study we have investigated the problem of cost effective wireless heart health monitoring from a service design perspective. Subject and Methods: There is a great medical and economic need to support the diagnosis of a wide range of debilitating and indeed fatal non-communicable diseases, like Cardiovascular Disease (CVD), Atrial Fibrillation (AF), diabetes, and sleep disorders. To address this need, we put forward the idea that the combination of Heart Rate (HR) measurements, Internet of Things (IoT), and advanced Artificial Intelligence (AI), forms a Heart Health Monitoring Service Platform (HHMSP). This service platform can be used for multi-disease monitoring, where a distinct service meets the needs of patients having a specific disease. The service functionality is realized by combining common and distinct modules. This forms the technological basis which facilitates a hybrid diagnosis process where machines and practitioners work cooperatively to improve outcomes for patients. Results: Human checks and balances on independent machine decisions maintain safety and reliability of the diagnosis. Cost efficiency comes from efficient signal processing and replacing manual analysis with AI based machine classification. To show the practicality of the proposed service platform, we have implemented an AF monitoring service. Conclusion: Having common modules allows us to harvest the economies of scale. That is an advantage, because the fixed cost for the infrastructure is shared among a large group of customers. Distinct modules define which AI models are used and how the communication with practitioners, caregivers and patients is handled. That makes the proposed HHMSP agile enough to address safety, reliability and functionality needs from healthcare providers

Assessment of surface water quality in the Malaysian coastal waters by using multivariate analyses.

Coastal water samples were collected from 20 sampling sites in the southern part of Peninsular Malaysia. Seven physico-chemical parameters were measured directly in-situ while water samples were collected and analysed for 6 dissolved trace metal concentrations. The surface water (0-20 cm) physico-chemical parameters including temperature, salinity, dissolved oxygen (DO), pH, total dissolved solids (TDS), specific conductance (SpC) and turbidity while the dissolved trace metals were Cd, Cu, Fe, Ni, Pb and Zn. The ranges for the physico-chemical parameters were 28.07-35.6°C for temperature, 0.18-32.42 ppt for salinity, 2.20-12.03 mg/L for DO, 5.50-8.53 for pH, 0.24-31.65 mg/L for TDS, 368-49452 μ/cm for SpC and 0-262 NTU for turbidity while the dissolved metals (mg/L) were 0.013-0.147 for Cd, 0.024-0.143 for Cu, 0.266-2.873 for Fe, 0.027-0.651 for Ni, 0.018-0.377 for Pb and 0.032-0.099 for Zn. Based on multivariate analysis (including correlation, cluster and principal component analyses), the polluted sites were found at Kg. Pasir Puteh and Tg. Kupang while Ni and Pb were identified as two major dissolved metals of high variation in the coastal waters. Therefore, water quality monitoring and control of release of untreated anthropogenic wastes into rivers and coastal waters are strongly needed

Insights into the antimicrobial potential of Dithiocarbamate anions and metal-based species

Bacterial infection remains a worldwide problem that requires urgent addressing. Overuse and poor disposal of antibacterial agents abet the emergence of bacterial resistance mechanisms. There is a clear need for new approaches for the development of antibacterial therapeutics. Herein, the antibacterial potential of molecules based on dithiocarbamate anions, of general formula R(R’)NCS2(−), and metal salts of transition metals and main group elements, is summarized. Preclinical studies show a broad range of antibacterial potential, and these investigations are supported by appraisals of possible biological targets and mechanisms of action to guide chemical syntheses. This bibliographic review of the literature points to the exciting potential of dithiocarbamate-based therapeutics in the crucial battle against bacteria. Additionally, included in this overview, for the sake of completeness, is mention of the far fewer studies on the antifungal potential of dithiocarbamates and even less work conducted on antiparasitic behavior

The Importance of Eurekan Mountains on Cenozoic Sediment Routing on the Western Barents She

The importance of topography generated by Eocene Eurekan deformation as a sediment source for sandstones deposited on the western Barents Shelf margin is evaluated through a sediment provenance study conducted on wellbore materials retrieved from Spitsbergen and from the Vestbakken Volcanic Province and the Sørvestsnaget Basin in the southwest Barents Sea. A variety of complementary techniques record a provenance change across the Paleocene-Eocene boundary in wellbore BH 10-2008, which samples Paleogene strata of the Central Tertiary Basin in Spitsbergen. Sandstones containing K-feldspar with radiogenic Pb isotopic compositions, chrome spinel in the heavy mineral assemblage, and detrital zircons and rutiles with prominent Palaeoproterozoic and Late Palaeozoic—Early Mesozoic U-Pb age populations are up-section replaced by sandstone containing albitic plagioclase feldspar, metasedimentary schist rock fragments, a heavy mineral assemblage with abundant chloritoid, metamorphic apatite with low REE contents, metapelitic rutile with Silurian U-Pb ages and zircons with predominantly Archaean and Palaeoproterozoic U-Pb age populations. Our results clearly demonstrate the well-known regional change in source area from an exposed Barents Shelf terrain east of the Central Tertiary Basin during the Paleocene to the emerging Eurekan mountains west and north of the Central Tertiary Basin during the Eocene. Eocene sandstones deposited in the marginal basins of the southwestern Barents Shelf, which were sampled in wellbores 7316/5-1 and 7216/11-1S, contain elements of both the Eurekan and the eastern Barents Shelf provenance signatures. The mixing of the two sand types and delivery to the southwest margin of the Barents Shelf is consistent with a fill and spill model for the Central Teritary Basin, with transport of Eurekan-derived sediment east then south hundreds of kilometres across the Shelf

Crystal structure of chlorido-(O-ethyl phenylcarbamothioamide-κS)-bis(triphenylphosphane-κP)-silver(I), C45H41AgClNOP2S

C45H41AgClNOP2S, monoclinic, P21/c (no. 14), a = 10.1930(3) Å, b = 18.3087(6) Å, c = 21.3088(6) Å, β = 94.516(3)°, V = 3964.3(2) Å3, Z = 4, Rgt(F) = 0.0353, wRref(F2) = 0.0810, T = 100(2) K

Crystal structure of chlorido-(O-methyl phenylcarbamothioamide-κS)-bis(triphenylphosphane-κP)silver(I), C44H39AgClNOP2S

C44H39AgClNOP2S, triclinic, P1̄ (no. 2), a = 10.2520(3) Å, b = 13.2252(4) Å, c = 14.9378(3) Å, α = 78.424(2)°, β = 78.388(2)°, γ = 84.534(3)°, V = 1940.35(9) Å3, Z = 2, Rgt(F) = 0.0382, wRref(F2) = 0.0807, T = 100(2) K

Aerosol meteorology of Maritime Continent for the 2012 7SEAS southwest monsoon intensive study - Part 2: Philippine receptor observations of fine-scale aerosol behavior

Abstract. The largest 7 Southeast Asian Studies (7SEAS) operations period within the Maritime Continent (MC) occurred in the August–September 2012 biomass burning season. Data included were observations aboard the M/Y Vasco, dispatched to the Palawan Archipelago and Sulu Sea of the Philippines for September 2012. At these locations, the Vasco observed MC smoke and pollution entering the southwest monsoon (SWM) monsoonal trough. Here we describe the research cruise findings and the finer-scale aerosol meteorology of this convectively active region. This 2012 cruise complemented a 2-week cruise in 2011 and was generally consistent with previous findings in terms of how smoke emission and transport related to monsoonal flows, tropical cyclones (TC), and the covariance between smoke transport events and the atmosphere's thermodynamic structure. Biomass burning plumes were usually mixed with significant amounts of anthropogenic pollution. Also key to aerosol behavior were squall lines and cold pools propagating across the South China Sea (SCS) and scavenging aerosol particles in their path. However, the 2012 cruise showed much higher modulation in aerosol frequency than its 2011 counterpart. Whereas in 2011 large synoptic-scale aerosol events transported high concentrations of smoke into the Philippines over days, in 2012 measured aerosol events exhibited a much shorter-term variation, sometimes only 3–12 h. Strong monsoonal flow reversals were also experienced in 2012. Nucleation events in cleaner and polluted conditions, as well as in urban plumes, were observed. Perhaps most interestingly, several cases of squall lines preceding major aerosol events were observed, as opposed to 2011 observations where these lines largely scavenged aerosol particles from the marine boundary layer. Combined, these observations indicate pockets of high and low particle counts that are not uncommon in the region. These perturbations are difficult to observe by satellite and very difficult to model. Indeed, the Navy Aerosol Analysis and Prediction System (NAAPS) simulations captured longer period aerosol events quite well but largely failed to capture the timing of high-frequency phenomena. Ultimately, the research findings of these cruises demonstrate the real world challenges of satellite-based missions, significant aerosol life cycle questions such as those the future Aerosol/Clouds/Ecosystems (ACE) will investigate, and the importance of small-scale phenomena such as sea breezes, squall lines, and nucleation events embedded within SWM patterns in dominating aerosol life cycle and potential relationships to clouds