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Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
The Working Party has produced this report in order to prompt readers to engage at an early stage in InsurTech projects, through considering (i) the full range of risks associated with InsurTech developments, (ii) the lifecycle of an InsurTech venture and how any risk considerations may vary over this lifecycle and (iii) the extent to which InsurTech ventures align with risk strategy and risk appetite.
The report contains practical guidance for actuaries, risk professionals, insurance companies and their Boards on these considerations, and can be used to facilitate appropriate questioning, to help ensure that InsurTech-related business decisions are fully cognisant of the risk management issues and to help ensure the success of projects.
The Working Party developed this guidance having carried out an industry survey on a number of risk management topics relating to InsurTech, as well as having carried out interviews with a number of relevant senior stakeholders across the insurance industry, in order to better understand current sentiment and how risk management plays a part when considering opportunities in InsurTech. The Working Party views on the findings from these activities are summarised in the report.
Ferroelectric single-crystal-architecture-in-glass is a new class of metamaterials that would enable active integrated optics if the ferroelectric behavior is preserved within the confines of glass. We demonstrate using lithium niobate crystals fabricated in lithium niobosilicate glass by femtosecond laser irradiation that not only such behavior is preserved, the ferroelectric domains can be engineered with a DC bias. A piezoresponse force microscope is used to characterize the piezoelectric and ferroelectric behavior. The piezoresponse correlates with the orientation of the crystal lattice as expected for unconfined crystal, and a complex micro- and nano-scale ferroelectric domain structure of the as-grown crystals is revealed.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Breast-fed infants are susceptible to vitamin D deficiency rickets. The current vitamin D ‘adequate intake’ (AI) for 0–6-month-old infants is 10 µg/d, corresponding with a human milk antirachitic activity (ARA) of 513 IU/l. We were particularly interested to see whether milk ARA of mothers with lifetime abundant sunlight exposure reaches the AI. We measured milk ARA of lactating mothers with different cultural backgrounds, living at different latitudes. Mature milk was derived from 181 lactating women in the Netherlands, Curaçao, Vietnam, Malaysia and Tanzania. Milk ARA and plasma 25-hydroxyvitamin D (25(OH)D) were analysed by liquid-chromatography-MS/MS; milk fatty acids were analysed by GC-flame ionisation detector (FID). None of the mothers reached the milk vitamin D AI. Milk ARA (n; median; range) were as follows: Netherlands (n 9; 46 IU/l; 3–51), Curaçao (n 10; 31 IU/l; 5–113), Vietnam: Halong Bay (n 20; 58 IU/l; 23–110), Phu Tho (n 22; 28 IU/l; 1–62), Tien Giang (n 20; 63 IU/l; 26–247), Ho-Chi-Minh-City (n 18; 49 IU/l; 24–116), Hanoi (n 21; 37 IU/l; 11–118), Malaysia–Kuala Lumpur (n 20; 14 IU/l; 1–46) and Tanzania-Ukerewe (n 21; 77 IU/l; 12–232) and Maasai (n 20; 88 IU/l; 43–189). We collected blood samples of these lactating women in Curaçao, Vietnam and from Tanzania–Ukerewe, and found that 33·3 % had plasma 25(OH)D levels between 80 and 249·9 nmol/l, 47·3 % between 50 and 79·9 nmol/l and 19·4 % between 25 and 49·9 nmol/l. Milk ARA correlated positively with maternal plasma 25(OH)D (range 27–132 nmol/l, r 0·40) and milk EPA+DHA (0·1–3·1 g%, r 0·20), and negatively with latitude (2°S-53°N, r −0·21). Milk ARA of mothers with lifetime abundant sunlight exposure is not even close to the vitamin D AI for 0–6-month-old infants. Our data may point at the importance of adequate fetal vitamin D stores.
A primary concern with dating skeletal material from oceanic environments is the effect of marine-derived carbon on resulting radiocarbon ages. Due to uncertainties in local marine reservoir effects and the proportion of marine carbon incorporated in bone, dates from archaeological skeletal material exhibiting marine dietary signatures have previously been characterized as problematic and removed from further analysis. While in certain instances this may be appropriate, in others it is not. This article presents 26 new 14C dates obtained from human teeth (dentin collagen) on Rapa Nui. The effect of the local marine reservoir on 14C ages is evaluated assuming a range of incorporated marine-derived carbon. The results indicate that the Rapa Nui 14C ages are not significantly different under varying realistic extreme ranges in estimates of the proportion of marine carbon consumed. The article argues that this is primarily due to the small local marine reservoir effect measured in Rapa Nui and relatively lower reliance on marine resources in the prehistoric and protohistoric population.
Of all the different methods employed to estimate the mean absolute magnitude of RR Lyrae variables, only an analysis of the Baade-Wesselink type can determine this quantity directly. The distance to a globular cluster can therefore be measured by determining <MV>RR for that cluster instead of being forced to assume that <MV>RR is the same as that of the nearby field variables. This is important in that the field stars may have a different luminosity than cluster variables. In addition, since <MV>RR should depend on the composition (especially helium) and history of mass loss of these stars, this quantity may vary from cluster to cluster.
We discuss results from radial velocity data for a sample of metal-poor kinematically-unbiased red giants. We determine the motions of the stars with respect to the Local Standard of Rest, and estimate their velocity dispersions.
Using optical and infrared photometry and echelle spectroscopy of variable V8 in the globular cluster M5, we derive a cluster distance of 6.8 kpc using the Baade-Wesselink method. This agrees with the prediction obtained for the cluster’s metallicity using a sample of 19 field stars studied by us and by Liu and Janes (this volume). It also agrees well with estimates for Mv obtained from statistical parallaxes of field stars. It agrees as well with the main sequence fitting procedure where we have used only HD 103095, the field halo dwarf with the most accurate trigonometric parallax (3% error), and which has a metallicity almost identical to that of M5. The star is also cool, hence unevolved, and is not a binary. Using the luminosity of the cluster’s main sequence, both Yale and Victoria isochrones yield a cluster age of 18 ± 3 Gyrs.
Tracking the geometry of all 597 ammonoid genera from the Lower Devonian into the Lower Triassic, a 145–Myr period that spans three mass extinctions, shows that Paleozoic ammonoid shell geometries were strongly biased for a few combinations of whorl expansion (W), whorl overlap (D), and whorl shape (S). Just three modal combinations accommodated approximately 432 genera (72% of total) and just one combination accommodated 239 genera (40%). All three primary modal forms have similar low expansion rates (W ≈ 1.75) and differ only in coiling tightness (D). These geometries resulted in long body chambers (≈400°) with Nautilus-like static in-life aperture orientations (≈30°) for the great majority (>80%) of Paleozoic ammonoids. The ancestral clade Agoniatitida included a unique spectrum of openly coiled geometries that went extinct at the Frasnian/Famennian boundary (and were not seen again until the Triassic). The Devonian/Mississippian extinction terminated the brief, explosive radiation of the Clymeniida (64 genera). The dominant Paleozoic clade, the Goniatitida (ca. 130 Myr, 374 genera [64% of total]), survived both the F/F and D/M extinctions, but began declining well before the Permian/Triassic crisis. The long-lived Prolecanitida (40 genera [7%]) appeared shortly after the D/M extinction, persisted as a low-diversity clade through the Carboniferous, and gave rise to the Ceratitida in the mid-Permian, from which were derived all Mesozoic ammonoids. After each major extinction event the phylogenetic composition of ammonoid stocks was fundamentally reordered and geometries were recanalized. Without external disturbances, as the relatively uninterrupted Mississippian through Permian record shows, the history of ammonoid shell geometry would probably have been a record of much greater constancy, perhaps tied much more closely to the Lower Devonian geometric landscape.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to ‘test and treat’ those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.
Background: Studies have reported that Cognitive Behavioural Therapy (CBT) and Graded Exercise Therapy (GET) are effective treatments for Chronic Fatigue Syndrome (CFS). Method: One hundred and seventy-one patients undertook a course of either CBT (n = 116) or GET (n = 55) and were assessed on a variety of self-report measures at pre- and posttreatment and follow-up. Aims: In this paper we present analyses on treatment outcomes for CBT and GET in routine clinical practice and evaluate whether changes on subscales of the Metacognitions Questionnaire-30 (MCQ-30) predict fatigue severity independently of changes in other covariates, and across the two treatment modalities. Results: Both CBT and GET were equally effective at decreasing fatigue, anxiety, and depression, and at increasing physical functioning. Changes on the subscales of the MCQ-30 were also found to have a significant effect on fatigue severity independently of changes in other covariates and across treatment modalities. Conclusion: The findings from the current study suggest that CFS treatment protocols for CBT and GET, based on those from the PACE trial, achieve similar to poorer outcomes in routine clinical practice as in a RCT.
Two broad aims drive weed science research: improved management and improved understanding of weed biology and ecology. In recent years, agricultural weed research addressing these two aims has effectively split into separate subdisciplines despite repeated calls for greater integration. Although some excellent work is being done, agricultural weed research has developed a very high level of repetitiveness, a preponderance of purely descriptive studies, and has failed to clearly articulate novel hypotheses linked to established bodies of ecological and evolutionary theory. In contrast, invasive plant research attracts a diverse cadre of nonweed scientists using invasions to explore broader and more integrated biological questions grounded in theory. We propose that although studies focused on weed management remain vitally important, agricultural weed research would benefit from deeper theoretical justification, a broader vision, and increased collaboration across diverse disciplines. To initiate change in this direction, we call for more emphasis on interdisciplinary training for weed scientists, and for focused workshops and working groups to develop specific areas of research and promote interactions among weed scientists and with the wider scientific community.
We studied the effect of a cross-conjugated bridging group (χC) on charge-transfer in a push-pull chromophore system. The hyperpolarizability of such molecules was found to be comparable to that of a fully π-conjugated molecule (πC) with the same donor and acceptor. The cross-conjugated moiety was then applied as a pendant to a fully π-conjugated chromophore containing a tricyanopyrroline acceptor (TCP). The addition of a χC moiety did not alter the intrinsic hyperpolarizability and provides an avenue for extending and aiding πC systems. The molecules were examined by X-ray diffraction (XRD), hyper-Raleigh scattering (HRS) and UV-visible (UV-vis) spectroscopy. Experimental results were compared with the predictions of density functional theory (DFT). Cross-conjugated molecules have comparable β values, relative to πC molecules, due to reduced spatial overlap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Thus, the χC architecture could facilitate independent modification of donor and acceptor strengths while minimizing unfavorable effects on electronic transitions and dipole moments.