Assessing sources and ages of organic matter supporting river and estuarine bacterial production: A multiple-isotope (D14C, d13C, and d15N) approach

We used radiocarbon (D14C) and stable isotopic (d13C, d15N) signatures of bacterial nucleic acids to estimate the sources and ages of organic matter (OM) assimilated by bacteria in the Hudson River and York River estuary. Dualisotope plots of D14C and d13C coupled with a three-source mixing model resolved the major OM sources supporting bacterial biomass production (BBP). However, overlap in the stable isotopic (d13C and d15N) values of potential source end members (i.e., terrestrial, freshwater phytoplankton, and marsh-derived) prohibited unequivocal source assignments for certain samples. In freshwater regions of the York, terrigenous material of relatively recent origin (i.e., decadal in age) accounted for the majority of OM assimilated by bacteria (49–83%). Marsh and freshwater planktonic material made up the other major source of OM, with 5–33% and 6–25% assimilated, respectively. In the mesohaline York, BBP was supported primarily by estuarine phytoplankton–derived OM during spring and summer (53–87%) and by marsh-derived OM during fall (as much as 83%). Isotopic signatures from higher salinity regions of the York suggested that BBP there was fueled predominantly by either estuarine phytoplankton-derived OM (July and November) or by material advected in from the Chesapeake Bay proper (October). In contrast to the York, BBP in the Hudson River estuary was subsidized by a greater portion (up to ;25%) of old (;24,000 yr BP) allochthonous OM, which was presumably derived from soils. These findings collectively suggest that bacterial metabolism and degradation in rivers and estuaries may profoundly alter the mean composition and age of OM during transport within these systems and before its export to the coastal ocean

Miocene initiation and acceleration of extension in the South Lunggar rift, western Tibet: Evolution of an active detachment system from structural mapping and (U-Th)/He thermochronology

This is the publisher's version, also available electronically from http://onlinelibrary.wiley.com/doi/10.1002/tect.20053/abstractOngoing extension in Tibet may have begun in the middle to late Miocene, but there are few robust estimates of the rates, timing, or magnitude of Neogene deformation within the Tibetan plateau. We present a comprehensive study of the seismically active South Lunggar rift in southwestern Tibet incorporating mapping, U-Pb geochronology and zircon (U-Th)/He thermochronology. The South Lunggar rift is the southern continuation of the North Lunggar rift and comprises a ~50 km N-S central horst bound by two major normal faults, the west-dipping South Lunggar detachment and the east-dipping Palung Co fault. The SLD dips at the rangefront ~20°W and exhumes a well-developed mylonite zone in its footwall displaying fabrics indicative of normal-sense shear. The range is composed of felsic orthogneiss, mafic amphibolite, and leucogranite intrusions dated at ~16 and 63 Ma. Zircon (U-Th)/He cooling ages are Oligocene through late Pliocene, with the youngest ages observed in the footwall of the SLD. We tested ~25,000 unique thermokinematic forward models in Pecube against the structural and (U-Th)/He data to fully bracket the allowable ranges in fault initiations, accelerations, and slip rates. We find that normal faulting in the SLR began in the middle Miocene with horizontal extension rates of ~1 mm a−1, and in the north accelerated at 8 Ma to 2.5–3.0 mm a−1 as faulting commenced on the SLD. Cumulative horizontal extension across the SLR ranges from <10 km in the south to 19–21 km in the north

The future of social is personal: the potential of the personal data store

This chapter argues that technical architectures that facilitate the longitudinal, decentralised and individual-centric personal collection and curation of data will be an important, but partial, response to the pressing problem of the autonomy of the data subject, and the asymmetry of power between the subject and large scale service providers/data consumers. Towards framing the scope and role of such Personal Data Stores (PDSes), the legalistic notion of personal data is examined, and it is argued that a more inclusive, intuitive notion expresses more accurately what individuals require in order to preserve their autonomy in a data-driven world of large aggregators. Six challenges towards realising the PDS vision are set out: the requirement to store data for long periods; the difficulties of managing data for individuals; the need to reconsider the regulatory basis for third-party access to data; the need to comply with international data handling standards; the need to integrate privacy-enhancing technologies; and the need to future-proof data gathering against the evolution of social norms. The open experimental PDS platform INDX is introduced and described, as a means of beginning to address at least some of these six challenges

Mirror Symmetry and Other Miracles in Superstring Theory

The dominance of string theory in the research landscape of quantum gravity physics (despite any direct experimental evidence) can, I think, be justified in a variety of ways. Here I focus on an argument from mathematical fertility, broadly similar to Hilary Putnam's 'no miracles argument' that, I argue, many string theorists in fact espouse. String theory leads to many surprising, useful, and well-confirmed mathematical 'predictions' - here I focus on mirror symmetry. These predictions are made on the basis of general physical principles entering into string theory. The success of the mathematical predictions are then seen as evidence for framework that generated them. I attempt to defend this argument, but there are nonetheless some serious objections to be faced. These objections can only be evaded at a high (philosophical) price.Comment: For submission to a Foundations of Physics special issue on "Forty Years Of String Theory: Reflecting On the Foundations" (edited by G. `t Hooft, E. Verlinde, D. Dieks and S. de Haro)

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study

BACKGROUND: Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved renal and bone safety compared with TDF-containing regimens. We report the 48 week safety and efficacy of a once-daily single tablet regimen of elvitegravir 150 mg (E), cobicistat 150 mg (C), emtricitabine 200 mg (F), and TAF 10 mg (E/C/F/TAF) in HIV-1-infected patients with mild to moderate renal impairment. METHODS: We enrolled virologically suppressed HIV-1-infected subjects with estimated creatinine clearance (CrCl) 30-69 mL/min in a single-arm, open-label study to switch regimens to E/C/F/TAF. The primary endpoint was the change from baseline in glomerular filtration rate estimated using various formulae. This study is registered with ClinicalTrials.gov, number NCT01818596. FINDINGS: We enrolled and treated 242 patients with mean age 58 years, 18% Black, 39% hypertension, 14% diabetes. Through week 48, no significant change in estimated CrCl was observed. Two patients (0.8%) discontinued study drug for decreased creatinine clearance, neither had evidence of renal tubulopathy and both had uncontrolled hypertension. Subjects had significant improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001 for all). Hip and spine bone mineral density significantly increased from baseline to week 48 (mean percent change +1.47 and +2.29, respectively, P < 0.05). Ninety-two percent (222 patients) maintained HIV-1 RNA <50 copies per milliliter at week 48. INTERPRETATION: Switch to E/C/F/TAF was associated with minimal change in GFR. Proteinuria, albuminuria and bone mineral density significantly improved. These data support the efficacy and safety of once daily E/C/F/TAF in HIV+ patients with mild or moderate renal impairment without dose adjustment

Driven to excess? Linking calling, character and the (mis)behaviour of marketers

We are presently at a point of unique circumstantial convergence where recession, an increased emphasis on business ethics, and marketer’s reluctance to accept shifting social agendas have combined to identify the need for a new approach to marketing. Using concepts from the human resources, marketing and psychology literatures, and especially Erich Fromm’s ideas concerning economic character, this paper posits that marketers – as a professional community – are driven to promote consumerist outcomes; victims of an automaton amalgam of calling and character. The analysis suggests the vulnerability of both marketer and consumer are mutually reinforcing and that we need, somehow, to break this damaging cycle of dependence. We know little, however, about how marketers think and feel about their discipline, so this paper also promotes an agenda for marketer behaviour research, as a countervailing balance to a currently disproportionate focus on the consumer

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Facing Adversity during Graduate Medical Training: The Concept of ‘Coping Intelligence’

Effective coping strategies are of great importance for trainees actively navigating the challenges and stresses of graduate medical education (GME). Although there is increasing emphasis on the concept of emotional intelligence (EI) in medical curricula, the range of behavioral skills learned in typical EI training may not be sufficient when dealing with extreme stress – something that healthcare students in general, and GME trainees as a subset, continue to struggle with. Under the conditions of extreme stress, multiple competing priorities and high cognitive load, even those with excellent command of EI skills may not be able to universally maintain sufficient emotional control. This, in turn, exposes a significant opportunity for further understanding and development in this dynamically evolving area of investigation. Increasing amount of research suggests that a unique skill set exists, known as ‘coping intelligence’ (CI), that may help fill the gap under the conditions of extreme stress and significantly elevated cognitive load. This chapter will discuss CI as a unique and novel concept, further exploring the possibility of introducing this new construct into the realm of GME

An Assessment of H1N1 Influenza-Associated Acute Respiratory Distress Syndrome Severity after Adjustment for Treatment Characteristics

Pandemic influenza caused significant increases in healthcare utilization across several continents including the use of high-intensity rescue therapies like extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation (HFOV). The severity of illness observed with pandemic influenza in 2009 strained healthcare resources. Because lung injury in ARDS can be influenced by daily management and multiple organ failure, we performed a retrospective cohort study to understand the severity of H1N1 associated ARDS after adjustment for treatment. Sixty subjects were identified in our hospital with ARDS from “direct injury” within 24 hours of ICU admission over a three month period. Twenty-three subjects (38.3%) were positive for H1N1 within 72 hours of hospitalization. These cases of H1N1-associated ARDS were compared to non-H1N1 associated ARDS patients. Subjects with H1N1-associated ARDS were younger and more likely to have a higher body mass index (BMI), present more rapidly and have worse oxygenation. Severity of illness (SOFA score) was directly related to worse oxygenation. Management was similar between the two groups on the day of admission and subsequent five days with respect to tidal volumes used, fluid balance and transfusion practices. There was, however, more frequent use of “rescue” therapy like prone ventilation, HFOV or ECMO in H1N1 patients. First morning set tidal volumes and BMI were significantly associated with increased severity of lung injury (Lung injury score, LIS) at presentation and over time while prior prescription of statins was protective. After assessment of the effect of these co-interventions LIS was significantly higher in H1N1 patients. Patients with pandemic influenza-associated ARDS had higher LIS both at presentation and over the course of the first six days of treatment when compared to non-H1N1 associated ARDS controls. The difference in LIS persisted over the duration of observation in patients with H1N1 possibly explaining the increased duration of mechanical ventilation