Drivers of Microbial Risk for Direct Potable Reuse and de Facto Reuse Treatment Schemes: The Impacts of Source Water Quality and Blending.

Although reclaimed water for potable applications has many potential benefits, it poses concerns for chemical and microbial risks to consumers. We present a quantitative microbial risk assessment (QMRA) Monte Carlo framework to compare a de facto water reuse scenario (treated wastewater-impacted surface water) with four hypothetical Direct Potable Reuse (DPR) scenarios for Norovirus, Cryptosporidium, and Salmonella. Consumer microbial risks of surface source water quality (impacted by 0-100% treated wastewater effluent) were assessed. Additionally, we assessed risks for different blending ratios (0-100% surface water blended into advanced-treated DPR water) when source surface water consisted of 50% wastewater effluent. De facto reuse risks exceeded the yearly 10-4 infections risk benchmark while all modeled DPR risks were significantly lower. Contamination with 1% or more wastewater effluent in the source water, and blending 1% or more wastewater-impacted surface water into the advanced-treated DPR water drove the risk closer to the 10-4 benchmark. We demonstrate that de facto reuse by itself, or as an input into DPR, drives microbial risks more so than the advanced-treated DPR water. When applied using location-specific inputs, this framework can contribute to project design and public awareness campaigns to build legitimacy for DPR

Adverse effect of increased left ventricular wall thickness on five year outcomes of patients with negative dobutamine stress

<p>Abstract</p> <p>Background</p> <p>To determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis.</p> <p>Results</p> <p>Between 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducible WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization.</p> <p>In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT ≥12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization (HR 3.0, p = 0.0005).</p> <p>Conclusion</p> <p>Similar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.</p

Limb lengthening and peripheral nerve function—factors associated with deterioration of conduction

Background and purpose Limb lengthening is performed for a diverse range of orthopedic problems. A high rate of complications has been reported in these patients, which include motor and sensory loss as a result of nerve damage. We investigated the effect of limb lengthening on peripheral nerve function.Patients and methods 36 patients underwent electrophysiological testing at 3 points: (1) preoperatively, (2) after application of external fixator/corticotomy but before lengthening, and (3) after lengthening. The limb-length discrepancy was due to a congenital etiology (n = 19), a growth disturbance (n = 9), or a traumatic etiology (n = 8).Results 2 of the traumatic etiology patients had significant changes evident on electrophysiological testing preoperatively. They both deteriorated further with lengthening. 7 of the 21 patients studied showed deterioration in nerve function after lengthening, but not postoperatively, indicating that this was due to the lengthening process and not to the surgical procedure. All of these patients had a congenital etiology for their leg-length discrepancy.Interpretation As detailed electrophysiological tests were carried out before surgery, after surgery but before lengthening, and finally after completion of lengthening, it was possible to distinguish between the effects of the operation and the effects of lengthening on nerve function. The results indicate that the etiology, site (femur or tibia), and nerve (common peroneal or tibial) had a bearing on the risk of nerve injury and that these factors had a far greater effect than the total amount of lengthening

The Utility of Transient Sensitivity for Wildlife Management and Conservation: Bison as a Case Study

Developing effective management strategies is essential to conservation biology. Population models and sensitivity analyses on model parameters have provided a means to quantitatively compare different management strategies, allowing managers to objectively assess the resulting impacts. Inference from traditional sensitivity analyses (i.e., eigenvalue sensitivity methods) is only valid for a population at its stable age distribution, while more recent methods have relaxed this assumption and instead focused on transient population dynamics. However, very few case studies, especially in long-lived vertebrates where transient dynamics are potentially most relevant, have applied these transient sensitivity methods and compared them to eigenvalue sensitivity methods. We use bison (Bison bison) at Badlands National Park as a case study to demonstrate the benefits of transient methods in a practical management scenario involving culling strategies. Using an age and stage-structured population model that incorporates culling decisions, we find that culling strategies over short time-scales (e.g., 1–5 years) are driven largely by the standing population distribution. However, over longer time-scales (e.g., 25 years), culling strategies are governed by reproductive output. In addition, after 25 years, the strategies predicted by transient methods qualitatively coincide with those predicted by traditional eigenvalue sensitivity. Thus, transient sensitivity analyses provide managers with information over multiple time-scales in contrast to the long time-scales associated with eigenvalue sensitivity analyses. This flexibility is ideal for adaptive management schemes and allows managers to balance short-term goals with long-term viability

Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes is a risk factor for Alzheimer's disease (AD), most likely linked to an impairment of insulin signalling in the brain. Therefore, drugs that enhance insulin signalling may have therapeutic potential for AD. Liraglutide (Victoza) and exenatide (Byetta) are novel long-lasting analogues of the GLP-1 incretin hormone and are currently available to treat diabetes. They facilitate insulin signalling via the GLP-1 receptor (GLP-1R). Numerous <it>in vitro </it>and <it>in vivo </it>studies have shown that GLP-1 analogues have a range of neuroprotective properties. GLP-1Rs are expressed in the hippocampal area of the brain an important site of adult neurogenesis and maintenance of cognition and memory formation. Therefore, if GLP-1 analogues can cross the blood brain barrier, diffuse through the brain to reach the receptors and most importantly activate them, their neuroprotective effects may be realized.</p> <p>Results</p> <p>In the present study we profiled the GLP-1 receptor agonists liraglutide (Victoza) and lixisenatide (Lyxumia). We measured the kinetics of crossing the blood brain barrier (BBB), activation of the GLP-1R by measuring cAMP levels, and physiological effects in the brain on neuronal stem cell proliferation and neurogenesis. Both drugs were able to cross the BBB. Lixisenatide crossed the BBB at all doses tested (2.5, 25, or 250 nmol/kg bw ip.) when measured 30 min post-injection and at 2.5-25 nmol/kg bw ip. 3 h post-injection. Lixisenatide also enhanced neurogenesis in the brain. Liraglutide crossed the BBB at 25 and 250 nmol/kg ip. but no increase was detectable at 2.5 nmol/kg ip. 30 min post-injection, and at 250 nmol/kg ip. at 3 h post-injection. Liraglutide and lixisenatide enhanced cAMP levels in the brain, with lixisenatide being more effective.</p> <p>Conclusions</p> <p>Our results suggest that these novel incretin analogues cross the BBB and show physiological activity and neurogenesis in the brain, which may be of use as a treatment of neurodegenerative diseases.</p

The import and export of organic nitrogen species at a Scottish ombrotrophic peatland

Dissolved organic nitrogen (DON) contributes significantly to the overall nitrogen budget, but is not routinely measured in precipitation or stream water. In order to investigate the contribution of DON to the deposition and export of N, precipitation, stream and soil water samples were collected from an ombrotrophic peatland and analysed for DON over a 2-year period. In wet-only deposition DON contributed up to 10 % of the total dissolved nitrogen (TDN) and was the most dominant fraction in soil water (99 %) and stream water (75 %). NH4 + was the most dominate form of N in precipitation, with NO3 - contributing the least to precipitation, soil water and stream water. Precipitation and stream DON were qualitatively analysed by a two-dimensional gas chromatograph coupled to a nitrogen chemiluminescence detector (GC × GC-NCD) after trapping onto C18 solid phase extraction (SPE) cartridges. Ten unique compounds were detected and five identified as pyrrole, benzonitrile, dodecylamine, N-nitrosodipropylamine and decylamine. Five compounds were present in both precipitation and stream samples: pyrrole, benzonitrile and three unidentified compounds. The SPE-extraction efficiency for DON was very low (11 %), but with improvements DON speciation could become a valuable tool to provide information on its sources and pathways and inform chemical transport models

Rhamm-/- mice are defective in skin wound repair due to aberrantERK1,2 signaling in fibroblast migration

Rhamm (receptor for hyaluronan-mediated motility) is an hyaluronan binding protein with limited expression in normal tissues and high expression in advanced cancers. To understand its physiological functions and identify the molecular mechanisms underlying these functions, we created mice with a genetic deletion of Rhamm. We show that Rhamm(−/−) fibroblasts fail to resurface scratch wounds >3 mm or invade hyaluronan-supplemented collagen gels in culture. We identify a requirement for Rhamm in the localization of CD44 to the cell surface, formation of CD44–ERK1,2 (extracellular-regulated kinase 1,2) complexes, and activation/subcellular targeting of ERK1,2 to the cell nucleus. We also show that cell surface Rhamm, restricted to the extracellular compartment by linking recombinant protein to beads, and expression of mutant active mitogen-activated kinase kinase 1 (Mek1) are sufficient to rescue aberrant signaling through CD44–ERK1,2 complexes in Rh(−/−) fibroblasts. ERK1,2 activation and fibroblast migration/differentiation is also defective during repair of Rh(−/−) excisional skin wounds and results in aberrant granulation tissue in vivo. These results identify Rhamm as an essential regulator of CD44–ERK1,2 fibroblast motogenic signaling required for wound repair

Pinpointing drivers of widespread colonization of Legionella pneumophila in a green building: Roles of water softener system, expansion tank, and reduced occupancy

IntroductionLegionella pneumophila is an opportunistic pathogen that is a key contributor to drinking water-associated disease outbreaks in the United States. Prolonged water stagnation periods in building plumbing systems due to low occupancy, especially during building shutdowns, breaks, and holidays, can lead to water quality deterioration and (re)colonization of buildings with L. pneumophila. Water monitoring in buildings typically relies on grab samples with small datasets.MethodsIn this study, a larger dataset was created by sampling a Leadership in Energy and Environmental Design (LEED)-certified data-rich commercial building for L. pneumophila and physical-chemical water quality during the COVID-19 pandemic after reduced building occupancy. A proxy for human occupancy rates using WIFI logins was recorded throughout the study period.ResultsL. pneumophila was observed in grab samples taken throughout the building, where concentrations generally increased with greater distances from the building point of entry to locations throughout the building. Factors conducive to microbial growth were identified in the building including fluctuations in water temperatures, lack of chlorine residual, a low water heater setpoint, colonized water-saving fixtures, prolonged stagnation throughout the building; especially in an expansion tank designed to reduce pressure issues during demand fluctuations, and the presence of oversized softener tanks with ion exchange resin that contributed to chlorine residual removal as well as colonization of the resin with L. pneumophila.DiscussionFlushing and thermal disinfection alone did not resolve the problem, and replacement of the expansion tank ultimately resolved the L. pneumophila issue. As ad-hoc approaches are logistically- and time-intensive, more proactive approaches are needed for informing preventative and corrective actions for reducing the risk of exposure to opportunistic pathogens in the building plumbing

Island precipitation enhancement and the diurnal cycle in radiative-convective equilibrium

To understand why tropical islands are rainier than nearby ocean areas, we explore how a highly idealized island, which differs from the surrounding ocean only in heat capacity, might respond to the diurnal cycle and influence the tropical climate, especially the spatial distribution of rainfall and the thermal structure of the troposphere. We perform simulations of three-dimensional radiative-convective equilibrium with the System for Atmospheric Modeling (SAM) cloud-system-resolving model, with interactive surface temperature, where a highly idealized, low heat capacity circular island is embedded in a slab-ocean domain. The calculated precipitation rate over the island can be more than double the domain average value, with island rainfall occurring primarily in an intense, regular thunderstorm system that forms in the afternoon to early evening each day. Island size affects the magnitude of simulated island rainfall enhancement, the intensity of the convection, and the timing of the rainfall maximum relative to solar noon. A combination of dynamic and thermodynamic mechanisms leads to a monotonic enhancement of domain-averaged tropospheric temperature with increasing fraction of island surface, which may contribute to localization of ascent over the Maritime Continent and its relationship to the Walker Circulation.National Science Foundation (U.S.) (Grant AGS 1136466)National Science Foundation (U.S.) (Grant AGS 1136480

Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice.

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding