To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Annual grass weeds reduce profits of wheat farmers in the Pacific Northwest. The very-long-chain fatty acid elongase (VLCFA)-inhibiting herbicides S-metolachlor and dimethenamid-P could expand options for control of annual grasses but are not registered in wheat, because of crop injury. We evaluated a safener, fluxofenim, applied to wheat seed for protection of 19 soft white winter wheat varieties from S-metolachlor, dimethenamid-P, and pyroxasulfone herbicides; investigated the response of six varieties (UI Sparrow, LWW 15-72223, UI Magic CL+, Brundage 96, UI Castle CL+, and UI Palouse CL+) to incremental doses of fluxofenim; established the fluxofenim dose required to optimally protect the varieties from VLCFA-inhibiting herbicides; and assessed the impact of fluxofenim dose on glutathione S-transferase (GST) activity in three wheat varieties (UI Sparrow, Brundage 96, and UI Castle CL+). Fluxofenim increased the biomass of four varieties treated with S-metolachlor or dimethenamid-P herbicides and one variety treated with pyroxasulfone. Three varieties showed tolerance to the herbicides regardless of the fluxofenim treatment. Estimated fluxofenim doses resulting in 10% biomass reduction of wheat ranged from 0.55 to 1.23 g ai kg−1 seed. Fluxofenim doses resulting in 90% increased biomass after treatment with S-metolachlor, dimethenamid-P, and pyroxasulfone ranged from 0.07 to 0.55, 0.09 to 0.73, and 0.30 to 1.03 g ai kg−1 seed, respectively. Fluxofenim at 0.36 g ai kg−1 seed increased GST activity in UI Castle CL+, UI Sparrow, and Brundage 96 by 58%, 30%, and 38%, respectively. These results suggest fluxofenim would not damage wheat seedlings up to three times the rate labeled for sorghum, and fluxofenim protects soft white winter wheat varieties from S-metolachlor, dimethenamid-P, or pyroxasulfone injury at the herbicide rates evaluated.
Background: Although antibiotic stewardship programs (ASP) are now required in nursing homes, assimilating and responding to data to improve prescribing in nursing homes is novel. Four Atlanta-based skilled nursing facilities (SNFs) began collaborating (EASIL: Emory Antibiotic Stewardship in Long-Term Care) to share standardized prescribing data to allow interfacility comparisons and action. Methods: After SNF ASPs were evaluated and trained, standardized prescribing logs were submitted (January 2019 to June 2019) including the following data: start date, treatment site, prescriber attribution of order (ie, SNF order vs hospital order) and monthly resident days. SNF-specific point estimates of usage rates were calculated as pooled means for all antibiotic starts, SNF-order starts, and days of therapy (DOT), by treatment site per 1,000 resident days. Duration of urinary tract infection (UTI) therapy was assessed by calculating percentage of SNF-UTI starts over recommended duration defined by the local treatment guideline. Rate ratios (RRs) of use were calculated to compare SNF-specific rates to the largest SNF. The 95% CIs were calculated using normal approximation. Results: Monthly starts ranged from 124 to 177, with a pooled mean of 7.8 antibiotic starts (any type), 4.5 SNF-order starts, and 1.2 SNF-UTI starts per 1,000 resident days. Approximately half of all starts were SNF starts (range, 43%–53%), and less than half of DOT were attributed to SNF starts (range, 35%–45%). Overall, SNF-order treatment sites were most often UTIs (29%), lower respiratory infections (17%), and skin and soft-tissue infections (17%). SNF-order UTI starts per 1,000 patient days varied at 1 SNF (SNF B RR, 1.57; 95% CI, 1.04–2.36). SNF-order UTI DOT per 1,000 patient days was more variable, with SNFs B and C having significantly higher rates (B RR, 1.49, 1.24, and 1.82; C RR, 5.42; 95% CI, 4.65–6.34) than SNF A (Fig. 1). The percentage of SNF-order UTI starts that were over recommended duration ranged from 8% (nitrofurantoin, SNF A) to 100% (fluoroquinolones, SNF C) (Fig. 1). Conclusions: Although UTIs are the single most common reason to prescribe antibiotics after arriving in a SNF, they account for a small fraction of overall starts and an even smaller fraction of DOT. We identified outlier prescribing by different SNFs using 3 metrics, suggesting that distinct corrective actions are necessary to target distinct prescribing challenges (starts, duration, and transitions of care).
Disclosures: Scott Fridkin reports that his spouse receives consulting fees from the vaccine industry.
Antarctica's ice shelves modulate the grounded ice flow, and weakening of ice shelves due to climate forcing will decrease their ‘buttressing’ effect, causing a response in the grounded ice. While the processes governing ice-shelf weakening are complex, uncertainties in the response of the grounded ice sheet are also difficult to assess. The Antarctic BUttressing Model Intercomparison Project (ABUMIP) compares ice-sheet model responses to decrease in buttressing by investigating the ‘end-member’ scenario of total and sustained loss of ice shelves. Although unrealistic, this scenario enables gauging the sensitivity of an ensemble of 15 ice-sheet models to a total loss of buttressing, hence exhibiting the full potential of marine ice-sheet instability. All models predict that this scenario leads to multi-metre (1–12 m) sea-level rise over 500 years from present day. West Antarctic ice sheet collapse alone leads to a 1.91–5.08 m sea-level rise due to the marine ice-sheet instability. Mass loss rates are a strong function of the sliding/friction law, with plastic laws cause a further destabilization of the Aurora and Wilkes Subglacial Basins, East Antarctica. Improvements to marine ice-sheet models have greatly reduced variability between modelled ice-sheet responses to extreme ice-shelf loss, e.g. compared to the SeaRISE assessments.
NMDA receptor ligands have been shown to rapidly treat depression but are associated with psychotomimetic effects. GLYX-13 is an NMDA receptor glycine site functional partial agonist with ~ 25% of the agonist activity of glycine or Dserine. Animal models suggest a single intravenous dose may produce long-term efficacy without psychotomimetic effects.
A phase II randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy of GLYX-13 with central raters.
To examine the effects of a single dose of GLYX-13 in subjects with inadequate response to previous treatment for MDD.
48 male and 68 female subjects received a single dose of GLYX-13 (1-/5-/10-/30-mg/kg) or placebo. Central raters assessed subjects via telephone using the HDRS-17 at Screening, Baseline, Days 1, 3, 7, 14, 21 and 28.
The a priori primary efficacy ANCOVA on pooled drug dose versus placebo was not significant for change from baseline to Day 1 on HDRS-17 total score. MMRM revealed a statistically significant reduction in HDRS-17 total score versus placebo at Day 3 for 5-mg/kg (−4.4; p < .05) and a trend at Day 1 for 5-mg/kg (−3.5; p = .068) and at Day 7 for 5 and 10-mg/kg (−4.0 for both; p's = .059 and .073). GLYX-13 did not cause psychotomimetic side effects at any dose studied.
This study suggests that GLYX-13, an NMDA receptor glycine site functional partial agonist, rapidly reduces depression scores without eliciting psychotomimetic effects at therapeutic doses as assessed by central raters. Further study is indicated.
Single nucleotide polymorphisms (SNPs) contribute small increases in risk for late-onset Alzheimer's disease (LOAD). LOAD SNPs cluster around genes with similar biological functions (pathways). Polygenic risk scores (PRS) aggregate the effect of SNPs genome-wide. However, this approach has not been widely used for SNPs within specific pathways.
We investigated whether pathway-specific PRS were significant predictors of LOAD case/control status.
We mapped SNPs to genes within 8 pathways implicated in LOAD. For our polygenic analysis, the discovery sample comprised 13,831 LOAD cases and 29,877 controls. LOAD risk alleles for SNPs in our 8 pathways were identified at a P-value threshold of 0.5. Pathway-specific PRS were calculated in a target sample of 3332 cases and 9832 controls. The genetic data were pruned with R2 > 0.2 while retaining the SNPs most significantly associated with AD. We tested whether pathway-specific PRS were associated with LOAD using logistic regression, adjusting for age, sex, country, and principal components. We report the proportion of variance in liability explained by each pathway.
The most strongly associated pathways were the immune response (NSNPs = 9304, = 5.63 × 10−19, R2 = 0.04) and hemostasis (NSNPs = 7832, P = 5.47 × 10−7, R2 = 0.015). Regulation of endocytosis, hematopoietic cell lineage, cholesterol transport, clathrin and protein folding were also significantly associated but accounted for less than 1% of the variance. With APOE excluded, all pathways remained significant except proteasome-ubiquitin activity and protein folding.
Genetic risk for LOAD can be split into contributions from different biological pathways. These offer a means to explore disease mechanisms and to stratify patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
This chapter provides an outline of developments in the Church in Wales since 1920. It seeks to place the specialised chapters which follow in their broader ecclesial context. The study uses the tried and tested technique of periodisation as a convenient way of approaching the subjects treated. The landmark developments in the first period (1920-1945) include the creation of the administration of the Church, forming new dioceses, and establishing sound ecclesiastical finances. The second period (1946-1970) is one of greater self-confidence in the Church, with modest liturgical development and ecumenical cooperation. The third period (1971-1995) is characterised by liturgical innovation and greater ecumenical progress, the ordination of female deacons, but also an increasing reduction in clergy numbers. The final period (1996-2020) is one of rapid change, including the ordination of female priests and bishops, a reorganisation of parochial structures, and a severe decline in Church membership.
Approximately 20% of children with attention-deficit hyperactivity disorder (ADHD) experience clinical levels of impairment into adulthood. In the UK, there is a sharp reduction in ADHD drug prescribing over the period of transition from child to adult services, which is higher than expected given estimates of ADHD persistence, and may be linked to difficulties in accessing adult services. Little is currently known about geographical variations in prescribing and how this may relate to service access.
To analyse geographic variations in primary care prescribing of ADHD medications over the transition period (age 16–19 years) and adult mental health service (AMHS) referrals, and illustrate their relationship with UK adult ADHD service locations.
Using a Clinical Practice Research Datalink cohort of people with an ADHD diagnosis aged 10–20 in 2005 (study period 2005–2013; n = 9390, 99% diagnosed <18 years), regional data on ADHD prescribing over the transition period and AMHS referrals, were mapped against adult ADHD services identified in a linked mapping study.
Differences were found by region in the mean age at cessation of ADHD prescribing, range 15.8–17.4 years (P<0.001), as well as in referral rates to AMHSs, range 4–21% (P<0.001). There was no obvious relationship between service provision and prescribing variation.
Clear regional differences were found in primary care prescribing over the transition period and in referrals to AMHSs. Taken together with service mapping, this suggests inequitable provision and is important information for those who commission and deliver services for adults with ADHD.
A 3-yr watermelon experiment was established in fall 2013 to evaluate cover crop, polyethylene mulch, tillage, and herbicide application components for weed control, yield, and profitability. Conservation tillage, either with a cereal rye cover crop alone or integrated with polyethylene mulch, was compared to the standard industry practice of conventional tillage with bedded polyethylene mulch. The study also used a non-bedded conventional tillage system without polyethylene to determine polyethylene and cover crop residue effects. Within each of the four systems, herbicide treatments comprised halosulfuron applied (1) at 26.3 g ai ha–1 PRE, (2) at 26.3 g ai ha–1 POST, or (3) sequentially at 26.3 g ai ha–1 PRE and POST. Each system also had a nontreated control. In addition, clethodim was applied in all plots twice POST at 140 g ai ha–1, except for nontreated in each system. In 2014, polyethylene or cereal rye cover crop effectively controlled tall morningglory, coffee senna, and carpetweed early season in nontreated plots, whereas the integration of the two was effective at controlling common purslane. Tall morningglory and purslane control was insufficient late season regardless of production system and herbicide application. In 2015, polyethylene effectively controlled cutleaf eveningprimrose, sicklepod, and arrowleaf sida early season in nontreated plots. Yellow nutsedge control was insufficient late season regardless of production system and herbicide application. Utilizing sequential halosulfuron applications did not increase weed control over PRE or POST alone in all years. Polyethylene use resulted in yields higher than systems without in all years. Across all 3 yr, net returns were highest for polyethylene mulch systems. The results of this experiment underscore the need for more progress in developing integrated conservation systems for watermelon production. Effective herbicides, low-disturbance cultivation, and/or hand weeding are most likely the key to success in conservation specialty crop systems.
Isotopic investigations of human burials from excavations of the Autonomous University of Campeche (CIHS) at the prehispanic Maya capital of Calakmul in southeastern Mexico, near the border with Guatemala, include determination of radiocarbon dates; carbon and nitrogen isotope ratios in collagen; and strontium, carbon, and oxygen isotope ratios in tooth enamel. A total of 22 human and 5 faunal samples analyzed for strontium isotopes reveal a narrow range of variation in values, pointing to the likely local origin of over two-thirds of the central population of Calakmul, including two of its rulers. Carbon and nitrogen data confirm a typical Classic Maya diet at the site and identify a diet high in meat consumption for one dynastic individual. Interpreted jointly, the isotopic information offers new perspectives on the provenience and lifestyles of the residents of Calakmul, including a potential place of origin for the royal occupant of chamber tomb Burial VII-1.
Fomesafen provides effective control of glyphosate-resistant Palmer amaranth in cotton. However, cotton seedlings can be injured when fomesafen is applied PRE. Therefore, greenhouse and field experiments were conducted at Athens, GA, and at six locations in Alabama and Georgia in 2013 and 2016 to evaluate cotton growth and yield response to fomesafen applied PRE at 70, 140, 280, 560, 1,120, or 2,240 g ai ha−1, and in combination with pendimethalin, diuron, acetochlor, and fluridone at 1×label rates. Greenhouse bioassays indicated that fomesafen reduced cotton height and dry weight with increasing rate in Cecil sandy loam and Tifton loamy sand but not in Greenville sandy clay loam––possibly as a result of this soil’s higher organic matter (OM) and clay content. Fomesafen applied at 2,240 g ai ha−1 reduced cotton stand by as much as 83% compared to the nontreated check (NTC) at all field locations except Alabama’s Macon and Baldwin counties, and 1,120 g ai ha−1 reduced cotton stand only at Pulaski County, GA, by 52%. Cotton height was reduced by the two highest rates of fomesafen at all locations except Clarke County, GA, and Baldwin County, AL. Injury data indicated more visual injury followed increasing fomesafen rates, and high-rate treatments produced more injury in sandier soils. Cotton yield was unaffected by herbicide treatments at any location, except for the 1,120 g ai ha−1 rate at Pulaski County (49% yield loss compared to NTC), 2,240 g ai ha−1 at Pulaski County (72% yield loss), and Tift County (29% yield loss). These data indicated cotton yield should not be negatively affected by fomesafen applied PRE alone within label rates or in combination with pendimethalin, diuron, acetochlor, and fluridone at 1×label rates, although some visual injury, or stand or height reduction may occur early in the growing season.
Cauterisation techniques are commonly used and widely accepted for the management of epistaxis. This review assesses which methods of intranasal cautery should be endorsed as optimum treatment on the basis of benefits, risks, patient tolerance and economic assessment.
A systematic review of the literature was performed using a standardised methodology and search strategy.
Eight studies were identified: seven prospective controlled trials and one randomised controlled trial. Pooling of data was possible from 3 studies, yielding a total of 830 patients. Significantly lower re-bleed rates were identified (p < 0.01) using electrocautery (14.5 per cent) when compared to chemical cautery (35.1 per cent). No evidence suggested that electrocautery was associated with more adverse events or discomfort. Limited evidence supported the use of a vasoconstrictor agent and operating microscope during the procedure. The included studies had considerable heterogeneity in terms of design and outcome measures.
Consistent evidence suggests that electrocautery has higher success rates than chemical cautery, and is not associated with increased complications or patient discomfort. Lower quality evidence suggests that electrocautery reduces costs and duration of hospital stay.
Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9–13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.
Nearly 258 million ha (28%) of the United States is publicly owned land that is managed by federal government agencies. For example, the US Department of Agriculture's Forest Service (USFS) manages over 77 million ha of national forests and grasslands for the benefit of the American public. Given its legal directive to manage multiple uses, it is not surprising that conflicts arise among stakeholders over how this land should be used (Lansky, 1992). The USFS has much discretion in how land is managed, yet must often balance conflicting values of public use and benefit (Nie, 2004). As national priorities, social preferences and public awareness of national forest goods, services and values have changed over time, USFS managers have faced increased pressure to balance consumptive uses with the need for environmental protection. Competing stakeholder demands coupled with increased environmental risks (wildfires, tree diseases and insect epidemics) have resulted in an escalating conservation conflict that is manifested in administrative appeals, lawsuits and a growing distrust of the agency.
Over time, the USFS has embraced new directions and management paradigms to reduce conflict. Some of these have been ecosystem management, adaptive management and now collaborative management (e.g. Holling, 1978; Maser, 1988; Franklin, 1992; Boyce and Haney, 1997; Wondolleck and Yaffee, 2000; Brown et al., 2004). These approaches reflect changing societal values, political pressures and new scientific information.
A persistent conflict has been the logging of trees in national forests and related impacts on forest ecosystems (Lansky, 1992). The USFS’ timber sale programme has supported jobs and community stability through economic development. Logging has also been a mechanism to reduce the risk of wildfire by reducing tree density (fuel for fires) and vertical stand diversity (‘ladder’ fuels; North et al., 2009). However, logging can also negatively affect forest integrity, watershed quality, wildlife, aesthetic and spiritual values of forests (Satterfield, 2002; North et al., 2009).
We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008–September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005–June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures.
During the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes.
In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.
Background: Children with decompensated heart failure are at high risk for arrhythmias, and ventricular assist device placement is becoming a more common treatment strategy. The impact of ventricular assist devices on arrhythmias and how arrhythmias affect the clinical course of this population are not well described. Methods and results: A single-centre retrospective analysis of children receiving a ventricular assist device between 1998 and 2011 was performed. In all, 45 patients received 56 ventricular assist devices. The median age at initial placement was 13 years (interquartile range 6–15). The median duration of support was 10 days (range 2–260). The aetiology of heart failure included cardiomyopathy, transplant rejection, myocarditis, and congenital heart disease. In all, 32 patients (71%) had an arrhythmia; 19 patients (42%) had an arrhythmia before ventricular assist device and eight patients (18%) developed new arrhythmias on ventricular assist device. Ventricular tachycardia was most common (25/32, 78%). There was no correlation between arrhythmia and risk of death or transplantation (p=0.14). Of the 15 patients who weaned from ventricular assist device, post-ventricular assist device arrhythmias occurred in nine (60%), with five (33%) having their first arrhythmia after weaning. Patients with ventricular dysfunction after ventricular assist device were more likely to have arrhythmias (p<0.02). Conclusions: Arrhythmias, especially ventricular, are common in children requiring ventricular assist device. They frequently persist for those able to wean from ventricular assist device.