To save 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 saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
After implementation of a molecular syndromic panel for infectious diarrhea, a significantly greater proportion of C. difficile results were classified as colonization rather than infection compared to the pre-implementation period. Routine C. difficile reporting from multiplex panels should be re-evaluated to minimize diagnostic uncertainty in some patients.
The question arises when developing and testing Unmanned Surface Vessel (USV) Manoeuvring Autonomy (MA): ‘is the performance we are seeing in our current on-water tests better than that of the last autonomy software version we deployed?’ An approach to answer this question is inspired by educators’ rubrics, in which a teacher grades a student’s work to objective criteria and then sums the individual criteria to determine the student’s overall grade. Here, individual metrics are used to evaluate a USV manoeuvring within range of another vessel. A weighted average is then applied to determine the overall score. With that objective performance value now obtained, similar manoeuvring tests can be compared between autonomy software versions to determine if the autonomy under development is progressively improving. This paper does not determine the threshold score needed to establish that a USV is safe to operate; thresholding of sufficient performance is recommended for future study.
Exposure to traumatic experiences during childhood and adolescence is a significant risk factor for the development of psychiatric disorders in adulthood. An estimated 50% of the worldwide incidence of depression and anxiety can be attributed to childhood maltreatment (Li et al., 2016). In addition, approximately one-third of psychotic experiences are attributable to a history of developmental trauma (McGrath et al., 2017). It is thought that long-lasting, trauma-induced adaptive changes in neurobiological function may lead to a predisposition towards pathophysiology (McCrory and Viding, 2015). However, the precise mechanisms through which developmental trauma exposure alters brain function on cellular and circuit levels remain poorly elucidated.
Methods
A systematic literature search and meta-analysis was performed to establish how dopaminergic functioning in adulthood is affected by developmental stress in rodents. Three databases, Medline®, Embase®, and PsycINFO®, were systematically searched initially on 2nd December 2023. Terms for three superordinate concepts (‘childhood’ terms, ‘trauma’ terms, and ‘dopamine’ terms) were combined. Cohen's d statistic was used for effect sizes. This protocol is pre-registered on PROSPERO® (ID: CRD42018106382).
Results
A total of 104 studies met our inclusion criteria. Meta-analysis indicated that developmental stress exposure leads to complex and long-lasting effects in basal and post-amphetamine extracellular dopamine concentrations in the medial prefrontal cortex, amygdala, and nucleus accumbens. In addition, there is a significant downregulation of D1 receptors and upregulation of D2 receptors in prefrontal and striatal regions involved in threat and reward processing. Effect sizes ranged from 0.36 to 1.55.
Conclusion
These findings strongly suggest that dopaminergic dysfunction is a mechanistic link between developmental trauma and vulnerability towards mental illness in adulthood.
Efficient conservation and sustainable use of crop diversity is critical to support global food and nutritional security with ex situ collections stored in over 800 genebanks in 115 countries. The challenge is to manage those collections for long-term conservation of crop diversity and sustainable use to respond to global challenges of food security and climate change. The Genebank Standards for Plant Genetic Resources for Food and Agricutlure (Genebank Standards) form the overall framework for curation of ex situ crop collections, allowing considerable flexibility to develop customized approaches to conserving different crops. Stratified curation involves strategically tailoring curation to specific genebank goals, crops, priorities and resources for each accession based on all available information to prioritize accessions for long-term conservation. It implies using scarce resources where they are most needed and recognizes that accessions can be (a) fully curated to international standards; (b) partially curated for storage for a limited time; (c) archived and stored but no longer curated and available from the genebank; or (d) historical and removed entirely from the genebank. The stratified approach is consistent with the Genebank Standards and the policy framework of the International Treaty on Plant Genetic Resources for Food and Agriculture. Stratified curation encourages curators to make difficult decisions on accession management to better respond to challenges of curating large collections of crop diversity.
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
An accurate estimate of the average number of hand hygiene opportunities per patient hour (HHO rate) is required to implement group electronic hand hygiene monitoring systems (GEHHMSs). We sought to identify predictors of HHOs to validate and implement a GEHHMS across a network of critical care units.
Design:
Multicenter, observational study (10 hospitals) followed by quality improvement intervention involving 24 critical care units across 12 hospitals in Ontario, Canada.
Methods:
Critical care patient beds were randomized to receive 1 hour of continuous direct observation to determine the HHO rate. A Poisson regression model determined unit-level predictors of HHOs. Estimates of average HHO rates across different types of critical care units were derived and used to implement and evaluate use of GEHHMS.
Results:
During 2,812 hours of observation, we identified 25,417 HHOs. There was significant variability in HHO rate across critical care units. Time of day, day of the week, unit acuity, patient acuity, patient population and use of transmission-based precautions were significantly associated with HHO rate. Using unit-specific estimates of average HHO rate, aggregate HH adherence was 30.0% (1,084,329 of 3,614,908) at baseline with GEHHMS and improved to 38.5% (740,660 of 1,921,656) within 2 months of continuous feedback to units (P < .0001).
Conclusions:
Unit-specific estimates based on known predictors of HHO rate enabled broad implementation of GEHHMS. Further longitudinal quality improvement efforts using this system are required to assess the impact of GEHHMS on both HH adherence and clinical outcomes within critically ill patient populations.
In this article we consider the spectral behaviour of turbulence-driven power fluctuations for a single horizontal-axis turbine. To this end, a small-scale instrumented axial-flow hydrokinetic turbine model ($\textrm {diameter}=0.724\ \textrm {m}$) is deployed in the long water flume situated in the laboratory facilities of IFREMER in Boulogne-sur-Mer, France, and synchronous measurements of the upstream velocity and the rotor are collected for different tip-speed ratios. The study confirms previous findings suggesting that the power spectra follow the velocity spectra behaviour in the large scales region and a steeper power law slope behaviour ($-11/3$) over the inertial frequency sub-range. However, we show that both the amplitude of the power spectra and low-pass filtering effect over the inertial sub-range also depend on the rotor aero/hydrodynamics (e.g. $\mathrm {d}C_L/\mathrm {d}\alpha$) and the approaching flow deceleration and not solely on the rotational effects. In addition, we present a novel semi-analytical model to predict the dominant blade-passing frequency harmonics in the high-frequency regime using the rotationally sampled spectra technique. For all calculations, the distortion of incoming turbulence is taken into account.
Background: Previous work suggests an intermingling of community and hospital transmission networks driving the MRSA epidemic, but how those with CO-HA infections fit into the network remains unclear. We integrated epidemiologic data and whole-genome sequencing (WGS) from existing MRSA clinical isolates to determine whether there were distinguishable features of CO-HA MRSA infections that could guide interventions. Methods: We examined 955 existing clinical MRSA isolates from 2011 to 2013 from patients at Cook County Health, the major public healthcare network in Chicago, Illinois. We performed electronic and manual chart review to ascertain community (eg, illicit drug use, incarceration history) and healthcare exposures and comorbidities. WGS was performed on all sequences, and sequences were typed with multilocus sequence typing (MLST). We assessed the distribution of epidemiological factors and sequence type (ST) across onset type. Results: Infections were more frequent in males (70%); 61% of individuals with infection were African American and 21% were Hispanic. Overall, wound infections were the most common (81%) followed by blood (7%) and respiratory (6%). 82% of infections were ST8 (most USA300), 8% were ST5 (USA100) and 10% were other STs (Fig. 1a). Using standard epidemiologic definitions, we identified 523 CO, 295 CO-HA, and 137 HO infections. USA300 infections were common across CO, CO-HA, and HO categories, whereas USA100 was more frequently observed among CO-HA and HO. Current illicit drug use and history of incarceration—factors typically associated with CO-MRSA—were observed among both CO-HA and HO infections. 38% of CO-HA and 36% of HO had a history of MRSA infection or nasal colonization in the prior 6 months. As expected, 73% of CO-HA had a history of recent hospitalization, but this was also true for 44% of HO cases; points for intervention for both groups, especially CO-HA patients, include outpatient, inpatient, and ER care. Diabetes was common across categories, and HIV was more commonly observed among CO-HA cases (Fig. 1b). Conclusions: We characterized the genomic and epidemiologic features of CO-HA MRSA infections relative to CO and HO. By MLST and epidemiological analysis, CO-HA infections share similarities to both CO and HO. Although USA300 infections were the most common strain type, our findings highlight the need for WGS to discern relationships between individuals to understand the intermixing of healthcare and community networks for CO-HA infections. Higher resolution genomic analysis may help guide whether interventions need to be at hospital discharge or in the community to have the most impact on decreasing CO-HA MRSA infections.
Funding: Funding: from CDC Broad Agency Announcement: Genomic Epidemiology of Community-Onset Invasive USA300 MRSA Infections; Contract ID: 75D30118C02923
Ab initio total energy calculations based on the local density approximation (LDA) and using a conjugate-gradient solver for the Kohn-Sham equations have been performed for cordierite, brucite, (Mg(OH)2) and diaspore (AlOOH). The calculated fractional coordinates of all structures are in good agreement with experimental diffraction data. The angle of the non-linear hydrogen bond in diaspore is reproduced well. The Raman active OH stretching frequency in brucite has been calculated using the frozen phonon approach and the calculated stretching frequency is in very good agreement with the observed value. The energetically most favourable calculated orientation of the proton-proton vector of an H2O molecule incorporated in the structural channels of cordierite agrees with findings deduced from spectroscopic data, and the calculated energy of hydration is in reasonable agreement with calorimetric data. It is therefore concluded that ab initio total energy calculations can confidently be used to predict properties of hydrogen bonded structures, which is difficult with conventional parameterized static lattice energy minimization calculations. An extension to the model is necessary to improve the agreement of the predicted to the observed lattice parameters for small structures.
Despite extensive research on organizational virtue, our understanding about factors that promote virtue within organizations remains unclear. Drawing on upper echelon theory, we examine the relationship between five top management team (TMT) characteristics and organizational virtue orientation (OVO)—the integrated set of values and beliefs that support ethical traits and virtuous behaviors of an organization. Specifically, we utilize prospectuses of initial public offering (IPO) firms and 10-K post-IPO filings to explore how TMT composition with respect to member age, tenure, education, functional background, and gender influences OVO. Additionally, we examine the moderating effects of organizational size, and argue that the more expansive structures and processes associated with larger organizations diminish the main relationships. Our findings, using two sources of data, are consistent, but somewhat mixed in their support for our hypotheses. Overall, TMT characteristics do appear to influence OVO, but in more complex and counterintuitive ways than initially expected.
Objectives: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. Methods: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Results: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Conclusions: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104–112)
Field surveys were conducted on 319 sites of the Western Australian grain belt in 2006 to determine the occurrence and distribution of summer fallow weed species. Sites were located across five growing season regions (north, north central, central, south central, and south) and three annual rainfall zones (high, medium, and low). A total of 51 species (or species groups) from 18 families were identified, with the large majority of species (35%) belonging to the Poaceae family. The most prevalent species found, being present at more than 10% of all sites, were wheat, “melons” (weedy watermelon and paddymelon), rigid ryegrass, capeweed, clover, mintweed, wild radish, fleabane, windmill grass, and rolypoly. Correspondence analysis revealed that the north, central, and southern regions of the grain belt could be predominately segregated according to dominant weed species occurrence; however, no segregation by rainfall zone was apparent. This study has given an overview of summer fallow weed occurrence in the Western Australian grain belt and highlights those weed species that are common and yet lack sufficient research into their ecology and management.
Low mass, main sequence stars like our Sun exhibit a wide variety of rotational and magnetic states. Observational and theoretical advances have led to a renewed emphasis on understanding the rotational and magnetic evolution of sun-like stars has become a pressing problem in stellar physics. We use global 3D convection and convective dynamo simulations in rotating spherical shells and with realistic stellar stratification to explore the behavior of “middle-aged” stars. We show that for stars with slightly less rotational influence than our Sun a transition occurs from solar-like (fast equator, slow poles) to anti-solar (slow equator, fast poles) differential rotation. We investigate this transition using two different treatments for the upper boundary of our simulations and we hypothesize that this transition from solar-like to anti-solar differential rotation may be responsible for observations of anomalously rapid rotation for stars older than our Sun.
Magnetic resonance imaging studies of maltreated children with posttraumatic stress disorder (PTSD) suggest that maltreatment-related PTSD is associated with adverse brain development. Maltreated youth resilient to chronic PTSD were not previously investigated and may elucidate neuromechanisms of the stress diathesis that leads to resilience to chronic PTSD. In this cross-sectional study, anatomical volumetric and corpus callosum diffusion tensor imaging measures were examined using magnetic resonance imaging in maltreated youth with chronic PTSD (N = 38), without PTSD (N = 35), and nonmaltreated participants (n = 59). Groups were sociodemographically similar. Participants underwent assessments for strict inclusion/exclusion criteria and psychopathology. Maltreated youth with PTSD were psychobiologically different from maltreated youth without PTSD and nonmaltreated controls. Maltreated youth with PTSD had smaller posterior cerebral and cerebellar gray matter volumes than did maltreated youth without PTSD and nonmaltreated participants. Cerebral and cerebellar gray matter volumes inversely correlated with PTSD symptoms. Posterior corpus callosum microstructure in pediatric maltreatment-related PTSD differed compared to maltreated youth without PTSD and controls. The group differences remained significant when controlling for psychopathology, numbers of Axis I disorders, and trauma load. Alterations of these posterior brain structures may result from a shared trauma-related mechanism or an inherent vulnerability that mediates the pathway from chronic PTSD to comorbidity.
Body size is one of the most studied phenotypic attributes because it is biologically important and easily measured. Despite a long history of study, however, the pattern of body-size change in diverse higher taxa over the Phanerozoic remains largely unknown because few relevant data sets span more than a single geological period or provide comprehensive, global coverage. In this study, we measured representative specimens of 3414 brachiopod genera illustrated in the Treatise on Invertebrate Paleontology. We applied these size data to stage-resolved stratigraphic ranges from the Treatise and the Paleobiology Database to develop a Phanerozoic record of trends in brachiopod size. Using a model comparison approach, we find that temporal variation in brachiopod size exhibits two distinct modes—a Paleozoic mode of size increase and a post-Paleozoic mode indistinguishable from a random walk. This transition reflects a change in the identities of the most diverse brachiopod orders rather than a shift in mode within any given order. Paleozoic size increase reflects a small, persistent bias toward the origination of new genera larger than those surviving from the previous stage and is identifiable as a statistically supported trend in three orders representing both Class Strophomenata (Order Productida) and Class Rhynchonellata (orders Atrypida and Spiriferida). Extinction exhibits no consistent bias with respect to size. The shift in evolutionary mode across the end-Permian mass extinction adds to long-standing evidence from studies of diversity and abundance that this biotic catastrophe suddenly and permanently altered the evolutionary history of what was, until that time, the most diverse animal phylum on Earth.
Each year, tobacco use causes over 6 million deaths and is responsible for hundreds of billions of dollars in health care and economic costs in the world (WHO, 2011). If current trends continue, tobacco is expected to kill over 1 billion people in the 21st century, making it one of the single greatest causes of preventable death and disease in history (WHO, 2011). Long-term abstinence from tobacco use dramatically improves individuals’ health, reduces the incidence of tobacco-related disease, and is clearly responsible for saving lives (Anthonisen et al., 2005). Most tobacco users express a desire to achieve long-term abstinence from tobacco use and make numerous unsuccessful quit attempts over the course of many years (Borland, Partos, Yong, Cummings, & Hyland, 2012; CDC, 2011). Evidence-based treatments for tobacco use and dependence greatly improve the chances that quit attempts result in long-term abstinence (Chambless & Hollon, 1998; Chambless et al., 1998; Compas, Haaga, Keefe, Leitenberg, & Williams, 1998; Fiore et al., 2008; Zwar et al., 2004). Increasing the availability of high-quality evidence-based treatment for tobacco use and dependence will make it more likely that tobacco users use evidence-based treatments and that quit attempts translate into long-term abstinence. The professionalisation of treatment for tobacco dependence by the development of a rigorous, unified Tobacco Treatment Specialist (TTS) certification process will increase the availability of high-quality evidence-based treatment for tobacco use and dependence for all tobacco users.
Previously we showed that 6-hydroxydopamine lesions of the substantia nigra eliminate corticostriatal LTP and that the neuroimmunolophilin ligand (NIL), GPI-1046, restores LTP.
Methods:
We used cDNA microarrays to determine what mRNAs may be over- or under-expressed in response to lesioning and/or GPI-1046 treatment. Patch clamp recordings were performed to investigate changes in NMDA channel function before and after treatments.
Results:
We found that 51 gene products were differentially expressed. Among these we found that GPI-1046 treatment up-regulated presenilin-1 (PS-1) mRNA abundance. This finding was confirmed using QPCR. PS-1 protein was also shown to be over-expressed in the striatum of lesioned/GPI-1046-treated rats. As PS-1 has been implicated in controlling NMDA-receptor function and LTP is reduced by lesioning we assayed NMDA mediated synaptic activity in striatal brain slices. The lesion-induced reduction of dopaminergic innervation was accompanied by the near complete loss of NDMA receptor-mediated synaptic transmission between the cortex and striatum. GPI-1046 treatment of the lesioned rats restored NMDA-mediated synaptic transmission but not the dopaminergic innervation. Restoration of NDMA channel function was apparently specific as the sodium channel current density was also reduced due to lesioning but GPI-1046 did not reverse this effect. We also found that restoration of NMDA receptor function was also not associated with either an increase in NMDA receptor mRNA or protein expression.
Conclusion:
As it has been previously shown that PS-1 is critical for normal NMDA receptor function, our data suggest that the improvement of excitatory neurotransmission occurs through the GPI-1046-induced up-regulation of PS-1.
The articles in this special issue survey comparatively the shape of power and finance. The introduction sketches the history of the study of the political role of financial markets and examines the reasons for the comparative neglect of the subject by the discipline of political science.