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 email@example.com
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.
Historical data can be used to evaluate water impacts from unconventional oil and gas extraction. “Grey” literature measurements of water quality before, during, and after unconventional extraction activities offer a potentially powerful resource for the evaluation of water quality impacts, and these data have rapidly expanded with regulatory response to the unconventional boom. However, historical data are limited in the variety of measured constituents and require substantial effort to reconstruct, revisit, and re-evaluate. Ultimately, available data were limited as data from only a single county (Bradford) included constituents necessary to use the vast majority of these elemental ratio systems. Further, even when data were available, they were often measured with relatively poor sensitivity, precluding their use as early indicators of contamination. This case study accentuates the continued need to establish background conditions, particularly in regions that have accumulated historical impacts, and further, ensure these characterizations incorporate sensitive testing for known chemistries associated with emerging and novel processes.
Public health authorities recommend symptom monitoring of healthcare personnel (HCP) after defined exposures to monkeypox. We report on the rapid development and implementation of mobile responsive survey solutions for notification of possible exposure, exposure risk assessment and stratification, and symptom monitoring.
An academic health center in Boston, Massachusetts, after admission of first diagnosed case of monkeypox in the United States during the current global outbreak.
Research Electronic Data Capture (REDCap) design and programmers, infection control, occupational health, and emergency preparedness specialists, and HCP with possible exposure to monkeypox.
Design and deployment of REDCap tools to identify HCP with possible exposure to monkeypox, to perform exposure risk assessment and stratification for postexposure prophylaxis (PEP), and to conduct symptom monitoring during the exposure window. Project enhancements included dashboards for HCP tracking and short message service (SMS text) reminders for symptom monitoring.
Tools to support the contact tracing and exposure investigation were deployed within 24 hours of identification of a patient with suspected monkeypox, with the full suite in production within 4 days of confirmation of the monkeypox diagnosis. Clinical follow-up of HCP was integrated into the design, and real-time versioning allowed for improvements in HCP symptom monitoring compliance and enhanced tracking.
During the current monkeypox outbreak, timely and comprehensive evaluation of potential HCP exposures is necessary but presents logistical challenges. Rapid development of monkeypox-specific solutions using REDCap facilitated flexibility in design and approach, and integration of targeted clinical support enhanced functionality.
To reduce both inappropriate testing for and diagnosis of healthcare-onset (HO) Clostridioides difficile infections (CDIs).
We performed a retrospective analysis of C. difficile testing from hospitalized children before (October 2017–October 2018) and after (November 2018–October 2020) implementing restrictive computerized provider order entry (CPOE).
Study sites included hospital A (a ∼250-bed freestanding children’s hospital) and hospital B (a ∼100-bed children’s hospital within a larger hospital) that are part of the same multicampus institution.
In October 2018, we implemented CPOE. No testing was allowed for infants aged ≤12 months, approval of the infectious disease team was required to test children aged 13–23 months, and pathology residents’ approval was required to test all patients aged ≥24 months with recent laxative, stool softener, or enema use. Interrupted time series analysis and Mann-Whitney U test were used for analysis.
An interrupted time series analysis revealed that from October 2017 to October 2020, the numbers of tests ordered and samples sent significantly decreased in all age groups (P < .05). The monthly median number of HO-CDI cases significantly decreased after implementation of the restrictive CPOE in children aged 13–23 months (P < .001) and all ages combined (P = .003).
Restrictive CPOE for CDI in pediatrics was successfully implemented and sustained. Diagnostic stewardship for CDI is likely cost-saving and could decrease misdiagnosis, unnecessary antibiotic therapy, and overestimation of HO-CDI rates.
Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.
We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.
The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.
These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.
Both logic programming in general and Prolog in particular have a long and fascinating history, intermingled with that of many disciplines they inherited from or catalyzed. A large body of research has been gathered over the last 50 years, supported by many Prolog implementations. Many implementations are still actively developed, while new ones keep appearing. Often, the features added by different systems were motivated by the interdisciplinary needs of programmers and implementors, yielding systems that, while sharing the “classic” core language, in particular, the main aspects of the ISO-Prolog standard, also depart from each other in other aspects. This obviously poses challenges for code portability. The field has also inspired many related, but quite different languages that have created their own communities. This article aims at integrating and applying the main lessons learned in the process of evolution of Prolog. It is structured into three major parts. First, we overview the evolution of Prolog systems and the community approximately up to the ISO standard, considering both the main historic developments and the motivations behind several Prolog implementations, as well as other logic programming languages influenced by Prolog. Then, we discuss the Prolog implementations that are most active after the appearance of the standard: their visions, goals, commonalities, and incompatibilities. Finally, we perform a SWOT analysis in order to better identify the potential of Prolog and propose future directions along with which Prolog might continue to add useful features, interfaces, libraries, and tools, while at the same time improving compatibility between implementations.
When do voters punish corrupt politicians? Heterogeneous views about the importance of corruption can determine whether or not increased information enhances accountability. If partisan cleavages correlate with the importance voters place on corruption, then the consequences of information may vary by candidate, even when voters identify multiple candidates as corrupt. We provide evidence of this mechanism from a field experiment in a mayoral election in Brazil where a reputable interest group declared both candidates corrupt. We distributed fliers in the runoff mayoral election in São Paulo. Informing voters about the challenger's record reduced turnout by 1.9 percentage points and increased the opponent's vote by 2.6 percentage points. Informing voters about the incumbent's record had no effect on behavior. We attribute this divergent finding to differences in how each candidate's supporters view corruption. Using survey data and a survey experiment, we show that the challenger's supporters are more willing to punish their candidate for corruption, while the incumbent's supporters lack this inclination.
To present an updated version of the ‘Post-acute Level Of Consciousness scale’ (PALOC-s), in accordance with the latest scientific insights.
Within the context of a research project, 20 years ago, the PALOC-s was developed for the purpose of following the development of the level of consciousness of young unconscious patients participating in a rehabilitation program. Meanwhile, the understanding of the behavior related to different levels of consciousness has developed and terminology has changed, resulting in the need to revise the PALOC-s. With the preservation of the original description of the eight hierarchical levels of PALOC-s, adaptations are made in the terminology and grouping of these levels.
Results and conclusion:
This manuscript presents the revised version of PALOC-sr, which is suitable for use in clinical practice. The validation of this scale is recommended for its optimal use in future (international) research projects.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
OBJECTIVES/GOALS: Rib fractures are common traumatic thoracic injuries and are associated with high rates of morbidity and mortality. In those age â‰¥ 65, the rate of these complications double. This study sought to identify the extent to which injury-related predictors influence clinical outcomes in geriatric patients with rib fractures. METHODS/STUDY POPULATION: A retrospective 5-year review was performed of a single Level 1 Trauma center registry. Geriatric patients (â‰¥65 years of age) diagnosed with rib fractures from January 1, 2014 to December 31, 2019 were included. The primary outcome of interest was in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay (HLOS and ICU LOS, respectively) and discharge disposition, as a surrogate for loss of independence. Further, subgroup analysis based on number of rib fractures (i.e. <4 and â‰¥4 rib fractures) was performed. RESULTS/ANTICIPATED RESULTS: 2,134 adult trauma patients were admitted with at least one rib fracture. Of these, 1,037 (49%) were â‰¥ 65 years old. This cohort had a mean age of 78.6 years old, injury severity score (ISS) of 11.4, HLOS of 7.4 days and 29% required ICU care with mean ICU LOS of 1.9 days. Only 36% were discharged home compared to 64% who were discharged to a care facility and thus had a loss of independence. Overall mortality was 6.3%. Compared to survivors, non-survivors had a higher ISS (19.3 vs. 10.8, p = < 0.0001) and longer ICU LOS (7.1 vs. 6.5 days, p = 0.04). Analysis based on number of rib fractures showed that those with â‰¥4 rib fractures had significantly higher mortality (8% vs. 4%, p = 0.008), longer HLOS (8.7 vs. 6.1 days, p < 0.0001), longer ICU LOS (2.6 vs. 1.3 days, p < 0.0001), and significantly lower discharge to home (32% vs. 39%, p = 0.02). DISCUSSION/SIGNIFICANCE: To our knowledge, this is the largest single-center study of geriatric patients with rib fractures. In this study, the observed mortality in patients â‰¥65 years of age was 6.3% which represents a lower mortality rate than historically reported. Despite this, only 36% were able to be discharged directly to home.
Inaccurate representations of iceberg calving from ice shelves are a large source of uncertainty in mass-loss projections from the Antarctic ice sheet. Here, we address this limitation by implementing and testing a continuum damage-mechanics model in a continental scale ice-sheet model. The damage-mechanics formulation, based on a linear stability analysis and subsequent long-wavelength approximation of crevasses that evolve in a viscous medium, links damage evolution to climate forcing and the large-scale stresses within an ice shelf. We incorporate this model into the BISICLES ice-sheet model and test it by applying it to idealized (1) ice tongues, for which we present analytical solutions and (2) buttressed ice-shelf geometries. Our simulations show that the model reproduces the large disparity in lengths of ice shelves with geometries and melt rates broadly similar to those of four Antarctic ice shelves: Erebus Glacier Tongue (length ~ 13 km), the unembayed portion of Drygalski Ice Tongue (~ 65 km), the Amery Ice Shelf (~ 350 km) and the Ross Ice Shelf (~ 500 km). These results demonstrate that our simple continuum model holds promise for constraining realistic ice-shelf extents in large-scale ice-sheet models in a computationally tractable manner.
While comorbidity of clinical high-risk for psychosis (CHR-P) status and social anxiety is well-established, it remains unclear how social anxiety and positive symptoms covary over time in this population. The present study aimed to determine whether there are more than one covariant trajectory of social anxiety and positive symptoms in the North American Prodrome Longitudinal Study cohort (NAPLS 2) and, if so, to test whether the different trajectory subgroups differ in terms of genetic and environmental risk factors for psychotic disorders and general functional outcome.
In total, 764 CHR individuals were evaluated at baseline for social anxiety and psychosis risk symptom severity and followed up every 6 months for 2 years. Application of group-based multi-trajectory modeling discerned three subgroups based on the covariant trajectories of social anxiety and positive symptoms over 2 years.
One of the subgroups showed sustained social anxiety over time despite moderate recovery in positive symptoms, while the other two showed recovery of social anxiety below clinically significant thresholds, along with modest to moderate recovery in positive symptom severity. The trajectory group with sustained social anxiety had poorer long-term global functional outcomes than the other trajectory groups. In addition, compared with the other two trajectory groups, membership in the group with sustained social anxiety was predicted by higher levels of polygenic risk for schizophrenia and environmental stress exposures.
Together, these analyses indicate differential relevance of sustained v. remitting social anxiety symptoms in the CHR-P population, which in turn may carry implications for differential intervention strategies.
How do coalitional dynamics matter for the capacity of states to maintain social inclusion in coordinated models of capitalism? Taking its departure in scholarship emphasizing the influence of employers on the extent of state intervention in post-industrial economies, this paper argues that employer influence depends on which actors they team up with – unions or parties. If unions depend on employers for their organizational influence in a policy field, unions become a strong coalitional partner for employers in weakening demands for inclusiveness from the parliamentary arena. Conversely, if unions have influence independent of any coalition with employers, both unions and employers are likely to team up with political parties aligned with their preferences. This makes the level of inclusion resulting from increased state intervention more fluctuating, depending on who holds government power. A comparative study of reforms of Danish and Austrian vocational education institutions corroborates the empirical purchase of the argument.
How is the tension between conflict and deliberation resolved in shareholder engagement? We address this question by studying shareholder engagement as a deliberative process with three stages: establishing dialogue, solution development, and solution implementation. We theorize that two interactionist mechanisms, deliberative interaction and the voicing of disagreement, play different roles at different stages of the process. We test our hypotheses with a proprietary database of 169 environmental, social, and governance engagements with US public companies over 2007–12. We find that while deliberative interaction does not help advance the engagement process, it positively moderates the effect of disagreement in the solution development stage. By contrast, in the solution implementation stage, deliberative interaction amplifies the negative effect of disagreement, thus hindering progress in the engagement. Our article contributes to shareholder engagement, deliberation theory, and interactionist organization theory by establishing that engagement effectiveness is an interactional achievement shaped by both deliberation and disagreement.
From a systematic review framework, we assessed the preclinical evidence on the effectiveness of drug combinations for visceral leishmaniasis (VL) treatment. Research protocol was based on the PRISMA guideline. Research records were identified from Medline, Scopus and Web of Science. Animal models, infection and treatment protocols, parasitological and immunological outcomes were analysed. The SYRCLE's (SYstematic Review Center for Laboratory Animal Experimentation) toll was used to evaluate the risk of bias in all studies reviewed. Fourteen papers using mice, hamster and dogs were identified. Leishmania donovani was frequently used to induce VL, which was treated with 23 drugs in 40 different combinations. Most combinations allowed to reduce the effective dose, cost and time of treatment, in addition to improving the parasitological control of Leishmania spp. The benefits achieved from drug combinations were associated with an increased drug's half-life, direct parasitic toxicity and improved immune defences in infected hosts. Selection, performance and detection bias were the main limitations identified. Current evidence indicates that combination chemotherapy, especially those based on classical drugs (miltefosine, amphotericin B antimony-based compounds) and new drugs (CAL-101, PAM3Cys, tufisin and DB766), develops additive or synergistic interactions, which trigger trypanocidal and immunomodulatory effects associated with reduced parasite load, organ damage and better cure rates in VL.
The presence of the prostate in female mammals has long been known. However, pieces of information related to its development are still lacking. The aim of this study was to explore the budding dynamic during the initial prostate development in female gerbils. Pregnant females were timed, the fetuses were euthanized, and the urogenital sinus was dissected out between the embryonic days 20 and 24 (E20–E24 groups). Newborn pups (1-day-old; P1 group) underwent the same procedures. The female prostate development was based on epithelial buds which arose far from the paraurethral mesenchyme (PAM). The epithelial buds reached the PAM at prenatal day 24, crossing a small gap in the smooth muscle layer between the periurethral mesenchyme (PEM) and the PAM. Steroid nuclear receptors such as the androgen receptor and estrogen receptor alpha were localized in the PEM through the urethral wall, although some epithelial labeling was also present in the urogenital sinus epithelium (UGE). P63-positive cells were found only in the UGE, becoming restricted to the basal compartment after the 23rd prenatal day. The results showed that the gerbil female prostate exhibits a distinct budding pattern as compared to the male prostate development.
Given the convergence of the long and challenging development path for medical devices with the need for diagnostic capabilities for mild traumatic brain injury (mTBI/concussion), the effective role of public–private partnership (PPP) can be demonstrated to yield Food and Drug Administration (FDA) clearances and innovative product introductions. An overview of the mTBI problem and landscape was performed. A detailed situation analysis of an example of a PPP yielding an innovative product was further demonstrated. The example of PPP has led to multiple FDA clearances and product introductions in the TBI diagnostic product category where there was an urgent military and public need. Important lessons included defining the primary public and military health objective for new product introduction, the importance of the government–academia–industry PPP triad with a “collaboration towards solutions” Quality-by-Design (QbD) mindset to assure clinical validity with regulatory compliance, the development of device comparators and integration of measurements into a robust, evidence-based statistical and FDA pathway, and the utility of top-down, flexible, practical action while operating within governmental guidelines and patient safety.