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Around 1000 years ago, Madagascar experienced the collapse of populations of large vertebrates that ultimately resulted in many species going extinct. The factors that led to this collapse appear to have differed regionally, but in some ways, key processes were similar across the island. This review evaluates four hypotheses that have been proposed to explain the loss of large vertebrates on Madagascar: Overkill, aridification, synergy, and subsistence shift. We explore regional differences in the paths to extinction and the significance of a prolonged extinction window across the island. The data suggest that people who arrived early and depended on hunting, fishing, and foraging had little effect on Madagascar’s large endemic vertebrates. Megafaunal decline was triggered initially by aridification in the driest bioclimatic zone, and by the arrival of farmers and herders in the wetter bioclimatic zones. Ultimately, it was the expansion of agropastoralism across both wet and dry regions that drove large endemic vertebrates to extinction everywhere.
Giant coronary artery aneurysms and myocardial fibrosis after Kawasaki disease may lead to devastating cardiovascular outcomes. We characterised the vascular and myocardial outcomes in five selected Kawasaki disease patients with a history of giant coronary artery aneurysms that completely regressed.
Methods:
Five patients were selected who had giant coronary artery aneurysm in early childhood that regressed when studied 12–33 years after Kawasaki disease onset. Coronary arteries were imaged by coronary CT angiography, and coronary artery calcium volume scores were determined. We used endocardial strain measurements from CT imaging to assess myocardial regional wall function. Calprotectin and galectin-3 (gal-3) as biomarkers of inflammation and myocardial fibrosis were measured by enzyme-linked immunosorbent assay.
Results:
The five selected patients with regressed giant coronary artery aneurysms had calcium scores of zero, normal levels of calprotectin and gal-3, and normal appearance of the coronary arteries by coronary computed tomography angiography. CT strain demonstrated normal peak systolic and diastolic strain patterns in four of five patients. In one patient with a myocardial infarction at the time of Kawasaki disease diagnosis at the age of 10 months, CT strain showed altered global longitudinal strain, reduced segmental peak strain, and reduced diastolic relaxation patterns in multiple left ventricle segments.
Conclusions:
These patients illustrate that regression of giant aneurysms after Kawasaki disease is possible with no detectable calcium, normal biomarkers of inflammation and fibrosis, and normal myocardial function. Individuals with regressed giant coronary artery aneurysm still require longitudinal surveillance to assess the durability of this favourable outcome.
Medications with anticholinergic properties are associated with a range of adverse effects that tend to be worse in older people.
Aims
To investigate medication regimens with high anticholinergic burden, prescribed for older adults under the care of mental health services.
Method
Clinical audit of prescribing practice, using a standardised data collection tool.
Results
Fifty-seven trusts/healthcare organisations submitted data on medicines prescribed for 7915 patients: two-thirds (66%) were prescribed medication with anticholinergic properties, while just under a quarter (23%) had a medication regimen with high anticholinergic burden (total score ≥3 on the anticholinergic effect on cognition (AEC) scale). Some 16% of patients with a diagnosis of dementia or mild cognitive impairment were prescribed medication regimens with a high anticholinergic burden, compared with 35% of those without such diagnoses. A high anticholinergic burden was mostly because of combinations of commonly prescribed psychotropic medications, principally antidepressant and antipsychotic medications with individual AEC scores of 1 or 2.
Conclusions
Adults under the care of older people's mental health services are commonly prescribed multiple medications for psychiatric and physical disorders; these medication regimens can have a high anticholinergic burden, often an inadvertent consequence of the co-prescription of medications with modest anticholinergic activity. Prescribers for older adults should assess the anticholinergic burden of medication regimens, assiduously check for adverse anticholinergic effects and consider alternative medications with less anticholinergic effect where indicated. The use of a scale, such as the AEC, which identifies the level of central anticholinergic activity of relevant medications, can be a helpful clinical guide.
Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.
Method:
Older adults with major depressive disorder (N = 228, ages 65–91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning.
Results:
Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity.
Conclusions:
Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.
The primary objective was to grade the potential impact of antimicrobial stewardship program (ASP) interventions on patient safety at a single center using a newly developed scoring tool, the Antimicrobial Stewardship Impact Scoring Tool (ASIST).
Design:
Retrospective descriptive study.
Setting:
A 367-bed free-standing, pediatric academic medical center.
Methods:
The ASP team developed the ASIST which scored each intervention on an impact level (low, moderate, high) based on patient harm avoidance and degree of antibiotic optimization. Intervention frequency and characteristics were collected between May 1, 2022 and October 31, 2023. Intervention rates per impact level were calculated monthly.
Results:
The ASP team made 1024 interventions further classified as low (45.1%), moderate (47%), and high impact (7.9%). The interventions for general pediatrics (53.9%) and those to modify formulation (62.2%), dose/frequency (58.1%), and duration (57.5%) were frequently low impact. Hematology/oncology (12.5%), sub-specialty (11.7%), and surgical services (11.3%) had the greatest rate of high-impact interventions. Interventions to broaden antibiotics (40.8%) and those associated with antibiotics used to treat bacteremia (20.6%) were frequently classified as high-impact.
Conclusion:
The ASIST is an effective tool to link ASP interventions to prevention of antimicrobial-associated patient harm. For our ASP team, it provided meaningful data to present to hospital leadership and identified opportunities to prevent future harm and reduce ASP team workload.
Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD.
Participants and Measurements:
Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity.
Results:
Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p = .031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety.
Conclusions:
Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
The ability to generate, plan for, and follow through with goals is essential to everyday functioning. Compared to young adults, cognitively normal older adults have more difficulty on a variety of cognitive functions that contribute to goal setting and follow through. However, how these age-related cognitive differences impact real-world goal planning and success remains unclear. In the current study, we aimed to better understand the impact of older age on everyday goal planning and success.
Participants and Methods:
Cognitively normal young adults (18-35 years, n= 57) and older adults (60-80 years, n= 49) participated in a 10-day 2-session study. In the first session, participants described 4 real-world goals that they hoped to pursue in the next 10 days. These goals were subjectively rated for personal significance, significance to others, and vividness, and goal descriptions were objectively scored for temporal, spatial, and event specificity, among other measures. Ten days later, participants rated the degree to which they planned for and made progress in their real-world goals since session one. Older adults also completed a battery of neuropsychological tests.
Results:
Some key results are as follows. Relative to the young adults, cognitively normal older adults described real-world goals which navigated smaller spaces (p=0.01) and that they perceived as more important to other people (p=0.03). Older adults also planned more during the 10-day window (p<0.001). There was not a statistically significant age group difference, however, in real-world goal progress (p=0.65). Nonetheless, among older participants, goal progress was related to higher mental processing speed as shown by the Trail Making Test Part A (r=0.36, p=0.02) and the creation of goals confined to specific temporal periods (r=0.35, p=0.01). Older participants who scored lower on the Rey Complex Figure Test (RCFT) long delay recall trial reported that their goals were more like ones that they had set in the past (r= -0.34, p=0.02), and higher episodic memory as shown by the RCFT was associated with more spatially specific goals (r=0.32, p=0.02), as well as a greater use of implementation intentions in goal descriptions(r=0.35, p=0.02).
Conclusions:
Although older adults tend to show decline in several cognitive domains relevant to goal setting, we found that cognitively normal older adults did not make significantly less progress toward a series of real-world goals over a 10-day window. However, relative to young adults, older adults tended to pursue goals which were more important to others, as well as goals that involved navigating smaller spaces. Older adults also appear to rely on planning more than young adults to make progress toward their goals. These findings reveal age group differences in the quality of goals and individual differences in goal success among older adults. They are also in line with prior research suggesting that cognitive aging effects may be more subtle in real-world contexts.
To investigate differences in the rate of firstline antibiotic prescribing for common pediatric infections in relation to different socioeconomic statuses and the impact of an antimicrobial stewardship program (ASP) in pediatric urgent-care clinics (PUCs).
Design:
Quasi-experimental.
Setting:
Three PUCs within a Midwestern pediatric academic center.
Patients and participants:
Patients aged >60 days and <18 years with acute otitis media, group A streptococcal pharyngitis, community-acquired pneumonia, urinary tract infection, or skin and soft-tissue infections who received systemic antibiotics between July 2017 and December 2020. We excluded patients who were transferred, admitted, or had a concomitant diagnosis requiring systemic antibiotics.
Intervention:
We used national guidelines to determine the appropriateness of antibiotic choice in 2 periods: prior to (July 2017–July 2018) and following ASP implementation (August 2018–December 2020). We used multivariable regression analysis to determine the odds ratios of appropriate firstline agent by age, sex, race and ethnicity, language, and insurance type.
Results:
The study included 34,603 encounters. Prior to ASP implementation in August 2018, female patients, Black non-Hispanic children, those >2 years of age, and those who self-paid had higher odds of receiving recommended firstline antibiotics for all diagnoses compared to male patients, children of other races and ethnicities, other ages, and other insurance types, respectively. Although improvements in prescribing occurred after implementation of our ASP, the difference within the socioeconomic subsets persisted.
Conclusions:
We observed socioeconomic differences in firstline antibiotic prescribing for common pediatric infections in the PUCs setting despite implementation of an ASP. Antimicrobial stewardship leaders should consider drivers of these differences when developing improvement initiatives.
OBJECTIVES/GOALS: The trabecular meshwork (TM) and Schlemm’s canal (SC), located within the iridocorneal angle (ICA), form the main outflow pathway and a major target for glaucoma treatments. We characterized the human ICA in vivo with Optical Coherence Tomography (OCT) imaging using a customized goniolens and a commercial OCT device (Heidelberg Spectralis). METHODS/STUDY POPULATION: Imaging these structures is difficult due to the optical limitations of imaging through the cornea at high angles. Therefore, a clinical gonioscopy lens was modified with a 12mm plano-convex lens placed on its anterior surface to focus light on the ICA structures, and capture returning light. Each subjects’ eye was anesthetized with 1 drop of Proparacaine 0.5%. The goniolens was coupled to the eye with gonio-gel and it was held by a 3D adjustable mount. OCT volume scans were acquired on 10 healthy subjects. The linear polarization of the OCT was rotated with a half-waveplate to measure dependence of the ICA landmarks on polarization orientation. RESULTS/ANTICIPATED RESULTS: The TM was seen in 9 of 10 subjects. Polarization rotation modified the brightness of the band of extracanalicular limbal lamina (BELL) and corneoscleral bands due to the birefringent nature of the collagenous structures, increasing the contrast of SC. SC width was 99 ± 20µm varying in size over space, including a subject with SC narrowing in the inferior-temporal quadrant. DISCUSSION/SIGNIFICANCE: This clinically suitable gonioscopic OCT approach has successfully been used to image the human ICA in 3D in vivo, providing detailed characterization of the TM and SC as well as enhancing their contrast against their birefringent backgrounds by rotating the polarization of the imaging beam.
Narcolepsy is not a common disorder, with best estimates finding it affects only about .025–.05% of the population. Nonetheless, it is a vital disorder for school psychologists to be familiar with on the basis that its symptoms frequently first occur during childhood and adolescence. If undiagnosed, this disorder causes significant distress and disadvantage to the student as well as frustration and difficulty for school staff. It is surprising that narcolepsy has received almost no attention in the school psychology literature. This article provides school psychologists with an overview of the central features, causes, diagnosis and treatment of narcolepsy in young people. It then outlines school management of the disorder, with specific consideration of the role of the school psychologist.
We numerically and theoretically investigate the Boussinesq Eady model, where a rapidly rotating density-stratified layer of fluid is subject to a meridional temperature gradient in thermal wind balance with a uniform vertically sheared zonal flow. Through a suite of numerical simulations, we show that the transport properties of the resulting turbulent flow are governed by quasigeostrophic (QG) dynamics in the rapidly rotating strongly stratified regime. The ‘vortex gas’ scaling predictions put forward in the context of the two-layer QG model carry over to this fully three-dimensional system: the functional dependence of the meridional flux on the control parameters is the same, the two adjustable parameters entering the theory taking slightly different values. In line with the QG prediction, the meridional heat flux is depth-independent. The vertical heat flux is such that turbulence transports buoyancy along isopycnals, except in narrow layers near the top and bottom boundaries, the thickness of which decreases as the diffusivities go to zero. The emergent (re)stratification is set by a simple balance between the vertical heat flux and diffusion along the vertical direction. Overall, this study demonstrates how the vortex-gas scaling theory can be adapted to quantitatively predict the magnitude and vertical structure of the meridional and vertical heat fluxes, and of the emergent stratification, without additional fitting parameters.
There is a well-established association between anger, hostility, and an increased risk of cardiovascular disease. Emerging evidence also suggests associations between anger/hostility and type 2 diabetes (T2D), though evidence from longitudinal studies has not yet been synthesized.
Objectives
To systematically review findings from existing prospective cohort studies on trait anger/hostility and the risk of T2D and diabetes-related complications.
Methods
Electronic searches of MEDLINE (PubMed), PsychINFO, Web of Science, and CINAHL were performed for articles/abstracts published up to December 15, 2020. Peer-reviewed longitudinal studies conducted with adult samples, with effect estimates reported for trait anger or hostility and incident T2D or diabetes-related complications, were eligible for inclusion. Risk of bias/study quality was assessed. The review protocol was published a priori in PROSPERO (CRD42020216356) and was in keeping with PRISMA guidelines. Screening for eligibility, data extraction, and quality assessment was conducted by two independent reviewers.
Results
Four studies with a total of 155,146 participants met the inclusion criteria. A narrative synthesis of extracted data was conducted according to the Synthesis Without Meta-Analysis guidelines. While results were mixed, our synthesis suggested a positive association between high trait-anger/hostility and increased risk of incident T2D. No longitudinal studies were identified relating to anger/hostility and incident diabetes-related complications. Geographical locations of the study samples were limited to the USA and Japan.
Conclusions
Further research is needed to investigate whether trait-anger/hostility predicts incident type 2 diabetes after adjustments for potential confounding factors. Longitudinal studies are needed to investigate trait-anger/hostility and the risk of diabetes-related vascular complications.
To evaluate efficiency and impact of a novel antimicrobial stewardship program (ASP) prospective-audit-with-feedback (PAF) review process using the Cerner Multi-Patient Task List (MPTL).
Design:
Retrospective cohort study.
Setting:
A 367-bed free-standing, pediatric academic medical center.
Methods:
The ASP PAF review process expanded to monitor all systemic and inhaled antibiotics through use of the MPTL on July 23, 2020. Average number of daily ASP reviews, absolute number of monthly interventions, and time to conduct ASP reviews were compared between the preimplementation period and the postimplementation period following expansion. Antibiotic days of therapy (DOT) per 1,000 patient days for overall and select antibiotics were compared between periods. ASP intervention characteristics were assessed.
Results:
Average daily ASP reviews significantly increased following program expansion (9 vs 14 reviews; P < .0001), and the absolute number of ASP interventions each month also increased (34 vs 52 interventions; P ≤ .0001). Time to conduct daily ASP reviews increased in the postimplementation period (1.03 vs 1.32 hours). Overall antibiotic DOT per 1,000 patient days significantly decreased in the postimplementation period (457.9 vs 427.9; P < .0001) as well as utilization of select, narrow-spectrum antibiotics such as ampicillin and clindamycin. Intervention type and antibiotics were similar between periods. The ASP documented 128 “nonantibiotic interventions” in the postimplementation period, including culture and/or susceptibility testing (32.8%), immunizations (25.8%), and additional diagnostic testing (22.7%).
Conclusions:
Implementation of an ASP PAF review process using the MPTL allowed for efficient expansion of a pre-existing ASP and a decrease in overall antibiotic utilization. ASP documentation was enhanced to fully track the impact of the program.
“Fragmentation” – the breakdown in communication among many providers treating a single patient, such that multiple decision makers make a set of health care decisions that would be made better through unified decision-making1 – is frequently cited as a major problem in the US health care system.2 It plagues both the payment system (which has multiple payers) as well as the delivery system (which has siloed providers). This chapter focuses on the latter problem of fragmentation among care providers and calls to correct it via “care coordination.” The problem is not just provider fragmentation, however. It is also the lack of clarity regarding what care coordination (the proposed solution) means, what benefits it confers, and how to do it.
There has been growing interest in the vertical integration of physicians and hospitals during the past decade, as evidenced by multiple literature reviews and research investigations.1 Historically, physicians operated small firms that provided “physicians’ services” to patients who sometimes used facilities provided by separate hospital firms at which many physicians would have “privileges.” This interest in combining the two types of organizations culminated in a December 2020 issue of Health Services Research devoted to the topic that expressed surprise (and disappointment) that integration is not “a miracle cure”.2 Just months earlier, two of the major proponents of vertical integration published a study in the August issue of Health Affairs that came to a similar, “startling” conclusion: the financial integration of physicians and hospitals (e.g., via employment) had no impact on their clinical integration (and perhaps none on quality).
Astrophysical flows are often subject to both rotation and large-scale background magnetic fields. Individually, each is known to two-dimensionalize the flow in the perpendicular plane. In realistic settings, both of these effects are simultaneously present and, importantly, need not be aligned. In this work, we numerically investigate three-dimensional forced magnetohydrodynamic turbulence subject to the competing effects of global rotation and a perpendicular background magnetic field. We focus on the case of a strong background field and find that increasing the rotation rate from zero produces significant changes in the structure of the turbulent flow. Starting with a two-dimensional inverse energy cascade at zero rotation, the flow first transitions to a forward cascade of kinetic energy, then to a shear-layer dominated regime and finally to a second shear-layer regime where the kinetic energy flux is strongly suppressed and the energy transfer is mediated by the induced magnetic field. We show that the first two transitions occur at distinct values of the Rossby number, and the third occurs at a distinct value of the Lehnert number. The three-dimensional results are confirmed using an asymptotic two-dimensional, three-component model, which allows us to extend our results to the planetary-relevant case of an arbitrary angle between the rotation vector and guide field. More generally, our results demonstrate that, when considering the simultaneous limits of strong rotation and a strong guide field, the order in which those limits are taken matters in the misaligned case.
The new mineral paramarkeyite (IMA2021-024), Ca2(UO2)(CO3)3⋅5H2O, was found in the Markey mine, San Juan County, Utah, USA, where it occurs as a secondary phase on gypsum-coated asphaltum in association with andersonite, calcite, gypsum and natromarkeyite. Paramarkeyite crystals are transparent, pale green-yellow, striated tablets, up to 0.11 mm across. The mineral has white streak and vitreous lustre. It exhibits moderate bluish-white fluorescence (405 nm laser). It is very brittle with irregular, curved fracture and a Mohs hardness of 2½. It has an excellent {100} cleavage and probably two good cleavages on {010} and {001}. The measured density is 2.91(2) g cm–3. Optically, the mineral is biaxial (–) with α = 1.550(2), β = 1.556(2), γ = 1.558(2) (white light); 2V = 60(2)°; strong r > v dispersion; orientation: Y = b; nonpleochroic. The Raman spectrum exhibits bands consistent with UO22+, CO32– and O–H. Electron microprobe analysis provided the empirical formula (Ca1.83Na0.20Sr0.03)Σ2.05(UO2)(CO3)3⋅5H2O (+0.07 H). Paramarkeyite is monoclinic, P21/n, a = 17.9507(7), b = 18.1030(8), c = 18.3688(13) Å, β = 108.029(8)°, V = 5676.1(6) Å3 and Z = 16. The structure of paramarkeyite (R1 = 0.0647 for 6657 I > 2σI) contains uranyl tricarbonate clusters that are linked by Ca–O polyhedra to form heteropolyhedral layers. The structure of paramarkeyite is very similar to those of markeyite, natromarkeyite and pseudomarkeyite.