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The prospects are considered of deploying batteries and fuel cells in order to reduce the carbon emissions from various modes of transport. It is proposed that the government has not done enough to advance these technologies and that Britain is lagging behind other countries. The adequacy of Britain’s future supplies of energy is called into question.
In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI.
Methods:
We conducted a prospective cohort study of inpatients aged 2–17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available.
Results:
We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL (P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL (P < .001).
Conclusions:
Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.
Corrections are made to Stuart Fiedel’s (2022) recent errors and misrepresentations related to the late Pleistocene sites of Monte Verde and Huaca Prieta and to South American Fishtail projectile points.
OBJECTIVES/GOALS: Time restricted feeding (TRF) in diet induced obesity (DIO) has several health benefits, including improved metabolic rhythms and inflammation. Our lab has shown that TRF in DIO significantly reduces renal and aortic damage. The main goal of our research is to understand how TRF impacts aortic function, organ damage, and T cell activation in DIO. METHODS/STUDY POPULATION: We will use a 20-week DIO model, where mice will be on 20 weeks of normal fat diet (ND) or high fat diet (HFD). During weeks 18-20, mice will go through TRF intervention
where food is restricted to the 12-hour active period or continue ad libitum feeding. At the end of the 2-week TRF intervention or continued ad libitum feeding, aortic stiffness will be measured via pulse wave velocity measurements. We will also collect kidney, aorta, and small intestine at the end of the 20-week protocol for flow cytometric analysis of tissue T cell activation as well as histological assessments. This will allow us to determine the relationship with organ damage, organ function, and the T cell response. We will also analyze tissue and circulating levels of inflammatory T cell-derived cytokines such as interleukin-17A (IL-17A) via ELISA. RESULTS/ANTICIPATED RESULTS: DIO mice showed significantly increased aortic stiffness (measured by pulse wave velocity) compared to mice on ND. Interestingly, TRF intervention in DIO mice reduced aortic stiffness compared to DIO ad libitum. Histological assessments also showed that TRF abolished aortic and kidney fibrosis suggesting a role for the timing of feeding in regulating aortic function and organ damage from chronic HFD. We have several ongoing experiments to determine the T cell response with TRF in DIO mice. We predict that TRF in DIO mice will significantly decrease inflammatory T cells and reduce cytokine abundance in target organs. DISCUSSION/SIGNIFICANCE: Our lab has shown that TRF reduces aortic thickness and aortic and kidney fibrosis, but the driving mechanisms are unknown. We propose that TRF reduces T cell activation in DIO mice leading to reduced organ damage. Our work will provide insight on how TRF in DIO regulates the T cell response and may improve inflammation in the kidney and aorta.
To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.
Design:
Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed.
Setting:
Community-based multi-centered study based in Toronto across 5 academic sites.
Participants:
Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls.
Measurements:
We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores.
Results:
A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD.
Conclusions:
This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.
Data reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network (CDC NHSN) were analyzed to understand the potential impact of the COVID-19 pandemic on central-line–associated bloodstream infections (CLABSIs) in acute-care hospitals. Descriptive analysis of the standardized infection ratio (SIR) was conducted by location, location type, geographic area, and bed size.
The California Department of State Hospitals (DSH) manages the psychiatric care of almost 7,000 patients admitted to any of its five hospitals. Over 90% of these patients have forensic commitments, meaning they have been charged with, or convicted of, a crime. Treating patients with mental illness and criminal behavior reflects a general trend within state psychiatric facilities.An increase in physical violence towards staff and patients has been attributed to this mandate to care for patients with both severe mental illness and criminal backgrounds. Addressing violence is a pressing need within state hospital systems, as a safe treatment environment is quintessential to the delivery of effective care.
A shift within state psychiatric hospitals toward serving a predominantly forensic population has resulted in increased violent incidents within those settings. Thus, addressing criminogenic needs in addition to mental illness is an important paradigm shift. Relying on seclusion or restraint as the primary mechanisms to address violence interferes with the provision of effective care to patients struggling with aggressive behaviors. Implementing new treatment programs aimed at reducing violence in forensic inpatient settings is warranted. This article focuses on the step-by-step process of developing such a specialized treatment program within the California Department of State Hospitals. Leadership within this hospital system collaborated with labor unions and other stakeholders to obtain funding to create a novel treatment environment. This treatment program includes a ward design aimed to improve safety and delivers treatment based on the Risk Needs Responsivity Model. Treatment is guided by violence risk assessment and primarily focused on addressing criminogenic needs. The selection of treatments with a focus on violence reduction is discussed.
The Little East Lake Formation represents a spectrum of Late Ordovician (Ashgill) nearshore environments. These physical environments are characterized by a variety of quartz- and feldspar-rich sandstone and slate. Depositional environments include neritic nearshore, beach, tidal flat, and alluvial(?). The beach and neritic nearshore environments contain a variety of fossil invertebrates. The majority of the brachiopod fauna is confined to two taxa: Eodinobolus rotundus Harper, 1984, and Dalmanella testudinaria ripae Mitchell, 1978 (in Cocks, 1978). Some of the specimens have been broken and abraded suggesting transport within the beach swash zone. Gastropods include Lophospira cf. L. milleri (Hall), Lophospira(?), Trochonemella cf. T. notabilis (Ulrich and Scofield), and Daidia cerithioides (Salter). Tidal-flat environment contains the trace fossils Palaeophycus and Planolites.
The Late Ordovician (Caradoc and Ashgill) sedimentary basins developed subsequent to the collisional Taconian orogeny, wherein an arc accreted to the eastern Laurentian margin. Prior paleomagnetic reconstructions place the southeastern continental margin of Laurentia at approximately 25° south latitude during the Late Ordovician. Using these reconstructions, the siliciclastic Ashgill rocks discussed here would have been deposited in an elongated, northeast-trending basin on the southeastern Laurentian margin. The fauna developed along this margin, but in contrast to possibly adjacent Irish and Scottish assemblages, was located in much shallower water.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
Methods:
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Results:
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
Conclusions:
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
The cholinergic system is a major neuromodulatory neurotransmitter system, interacting with core regions of the brain and affecting learning and memory function. Cholinergic function is severely reduced in patients with pathologic conditions, such as Alzheimer's disease. Muscarinic receptors M1–M5 are located at the postsynaptic level of the central cholinergic synapse. Blockage of certain muscarinic receptors has been shown to affect cognitive functioning. The roles of the individual receptor subtypes has implications for pharmacotherapy; eg, nonselective antimuscarinic/anticholinergic medications may block muscarinic neurotransmission, causing deficits in recall and new learning, while M1-receptor agonists and M2-receptor antagonists may not interfere with cognitive functioning. Studies investigating central nervous system (CNS) depressant effects of drugs have shown that antimuscarinic agents have the potential to cause impairment of CNS functioning. CNS dysfunction may be manifested as changes in memory, disruption of sleep, hallucinations, confusion, and delirium.
Anticholinergic load refers to the cumulative effect of taking multiple drugs with anticholinergic activity. The extent to which a particular drug affects the cholinergic system can be determined by its ability to cross the blood-brain barrier, the integrity of which decreases with age. Elderly individuals are also at high risk for increased anticholinergic load due to reductions in metabolism and elimination as well as pharmacokinetic drug interactions. In addition, elderly people are often prescribed several medications that have direct anticholinergic properties and take over-the-counter medications which may also carry substantial anticholinergic burden. The cumulative effect of these medications in vulnerable elderly patients may precipitate early cognitive declines or further exacerbate cognitive deficits in those already suffering from dementia. Risk of cognitive impairment in patients with overactive bladder can thus be reduced through use of M3-selective antagonists, such as darifenacin, and via alternatives to pharmacotherapy, such as behavioral modification, pelvic floor strengthening, and bladder-retraining exercises.
The objective of this study was to assess the similarities and differences between selected bioindicator groups within tallgrass prairie and adjacent aspen forest. Based on pitfall trapping from 1998 to 2000, species richness and abundance of ground beetles and spiders were examined across a tallgrass prairie – aspen forest ecotone located near Winnipeg, Manitoba. The abundance of spiders and ground beetles was higher in the forested portion of the transect than in the prairie section. There were 639 specimens of ground beetles collected, representing 53 species; 19 species were found only on the prairie, 19 species were found only in the forest, and 15 species were found in both habitats, although the abundance of most species was too low to confidently assign them to either habitat type. Excluding single records in any sampling year yielded 9 prairie species, 5 forest species, and 10 species found in both aspen forest and tallgrass prairie. The five most abundant species of ground beetles were Agonum placidum (Say), Pterostichus caudicalis (Say), P. femoralis (Kirby), P. melanarius (Illiger), and Synuchus impunctatus (Say). There were 4499 specimens of spiders collected, representing 92 species; 25 species were found only in the prairie, 15 species were unique to the aspen forest, and 52 species were found in both habitats. Excluding single records in any sampling year yielded 26 prairie species, 15 forest species, and 22 species found in both habitats. The five most abundant species of spiders were Pardosa moesta Banks, P. distincta (Blackwall), Agroeca ornata Banks, Centromerus sylvaticus (Blackwall), and Alopecosa aculeata (Clerck). Our study concurs with other studies in demonstrating that there are distinct assemblages of both groups of predators in each of the two habitat types.
UK policy promotes third sector organisations as providers of NHS funded health and social care. We examine the evidence for this policy through a systematic literature review. Our results highlight several problems of studies comparing non-profits with other provider forms, questioning their usefulness for drawing lessons outside the place of study. Most studies deem contextual factors and the regulatory framework in which providers operate as much more important than ownership form. We conclude that the literature does not support the policy of a larger role for the third sector in healthcare, let alone a switch to a market-based system.
Grey matter and other structural brain abnormalities are consistently
reported in first-onset schizophrenia, but less is known about the extent
of neuroanatomical changes in first-onset affective psychosis
Aims
To determine which brain abnormalities are specific to (a) schizophrenia
and (b) affective psychosis
Method
We obtained dual-echo (proton density/T2-weighted) magnetic resonance
images and carried out voxel-based analysis on the images of 73 patients
with first-episode psychosis (schizophrenia n=44,
affective psychosis n=29) and 58 healthy controls
Results
Both patients with schizophrenia and patients with affective psychosis
had enlarged lateral and third ventricle volumes. Regional cortical grey
matter reductions (including bilateral anterior cingulate gyrus, left
insula and left fusiform gyrus) were evident in affective psychosis but
not in schizophrenia, although patients with schizophrenia displayed
decreased hippocampal grey matter and increased striatal grey matter at a
more liberal statistical threshold
Conclusions
Both schizophrenia and affective psychosis are associated with volumetric
abnormalities at the onset of frank psychosis, with some of these evident
in common brain areas
We isolated over 650 yeasts over a three year period from the gut of a variety of beetles and characterized them on the basis of LSU rDNA sequences and morphological and metabolic traits. Of these, at least 200 were undescribed taxa, a number equivalent to almost 30% of all currently recognized yeast species. A Bayesian analysis of species discovery rates predicts further sampling of previously sampled habitats could easily produce another 100 species. The sampled habitat is, thereby, estimated to contain well over half as many more species as are currently known worldwide. The beetle gut yeasts occur in 45 independent lineages scattered across the yeast phylogenetic tree, often in clusters. The distribution suggests that the some of the yeasts diversified by a process of horizontal transmission in the habitats and subsequent specialization in association with insect hosts. Evidence of specialization comes from consistent associations over time and broad geographical ranges of certain yeast and beetle species. The discovery of high yeast diversity in a previously unexplored habitat is a first step toward investigating the basis of the interactions and their impact in relation to ecology and evolution.
Six hundred and seventeen isolates of Staphylococcus aureus from sub-clinical mastitis cases in 63 dairy herds in Northern Ireland were typed using a set of 25 phages. Ninety-four per cent of the isolates were typable, with nine phages, predominantly from groups I and III, being responsible for almost all of the lysis. Although 68 phage patterns were found, six of them typed 47·2 % of the isolates. One strain accounted for 14·7% of the isolates, but the largest number of strains (44) was restricted to individual farms. The epidemiological significance of these findings for on-farm mastitis control is discussed.