Abstract
Continued urbanization is likely to reduce human‐nature experience, transforming human‐dwelt spaces into increasingly artificial environments and removing humans from interaction with ...non‐human living things and their ecosystems. In urban spaces, outdoor experiential educational activities can help students increase their familiarity with the outdoors and get their hands dirty. This case study reports on an environmental field day for middle school students from an urban Kentucky middle school. Students rotated through three activities (picking insects out of leaf packs, testing water quality, and planting trees), then completed a brief survey designed and administered by their faculty. Students rated the tree planting activity more highly than the other two activities (p < 0.0001), suggesting that this activity was more accessible, interesting, and engaging to a broader range of students. However, student qualitative responses to the water quality and leaf pack activities demonstrated an ability to make connections between those activities and the broader world, such as the importance of their stream‐water quality for the Gulf of Mexico, or the implications of finding pollution‐tolerant insects for understanding stream health. Overall, we recommend planning field days with multiple activities that offer various entry points for students with a range of prior experience of nature. We also emphasize the potential for these sorts of activities to help students develop a sense of awe or wonder in nature—seeing and handling things they never considered before but now experience as profound and interesting. These observations are consistent with the literature demonstrating the need for human‐nature experience (especially in urban areas) to support developing a sense of affectivity for the environment and interest in taking environmentally beneficial actions, as well as the role of place‐based experiential education in helping students bridge that gap.
Background
Failure to engage and enroll participants from diverse backgrounds is among the biggest challenges slowing generalizable research efforts to treat and prevent Alzheimer’s disease and ...related dementias. Pivoting to a ‘service first’ approach for engaging all communities may increase research participation by improving the value proposition.
Method
The University of Kansas Alzheimer’s Disease Research Center is taking a programmatic approach to accelerate participation in research and emphasize reaching under‐represented groups (URG: predominantly African Americans, Latinos, and rural residents in the region). The program is a community and service‐oriented strategy for engaging a diverse population through 1) a PCP Network to improve dementia care through a financially‐sustainable Chronic Care Management program, 2) a Patient Network (MyAlliance Research Registry, derived from patients in the PCP network), and 3) a Community Network of diverse stakeholders delivering robust outreach and education. We hypothesized that the sustaining value of this approach would increase enrollee diversity.
Result
To date, MyAlliance has provided social work support to 71 practices and 1169 unique individuals with dementia and their families. Over 2100 individuals receive our weekly communications, and 4 community organizations have trained more than 80 staff members in dementia‐capable engagement with the community. The result has been that since implementation of MyAlliance, 29% of enrollments (255 of 868) identify as URG, double the URG enrollment prior to implementation (14.5%, 658 of 4551).
Conclusion
Service‐based approaches that emphasize community needs and community access points may increase enrollment and enrich the diversity of the participants.
Aims
The coronavirus disease 2019 (COVID‐19) pandemic has created significant challenges to healthcare globally, necessitating rapid restructuring of service provision. This questionnaire survey was ...conducted amongst adult heart failure (HF) patients in the United Kingdom (UK), to understand the impact of COVID‐19 upon HF services.
Methods and results
The survey was conducted by the Pumping Marvellous Foundation, a UK HF patient charity. ‘Survey Monkey’ was used to disseminate the questionnaire in the Pumping Marvellous Foundation 's online patient group and in 10 UK hospitals (outpatient hospital and community HF clinics). There were 1050 responses collected (693/1050—66% women); 55% (579/1050) were aged over 60 years. Anxiety level was significantly higher regarding COVID‐19 (mean 7 ± 2.5 on anxiety scale of 0 to 10) compared with anxiety regarding HF (6.1 ± 2.4; P < 0.001). Anxiety was higher amongst patients aged ≤60 years about HF (6.3 ± 2.2 vs. 5.9 ± 2.5 in those aged >60 years; P = 0.005) and COVID‐19 (7.3 ± 2.3 vs. 6.7 ± 2.6 those aged >60 years; P < 0.001). Sixty‐five per cent of respondents (686/1050) reported disruption to HF appointments (cancellation or postponement) during the lockdown period. Thirty‐seven per cent reported disruption to medication prescription services, and Thirty‐four per cent reported inability to access their HF teams promptly. Thirty‐two per cent expressed reluctance to attend hospital (25% stated they would only attend hospital if there was no alternative, and 7% stated that they would not attend hospital at all).
Conclusions
The COVID‐19 pandemic has caused significant anxiety amongst HF patients regarding COVID‐19 and HF. Cancellation or postponement of scheduled clinic appointments, investigations, procedures, prescription, and monitoring services were implicated as sources of anxiety.
Early mobilisation (> 24 h post-stroke) is recommended for people with stroke. However, there is a paucity of evidence about how to implement early mobilisation for people who have had a severe ...stroke. Prolonged standing and task-specific training (sit-to-stand repetitions) have separately been evaluated in the literature; however, these functionally linked tasks have not been evaluated in combination for people with severe sub-acute stroke.
The objective was to determine the feasibility of conducting a randomised controlled trial (RCT) of a functional standing frame programme compared with usual physiotherapy for people with severe sub-acute stroke. An assessor-blinded feasibility RCT with nested qualitative component (interviews and focus group) and process evaluation was adopted. Participants were aged ≥ 18 years with new diagnosis of severe sub-acute stroke (modified Rankin Scale (mRS) 4/5) from four Stroke Rehabilitation Units across South West England. Participants were randomised to receive either: (1) functional standing frame programme (30 min. standing plus sit-to-stand repetitions) plus 15 min of usual physiotherapy daily (intervention); (2) usual physiotherapy (45 min) daily (control). Both programmes were protocolised to be undertaken a minimum of five sessions per week for 3 weeks. Feasibility indicators included process, resource, management, and safety. Adherence, fidelity, and acceptability of the trial and intervention were evaluated using data recorded by therapists, observation of intervention and control sessions, interviews and one focus group. Patient measures of motor impairment, activities/participation, and quality of life were carried out by blinded assessors at baseline, 3, 15, 29, and 55 weeks post-randomisation.
Forty-five participants (51-96 years; 42% male, mRS 4 = 80% 5 = 20%) were randomised (n = 22 to intervention). Twenty-seven (60%) participants were followed-up at all time points. Twelve participants (27%) died during the trial; no deaths were related to the trial. Adherence to the minimum number of sessions was low: none of the participants completed all 21 sessions, and only 8 participants (18%) across both groups completed ≥ 15 sessions, over the 3 weeks; 39% intervention; 51% control sessions were completed; mean session duration 39 min (SD 19) control, 37 min intervention (SD 11). Intervention group: mean standing time 13 min (SD 9); mean sit-to-stand repetitions/session 5 (SD 4). Interviews were conducted with 10 participants, four relatives and six physiotherapists. Five physiotherapists attended a focus group.
The majority of progression criteria for this feasibility trial were met. However, adherence to the interventions was unacceptably low. This aspect of the trial design needs to be addressed prior to moving to a definitive RCT of this standing frame intervention in people with severe sub-acute stroke. Solutions have been identified to address these concerns.
International Standard Randomised Controlled Trial Number ISRCTN15412695 . Registration 19 December 2016.
AbstractFlea-borne (murine) typhus is a global rickettsiosis caused by
. Although flea-borne typhus is no longer nationally notifiable, cases are reported for surveillance purposes in a few U.S. ...states. The infection is typically self-limiting, but may be severe or life-threatening in some patients. We performed a retrospective review of confirmed or probable cases of fatal flea-borne typhus reported to the Texas Department of State Health Services during 1985-2015. When available, medical charts were also examined. Eleven cases of fatal flea-borne typhus were identified. The median patient age was 62 years (range, 36-84 years) and 8 (73%) were male. Patients presented most commonly with fever (100%), nausea and vomiting (55%), and rash (55%). Respiratory (55%) and neurologic (45%) manifestations were also identified frequently. Laboratory abnormalities included thrombocytopenia (82%) and elevated hepatic transaminases (63%). Flea or animal contact before illness onset was frequently reported (55%). The median time from hospitalization to administration of a tetracycline-class drug was 4 days (range, 0-5 days). The median time from symptom onset to death was 14 days (range, 1-34 days). Flea-borne typhus can be a life-threatening disease if not treated in a timely manner with appropriate tetracycline-class antibiotics. Flea-borne typhus should be considered in febrile patients with animal or flea exposure and respiratory or neurologic symptoms of unknown etiology.
OBJECTIVE:To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1).
METHODS:A ...multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8–15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population.
RESULTS:Lovastatin had no significant effect on primary outcomes after 16 weeks of treatmentvisuospatial learning (Cohen d = −0.15, 95% confidence interval −0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval −0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo.
CONCLUSIONS:Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population.
CLINICALTRIALS.GOV IDENTIFIER:This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493).
CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.
The antifolate methotrexate is one of the most successful drugs in cancer chemotherapy. Although its efficacy is widely attributed to a decrease in nucleotide biosynthesis (1), methotrexate is known ...to increase homocysteine (2), a compound associated with an elevated risk of heart disease, Alzheimer's disease (3), and neural tube defects (4). A potential mechanism for the detrimental effects of homocysteine is cellular hypomethylation from an increase in S-adenosylhomocysteine (5), an inhibitor of methyltransferases including isoprenylcysteine carboxyl methyltransferase (Icmt). Among the substrates of Icmt is the monomeric G protein Ras, a critical component of many signaling pathways that regulate cell growth and differentiation. Because carboxyl methylation of Ras is important for proper plasma membrane localization and function (6), we investigated the role of Icmt in the antiproliferative effect of methotrexate. After methotrexate treatment of DKOB8 cells, Ras methylation is decreased by almost 90%. This hypomethylation is accompanied by a mislocalization of Ras to the cytosol and a 4-fold decrease in the activation of p44 mitogen-activated protein kinase and Akt. Additionally, cells lacking Icmt are highly resistant to methotrexate. Whereas cells expressing wild-type levels of Icmt are inhibited by methotrexate, stable expression of myristoylated H-Ras, which does not require carboxyl methylation for membrane attachment (7), confers resistance to methotrexate. These results suggest that inhibition of Icmt is a critical component of the antiproliferative effect of methotrexate, expanding our understanding of this widely used drug and identifying Icmt as a target for drug discovery.
Thirty percent of all inherited retinal disease (IRD) is accounted for by conditions with extra-ocular features. This study aimed to establish the genetic diagnostic pick-up rate for IRD patients ...with one or more extra-ocular features undergoing panel-based screening in a clinical setting. One hundred and six participants, tested on a gene panel which contained both isolated and syndromic IRD genes, were retrospectively ascertained from the Manchester Genomic Diagnostics Laboratory database spanning 6 years (2012-2017). Phenotypic features were extracted from the clinical notes and classified according to Human Phenotype Ontology; all identified genetic variants were interpreted in accordance to the American College of Medical Genetics and Genomics guidelines. Overall, 49% (n = 52) of patients received a probable genetic diagnosis. A further 6% (n = 6) had a single disease-associated variant in an autosomal recessive disease-relevant gene. Fifty-two percent (n = 55) of patients had a clinical diagnosis at the time of testing. Of these, 71% (n = 39) received a probable genetic diagnosis. By contrast, for those without a provisional clinical diagnosis (n = 51), only 25% (n = 13) received a probable genetic diagnosis. The clinical diagnosis of Usher (n = 33) and Bardet-Biedl syndrome (n = 10) was confirmed in 67% (n = 22) and 80% (n = 8), respectively. The testing diagnostic rate in patients with clinically diagnosed multisystemic IRD conditions was significantly higher than those without one (71% versus 25%; p value < 0.001). The lower pick-up rate in patients without a clinical diagnosis suggests that panel-based approaches are unlikely to be the most effective means of achieving a molecular diagnosis for this group. Here, we suggest that genome-wide approaches (whole exome or genome) are more appropriate.