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The current study explored the experiences and aspirations of a cohort of Aboriginal and Torres Strait Islander adults with neurocognitive disability residing in a homeless shelter in regional Queensland, Australia. Neurocognitive disability (NCD) refers to any acquired disorder or injury to the brain where the primary clinical deficit is in cognitive function.
The data reported on in this paper emerged from a broader study that aimed to understand the extent and nature of neurocognitive disability amongst homeless Aboriginal and Torres Strait Islander people. The broader study found high levels of NCD which impacted on people’s ability to participate in society. As part of the study, qualitative information was sought regarding participant life experiences. A culturally safe and acceptable structure of “past, present and future” was applied to open-ended questions.
Thematic analysis of the data identified four broad themes of i) normalisation of illness and disability; ii) trauma and loss; iii) socioeconomic disadvantage; and iv) hope and disempowerment. This paper reports on these themes and experiences, which occurred across the life span, intersected with NCD, and contributed to what we have termed ‘complex disablement’ amongst this cohort.
While causal links between life experience, disability and disablement are not always clear, our findings suggest that attempts to address homelessness must engage with this complexity. The application of holistic, intersectoral supports, which encompass culturally informed, community driven approaches are needed. Understanding the impacts of individual and intergenerational trauma is crucial to safe and effective service provision for this cohort.
Major depressive disorder (MDD) is a prevalent and heterogeneous disorder. Although there are many treatment options for MDD, patients with treatment-resistant depression (TRD) remain prevalent, wherein delayed time to response results in inferior chances of achieving remission. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis of depression and focus instead on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. The literature suggests that the foregoing systems are implicated in the pathophysiology of MDD and preclinical trials have informed the development of pharmaceuticals using these systems as therapeutic targets. Pharmaceuticals that target the glutamatergic system include ketamine, esketamine, and rapastinel; brexanolone and SAGE-217 target the GABAergic system; minocycline targets the inflammatory system; and the combinatory agent buprenorphine + samidorphan targets the opioidergic system. The aforementioned agents have shown efficacy in treating MDD in clinical trials. Of particular clinical relevance are those agents targeting the glutamatergic and GABAergic systems as they exhibit rapid response relative to conventional antidepressants. Rapid response pharmaceuticals have the potential to transform the treatment of MDD, demonstrating reduction in depressive symptoms within 24 hours, as opposed to weeks noted with conventional antidepressants. Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Environmental rights, also known as the human rights or constitutional rights that are used for the protection of the environment, have proliferated over the last forty-five years. However, the precise levels of protection that they represent has since been a major question associated with this phenomenon. Environmental Rights: The Development of Standards systematically investigates this question by analyzing the emerging standards of environmental protection that are associated with such rights and the way that those associations are becoming formalized. It covers all of the relevant human rights treaties to illustrate how environmental rights standards are emerging in this dynamic area. Bringing together an elite group of scholars, this book discusses significant new insights into the way that environmental rights are developing, the standards of protection that they confer, and the way that standards in the field of environmental rights can potentially be further developed in the future.
Speleothem organic matter can be a powerful tracer for past environmental conditions and karst processes. Carbon isotope measurements (δ13C and 14C) in particular can provide crucial information on the provenance and age of speleothem organic matter, but are challenging due to low concentrations of organic matter in stalagmites. Here, we present a method development study on extraction and isotopic characterization of speleothem organic matter using a rapid procedure with low laboratory contamination risk. An extensive blank assessment allowed us to quantify possible sources of contamination through the entire method. Although blank contamination is consistently low (1.7 ± 0.34 – 4.3 ± 0.86 μg C for the entire procedure), incomplete sample decarbonation poses a still unresolved problem of the method, but can be detected when considering both δ13C and 14C values. We test the method on five stalagmites, showing reproducible results on samples as small as 7 μg C for δ13C and 20 μg C for 14C. Furthermore, we find consistently lower non-purgeable organic carbon (NPOC) 14C values compared to the carbonate 14C over the bomb spike interval in two stalagmites from Yok Balum Cave, Belize, suggesting overprint of a pre-aged or even fossil source of carbon on the organic fraction incorporated by these stalagmites.
We aim to evaluate the effect of caloric restriction (CR) in cognition by comparing performance in neuropsychological tests for working memory between a group of non-obese healthy subjects doing CR for 2 years with another consuming ad libitum diet (AL).
This study was part of a larger multicenter trial called CALERIE that consisted of a randomized clinical trial with parallel-group comparing 2 years of 25% CR and AL in 220 volunteers with a BMI between 22 and 28 kg/m2, across 3 sites. The cognitive tests used were the Cambridge Neuropsychological Tests Automated Battery (CANTAB) for Spatial Working Memory (SWM) including the total number of errors (SWMTE) and strategy (SWMS). Included as possible moderators were sleep quality, mood states, perceived stress, and energy expenditure. Analyses were performed at baseline and months 12 and 24.
After adjustments, there was a significantly greater improvement in working memory assessed by the SWM for CR individuals, compared to AL. At month 24, it was related mostly to lower protein intake, compared to other macronutrients. Changes in SWM were moderated by changes in sleep quality, physical activity, and energy expenditure.
On the long term, CR in healthy individuals seems to have a slightly positive effect on working memory. The study of brain CR targets opens new possibilities to prevent and treat cognitive deficits.
Quantitative analysis of major elements (Na, Mg, Al, Si, K, Ca, Ti, and Fe) in rocks by classic wet-chemical procedures, in addition to being a costly and laborious process, has been shown to be subject to significant errors. Mineralogists and petrologists, increasingly concerned with determining small elemental differences in rock bodies, have turned to more rapid and precise methods in the field of spectral analysis. The development of X-ray spectrographic techniques in the light-element range has therefore been of particular interest. This paper summarizes the results of a test of the precision and sources of error in the X-ray method as applied to major elements in granitic rocks.
The test, using commerically available equipment and the fusion technique of specimen preparation, was designed for a five-way, completely nested variance analysis. Sources of variance are (1) different lengths of fusion time, (2) replications of a single fusion time, (3) replications of briquetting the fused specimens, (4) replications of individual runs in the spectrograph, and (5) replications of individual spectrograph readings of the Kα line intensity. A total of 64 readings per element were obtained and the significance of each factor tested for each element. Greatest sources of error are shown to be in factors 2 and 4. The total variance for each element is expressed as per cent relative deviation of counts per second. Calibration curves of natural and synthetic granitic rocks, fused with dilutions ranging from 13 to 36% rock in borax, provide conversions from relative deviation in counts per second to relative deviation in weight per cent. These values indicate that the precision of the X-ray method is directly comparable with wet chemistry for Si, probably better for Al, and distinctly superior for K, Ca, Ti, and Fe. Of the major rock-forming elements only Na and Mg are presently beyond the scope of the fusion method.