Allelic segregation and independent assortment in <i>T. brucei</i> crosses: proof that the genetic system is Mendelian and involves meiosis

The genetic system on Trypanosoma brucei has been analysed by generating large numbers of independent progeny clones from two crosses, one between two cloned isolates of Trypanosoma brucei brucei and one between cloned isolates of T. b. brucei and Trypanosoma brucei gambiense, Type 2. Micro and minisatellite markers (located on each of the 11 megabase housekeeping chromosomes) were identified, that are heterozygous in one or more of the parental strains and the segregation of alleles at each locus was then determined in each of the progeny clones. The results unequivocally show that alleles segregate in the predicted ratios and that alleles at loci on different chromosomes segregate independently. These data provide statistically robust proof that the genetic system is Mendelian and that meiosis occurs. Segregation distortion is observed with the minisatellite locus located on chromosome I of T. b. gambiense Type 2 and neighboring markers, but analysis of markers further along this chromosome did not show distortion leading to the conclusion that this is due to selection acting on one part of this chromosome. The results obtained are discussed in relation to previously proposed models of mating and support the occurrence of meiosis to form haploid gametes that then fuse to form the diploid progeny in a single round of mating

Reliability and Convergent Validity of the Klontz Money Script Inventory-Revised (KMSI-R)

Few contemporary, empirically-based instruments exist to assess attitudes and beliefs about money despite a large research base linking mental health outcomes to financial beliefs. An abbreviated form of the Klontz Money Script Inventory (KMSI), the Klontz Money Script Inventory-Revised (KMSI-R), has been developed to inform mental health practitioners and financial advisors about the money attitudes and beliefs of their clients using an empirically-based instrument. This study examined the technical adequacy of the KMSI-R among a sample of college students (n = 326). Results indicate high reliability for the KMSI-R as well as weak-to-moderate positive correlations when compared to the Money Attitude Scales

Internal Consistency and Convergent Validity of the Klontz Money Behavior Inventory (KMBI)

The Klontz Money Behavior Inventory (KMBI) is a standalone, multi-scale measure than can screen for the presence of eight distinct money disorders. Given the well-established relationship between mental health and financial behaviors, results from the KMBI can be used to inform both mental health care professionals and financial planners. The present study examined the internal consistency and convergent validity of the KMBI, through comparison with similar measures, among a sample of college students (n = 232). Results indicate that the KMBI demonstrates acceptable internal consistency reliability and some convergence for most subscales when compared to other analogous measures. These findings highlight a need for literature and assessments to identify and describe disordered money behaviors

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans

Genetic analysis of drug resistance in Trypanosoma brucei

Genetic mapping, positional cloning and reverse genetics provide an alternative to the biochemical and molecular approaches used to date, to determine the basis of arsenical resistance in Trypanosoma brucei. Genetic mapping of loci determining phenotypes of relevance to diseases has proved to be a powerful approach in a number of organisms including humans and Plasmodium falciparum, particularly when coupled with a full genome sequence. In this thesis, this approach has been established in T. brucei by determining the genetic basis of naturally occurring arsenical resistance and undertaking linkage analysis using our recently developed genetic map. I adapted a simple, verified screening assay for assessing drug sensitivity based on the use of AlamarBlue. Three stocks used as parents in genetic crosses differed in drug sensitivity; STIB 247-Sensitive, STIB 386-Resistant and TREU 927-Resistant. Genetic linkage analysis using 101 polymorphic markers Identified from the extensive sequence available from the genome project was then used to examine inheritance of the drug resistance phenotype in T. brucei. From this, the co-segregation (into F1 progeny) of markers and the resistance phenotype was determined using crosses, 247 x 386 and 247 x 927. Inheritance of resistance in both crosses was compatible with a simple single locus genetic model with one dominant allele determining resistance. Linkage analysis showed that the locus conferring resistance lay within an ~25 kilobase region on Chromosome II, which contains 6 open reading frames (ORFs). A reverse genetic approach was then used to disrupt alleles for each of the six ORFs in turn. An allele of one gene, Tb927.2.2380, was shown to determine resistance and this was confirmed by transfecting the resistance allele into a drug sensitive stock to generate an arsenical resistant line. This gene also determines cross-resistance to the major veterinary trypanocide, diminazene aceturate and has been named the arsenical and diamidine (ard) resistance gene

Classification of Health Risk Factors to Predict the Risk of Falling in Older Adults

Cognitive decline and frailty is apparent in older adults leading to an increased likelihood of the risk of falling. Currently health care professionals have to make professional decisions regarding such risks, and hence make difficult decisions regarding the future welfare of the ageing population. This study uses health data from The Irish Longitudinal Study on Ageing (TILDA), focusing on adults over the age of 50 years, in order to analyse health risk factors and predict the likelihood of falls. This prediction is based on the use of machine learning algorithms whereby health risk factors are used as inputs to predict the likelihood of falling. Initial results show that health risk factors such as long-term health issues contribute to the number of falls. The identification of such health risk factors has the potential to inform health and social care professionals, older people and their family members in order to mitigate daily living risks

Addressing racial and ethnic disparities in premature exits from permanent supportive housing among residents with substance use disorders.

BACKGROUND: Permanent supportive housing (PSH) is an evidence-based practice for reducing homelessness that subsidizes permanent, independent housing and provides case management-including linkages to health services. Substance use disorders (SUDs) are common contributing factors towards premature, unwanted (negative) PSH exits; little is known about racial/ethnic differences in negative PSH exits among residents with SUDs. Within the nations largest PSH program at the Department of Veterans Affairs (VA), we examined relationships among SUDs and negative PSH exits (for up to five years post-PSH move-in) across racial/ethnic subgroups. METHODS: We used VA administrative data to identify a cohort of homeless-experienced Veterans (HEVs) (n = 2,712) who were housed through VA Greater Los Angeles PSH program from 2016-2019. We analyzed negative PSH exits by HEVs with and without SUDs across racial/ethnic subgroups (i.e., African American/Black, Non-Hispanic White, Hispanic/Latino, and Other/Mixed [Asian, American Indian or Alaskan Native, and Native Hawaiian or Other Pacific Islander, and mixed race/ethnicity]) in controlled models and accounting for competing risk of death. RESULTS: In competing risk models, HEVs with at least one SUD had 1.3 times the hazard of negative PSH exits compared to those without SUDs (95% CI: 1.00, 1.61). When stratifying by race/ethnicity, Other/Mixed race residents with at least one SUD had 6.4 times the hazard of negative PSH exits compared to their peers without SUDs (95% CI: 1.61-25.50). Hispanic/Latino residents with at least one SUD had 1.9 times the hazard compared to those without SUDs; however, this association was not statistically significant (95% CI: 0.85-4.37). African American/Black residents with at least one SUD had 1.2 times the hazard compared to those without SUDs (95% CI: 0.85-1.64), indicating no evidence of an association with negative PSH exits. Non-Hispanic White residents with at least one SUD had 1.1 times the hazard compared to those without SUDs (95% CI: 0.75-1.66), similarly indicating no evidence to suggest an association with negative PSH exits. CONCLUSIONS: These findings suggest relationships between SUDs and negative PSH exits differ between racial/ethnic groups and suggest there may be value in culturally specific tailoring and implementation of SUD services for these subgroups

Examining Homeless-Experienced Adults Smoking Cessation Treatment Use Pre- and Post-Entry into Permanent Supportive Housing.

BACKGROUND: Homeless-experienced adults smoke at rates 5 times that of the general adult population, and often have limited access to cessation treatments while homeless. Permanent Supportive Housing (PSH) can be a catalyst for cessation treatment utilization, yet little is known about use of these treatments following PSH entry, or how to tailor and implement cessation care that meets homeless-experienced adults vulnerabilities. METHODS: Using Department of Veterans Affairs (VA) administrative data, we assessed smoking status (ie, current, former, non/never) among a cohort of homeless-experienced Veterans (HEVs) housed in Los Angeles-based PSH. We compared cessation treatment use rates (ie, nicotine replacement therapies, cessation medications, psychosocial counseling) pre- and post-housing using Chi-square tests. Predisposing (ie, demographics), enabling (eg, primary care, benefits), and need characteristics (ie, health, mental health, substance use diagnoses) were examined as correlates of cessation treatment utilization pre- and post-housing in univariable and multivariable logistic regression models. RESULTS: Across HEVs (N = 2933), 48.6% were identified as currently-smoking, 17.7% as formerly-smoking, and 14.0% as non/never smoking. Among currently- and formerly-smoking HEVs (n = 1944), rates of cessation treatment use post-housing were significantly lower, compared to pre-housing, across all treatment types. Health, mental health, and substance use was more prevalent among currently- and formerly-smoking HEVs compared to non/never-smoking HEVs, and most diagnoses were positively associated with utilization univariably. However, in multivariable models, cessation clinic referrals and primary care engagement were the only significant (P &lt; .001) predictors of pre-housing and post-housing cessation treatment utilization. CONCLUSION: Among HEVs, we found high smoking rates and low cessation treatment utilization pre- and post-PSH entry. Efforts to educate providers about this populations desire to quit smoking, support primary care engagement, and increase cessation clinic referrals may bolster their utilization. For homeless-experienced adults, optimizing cessation treatment accessibility by embedding cessation services within PSH and homeless service settings may reduce utilization impediments