Background: Adolescent drug use increases the risk of mental, physical and social problems later in life and so it is important to understand its complex etiology that likely includes socioeconomic ...status (SES). We undertook the present analysis using data from a population-based retrospective cohort study to examine the influence of family and community SES in relation to adolescent drug use. We hypothesized that lower levels of community and parental SES would increase the risk of use and that there would be stronger associations for the more proximate family-level factors. Methods: We used self-administered questionnaires (N=1,402) to obtain information on use of marijuana, inhalants, heroin, cocaine/crack, psychedelics/hallucinogens, Ritalin without a prescription, and club drugs during adolescence. Family SES was gathered from birth certificate data on maternal educational level and paternal occupation. Community SES characteristics at birth, age 10 and age 18 were obtained from the US Census Bureau. Results: An increased risk of adolescent drug use was associated with lower maternal education, non-white collar occupations among fathers, and lower community median income, and poverty and unemployment levels at age 18. The strongest associations were seen for the use of multiple drugs (Risk Ratio (RR): 1.7, 95% CI: 1.4-2.2), inhalants (RR: 2.5, 95% CI: 1.5-2.2), crack/cocaine (RR: 2.8, 95% CI: 1.7-4.5), psychedelics/hallucinogens (RR: 1.8, 95% CI: 1.4-2.4), and club/designer drugs (RR: 1.8, 95% CI: 1.2-2.7) among adolescents whose mothers had only a high school education. Conclusions: These results suggest that use of certain drugs during adolescence is associated with both family and community SES measures. However, maternal education appears to have the greatest influence on use, suggesting that a multi-level approach that engages mothers is needed to prevent adolescent drug use.
Abstract
Certain physical and mental health issues are particularly prevalent in farming occupations, yet frequently, farmers, particularly males, are resistant to seeking help from primary care ...practitioners. A qualitative approach examined the perspective of stakeholders at livestock auction marts to identify the determinants for, or barriers to, seeking help, perceptions regarding basing primary care services on-site at livestock auction marts, and the role of a site-based approach, i.e. placing primary healthcare services within a traditional farmers’ meeting place, in facilitating changes in help-seeking beliefs and behaviors. Findings support previous studies regarding barriers to seeking help, but demonstrate that by deconstructing these barriers through specifically designed workplace/site-oriented support services, more positive behaviors are facilitated. The study highlights how collaboration between livestock auction marts and primary healthcare services allows access to a hard-to-reach demographic in terms of healthcare, and illustrates how such socially integrative opportunities can contribute to the improvement of the mental and physical health and wellbeing of the agricultural community.
Accurate predictions of T-cell epitopes would be useful for designing vaccines, immunotherapies for cancer and autoimmune diseases, and improved protein therapies. The humoral immune response ...involves uptake of antigens by antigen presenting cells (APCs), APC processing and presentation of peptides on MHC class II (pMHCII), and T-cell receptor (TCR) recognition of pMHCII complexes. Most in silico methods predict only peptide-MHCII binding, resulting in significant over-prediction of CD4 T-cell epitopes. We present a method, ITCell, for prediction of T-cell epitopes within an input protein antigen sequence for given MHCII and TCR sequences. The method integrates information about three stages of the immune response pathway: antigen cleavage, MHCII presentation, and TCR recognition. First, antigen cleavage sites are predicted based on the cleavage profiles of cathepsins S, B, and H. Second, for each 12-mer peptide in the antigen sequence we predict whether it will bind to a given MHCII, based on the scores of modeled peptide-MHCII complexes. Third, we predict whether or not any of the top scoring peptide-MHCII complexes can bind to a given TCR, based on the scores of modeled ternary peptide-MHCII-TCR complexes and the distribution of predicted cleavage sites. Our benchmarks consist of epitope predictions generated by this algorithm, checked against 20 peptide-MHCII-TCR crystal structures, as well as epitope predictions for four peptide-MHCII-TCR complexes with known epitopes and TCR sequences but without crystal structures. ITCell successfully identified the correct epitopes as one of the 20 top scoring peptides for 22 of 24 benchmark cases. To validate the method using a clinically relevant application, we utilized five factor VIII-specific TCR sequences from hemophilia A subjects who developed an immune response to factor VIII replacement therapy. The known HLA-DR1-restricted factor VIII epitope was among the six top-scoring factor VIII peptides predicted by ITCall to bind HLA-DR1 and all five TCRs. Our integrative approach is more accurate than current single-stage epitope prediction algorithms applied to the same benchmarks. It is freely available as a web server (http://salilab.org/itcell).
ATP-binding cassette (ABC) transporters translocate substrates across cell membranes, using energy harnessed from ATP binding and hydrolysis at their nucleotide-binding domains. ABC exporters are ...present both in prokaryotes and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, as well as in many human diseases. TmrAB is a heterodimeric ABC exporter from the thermophilic Gram-negative eubacterium Thermus thermophilus; it is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif. Here we report a subnanometre-resolution structure of detergent-solubilized TmrAB in a nucleotide-free, inward-facing conformation by single-particle electron cryomicroscopy. The reconstructions clearly resolve characteristic features of ABC transporters, including helices in the transmembrane domain and nucleotide-binding domains. A cavity in the transmembrane domain is accessible laterally from the cytoplasmic side of the membrane as well as from the cytoplasm, indicating that the transporter lies in an inward-facing open conformation. The two nucleotide-binding domains remain in contact via their carboxy-terminal helices. Furthermore, comparison between our structure and the crystal structures of other ABC transporters suggests a possible trajectory of conformational changes that involves a sliding and rotating motion between the two nucleotide-binding domains during the transition from the inward-facing to outward-facing conformations.
•The usability of digital family history tools has important implications for the quality of the data collected.•Use of a virtual counselor to collect family histories can overcome literacy-related ...barriers to using digital tools.•Additional research is needed to understand factors (e.g., language version, stigma) that may influence accuracy outcomes.
This study is a randomized controlled trial comparing the efficacy of a virtual counselor (VICKY) to the My Family Health Portrait (MFHP) tool for collecting family health history (FHx).
A total of 279 participants were recruited from a large safety-net hospital and block randomized by health literacy to use one of the digital FHx tools, followed by a genetic counselor interview. A final sample of 273 participants were included for analyses of primary study aims pertaining to tool concordance, which assessed agreement between tool and genetic counselor.
Tool completion differed significantly between tools (VICKY = 97%, MFHP = 51%; p < .0001). Concordance between tool and genetic counselor was significantly greater for participants randomized to VICKY compared to MFHP for ascertaining first- and second-degree relatives (ps<.0001), and most health conditions examined. There was significant interaction by health literacy, with greater differences in concordance observed between tools among those with limited literacy.
A virtual counselor overcomes many of the literacy-related barriers to using traditional digital tools and highlights an approach that may be important to consider when collecting health histories from vulnerable populations.
The usability of digital health history tools will have important implications for the quality of the data collected and its downstream clinical utility.
This paper provides a critical commentary on the conception of food miles followed by an empirical application of food miles to two contrasting food distribution systems based on carbon emissions ...accounting within these systems. The comparison is between the carbon emissions resultant from operating a large-scale vegetable box system and those from a supply system where the customer travels to a local farm shop. The study is based on fuel and energy use data collected from one of the UK’s largest suppliers of organic produce. The findings suggest that if a customer drives a round-trip distance of more than 6.7
km in order to purchase their organic vegetables, their carbon emissions are likely to be greater than the emissions from the system of cold storage, packing, transport to a regional hub and final transport to customer’s doorstep used by large-scale vegetable box suppliers. Consequently some of the ideas behind localism in the food sector may need to be revisited.
Polysubstance use is common among people with HIV infection (PWH) and with substance use disorder (SUD), but its effects are understudied. We aimed to identify polysubstance use patterns over time ...and assess their associations with HIV disease severity.
In 233 PWH with current or past SUD, latent class analysis identified polysubstance use patterns based on the Alcohol Use Disorders Identification Test-Consumption and past-30-day use of cannabis, cocaine, opioids, and tranquilizers at baseline. We categorized changes in use patterns and tested associations between those changes and CD4 count and HIV viral suppression at 12 months in linear and logistic regressions.
Three patterns were identified at baseline: 18% did not use any substance (NONE--a priori defined); 63% used mostly cannabis and alcohol (CA); and 19% used opioids along with other drugs, including cocaine, tranquilizers, cannabis, and alcohol (MULTI). At 12 months, 40% moved from a high to a lower substance use class (MULTI to CA, either to NONE) or remained as NONE, 43% were in CA both times and 17% increased (NONE to CA, either to MULTI) or remained as MULTI. The adjusted mean CD4 count (for baseline covariates and baseline CD4 count) was significantly lower among participants increasing or remaining in MULTI (523, 95% CI 448, 598, cells/mm3) compared with those who decreased/abstained throughout (607, 95% CI 552, 663,
= .02). No significant difference was observed for HIV viral suppression.
We identified distinct polysubstance use patterns among PWH with SUD: cannabis/alcohol and opioids with alcohol and other drugs. Changes over time toward fewer substances/no use were associated with lower HIV disease severity based on CD4 count but not based on HIV viral suppression.
Atrial fibrillation (AF) during sepsis is associated with increased morbidity and mortality, but practice patterns and outcomes associated with rate- and rhythm-targeted treatments for AF during ...sepsis are unclear.
This was a retrospective cohort study using enhanced billing data from approximately 20% of United States hospitals. We identified factors associated with IV AF treatments (?-blockers BBs, calcium channel blockers CCBs, digoxin, or amiodarone) during sepsis. We used propensity score matching and instrumental variable approaches to compare mortality between AF treatments.
Among 39,693 patients with AF during sepsis, mean age was 77 ± 11 years, 49% were women, and 76% were white. CCBs were the most commonly selected initial AF treatment during sepsis (14,202 patients 36%), followed by BBs (11,290 28%), digoxin (7,937 20%), and amiodarone (6,264 16%). Initial AF treatment selection differed according to geographic location, hospital teaching status, and physician specialty. In propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (n = 18,720; relative risk RR, 0.92; 95% CI, 0.86-0.97), digoxin (n = 13,994; RR, 0.79; 95% CI, 0.75-0.85), and amiodarone (n = 5,378; RR, 0.64; 95% CI, 0.61-0.69). Instrumental variable analysis showed similar results (adjusted RR fifth quintile vs first quintile of hospital BB use rate, 0.67; 95% CI, 0.58-0.79). Results were similar among subgroups with new-onset or preexisting AF, heart failure, vasopressor-dependent shock, or hypertension.
Although CCBs were the most frequently used IV medications for AF during sepsis, BBs were associated with superior clinical outcomes in all subgroups analyzed. Our findings provide rationale for clinical trials comparing the effectiveness of AF rate- and rhythm-targeted treatments during sepsis.
Process model comprehension is essential in order to understand the five Ws (i.e., who, what, where, when, and why) pertaining to the processes of organizations. However, research in this context ...showed that a proper comprehension of process models often poses a challenge in practice. For this reason, a vast body of research exists studying the factors having an influence on process model comprehension. In order to point research towards a neuro-centric perspective in this context, the paper at hand evaluates the appropriateness of measuring the electrodermal activity (EDA) during the comprehension of process models. Therefore, a preliminary test run and a feasibility study were conducted relying on an EDA and physical activity sensor to record the EDA during process model comprehension. The insights obtained from the feasibility study demonstrated that process model comprehension leads to an increased activity in the EDA. Furthermore, EDA-related results indicated significantly that participants were confronted with a higher cognitive load during the comprehension of complex process models. In addition, the experiences and limitations we learned in measuring the EDA during the comprehension of process models are discussed in this paper. In conclusion, the feasibility study demonstrated that the measurement of the EDA could be an appropriate method to obtain new insights into process model comprehension.
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