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429 result(s) for "Garza, John"
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Impact of history of mental disorders on short-term mortality among hospitalized patients with sepsis: A population-based cohort study
Mental disorders are associated with markedly reduced life expectancy, in part due to an increased risk of death due to infection, likely reflecting sepsis-associated mortality. Patients with mental disorders are at an increased risk of sepsis, but data on the prognostic impact of mental disorders in sepsis are sparse, showing conflicting findings. We used statewide data to identify hospitalizations aged ≥18 years with sepsis in Texas during 2014-2017. Mental disorders, including mood, anxiety, psychosis, and personality disorders were identified using Clinical Classification Software codes. Multilevel, multivariable logistic regression with propensity adjustment (primary model), with propensity score matching, and multivariable logistic regression as alternative models, were used to estimate the association between mental disorders and short-term mortality (defined as in-hospital mortality or discharge to hospice). Additional models were fitted for sensitivity analyses and to estimate the prognostic associations of individual categories of mental disorders. Among 283,025 hospitalizations with sepsis, 56,904 (20.1%) had mental disorders. Hospitalizations with vs without mental disorders were younger (age 18-44 years 12.2% vs 10.6%), more commonly white (61.0% vs 49.8%), with lower burden of comorbidities (mean [SD] Deyo comorbidity index 2.53 [2.27] vs 2.73 [2.47]), and with lower need for organ support (mechanical ventilation 32.8% vs 36.0%); p<0.0001 for all comparisons. Crude short-term mortality among sepsis hospitalizations with and without mental disorders was 25.0% vs 32.8%, respectively. On adjusted analyses, mental disorders remained associated with lower odds of short-term mortality (adjusted odds ratio 0.792 [95% CI 0.772-0.812]). This finding was consistent on the alternative modeling approaches, sensitivity analyses, and examination of individual categories of mental disorders. Mental disorders were associated, unexpectedly, with markedly lower risk of short-term mortality in sepsis. Further studies to examine the mechanisms underlying these findings may inform future efforts to improve sepsis outcomes.
Rapid parallel evolution of standing variation in a single, complex, genomic region is associated with life history in steelhead/rainbow trout
Rapid adaptation to novel environments may drive changes in genomic regions through natural selection. Such changes may be population-specific or, alternatively, may involve parallel evolution of the same genomic region in multiple populations, if that region contains genes or co-adapted gene complexes affecting the selected trait(s). Both quantitative and population genetic approaches have identified associations between specific genomic regions and the anadromous (steelhead) and resident (rainbow trout) life-history strategies of Oncorhynchus mykiss. Here, we use genotype data from 95 single nucleotide polymorphisms and show that the distribution of variation in a large region of one chromosome, Omy5, is strongly associated with life-history differentiation in multiple above-barrier populations of rainbow trout and their anadromous steelhead ancestors. The associated loci are in strong linkage disequilibrium, suggesting the presence of a chromosomal inversion or other rearrangement limiting recombination. These results provide the first evidence of a common genomic basis for life-history variation in O. mykiss in a geographically diverse set of populations and extend our knowledge of the heritable basis of rapid adaptation of complex traits in novel habitats.
Nicotine dependence among critically ill COVID-19 patients: A population-based cohort study
Nicotine dependence is associated with lower life expectancy and patients who use nicotine are at an increased risk of diseases of the respiratory system. Data on the prognostic impact of nicotine dependence in COVID-19 is inconclusive. We used publicly available, statewide, and deidentified records to study hospitalizations of patients aged ≥ 18 years with a principal diagnosis of COVID-19 admitted to the intensive care units of acute care hospitals in Texas from Q2 2020 through Q4 2024. We measured the effect of nicotine dependence on mortality in the overlap population using weighted multivariable logistic regression and g-computation. We identified 142,045 hospitalizations admitted to intensive care units with a principal diagnosis of COVID-19 of which 10,452 (7.3%) were classified as currently nicotine dependent, 23,671 (16.7%) as formerly nicotine dependent, and 107,922 (76.0%) as never nicotine dependent. Currently and formerly nicotine dependent individuals had significantly higher burden of comorbidities compared to never nicotine dependent individuals; mean [standard deviation] Deyo comorbidity index 1.8 [1.9] and 1.8 [1.9] vs 1.4 [1.8] but lower rates of in-hospital mortality 10.7% and 13.8% vs 16.1%. On adjusted analysis, current nicotine dependence and former nicotine dependence remained associated with reduced in-hospital and short-term mortality. Additional investigations exploring the mechanisms leading to these findings are necessary.
Epidemiology and outcomes of invasive mechanical ventilation without ICU admission in acute care hospitals in Texas: A population-based cohort study
The high ICU bed capacity in the United States (US) allows ICU care of patients requiring invasive mechanical ventilation (IMV), absent public health crisis. The use of IMV without ICU admission (non-ICU) in acute care hospitals in the US and its impact on patients' outcomes were not examined. A retrospective cohort study was performed using statewide inpatient data in Texas to identify hospitalizations aged ≥18 years receiving IMV in acute care hospitals with ICU care capability during January 2014 through September 2015. Use of non-ICU IMV, patient characteristics, and hospital mortality were examined. Among 136,728 IMV hospitalizations, 4531 (3.3%) were non-ICU. As compared to ICU admissions, non-ICU IMV hospitalizations were younger (age 18–44 years: 24.9% vs. 17.2%), with lower burden of major comorbidities (no major comorbidity: 24.7% vs. 14.5%), and lower occurrence of non-respiratory organ failures (no non-respiratory organ failure: 32.7% vs. 19.8%). Risk-adjusted hospital mortality of non-ICU vs. ICU IMV hospitalizations was 48.7% (95% CI 48.1–49.4) and 29.9% (95% CI 29.8–30.0), respectively. Non-ICU IMV was provided in 1 in 30 IMV hospitalizations in acute care hospitals. Although non-ICU IMV hospitalizations were younger and healthier than those admitted to ICU, their hospital mortality was markedly higher. •Mechanical ventilation (MV) is provided outside the ICU in resource-limited countries.•In-ICU MV can be expected with ample ICU bed resources as in the United States.•MV without ICU admission was found in 1 in 30 hospitalizations in Texas.•Patients without ICU admission were younger and healthier than those admitted to ICU.•MV without ICU admission more the doubled the risk of hospital death.
Association of multiple sclerosis with mortality in sepsis: a population-level analysis
Background Multiple sclerosis (MS) is associated with increased risk of sepsis and higher sepsis-related mortality, compared to the general population. However, the evidence on the prognostic impact of MS in sepsis has been scarce. We aimed to evaluate the population-level association of MS with short-term mortality in sepsis. Methods We performed a retrospective population-based cohort study using a statewide data set to identify hospitalizations aged ≥ 18 years in Texas with sepsis, with and without MS during 2010–2017. Multilevel logistic models were fit to estimate the association of MS with short-term mortality among all sepsis hospitalizations, and for sensitivity analyses among hospitalizations with septic shock and those admitted to ICU. Results Among 283,025 sepsis hospitalizations, 1687 (0.6%) had MS. Compared to sepsis hospitalizations without MS, those with MS were younger (aged ≥ 65 years 35.0% v s 56.8%), less commonly racial/ethnic minority (36.2% vs 48.1%), and had lower mean Deyo comorbidity index (1.6 vs 2.7). The rates of septic shock and ICU admission were similar for sepsis hospitalizations with and without MS (58.7% vs 59.6% and 46.7% vs 46.0%, respectively). The unadjusted short-term mortality among sepsis hospitalizations with and without MS for the whole cohort, among those with septic shock, and among ICU admissions were 20.2% vs 31.3%, 25.6% vs 40.0%, and 24.0% vs 34.8%, respectively. On adjusted analyses, MS was associated with 17% lower odds of short-term mortality (adjusted odds ratio [aOR] 0.828 [95% CI 0.723–0.947]). Similar findings were observed on sensitivity analyses of patients with septic shock (aOR 0.764 [95% CI 0.651–0.896]), but MS was not associated with mortality among sepsis hospitalizations admitted to ICU (aOR 0.914 [95% CI 0.759–1.101]). Conclusions MS was associated with lower short-term mortality among septic patients, with findings consistent among the subset with septic shock. Among septic patients admitted to ICU, MS was not associated with mortality.
Genetic assignment of fisheries bycatch reveals disproportionate mortality among Alaska Northern Fulmar breeding colonies
Global fisheries kill millions of seabirds annually through bycatch, but little is known about population‐level impacts, particularly in species that form metapopulations. U.S. North Pacific groundfish fisheries catch thousands of Northern Fulmars (Fulmarus glacialis rodgersii) each year, making fulmars the most frequently caught seabird in federally managed U.S. fisheries. Here, we used genetic stock identification to assign 1,536 fulmars sampled as bycatch to one of four Alaska breeding colonies and quantified the similarity of bycatch locations at sea among colonies. We found disproportionately high bycatch from the Pribilof Islands (6% of metapopulation, 23% of bycatch), and disproportionately low bycatch from Chagulak Island (34% of metapopulation, 14% of bycatch). Overlap between fisheries and colony‐specific foraging areas diverge more during the summer breeding season, leading to greater differences in bycatch susceptibility. Contemporary and historical gene flow likely contributes to low genetic differentiation among colonies (FST = 0.003–0.01), yet these values may not represent present connectivity. Our findings illustrate how genetic stock identification can link at‐sea threats to colonies and inform management to reduce bycatch from impacted colonies.
Llama Single Domain Antibodies Specific for the 7 Botulinum Neurotoxin Serotypes as Heptaplex Immunoreagents
There are currently 7 known serotypes of botulinum neurotoxin (BoNT) classified upon non-cross reactivity of neutralizing immunoglobulins. Non-neutralizing immunoglobulins, however, can exhibit cross-reactivities between 2 or more serotypes, particularly mosaic forms, which can hamper the development of highly specific immunoassays, especially if based on polyclonal antisera. Here we employ facile recombinant antibody technology to subtractively select ligands to each of the 7 BoNT serotypes, resulting in populations with very high specificity for their intended serotype. A single llama was immunized with a cocktail of 7 BoNT toxoids to generate a phage display library of single domain antibodies (sdAb, VHH or nanobodies) which were selected on live toxins. Resulting sdAb were capable of detecting both toxin and toxin complex with the best combinations able to detect 100s-10s of pg per 50 microL sample in a liquid bead array. The most sensitive sdAb were combined in a heptaplex assay to identify each of the BoNT serotypes in buffer and milk and to a lesser extent in carrot juice, orange juice and cola. Several anti-A(1) sdAb recognized A2 complex, showing that subtype cross-reactivity within a serotype was evident. Many of our sdAb could act as both captor and tracer for several toxin and toxin complexes suggesting sdAb can be used as architectural probes to indicate BoNT oligomerisation. Six of 14 anti-A clones exhibited inhibition of SNAP-25 cleavage in the neuro-2A assay indicating some sdAb had toxin neutralizing capabilities. Many sdAb were also shown to be refoldable after exposure to high temperatures in contrast to polyclonal antisera, as monitored by circular dichroism. Our panel of molecularly flexible antibodies should not only serve as a good starting point for ruggedizing assays and inhibitors, but enable the intricate architectures of BoNT toxins and complexes to be probed more extensively.
Genetic and life-history consequences of extreme climate events
Climate change is predicted to increase the frequency and intensity of extreme climate events. Tests on empirical data of theory-based predictions on the consequences of extreme climate events are thus necessary to understand the adaptive potential of species and the overarching risks associated with all aspects of climate change. We tested predictions on the genetic and life-history consequences of extreme climate events in two populations of marble trout Salmo marmoratus that have experienced severe demographic bottlenecks due to flash floods. We combined long-term field and genotyping data with pedigree reconstruction in a theory-based framework. Our results show that after flash floods, reproduction occurred at a younger age in one population. In both populations, we found the highest reproductive variance in the first cohort born after the floods due to a combination of fewer parents and higher early survival of offspring. A small number of parents allowed for demographic recovery after the floods, but the genetic bottleneck further reduced genetic diversity in both populations. Our results also elucidate some of the mechanisms responsible for a greater prevalence of faster life histories after the extreme event.
Grab it! Biased attention in functional hand and tool space
This study explored whether functional properties of the hand and tools influence the allocation of spatial attention. In four experiments that used a visual-orienting paradigm with predictable lateral cues, hands or tools were placed near potential target locations. Results showed that targets appearing in the hand’s grasping space (i.e., near the palm) and the rake’s raking space (i.e., near the prongs) produced faster responses than did targets appearing to the back of the hand, to the back of the rake, or near the forearm. Validity effects were found regardless of condition in all experiments, but they did not interact with the target-in-grasping/raking-space bias. Thus, the topology of the facilitated space around the hand is, in part, defined by the hand’s grasping function and can be flexibly extended by functional experience using a tool. These findings are consistent with the operation of bimodal neurons, and this embodied component is incorporated into a neurally based model of spatial attention.
Within- and among-population variation in vital rates and population dynamics in a variable environment
Understanding the causes of within- and among-population differences in vital rates, life histories, and population dynamics is a central topic in ecology. To understand how within- and among-population variation emerges, we need long-term studies that include episodic events and contrasting environmental conditions, data to characterize individual and shared variation, and statistical models that can tease apart shared and individual contribution to the observed variation. We used long-term tag–recapture data to investigate and estimate within- and among-population differences in vital rates, life histories, and population dynamics of marble trout Salmo marmoratus, an endemic freshwater salmonid with a narrow range. Only ten populations of pure marble trout persist in headwaters of Alpine rivers in western Slovenia. Marble trout populations are also threatened by floods and landslides, which have already caused the extinction of two populations in recent years. We estimated and determined causes of variation in growth, survival, and recruitment both within and among populations, and evaluated trade-offs between them. Specifically, we estimated the responses of these traits to variation in water temperature, density, sex, early life conditions, and extreme events. We found that the effects of population density on traits were mostly limited to the early stages of life and that growth trajectories were established early in life. We found no clear effects of water temperature on vital rates. Population density varied over time, with flash floods and debris flows causing massive mortalities (>55% decrease in survival with respect to years with no floods) and threatening population persistence. Apart from flood events, variation in population density within streams was largely determined by variation in recruitment, with survival of older fish being relatively constant over time within populations, but substantially different among populations. Marble trout show a fast to slow continuum of life histories, with slow growth associated with higher survival at the population level, possibly determined by food conditions and age at maturity. Our work provides unprecedented insight into the causes of variation in vital rates, life histories, and population dynamics in an endemic species that is teetering on the edge of extinction.