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OBJECTIVES: Peritonsillar abscess (PTA) is a common deep space head and neck infection, which can be diagnosed with or without computed tomography (CT). CT poses a risk for false positives, leading to unnecessary abscess drainage attempts without benefit, whereas needle or open aspiration without imaging could potentially lead to missed abscess in need of treatment. This study considered the utility and impact of obtaining CT scans in patients with suspected PTA by comparing outcomes between CT and non-CT usage. METHODS: Retrospective cohort analysis using TriNetX datasets compared the outcomes of two cohorts: PTA without CT and PTA with CT. Measured outcomes included incision and drainage; quinsy adenotonsillectomy; recurrent PTA; airway emergency/obstruction; repeat emergency department (ED) visits; and need for antibiotics, opiates, or steroids. Odds ratios (OR) were calculated using a cohort analysis. RESULTS: The CT usage group had increased odds of receiving antibiotics (OR 3.043, [2.043-4.531]), opiates (OR 1.614, [1.138-1.289]), and steroids (OR 1.373, [1.108-1.702]), as well as a higher likelihood of returning to the ED (OR 5.900, [3.534-9.849]) and developing a recurrent PTA (OR 1.943, [1.410-2.677]). No significant differences were observed in the incidence of incision and drainage, quinsy adenotonsillectomy, or airway emergency/obstruction. CONCLUSION: Our study indicated that CT scans for PTA diagnosis were associated with increased prescription of antibiotics, opioids, steroids, return ED visits, and recurrent PTA. Future prospective trials are needed to determine if the use of CT scans indicates higher patient acuity that explains the potential negative outcomes. LEVEL OF EVIDENCE: Level II Laryngoscope, 2024.
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High-resolution imaging, 3D modeling, and quantitative analyses are equipping evolutionary biologists with new approaches to understanding the variation and evolution of the musculoskeletal system. However, challenges with interpreting DiceCT data and higher order use of modeled muscles have not yet been fully explored, and the error in and accuracy of some digital methods remain unclear. West Indian Anolis lizards are a model clade for exploring patterns in functional adaptation, ecomorphology, and sexual size dimorphism in vertebrates. These lizards possess numerous jaw muscles with potentially different anatomies that sculpt the adductor chamber of the skull. Here we test approaches to quantifying the musculoskeletal shape of the heads of two species of Anolis: A. pulchellus and A. sagrei. We employ comparative approaches such as DiceCT segmentation of jaw muscles, 3D surface attachment mapping, and 3D landmarking with the aim of exploring muscle volumes, 3D muscle fiber architecture, and sexual dimorphism of the skull. We then compare sources of measurement error in these 3D analyses while also presenting new 3D musculoskeletal data from the Anolis feeding apparatus. These findings demonstrate the accessibility and repeatability of these emerging techniques as well as provide details regarding the musculoskeletal anatomy of the heads of A. pulchellus and A. sagrei which show potential for further research of comparative biomechanics and evolution in the clade.
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ABSTRACT: Witte, BC, Schouten, TC, Westphal, JA, VanZile, AW, Jones, DD, Widenhoefer, TL, Dobbs, WC, Jagim, AR, Luedke, JA, and Almonroeder, TG. The modified reactive strength index is a valid measure of lower-body explosiveness in male and female high school athletes. J Strength Cond Res 38(8): 1428-1432, 2024-The modified reactive strength index (mRSI) is a commonly used metric to quantify lower-body explosiveness during countermovement jump (CMJ) performance. However, few studies have attempted to examine its validity as a measure of explosiveness, particularly among high school athletes. The purpose of this study was to examine the validity of the mRSI as a measure of lower-body explosiveness among a relatively large sample of male and female high school athletes from various sports. As part of this study, male ( n = 132) and female ( n = 43) high school athletes performed CMJs, while ground reaction forces were recorded using a force platform. The vertical ground reaction force data collected during the CMJs were used to derive the following variables: peak force (PF), peak power, time to PF, time to take-off, peak rate of force development, and the mRSI. Principal component analysis was applied and reduced these variables into 2 components related to "force" and "speed." The mRSI loaded on both the force (loading = 0.82) and speed (loading = -0.46) components, indicating that it incorporates elements of both force and speed, although it loaded more strongly on the force component than the speed component. The observed pattern of cross-loading suggests that the mRSI is generally a valid measure of lower-body explosiveness for male and female high school athletes.
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Fuerza Muscular , Femenino , Masculino , Adolescente , Humanos , Fuerza Muscular/fisiología , Atletas , Rendimiento Atlético/fisiología , Extremidad Inferior/fisiología , Reproducibilidad de los Resultados , Prueba de Esfuerzo/métodosRESUMEN
A phylogenetic graph search relies on a large number of highly parameterized search procedures (e.g. branch-swapping, perturbation, simulated annealing, genetic algorithm). These procedures vary in effectiveness over datasets and at alternative points in analytical pipelines. The multi-armed bandit problem is applied to phylogenetic graph searching to more effectively utilize these procedures. Thompson sampling is applied to a collection of search and optimization "bandits" to favour productive search strategies over those that are less successful. This adaptive random sampling strategy is shown to be more effective in producing heuristically optimal phylogenetic graphs and more time efficient than existing uniform probability randomized search strategies. The strategy acts as a form of unsupervised machine learning that can be applied to a diversity of phylogenetic datasets without prior knowledge of their properties.
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Algoritmos , Filogenia , Aprendizaje Automático no SupervisadoRESUMEN
BACKGROUND: The estimation of body fat percentage (BF%) in wrestling is used to determine the minimum wrestling weight (MWW) and lowest allowable weight class (MWC) in which wrestlers are eligible to compete. A 12% minimum threshold is currently used for women wrestlers, yet a potential increase for safety has been discussed. Because of the novelty of collegiate women's wrestling, there is a paucity of literature available on the body composition norms of this population. The purpose of this study was to provide a descriptive summary of BF% and MWW values of female wrestlers and how MWW values would change with the use of different BF% thresholds. METHODS: Data from the 2022-2023 collegiate season were retrospectively analyzed resulting in a sample of 1,683 collegiate women wrestlers from the National Association of Intercollegiate Athletics (NAIA, n = 868) and the National Collegiate Athletics Association (NCAA, n = 815). All wrestlers completed skinfold assessments for weight certification at the start of the competition season. The skinfold values were used to estimate BF% using the Slaughter skinfold prediction equation. Frequency statistics and descriptive analysis were performed to compute normative MWW and BF% profiles. BF% thresholds of 12% (12MWW) and the BF% value defined as the lowest 5th percentile, which would be considered unusually lean, were used to determine the resulting MWW and MWC for each method. The lowest recorded weight and weight class division throughout the season was also recorded for each wrestler. RESULTS: There was a positively skewed (0.94) and platykurtic (1.86) distribution of MWW values. The median ± interquartile range BF% for all wrestlers was 27.4 ± 10.22%, with 17% BF representing the 5th percentile. Only 354 out of 1,579 (22.4%) wrestlers competed in their lowest allowable weight class, based on the 12MWW. Of these 354 wrestlers, the mean BF% was 21.3 ± 5.2% at weight certification with only n = 17 being at or below 12% body fat and an average weight loss of 11.1 ± 8.8 lbs. from the time of weight certification. Throughout the season, wrestlers competed at weights that were, on average (mean ± SD), 19.4 ± 16.9 lbs. higher than their 12MWW (95% CI: 18.6, 20.2 lbs. p < 0.001; effect size [ES] = 1.1), 13.4 ± 19.0 lbs. higher than the 17MWW (p < 0.001; ES = 0.70), and 8.7 ± 8.3 lbs. lower than their weight at the certification (95% CI: 8.3, 9.1 lbs. p < 0.001; ES = 1.1). CONCLUSIONS: Nearly all BF% values were well above the 12% threshold used to determine MWW. Increasing the minimum BF% threshold from 12% to 17% would affect a small percentage of wrestlers, likely reduce the need for excessive weight cutting, and minimize the deleterious health effects of an athlete at such a low BF%.
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Lucha , Humanos , Femenino , Estudios Retrospectivos , Grosor de los Pliegues Cutáneos , Tejido Adiposo , Pérdida de Peso , Composición Corporal , Peso CorporalRESUMEN
We present Phylogenetic Graph (PhyG), an open-source, phylogenetic search tool for diverse data types and graphs, including softwired and hardwired networks, in addition to trees. This allows for analysis of horizontal transfer and hybridization scenarios, as well as the necessary vertical inheritance of trees. PhyG is the successor to POY5 in performing combined data tree-alignment with enhancements in heuristic optimality (up to 7% in example data) and execution time (up to a factor of 200). Input data may exhibit a practically unlimited number of character states in qualitative or sequence (aligned and unaligned) types. Novel graph construction and refinement algorithms have been implemented and integrated into a variety of search procedures. Currently, PhyG implements parsimony and No-Common-Mechanism Likelihood optimization.
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Algoritmos , Motor de Búsqueda , Filogenia , ProbabilidadRESUMEN
BACKGROUND: The purpose of this study was to assess the effects of protein and carbohydrate supplementation, with and without creatine, on occupational performance in firefighters. METHODS: Using a randomized, double-blind approach, thirty male firefighters (age: 34.4 ± 8.4 yrs., height: 1.82 ± 0.07 m; weight: 88.6 ± 12.5 kg; BF%: 17.2 ± 5.8%) were randomized to receive either (A.) 25 g of whey protein isolate + 25 g of carbohydrate powder (ProCarb group); or (B.) ProCarb + 5 g of creatine (Creatine group) in a double-blind fashion over a period of 21-26 days (depending on shift rotations) to evaluate the impact of supplementation on occupation-specific performance. At baseline and following supplementation, firefighters completed a battery of tests. These tests included an aerobic speed test on an air-braked cycle ergometer followed by the hose carry, body drag, stair climb, and Keiser sled hammer for time. RESULTS: No significant differences in measures of performance were observed at baseline (p > 0.05). There was a significant main effect for time observed for rescue, stair climb, total time to completion, and time trial performance (p < 0.05). There was a significant group × time (p < 0.05) interaction for rescue and forcible entry. Independent sample t-tests indicated that the Creatine group experienced a greater reduction (from baseline) in completion time for the rescue (1.78 ± 0.57 s, 95% CI: 0.61, 2.95 s, p = 0.004) and forcible entry (2.66 ± 0.97 s, 95% CI: 0.68, 4.65 s, p = 0.01) tests compared to the ProCarb group. No significant group × time interactions were observed for the hose line advance, stair climb, total time to completion, and time trial performance (p > 0.05). CONCLUSIONS: The addition of supplemental creatine to a protein and carbohydrate supplement to the diet of career firefighters throughout a three week period improves occupational performance in firefighters in specific areas of high-intensity, repetitive actions.
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Creatina , Bomberos , Masculino , Humanos , Adulto , Creatina/farmacología , Suplementos Dietéticos , Carbohidratos , Método Doble CiegoRESUMEN
The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.
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Leucemia Mieloide Aguda , Humanos , Línea Celular , Leucemia Mieloide Aguda/metabolismo , Factor de Transcripción MafB/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Fenotipo , ARN Interferente PequeñoRESUMEN
An algorithm is described for the optimization of character data (e.g. qualitative, nucleic acid sequence) on softwired phylogenetic networks. The algorithm presented here is an extension of those developed for trees under the parsimony criterion and can form the basis for phylogenetic network search procedures. Although the problem is (in general) an NP-Hard optimization, the resolution-based algorithm we describe here capitalizes on the significant amount of shared structure in sub-graphs containing network edges, reducing the execution time and allowing for the analysis of empirical datasets.
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Algoritmos , Filogenia , Secuencia de BasesRESUMEN
The treatment of inapplicable characters has proved especially vexing to systematists. Investigators have wrestled with alternative coding scenarios to capture both the presence and absence of a feature, and its variation when present, in a reasonable manner. Three basic issues have presented themselves: (i) impossible states at internal nodes; (ii) action at a distance among disparate parts of the tree; and (iii) "secondary" (i.e. aspect variation) characters overwhelming "primary" (i.e. character presence/absence) patterns in grouping taxa. Multiple methods have been proposed to deal with these issues in the context of standard character coding with varying levels of complexity. Here, I show that these issues can be dealt with in a direct fashion by treating presence/absence not as a character, but as insertion/deletion of a character with all its potential variation. This approach removes these three problems in simple, straightforward manner.
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Mutación INDEL , FilogeniaRESUMEN
The objective of this study was to investigate the prediction of the wetting characteristics obtained from the equilibrium adsorption analysis using the Zeta adsorption isotherm approach with an experimental study. Water vapor's adsorption and wetting characteristics on a hydroxylated and nano-polished silica substrate were studied in near-equilibrium conditions at temperatures near 298 K. Using a UV-visible interferometer, water vapor adsorbate film thicknesses were measured and converted into amount adsorbed per unit area. The current results show that the wetting transition occurred at an average subcooling value of 0.39 K, less than the predicted value of 0.49 K. All the different experimental observations showed growth of film thickness as a function of subcooling value with a maximum film thickness of 12.6 nm. The analysis of the results further showed that the maximum stable film was in a metastable state that then condensed in a dropwise manner, if perturbed by increasing the subcooling. The study further revealed that the adsorbate is unstable after transitioning. The solid surface energy calculated by including the near-equilibrium observations was comparable and close to that of the equilibrium studies, thus supporting solid surface energy as a material property.
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Firefighters often complete air management courses (AMC) to assess the ability to tolerate personal protective equipment, appropriately manage the breathing system and assess occupational performance. Little information is known relative to the physiological demands of AMCs, nor how to assess work efficiency in order to characterize occupational performance and evaluate progress. PURPOSE: To assess the physiological demands of an AMC and examine differences across BMI categories. A secondary aim was to develop an equation to assess work efficiency in firefighters. METHODS: Fifty-seven firefighters (Women, n = 4; age: 37.2 ± 8.4 yr.; height: 182.0 ± 6.9 cm; body mass: 90.8 ± 13.1 kg; BMI: 27.8 ± 3.6 kg·m-2) completed an AMC per routine evaluation while wearing a department issued self-contained breathing apparatus and full protective gear. Course completion time, starting pounds per square inch (PSI) on the air cylinder, changes in PSI, and distance traveled were recorded. All firefighters were equipped with a wearable sensor integrated with a triaxial accelerometer and telemetry to assess movement kinematics, heart rate, energy expenditure, and training impulse. The AMC consisted of an initial section involving a hose line advance, rescue (body drag), stair climb, ladder raise, and forcible entry. This section was followed by a repeating loop, which consisted of a stair climb, search, hoist, and recovery walk. Firefighters repeated the course loop until the self-contained breathing apparatus air supply pressure reached 200 PSI, at which time they were instructed to lay down until the PSI reached zero. RESULTS: Average completion time was 22.8 ± 1.4 min, with a mean distance of 1.4 ± 0.3 km and an average velocity of 2.4 ± 1.2 m·s-1. Throughout the AMC, the mean heart rate was 158.7 ± 11.5 bpm equating to 86.8 ± 6.3% of the age-predicted max heart rate and a training impulse of 55 ± 3 AU. Mean energy expenditure was 464 ± 86 kcals and work efficiency was 49.8 ± 14.9 km·PSI-1·s. Regression analysis determined that fat-free mass index (R2 = 0.315; ß = -5.069), body fat percentage (R2 = 0.139; ß = -0.853), fat-free mass (R2 = 0.176; ß = -0.744), weight (R2 = 0.329; ß = -0.681), and age (R2 = 0.096; ß = -0.571) were significant predictors of work efficiency. CONCLUSIONS: The AMC is a highly aerobic task with near-maximal heart rates reached throughout the course. Smaller and leaner individuals achieved a higher degree of work efficiency during the AMC.
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BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
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COVID-19 , Trastornos por Estrés Postraumático , Femenino , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , COVID-19/epidemiología , Pandemias , Depresión/psicología , Estudios Retrospectivos , Estudios Prospectivos , SARS-CoV-2 , Ansiedad/psicología , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: South Africa (SA)'s high rate of interpersonal violence persists as a leading public health problem for the country. The first South African Comparative Risk Assessment Study (SACRA1) in 2000 quantified the long-term mental and physical health burden attributable to interpersonal violence by supplementing the direct injury burden of disease attributable to interpersonal violence injuries with the substantial contribution of mental health, behavioural and reproductive health consequences accruing from exposure to intimate partner violence (IPV) and child sexual abuse. OBJECTIVES: To revise and improve these estimates by including the additional burden from other forms of child maltreatment, community violence, sexual violence by non-partners, and bullying victimisation in SA for 2000, 2006 and 2012, and trends over time. METHODS: We used comparative risk assessment methods to calculate population attributable fractions (PAFs) for interpersonal violence. This method requires inputs on the prevalence of exposure to the interpersonal violence risk factor subtypes, namely child maltreatment, bullying, IPV, sexual violence by non-partners and other community violence; the burden of related health outcomes (mortality and morbidity); and relative risks of health outcomes in individuals exposed to the risk factor v. those unexposed. We estimated the PAF for the combinations of all interpersonal violence subtypes together to estimate the burden attributable to interpersonal violence overall for 2000, 2006 and 2012. RESULTS: Between 2000 and 2012, there was a decrease in interpersonal violence age-standardised attributable death rates from 100 to 71 per 100 000. In the second South African Comparative Risk Assessment Study (SACRA2), estimates of the attributable disability-adjusted life years (DALYs) for interpersonal violence for the year 2000 were revised, from 1.7 million to 2 million DALYs, taking into account attributable mortality and disability from additional forms of violence. There was a decrease in DALYs attributable to interpersonal violence from 2 million in 2000 to 1.75 million in 2012, accounting for 8.5% of the total burden for SA, ranking second highest, after unsafe sex, among 18 risk factors evaluated in 2012. CONCLUSION: Overall, interpersonal violence-attributable DALYs decreased substantially but remain high. The reduction in age-standardised attributable death rates indicates that some policy and social intervention aspects are effective. Further strengthening of existing laws pertaining to interpersonal violence, and other prevention measures, are needed to intensify the prevention of violence, particularly gender-based violence. Additional forms of violence included in this analysis have improved our understanding of the interpersonal violence burden, but the attributable burden in males, although exceedingly high, remains an underestimate. There is a need to improve the epidemiological data on prevalence and risks for the different types of interpersonal violence, particularly for males.
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Maltrato a los Niños , Violencia , Niño , Masculino , Humanos , Sudáfrica/epidemiología , Percepción Social , Costo de EnfermedadRESUMEN
The purpose of the study was to investigate the sensitivity of back squat bar velocity, isometric mid-thigh pull, heart rate variability parameters, perceived recovery scale and step counts for tracking the muscular fatigue time-course (reduction in countermovement jump [CMJ] performance) after strenuous acute lower limb resistance exercise. Sixteen healthy men performed heart rate variability assessment, perceived recovery scale, CMJ, back squat bar velocity, isometric mid-thigh pull, and daily step counts before and 24 h, 48 h and 72 h post a strenuous acute lower limb resistance exercise (8×10 repetitions). The CMJ height decreased at 24 and 48 h after exercise session (p≤0.017), evidencing the muscular fatigue. The perceived recovery scale presented lower values compared to baseline until 72 h after exercise session (p<0.001 for all). The heart rate variability parameters and step counts were not significantly different across time. At 24 h post, only mean force of mid-thigh pull was decreased (p=0.044), while at 48 h post, only peak force of mid-thigh pull was decreased (p=0.020). On the last day (72 h), only bar velocity (mean) presented reduction (p=0.022). Therefore, the perceived recovery scale was the only variable sensible to tracking muscular fatigue, i. e. presenting a similar time-course to CMJ height.
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Entrenamiento de Fuerza , Ejercicio Físico/fisiología , Fatiga , Humanos , Masculino , Fatiga Muscular/fisiología , Fuerza Muscular/fisiología , MusloRESUMEN
We performed a comparative analysis of human and 12 non-human primates to identify sequence variations in known cancer genes. We identified 395 human-specific fixed non-silent substitutions that emerged during evolution of human. Using bioinformatics analyses for functional consequences, we identified a number of substitutions that are predicted to alter protein function; one of these mutations is located at the most evolutionarily conserved domain of human BRCA2.
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Pan troglodytes , Primates , Animales , Proteína BRCA2/genética , Evolución Molecular , Humanos , Mutación/genética , Pan troglodytes/genética , Proteínas/metabolismoRESUMEN
Although a variety of tools to monitor recovery have been developed, many are impractical for daily use due to cost, time, and challenges with interpretation. The Perceived Recovery Status (PRS) scale was recently developed as an expeditious, noninvasive tool to assess recovery status. While PRS has been strongly associated with repeated sprinting performance, a paucity of research exists relating PRS and performance recovery following resistance exercise. PURPOSE: The purpose of this study was to evaluate the sensitivity of PRS as a subjective marker of recovery up to 72 hours after a high-volume back-squat protocol. METHODS: Eleven resistance-trained men reported to the laboratory on 5 separate occasions (1 familiarization session and 4 testing sessions). The first testing session was considered the baseline session and consisted of a nonfatiguing performance assessment (ie, countermovement jumps and back squats) and a fatiguing back-squat protocol of 8 sets of 10 at 70% 1-repetition maximum separated by 2 minutes of recovery. Participants returned 24, 48, and 72 hours following baseline to provide a PRS rating and complete the performance assessment. RESULTS: Repeated-measures correlations revealed strong associations between PRS countermovement jump (r = .84) and mean bar velocity (r = .80) (both P < .001). CONCLUSIONS: The current findings suggest that PRS can be used as a method to effectively assess daily recovery following a fatiguing bout of resistance exercise. Practitioners are cautioned that the relationship between PRS and performance recovery is individualized, and equivalent PRS scores between individuals are not indicative of similar recovery.
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Músculo Esquelético , Entrenamiento de Fuerza , Ejercicio Físico , Fatiga , Humanos , Masculino , Monitoreo Fisiológico , Postura , Entrenamiento de Fuerza/métodosRESUMEN
BACKGROUND: Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. MAIN TEXT: There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. CONCLUSION: Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
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Antiinfecciosos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar/microbiología , Humanos , Microbiota , Nebulizadores y Vaporizadores , Prevención SecundariaRESUMEN
Deciphering the evolutionary relationships of Chelicerata (arachnids, horseshoe crabs, and allied taxa) has proven notoriously difficult, due to their ancient rapid radiation and the incidence of elevated evolutionary rates in several lineages. Although conflicting hypotheses prevail in morphological and molecular data sets alike, the monophyly of Arachnida is nearly universally accepted, despite historical lack of support in molecular data sets. Some phylotranscriptomic analyses have recovered arachnid monophyly, but these did not sample all living orders, whereas analyses including all orders have failed to recover Arachnida. To understand this conflict, we assembled a data set of 506 high-quality genomes and transcriptomes, sampling all living orders of Chelicerata with high occupancy and rigorous approaches to orthology inference. Our analyses consistently recovered the nested placement of horseshoe crabs within a paraphyletic Arachnida. This result was insensitive to variation in evolutionary rates of genes, complexity of the substitution models, and alternative algorithmic approaches to species tree inference. Investigation of sources of systematic bias showed that genes and sites that recover arachnid monophyly are enriched in noise and exhibit low information content. To test the impact of morphological data, we generated a 514-taxon morphological data matrix of extant and fossil Chelicerata, analyzed in tandem with the molecular matrix. Combined analyses recovered the clade Merostomata (the marine orders Xiphosura, Eurypterida, and Chasmataspidida), but merostomates appeared nested within Arachnida. Our results suggest that morphological convergence resulting from adaptations to life in terrestrial habitats has driven the historical perception of arachnid monophyly, paralleling the history of numerous other invertebrate terrestrial groups.