COPD and OSA are both highly prevalent, which implies that both disorders occurring together (overlap syndrome) is likely to be common based on chance association alone. However, different clinical ...COPD phenotypes influence the likelihood of coexisting OSA in that the increased lung volumes and low BMI associated with the predominant emphysema phenotype protects against OSA, whereas the higher likelihood of peripheral edema and increased BMI associated with the predominant chronic bronchitis phenotype promotes OSA. Both COPD and OSA are associated with similar physiological and molecular consequences, such as hypoxia and systemic inflammation, that contribute to cardiovascular and other comorbidities, and pulmonary hypertension is highly prevalent in patients with the overlap syndrome. However, there have been few published reports that have evaluated systemic inflammation and other cardiovascular comorbidities in patients with overlap syndrome. The diagnosis of OSA in patients with COPD requires awareness of relevant clinical features, and screening questionnaires may help identify suitable patients for further overnight study. The recognition of coexisting OSA in patients with COPD has important clinical relevance, as the management of patients with overlap syndrome is different from the management of COPD alone, and the survival of patients with overlap syndrome that is not treated with nocturnal positive airway pressure is significantly inferior to that of patients with overlap syndrome that is appropriately treated.
Implementing Artificial Intelligence in medicine is revolutionizing how medicine is practiced. It has much promise in bringing about improved clinical outcomes and efficiency while decreasing costs. ...There are also concerns and unintended consequences that are being realized and significant efforts to consider ethical principles in the implementation of Artificial Intelligence in medicine. One potential consequence may be the loss of what has been described as the soul of medicine: the physician-patient relationship. This relationship is especially precious in the context of what the US Surgeon General Vivek H. Murthy MD has called an "Epidemic of Loneliness and Isolation." This commentary describes considerations and potential steps to protect this vital relationship while implementing Artificial Intelligence approaches to improving patient care. If not vigilant, Artificial Intelligence may unintentionally erode the physician-patient relationship resulting in physician/patient isolation.
Purpose
The optimal strategy of fluid resuscitation in the early hours of severe sepsis and septic shock is controversial, with both an aggressive and conservative approach being recommended.
Methods
...We used the 2013 Premier Hospital Discharge database to analyse the administration of fluids on the first ICU day, in 23,513 patients with severe sepsis and septic shock, who were admitted to an ICU from the emergency department. Day 1 fluid was grouped into categories 1 L wide, starting with 1–1.99 L up to ≥9 L, to examine the effect of day 1 fluids on patient mortality. We built binary response models for hospital mortality and the propensity for receiving more than 5 L of fluids on day 1, using patient age and acute conditions present on admission. Patients were grouped by the requirement for mechanical ventilation and the presence or absence of shock. We assessed trends in the difference between actual and expected mortality, in the low fluid range (1–5 L day 1 fluids) and the high fluid range (5 to ≥9 L day 1 fluids) categories, using weighted linear regression controlling for the effects of sample size and variation within the day 1 fluid category.
Results
Day 1 fluid administration averaged 4.4 L being lowest in the group with no mechanical ventilation and no shock (3.6 L) and highest (5.4 L) in the group receiving mechanical ventilation and in shock. The administration of day 1 fluids was remarkably consistent on the basis of hospital size, teaching status, rural/urban location, and region of the country. The hospital mortality in the entire cohort was 25.8%, with a mean ICU and hospital length of stay of 5.1 and 9.1 days, respectively. In the entire cohort, low volume resuscitation (1–4.99 L) was associated with a small but significant reduction in mortality, of −0.7% per litre (95% CI −1.0%, −0.4%;
p
= 0.02). However, in patients receiving high volume resuscitation (5 to ≥9 L), the mortality increased by 2.3% (95% CI 2.0, 2.5%;
p
= 0.0003) for each additional litre above 5 L. Total hospital cost increased by $999 for each litre of fluid above 5 L (adjusted
R
2
= 92.7%,
p
= 0.005).
Conclusion
The mean amount of fluid administered to patients with severe sepsis and septic shock in the USA during the first ICU day is less than that recommended by the Surviving Sepsis Campaign guidelines. The administration of more than 5 L of fluid during the first ICU day is associated with a significantly increased risk of death and significantly higher hospital costs.
Summary
Obstructive sleep apnea (OSA) is characterised by recurring episodes of upper airway obstruction during sleep and the fundamental abnormality reflects the inability of the upper airway ...dilating muscles to withstand the negative forces generated within the upper airway during inspiration. Factors that result in narrowing of the oropharynx such as abnormal craniofacial anatomy, soft tissue accumulation in the neck, and rostral fluid shift in the recumbent position increase the collapsing forces within the airway. The counteracting forces of upper airway dilating muscles, especially the genioglossus, are negatively influenced by sleep onset, inadequacy of the genioglossus responsiveness, ventilatory instability, especially post arousal, and loop gain. OSA is frequently associated with comorbidities that include metabolic, cardiovascular, renal, pulmonary, and neuropsychiatric, and there is growing evidence of bidirectional relationships between OSA and comorbidity, especially for heart failure, metabolic syndrome, and stroke. A detailed understanding of the complex pathophysiology of OSA encourages the development of therapies targeted at pathophysiological endotypes and facilitates a move towards precision medicine as a potential alternative to continuous positive airway pressure therapy in selected patients.
This research expands efforts to understand differences in NIH funding associated with the self-identified race and ethnicity of applicants. We collected data from 2,397 NIH Biographical Sketches ...submitted between FY 2003 and 2006 as part of new NIH R01 Type 1 applications to obtain detailed information on the applicants' training and scholarly activities, including publications. Using these data, we examined the association between an NIH R01 applicant's race or ethnicity and the probability of receiving an R01 award. The applicant's publication history as reported in the NIH biographical sketch and the associated bibliometrics narrowed the black/white funding gap for new and experienced investigators in explanatory models. We found that black applicants reported fewer papers on their Biosketches, had fewer citations, and those that were reported appeared in journals with lower impact factors. Incorporating these measures in our models explained a substantial portion of the black/white funding gap. Although these predictors influence the funding gap, they do not fully address race/ethnicity differences in receiving a priority score.
Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome represent two of the most prevalent chronic respiratory disorders in clinical practice, and cardiovascular diseases ...represent a major comorbidity in each disorder. The two disorders coexist (overlap syndrome) in approximately 1% of adults but asymptomatic lower airway obstruction together with sleep-disordered breathing is more prevalent. Although obstructive sleep apnea syndrome has similar prevalence in COPD as the general population, and vice versa, factors such as body mass index and smoking influence relationships. Nocturnal oxygen desaturation develops in COPD, independent of apnea/hypopnea, and is more severe in the overlap syndrome, thus predisposing to pulmonary hypertension. Furthermore, upper airway flow limitation contributes to nocturnal desaturation in COPD without apnea/hypopnea. Evidence of systemic inflammation in COPD and sleep apnea, involving C-reactive protein and IL-6, in addition to nuclear factor-kappaB-dependent pathways involving tumor necrosis factor-alpha and IL-8, provides insight into potential basic interactions between both disorders. Furthermore, oxidative stress develops in each disorder, in addition to activation and/or dysfunction of circulating leukocytes. These findings are clinically relevant because systemic inflammation may contribute to the pathogenesis of cardiovascular diseases and the cell/molecular pathways involved are similar to those identified in COPD and sleep apnea. However, the pathophysiological and clinical significance of systemic inflammation in COPD and sleep apnea is not proven, and thus, studies of patients with the overlap syndrome should provide insight into the mechanisms of systemic inflammation in COPD and sleep apnea, in addition to potential relationships with cardiovascular disease.
Recent studies have implicated microglia-the resident immune cells of the brain-in the pathophysiology of alcoholism. Indeed, post-mortem alcoholic brains show increased microglial markers and ...increased immune gene expression; however, the effects of ethanol on microglial functioning and how this impacts the brain remain unclear. In this present study, we investigate the effects of acute binge ethanol on microglia and how microglial depletion changes the brain neuroimmune response to acute binge ethanol withdrawal.
C57BL/6J mice were treated intragastrically with acute binge ethanol for time course and dose-response studies. Cultured mouse BV2 microglia-like cells were treated with ethanol in vitro for time course studies. Mice were also administered the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia from the brain. These mice were subsequently treated with acute binge ethanol and sacrificed during withdrawal. Brain and BV2 mRNA were isolated and assessed using RT-PCR to examine expression of microglial and neuroimmune genes.
Acute binge ethanol biphasically changed microglial (e.g., Iba1, CD68) gene expression, with initial decreases during intoxication and subsequent increases during withdrawal. Acute ethanol withdrawal dose dependently increased neuroimmune gene (e.g., TNFα, Ccl2, IL-1ra, IL-4) expression beginning at high doses. BV2 cells showed biphasic changes in pro-inflammatory (e.g., TNFα, Ccl2) gene expression following ethanol treatment in vitro. Administration of PLX5622 depleted microglia from the brains of mice. Although some neuroimmune genes were reduced by microglial depletion, many others were unchanged. Microglial depletion blunted pro-inflammatory (e.g., TNFα, Ccl2) gene expression and enhanced anti-inflammatory (e.g., IL-1ra, IL-4) gene expression during acute binge ethanol withdrawal.
These studies find acute binge ethanol withdrawal increases microglial and neuroimmune gene expression. Ethanol exposure also increases microglial pro-inflammatory gene expression in vitro. Furthermore, microglial depletion decreases expression of microglia-specific genes but has little effect on expression of many other neuroimmune signaling genes. Microglial depletion blunted the acute binge ethanol withdrawal induction of pro-inflammatory genes and enhanced induction of anti-inflammatory genes. These findings indicate microglia impact the brain response to acute binge ethanol withdrawal.
We address the question of verifying the quantumness of thermal machines. A Szilárd engine is truly quantum if its work output cannot be described by a local hidden state model, i.e., an objective ...local statistical ensemble. Quantumness in this scenario is revealed by a steering-type inequality which bounds the classically extractable work. A quantum Maxwell demon can violate that inequality by exploiting quantum correlations between the work medium and the thermal environment. While for a classical Szilárd engine an objective description of the medium always exists, any such description can be ruled out by a steering task in a truly quantum case.
We study dynamical phase transitions (DPT) in the driven and damped Dicke model, realizable for example by a driven atomic ensemble collectively coupled to a damped cavity mode. These DPTs are ...characterized by nonanalyticities of certain observables, primarily the overlap of time evolved and initial state. Even though the dynamics is dissipative, this phenomenon occurs for a wide range of parameters and no fine-tuning is required. Focusing on the state of the "atoms" in the limit of a bad cavity, we are able to asymptotically evaluate an exact path integral representation of the relevant overlaps. The DPTs then arise by minimization of a certain action function, which is related to the large deviation theory of a classical stochastic process. Finally, we present a scheme which allows a measurement of the DPT in a cavity-QED setup.
To analyze the relationship between gender, race/ethnicity, and the probability of being awarded an R01 grant from the National Institutes of Health (NIH).
The authors used data from the NIH ...Information for Management, Planning, Analysis, and Coordination grants management database for the years 2000-2006 to examine gender differences and race/ethnicity-specific gender differences in the probability of receiving an R01 Type 1 award. The authors used descriptive statistics and probit models to determine the relationship between gender, race/ethnicity, degree, investigator experience, and R01 award probability, controlling for a large set of observable characteristics.
White women PhDs and MDs were as likely as white men to receive an R01 award. Compared with white women, Asian and black women PhDs and black women MDs were significantly less likely to receive funding. Women submitted fewer grant applications, and blacks and women who were new investigators were more likely to submit only one application between 2000 and 2006.
Differences by race/ethnicity explain the NIH funding gap for women of color, as white women have a slight advantage over men in receiving Type 1 awards. Findings of a lower submission rate for women and an increased likelihood that they will submit only one proposal are consistent with research showing that women avoid competition. Policies designed to address the racial and ethnic diversity of the biomedical workforce have the potential to improve funding outcomes for women of color.
PDF
