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Minimally invasive hysterectomy is a commonly performed gynecologic procedure with associated postoperative pain managed with opioid medications. Uncontrolled postoperative pain leads to increased opioid use/abuse, longer hospital stays, increase in healthcare visits, and may negatively affect patient satisfaction. Current data suggests that reduced pneumoperitoneum insufflation pressure during laparoscopic surgery may impact postoperative pain. Given the current opioid epidemic, surgeons are proactively finding ways to reduce postoperative pain. It is unclear how reduced pneumoperitoneum pressure impacts the surgeon. We investigated the impact of reduced pneumoperitoneum insufflation pressure on surgeon satisfaction.This was a pilot, double-blinded, randomized controlled trial from March 2020 to July 2021 comparing pneumoperitoneum pressure of 15 mmHg to reduced pressures of 12 mmHg and 10 mmHg during laparoscopic hysterectomy.A total of 40 patients were randomized (13 - 15 mmHg, 13 - 12 mmHg, and 14 - 10 mmHg). The primary outcome was surgeon satisfaction. Secondary outcomes included patient satisfaction, operative time, blood loss, postoperative pain, opioid usage, and discharge timing. There were no differences in baseline demographics or perioperative characteristics. Surgeon satisfaction was negatively impacted with lower pneumoperitoneum pressures greatest with 10 mmHg, including overall satisfaction (p =.01), overall effect of the pneumoperitoneum (p =.04), and quality of visualization (p =.01). There was an apparent although not statistically significant difference in operative time (p =.06) and blood loss (p =.054). There was no difference in patient satisfaction, postoperative pain scores, opioid usage, or time to discharge.Reduced pneumoperitoneum insufflation pressure during laparoscopic hysterectomy negatively impacted surgeon satisfaction with a trend towards longer operative times and greater blood loss, and did not positively impact patient satisfaction, postoperative pain, opioid demand, or discharge timing.

Hypotension has a powerful effect on patient outcome after traumatic brain injury (TBI). The relative impact of hypotension occurring in the field versus during early hospital resuscitation is unknown. We evaluated the association between hypotension and mortality and non-mortality outcomes in four cohorts defined by where the hypotension occurred [neither prehospital nor hospital, prehospital only, hospital only, both prehospital and hospital].Subjects ≥10 years with major TBI were included. Standard statistics were used for unadjusted analyses. We used logistic regression, controlling for significant confounders, to determine the adjusted odds (aOR) for outcomes in each of the three cohorts.Included were 12,582 subjects (69.8% male; median age 44 (IQR 26-61). Mortality by hypotension status: No hypotension: 9.2% (95%CI: 8.7-9.8%); EMS hypotension only: 27.8% (24.6-31.2%); hospital hypotension only: 45.6% (39.1-52.1%); combined EMS/hospital hypotension 57.6% (50.0-65.0%); (p0.0001). The aOR for death reflected the same progression: 1.0 (reference-no hypotension), 1.8 (1.39-2.33), 2.61 (1.73-3.94), and 4.36 (2.78-6.84), respectively. The proportion of subjects having hospital hypotension was 19.0% (16.5-21.7%) in those with EMS hypotension compared to 2.0% (1.8-2.3%) for those without (p0.0001). Additionally, the proportion of patients with TC hypotension was increased even with EMS "near hypotension" up to an SBP of 120 mmHg [(aOR 3.78 (2.97, 4.82)].While patients with hypotension in the field or on arrival at the trauma center had markedly increased risk of death compared to those with no hypotension, those with prehospital hypotension that was not resolved before hospital arrival had, by far, the highest odds of death. Furthermore, TBI patients who had prehospital hypotension were five times more likely to arrive hypotensive at the trauma center than those who did not. Finally, even "near-hypotension" in the field was strongly and independently associated the risk of a hypotensive hospital arrival (90 mmHg). These findings are supportive of the prehospital guidelines that recommend aggressive prevention and treatment of hypotension in major TBI.

BackgroundThe biological consequences of stress from the social environment pattern health outcomes. This study investigated whether social stress is prospectively associated with fracture incidence among racially and ethnically diverse, postmenopausal women.MethodsData from 160 709 postmenopausal women in the Women’s Health Initiative was analysed using Cox proportional hazards regression models to examine prospective associations of social stress with time to total and hip fracture incidence. Self-reported questionnaires measuring social strain, social functioning and social support were used to assess social stress.ResultsAge and race/ethnicity modified associations between social stress and total and hip fractures. HRs for the associations between higher social support (indicating lower social stress) and total fractures among those age 50–59 years were 0.92 (95% CI: 0.90 to 0.94); HR=0.94 (95% CI: 0.93 to 0.95) for those age 60–69 years and HR=0.96 (95% CI: 0.95 to 0.98) for those age 70–79 years. Higher social strain was associated with greater hip fracture incidence among Native American women (HR=1.84, 95% CI: 1.10 to 3.10), Asian women (HR=1.37, 95% CI: 1.01 to 1.86) and white women (HR=1.04, 95% CI: 1.01 to 1.08).ConclusionIdentifying population patterns of fracture incidence as biological expressions of social environments reveals how race/ethnic specific social environmental factors influence disparities in fractures.

To identify the relationship between patient position during surgery and time to confirmation of ureteral patency on cystoscopy.Randomized controlled trial.Academic tertiary care medical center.A total of 91 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy between February 2021 and February 2022 were randomized to intervention (n = 45) or control (n = 46). Exclusion criteria included known kidney disease or urinary tract anomaly, current ureteral stent, pregnancy, malignancy, and recognized intraoperative urinary tract injury.Subjects in the control group were placed in a 0° supine position during cystoscopy. Subjects in the intervention group were placed in a 20° angle in reverse Trendelenburg (RT) position during cystoscopy.The primary outcome, time to confirmation of bilateral ureteral patency, was measured at the time the second ureteral jet was viewed during intraoperative cystoscopy. There was no significant difference in mean time to confirmation (66.5 seconds in supine vs 67 seconds in RT, p = .2) nor in total cystoscopy time (111 seconds in supine vs 104.5 seconds in RT, p = .39). There were no significant differences in need for alternative modalities to aid in ureteral efflux visualization, delayed diagnosis of ureteric injury, and operative time. RT position seemed to have reduced the time to confirmation for the small group of patients with longer confirmation time (120 seconds).RT position does not change time to confirmation of bilateral ureteral patency compared with supine position. However, there may be a benefit in position change if time to confirmation is120 seconds.

Missingness mechanism is in theory unverifiable based only on observed data. If there is a suspicion of missing not at random, researchers often perform a sensitivity analysis to evaluate the impact of various missingness mechanisms. In general, sensitivity analysis approaches require a full specification of the relationship between missing values and missingness probabilities. Such relationship can be specified based on a selection model, a pattern-mixture model or a shared parameter model. Under the selection modeling framework, we propose a sensitivity analysis approach using a nonparametric multiple imputation strategy. The proposed approach only requires specifying the correlation coefficient between missing values and selection (response) probabilities under a selection model. The correlation coefficient is a standardized measure and can be used as a natural sensitivity analysis parameter. The sensitivity analysis involves multiple imputations of missing values, yet the sensitivity parameter is only used to select imputing/donor sets. Hence, the proposed approach might be more robust against misspecifications of the sensitivity parameter. For illustration, the proposed approach is applied to incomplete measurements of level of preoperative Hemoglobin A1c, for patients who had high-grade carotid artery stenosisa and were scheduled for surgery. A simulation study is conducted to evaluate the performance of the proposed approach.

Introduction Emergency service vehicle crashes (ESVCs), including rollovers and collisions with other vehicles and fixed objects, are a leading cause of death among U.S. firefighters. Risk management (RM) is a proactive intervention to identifying and mitigating occupational risks and hazards. The goal of this study was to assess the effect of RM in reducing ESVCs. Methods: Three fire departments (A, B and C), representing urban and suburban geographies, and serving medium to large populations, participated in facilitated RM programs to reduce their ESVCs. Interventions were chosen by each department to address their department-specific circumstances and highest risks. Monthly crash rates per 10,000 calls were calculated for each department an average of 28 months before and 23 months after the start of the RM programs. Interrupted time series analysis was used to assess the effect of the RM programs on monthly crash rates. Poisson regression was used to estimate the number of crashes avoided. Economic data from Department A were analyzed to estimate cost savings. Results: Department A had a 15.4% (P = 0.30) reduction in the overall monthly crash rate immediately post-RM and a 1% (P = 0.18) decline per month thereafter. The estimated two-year average cost savings due to 167 crashes avoided was $253,100 (95%CI= $192,355 – $313,885). Department B had a 9.7% (P = 0.70) increase in the overall monthly crash rate immediately post-RM and showed no significant changes in their monthly crash rate. Department C had a 28.4% (P = 0.001) reduction in overall monthly crash rate immediately post-RM and a 1.2% (P = 0.09) increase per month thereafter, with an estimated 122 crashes avoided. Conclusions: RM programs have the potential to reduce ESVCs in the fire service and their associated costs; results may vary based on the interventions chosen and how they are implemented. Practical applications: Risk management may be an effective and broadly implemented intervention to reduce ESVCs in the US fire service.

Higher chest compression release velocity (CCRV) has been associated with better outcomes after out-of-hospital cardiac arrest (OHCA), and patient factors have been associated with variations in chest wall compliance and compressibility. We evaluated whether patient sex, age, weight, and time in resuscitation were associated with CCRV during pre-hospital resuscitation from OHCA.Observational study of prospectively collected OHCA quality improvement data in two suburban EMS agencies in Arizona between 10/1/2008 and 12/31/2016. Subject-level mean CCRV during the first 10 min of compressions was correlated with categorical variables by the Wilcoxon rank-sum test and with continuous variables by the Spearman's rank correlation coefficient. Generalized estimating equation and linear mixed-effect models were used to study the trend of CCRV over time.During the study period, 2535 adult OHCA cases were treated. After exclusion criteria, 1140 cases remained for analysis. Median duration of recorded compressions was 8.70 min during the first 10 min of CPR. An overall decline in CCRV was observed even after adjusting for compression depth. The subject-level mean CCRV was higher for minutes 0-5 than for minutes 5-10 (mean 347.9 mm/s vs. 339.0 mm/s, 95% CI of the difference -12.4 to -5.4, p 0.0001). Males exhibited a greater mean CCRV compared to females [344.4 mm/s (IQR 307.3-384.6) vs. 331.5 mm/s (IQR 285.3-385.5), p = 0.013]. Mean CCRV was negatively correlated with age and positively correlated with patient weight.CCRV declines significantly over the course of resuscitation. Patient characteristics including male sex, younger age, and increased weight were associated with a higher CCRV.

De novo donor-specific antibodies (DSAs) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSAs, but comparative data are lacking. We compared CLAD-free survival and the degree and duration of DSA depletion after treatment of LTRs with CFZ or RTX.LTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was CLAD-free survival. Secondary outcomes were change in MFI at corresponding loci within 6 months of treatment (ΔMFI), time to DSA rebound, and change in % predicted FEVForty-four LTRs were identified, 7 of whom had ≥2 drug events; therefore, 53 drug events were divided into 2 groups, CFZ (n = 17) and RTX (n = 36). Use of plasmapheresis, immunoglobulin, and mycophenolate augmentation was equivalent in both groups. CLAD-free survival with a single RTX event was superior to that after ≥2 drug events (p = 0.001) but comparable to that with a single CFZ event (p = 0.399). Both drugs significantly lowered the MFI at DQ locus, and the median ΔMFI was comparable. Compared to the RTX group, the CFZ group had a shorter median interval to DSA rebound (p = 0.015) and a lower ΔFEVAlthough both CFZ and RTX reduced the MFI of circulating DSAs, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV

Background: Studies show that EMS patients are often inadvertently hyperventilated (HV), resulting in hypocapnia. In TBI, HV markedly increases mortality. We evaluated continuous prehospital ETCO2 data in intubated TBI patients. Methods: Analysis of monitor data files (Philips MRx™) from a sample of intubated TBI cases in the EPIC Study (NIH-R01NS071049). Results: Among hundreds of cases, graphical display of continuous ETCO2 from 3 subjects dramatically exemplified commonly-occurring inadvertent HV. Fig 1 shows unrecognized HV lasting nearly 15 min. Fig 2 reveals nearly 14 min of increasing ventilatory rate and progressively worsening hypocapnia. Fig 3 shows nearly 4 min of HV that ends abruptly with clear, sudden recognition and slowing of ventilatory rate that leads to restoration of normal ETCO2 in only a few breaths. The corresponding EMS patient care records (PCR) failed to document the presence, severity, and duration of HV. Conclusions: In a study emphasizing prevention of HV, subsequent evaluation of continuous ETCO2 data revealed many cases of unintentionally rapid manual ventilation and severe hypocapnia, often occurring for long periods. These findings, even in the face of explicit guideline-based training, demonstrate a clear need for routine access to continuous monitor data among intubated patients for quality improvement and in clinical studies. Review of PCRs does not reliably identify mismanagement of ventilation. Furthermore, these findings make it likely that real-time audiovisual feedback technology would improve ventilatory management by alerting providers to unidentified HV that results from the frequent distractions occurring during EMS care.

Background: Little is known about the provision of care by law enforcement (LE) personnel within modern EMS systems. We evaluated LE performance of bystander CPR (BCPR) and associated outcomes in OHCA across Arizona. Methods: A total of 5,654 OHCA cases (1/1/2019-12/31/2019) were evaluated using the Save Hearts in Arizona Registry and Education (SHARE) cardiac arrest registry. Data were abstracted from all EMS patient care records (PCRs). If two parties provided BCPR, the first to give compressions was considered the provider for this analysis. Cases identified as “Stranger” or “Unknown” BCPR were manually evaluated for narrative data to identify BCPR provider when possible. Results: BCPR was provided in 2285 cases [48.8%; (95% CIs 47.4%, 50.3%)] after excluding 850 cases that occurred in healthcare facilities where personnel are duty-bound to provide CPR. LE provided BCPR in 444 patients [19.4% (17.8%, 21.1%)], second only to family/spouse [1143 pts; 50.0% (48.0%, 52.1%)]. Overall, 279 patients survived to hospital discharge [12.2%, (10.9%, 13.6%)]. The Table shows the rates of BCPR in each provider category and the associated rates of survival. Of note is that the rate of bystander AED use was more than four times higher in LE BCPR [6.3% (4.23%, 8.99%)] than family-provided BCPR [1.5% (0.87%, 2.37%; p < 0.0001)], but was still very low. Conclusions: In this statewide study that included more than 130 EMS agencies from frontier to urban settings, LE personnel were frequently involved in the care of OHCA patients within the 911 system response. To our knowledge, this magnitude of provision of BCPR by LE (nearly one in five BCPR cases) has not been reported previously. Furthermore, the consequential rate of LE response to OHCA provides the opportunity to significantly increase AED use. Our findings support the widespread and intentional training of LE in CPR and AED use and has the potential to improve survival in diverse settings.

Simple Summary The assessment of actinic keratoses (AKs) in prevention and therapeutic trials, as well as clinical practice, could significantly benefit from the incorporation of non-invasive imaging technology. Such technology has the potential to enhance the objective evaluation of clinical and subclinical AKs with the added advantage of sequential monitoring. In vivo reflectance confocal microscopy (RCM) allows for the non-invasive imaging of AKs at a cellular level. We aimed to establish an in in vivo RCM protocol for AK response monitoring, ultimately leading to more reliable characterization of longitudinal responses and therapy optimization. Abstract Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7–28.1), hyperkeratosis (OR: 13.6, CI: 5.3–34.9), stratum corneum disruption (OR: 7.8, CI: 3.5–17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9–14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

Few studies have focused on intraoperative positioning as a risk factor for venous thromboembolism (VTE). Positioning that places the legs in a dependent position may be a risk factor. We theorized that the reverse-Trendelenburg position specifically would increase the risk of postoperative VTE.374,017 subjects undergoing laparoscopic surgery in the 2015-2018 NSQIP database were included. Diagnosis of cancer and BMI ≥ 30 were excluded. Subjects were grouped based on positioning: reverse-Trendelenburg (RT), supine (S), and Trendelenburg (T).The RT, S, and T groups consisted of 117,887, 66,511, and 189,619 subjects, respectively. Overall median BMI was 25.7, and 82.8% of subjects were non-smokers. VTE within 30 days postoperative was seen in 0.25% RT, 0.23% S, and 0.4% T (p 0.0001); 30-day mortality was 0.34% RT, 0.25% S, and 0.19% T (p 0.0001). After adjusting for potential confounders and other risk factors, RT position was associated with a lower risk of VTE compared to S (OR 1.49 with 95% CI 1.16, 1.93) and T (OR 1.34 with 95% CI 1.15, 1.56) positions. VTE risk was significantly different across the three groups (p = 0.0001). Inpatient procedures had a higher VTE risk vs outpatient (OR 2.49 with 95% CI 2.10, 2.95). Increasing operative time was associated with higher VTE risk [4th ( 106 min) vs 1st (≤ 40 min) quartiles (OR 3.54 with 95% CI 2.79, 4.48)].Among other risk factors, inpatient procedures and longer operative times are associated with higher VTE risk in laparoscopic surgery performed for benign disease in non-obese patients. The risk was significantly different across the three positioning groups with lowest risk in the RT group and highest risk in the S group.

The goal of this study was to correlate upright and prone bolus transit time (BTT) on barium esophagography (BE) with esophageal peristalsis on high-resolution manometry (HRM) and self-reported dysphagia in patients with normal lower esophageal sphincter parameters on HRM.BTT on BE could be the gold standard for assessing the effectiveness of esophageal peristalsis if it can be quantified.Patients with normal lower esophageal sphincter parameters and standard-protocol BE from 2017 to 2020 were included. Patients were divided, based on the number of normal swallows (distal contractile integral450 mm Hg-s-cm), into 11 groups (10 normal swallows to 0 normal swallows). Liquid barium swallows in prone position were objectively evaluated for prone BTT. Patients reported difficulty in swallowing on a scale from 0 (none) to 4 (very severe). Fractional polynomial and logistic regression analysis were used to study the association (along with the rate of change) between BTT, peristalsis, and dysphagia.A total of 146 patients were included. Prone BTT increased as the number of normal swallows decreased ( P0.001). Two deflection points were noted on the association between peristalsis and prone BTT at 50% normal swallows, 40 seconds and 30% normal swallows, 80 seconds, after which peristaltic function declined independently of prone BTT. Patients with prone BTT40 seconds had nearly 6-fold higher odds of 0% normal swallows on HRM than patients with prone BTT40 seconds ( P =0.002). Increasing prone BTT was associated with increasing dysphagia grades 1 and 2 ( P ≤0.036).Esophageal motility can be quantified by BE. Prone BTT correlates with the proportion of normal esophageal swallows and dysphagia.

BackgroundBone loss is a major public health concern with large proportions of older women experiencing osteoporotic fractures. Previous research has established a relationship between psychosocial stressors and fractures. However, few studies have investigated bone loss as an intermediary in this relationship. This study investigates whether social stress is associated with bone loss during a 6-year period in postmenopausal women.MethodsData from 11 020 postmenopausal women from the USA was used to examine self-reported psychosocial stress in relation to change in bone mineral density (BMD) measured at the femoral neck, lumbar spine and total hip. Linear regression models were used to examine associations between social measures of psychosocial stress (social strain, social functioning and social support) and per cent change in BMD over 6 years.ResultsHigh social stress was associated with decreased BMD over 6 years. After adjustment for confounders, each point higher in social strain was associated with 0.082% greater loss of femoral neck BMD, 0.108% greater loss of total hip BMD and 0.069% greater loss of lumbar spine BMD (pConclusionThe findings provide evidence for an association between high social stress and greater bone loss over 6 years of follow-up. In agreement with the prior literature, the findings for social strain and social functioning suggest that poor quality of social relationships may be associated with bone loss in postmenopausal women.

Food Security within a health security context relates to systems dealing with the prevention and control of not only acute but also sporadic and chronic foodborne diseases. The description of food security and safety systems in this chapter will hence include oversight of both microbiological and chemical hazards, which both can cause acute as well as chronic disease events. The Chapter includes a description of existing national and international surveillance systems for foodborne diseases and regulatory systems enabling risk mitigation action for both chemical and microbiological hazards, with specific inclusion of the concerning increase in antimicrobial resistance (AMR) of foodborne microorganisms also related to the animal production systems. The Chapter also includes descriptions of methodology for the quantitative assessment of sustainability of food production systems.

Arthrobotrys oligospora is a typical nematode-trapping fungus capturing free-living nematodes by adhesive networks. Component of the low-affinity calcium uptake system (LACS) has been documented to involve in growth and sexual development of filamentous fungi. Bioassay showed incapacity of trap formation in A. oligospora on Water Agar plate containing 1 mM ethylene glycol tetraacetic acid (EGTA) due to Ca2+ absorbing block. The functions of homologous proteins (AoFIG_1 and AoFIG_2) of LACS were examined on conidiation and trap formation of A. oligospora. Compared with wild type, ΔAoFIG_1 (AOL_s00007g566) resulted in 90% of trap reduction, while ΔAoFIG_2 (AOL_s00004g576) reduced vegetative growth rate up to 44% and had no trap and conidia formed. The results suggest that LACS transmembrane protein fig1 homologs play vital roles in the trap-formation and is involved in conidiation and mycelium growth of A. oligospora. Our findings expand fig1 role to include development of complex trap device and conidiation.

Irregular coal faces, ineluctable in coal mines within the eastern mining area in China owing to its complex geological condition, face higher rock burst danger because of their high-stress concentration and complicated spatial structure. Considering geological characteristics, rock burst liability and in situ stress in the 3303 irregular coal face at the Yangcheng coal mine, rock burst danger during tunneling and mining was analyzed to select targeted mitigation measures. The results indicate that the dynamic pressure adjustment movement (DPAM) of the roof plays an important role in the occurrence of rock bursts. Rock burst danger in tunneling of the tailgate is caused by the combination of dynamic and static stress, where the static stress is from the large depth and nearby faults, and the dynamic stress is from the DPAM of the roof above the near the 3301 mined-out area. The tunneling construction was halted for 3 months to reduce the high dynamic stress σd, and destressing large-diameter holes were drilled to reduce the static stress σ0. The rest of the tunneling construction was deemed safe. Furthermore, the rock burst danger in mining was divided into two types: I (high static stress type) and II (high dynamic stress type). The former is located at the triangular coal pillar and within a 20–150 m range ahead of the coal face. The latter acts on the tailgate caused by the intense mine seismic activity arising from the secondary DPAM. More destress holes are drilled within the danger zones of the former to release the stress fully. A combination of rigid support and flexible support (i.e., single props, double T-steel shed, bolt, anchor rope and anchor net) and monitoring is an efficient method to address the latter. The results show safe mining during the rest of the mining period. This paper provides a reference for prevention and control of rock burst for similar coal faces.

Antifungal azoles are the most widely used antifungal drugs in clinical and agricultural practice. Fungi can mount adaptive responses to azole stress by modifying the transcript levels of many genes, and the responsive mechanisms to azoles are the basis for fungi to develop azole resistance. In this study, we identified a new Zn(II)(2)Cys(6) transcription factor, ADS-1, with a positive regulatory function in transcriptional responses to azole stress in the model filamentous fungal species Neurospora crassa. Under ketoconazole (KTC) stress, the ads-1 transcript level was significantly increased in N. crassa. Deletion of ads-1 increased susceptibility to different azoles, while its overexpression increased resistance to these azoles. The cdr4 gene, which encodes the key azole efflux pump, was positively regulated by ADS-1. Deletion of ads-1 reduced the transcriptional response by cdr4 to KTC stress and increased cellular KTC accumulation under KTC stress, while ads-1 overexpression had the opposite effect. ADS-1 also positively regulated the transcriptional response by erg11, which encodes the azole target lanosterol 14α-demethylase for ergosterol biosynthesis, to KTC stress. After KTC treatment, the ads-1 deletion mutant had less ergosterol but accumulated more lanosterol than the wild type, while ads-1 overexpression had the opposite effect. Homologs of ADS-1 are widely present in filamentous fungal species of Ascomycota but not in yeasts. Deletion of the gene encoding an ADS-1 homolog in Aspergillus flavus also increased susceptibility to KTC and itraconazole (ITZ). Besides, deletion of A. flavus ads-1 (Afads-1) significantly reduced the transcriptional responses by genes encoding homologs of CDR4 and ERG11 in A. flavus to KTC stress, and the deletion mutant accumulated more KTC but less ergosterol. Taken together, these findings demonstrate that the function and regulatory mechanism of ADS-1 homologs among different fungal species in azole responses and the basal resistance of azoles are highly conserved.

Background: Respiratory rate (RR) is a key component in commonly-used trauma scoring systems [e.g., Revised Trauma Score (RTS), TRISS]. Imprecise documentation of RR introduces misclassification when these tools are used in trauma research. By identifying each waveform, nasal cannula end tidal CO2 (NCCO2) accurately measures RR in non-intubated patients. Objective: Evaluate the relationship between EMS-documented RR measurements in patient care records (PCRs) vs. true RR recorded by non-invasive NCCO2 monitoring in major TBI patients who were never actively ventilated. Methods: Among spontaneously-breathing, major TBI cases (moderate/severe/critical), continuous NCCO2 data (Philips MRx™) were evaluated from the EPIC Prehospital TBI Study (NIH 1R01NS071049). RR classifications for RTS/TRISS were then established for each case using both PCR-documentation and monitor data. Routine monitor data (including RR) were available to EMS providers on the display at all times during care. Results: Included: 158 cases from 7 Arizona EMS agencies [(7/13-7/17; median age 55 (range 18-94); 65% male]. The Table shows RTS/TRISS case classification by PCR and monitor RR. PCR-documented RR frequently failed to correctly classify cases: RR 29: (11/34, 32.4%), normal (67/93, 72.0%; Table). In total, PCR documentation misclassified 48.7% of cases (77/158). Conclusion: These findings identify a major contributor to inaccurate trauma scoring. Since RTS and TRISS are used widely in research, this has important implications for study enrollment, case ascertainment, confounding, and risk-adjustment in injury studies. Whenever possible, QI and research studies should utilize monitor data to identify and evaluate RR and other vitals rather than relying on PCR documentation. Future development of monitor-based, real-time feedback technology might improve trauma scoring precision and provider identification of RR abnormalities.

Background: Recent studies have shown that prehospital systolic blood pressure (SBP) is strongly associated with mortality across a remarkably wide range (far above 90 mmHg) in traumatic brain injury (TBI). Furthermore, in TBI research, trial enrollment and risk-adjustment are highly dependent upon accurate documentation of BP. Our preliminary work identified potential discrepancies between EMS-documented vs. actual measured BP. Objective: In major TBI, evaluate concordance between SBP documented in EMS patient care records (PCR) and actual, monitor-recorded SBP. Methods: A subset of major TBI cases (mod/severe/critical) in the EPIC TBI Study (NIH 1R01NS071049) were analyzed (3/13-7/18). Cases from 6 EMS agencies reporting continuous monitor data (Philips MRx™) were included. All monitor data available for this analysis were displayed and accessible to the providers during EMS care. We compared the lowest PCR-documented SBP to the monitor-recorded value in each patient. Results: Included: 210 cases (median age: 52, 67% male). In 152 cases (72%), the lowest PCR-documented SBP was exactly concordant with the monitor. When concordance was defined by a difference of ≤5 mmHg, 171 (81%) were concordant. Among the 27 cases with monitor-identified hypotension ( Conclusions: Significant disparities existed between monitor-recorded and PCR-documented SBP. PCRs failed to reflect 33% of monitor-documented hypotensive cases. It appears that ongoing care responsibilities and scene distractions may cause providers to miss important BP readings. These findings identify a potential hidden contributor to poor outcomes if hypotension goes unrecognized and untreated, rather than simply not being documented. Furthermore, case ascertainment, trial enrollment, confounding, and risk-adjustment in TBI studies may be substantially impacted when these processes are based on EMS documentation. When possible, QI and research projects should utilize monitor data to identify hypotensive patients. Development of real-time audiovisual monitor feedback technology might improve provider recognition of hypotension.

Introduction: The Prehospital TBI Guidelines (PTGs) are intended for both isolated and multisystem TBI (ITBI/MTBI). However, uncontrolled hemorrhage and potential detrimental effects of fluid resuscitation in MTBI may lead to differential effectiveness compared to ITBI. Methods: Preplanned subgroup analysis of PTG effectiveness in ITBI and MTBI from EPIC (before/after system study; 133 agencies, >11,000 trained; NIH R01NS071049). Interventions: Prevention/treatment of hypoxia, hypotension, hyperventilation. Inclusion: Barell Matrix 1; 1/07-6/15. Severity subgroups [Head Region Severity Score (HRSS; AIS equivalent)]: Moderate = 1-2; Severe = 3-4; Critical = 5-6. Definitions: ITBI: TBI with no other RSS ≥3 injury. MTBI: TBI plus non-head region RSS ≥3 injuries. Pre (P1) and post-implementation (P3) cohorts were compared using logistic regression. Results: Cases: 21,852; median age 45 (IQR 24, 66); 67% male. ITBI: 16,663 (76.3%); P1 = 11,602, P3 = 5061. MTBI: 5189 (23.7%); P1 = 3626, P3 = 1563]. Hypotension occurred much more frequently in MTBI (15.8%) than ITBI (4.5%; OR = 3.9 (3.5, 4.4); p Conclusions: PTG implementation was independently associated with improved odds of survival in severe ITBI and MTBI. Despite a rate of hypotension 4 times higher in MTBI, survival improvement was at least as strong as for ITBI. Since the MTBI cohort was much more likely to receive fluid resuscitation, these findings support the PTG recommendation for aggressive treatment of hypotension in TBI even in patients with potential ongoing hemorrhage.

OBJECTIVE: To evaluate serum concentrations of polyfluoroalkyl substances (PFAS) in male firefighters and association with cardiometabolic markers. METHODS: Serum PFAS were evaluated in 38 Arizona firefighters and 49 participants from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). Cardiometabolic markers including carotid intima-medial thickness (CIMT) were measured in the firefighters. RESULTS: Firefighters had elevated perfluorohexane sulfonic acid (PFHxS) and lower perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) compared to NHANES participants; for nine of the other 12 PFAS the values were not significantly different. There were significant negative associations among firefighters between perfluorodecanoic acid (PFDeA) and total cholesterol and PFUA and interleukin-6. PFAS concentrations were not associated with CIMT. CONCLUSION: PFHxS levels were elevated and PFNA and PFUA levels were decreased in firefighters compared to NHANES subjects. Serum PFAS concentrations were not associated with increased cardiometabolic risk measures in this population of firefighters.

BACKGROUND Exosomes isolated from plasma of lung transplant recipients (LTxRs) with bronchiolitis obliterans syndrome (BOS) contain human leukocyte antigens and lung self-antigens (SAgs), K-alpha 1 tubulin (Kα1T) and collagen type V (Col-V). The aim was to determine the use of circulating exosomes with lung SAgs as a biomarker for BOS. METHODS Circulating exosomes were isolated retrospectively from plasma from LTxRs at diagnosis of BOS and at 6 and 12 months before the diagnosis (n = 41) and from stable time-matched controls (n = 30) at 2 transplant centers by ultracentrifugation. Exosomes were validated using Nanosight, and lung SAgs (Kα1T and Col-V) were detected by immunoblot and semiquantitated using ImageJ software. RESULTS Circulating exosomes from BOS and stable LTxRs demonstrated 61- to 181-nm vesicles with markers Alix and CD9. Exosomes from LTxRs with BOS (n = 21) showed increased levels of lung SAgs compared with stable (n = 10). A validation study using 2 separate cohorts of LTxRs with BOS and stable time-matched controls from 2 centers also demonstrated significantly increased lung SAgs–containing exosomes at 6 and 12 months before BOS. CONCLUSIONS Circulating exosomes isolated from LTxRs with BOS demonstrated increased levels of lung SAgs (Kα1T and Col-V) 12 months before the diagnosis (100% specificity and 90% sensitivity), indicating that circulating exosomes with lung SAgs can be used as a non-invasive biomarker for identifying LTxRs at risk for BOS.

Study Objective To investigate the impact of retained cystoscopy fluid after laparoscopic hysterectomy on time to spontaneous void, time to discharge, urinary retention, bladder discomfort, and patient satisfaction. Design Single-blind randomized controlled trial. Setting An academic medical center. Patients One hundred and twenty patients who underwent laparoscopic hysterectomy with universal cystoscopy for benign indications, excluding pelvic organ prolapse and urinary incontinence indications. Interventions From October 10, 2018, to October 17, 2019, we compared 200 mL retained cystoscopy fluid and complete bladder emptying after laparoscopic hysterectomy with universal cystoscopy. Measurements and Main Results A total of 120 patients were enrolled and randomized (59 in the retained cystoscopy fluid group and 61 in the emptied fluid group). The primary outcome was time to first spontaneous void. The secondary outcomes were time to discharge, urinary retention rates, bladder discomfort, and patient satisfaction. A sample size of 120 was calculated to detect a 57-minute difference in time to spontaneous void. There were minimal differences in baseline demographics and surgical characteristics between the groups. There was an apparent, although not significant, difference in time to void of 25 minutes (143 minutes vs 168 minutes, p = .20). Time to discharge and urinary retention rates did not differ (199 minutes vs 214 minutes, p = .40, and 13.6% vs 8.2%, p = .51, respectively). There was no difference in postoperative bladder discomfort and patient satisfaction. Conclusion Retained cystoscopy fluid after laparoscopic hysterectomy did not significantly affect time to first spontaneous void, time to discharge, urinary retention, bladder discomfort, or patient satisfaction.

Study objective We evaluate the effect of implementing the out-of-hospital pediatric traumatic brain injury guidelines on outcomes in children with major traumatic brain injury. Methods The Excellence in Prehospital Injury Care for Children study is the preplanned secondary analysis of the Excellence in Prehospital Injury Care study, a multisystem, intention-to-treat study using a before-after controlled design. This subanalysis included children younger than 18 years who were transported to Level I trauma centers by participating out-of-hospital agencies between January 1, 2007, and June 30, 2015, throughout Arizona. The primary and secondary outcomes were survival to hospital discharge or admission for children with major traumatic brain injury and in 3 subgroups, defined a priori as those with moderate, severe, and critical traumatic brain injury. Outcomes in the preimplementation and postimplementation cohorts were compared with logistic regression, adjusting for risk factors and confounders. Results There were 2,801 subjects, 2,041 in preimplementation and 760 in postimplementation. The primary analysis (postimplementation versus preimplementation) yielded an adjusted odds ratio of 1.16 (95% confidence interval 0.70 to 1.92) for survival to hospital discharge and 2.41 (95% confidence interval 1.17 to 5.21) for survival to hospital admission. In the severe traumatic brain injury cohort (Regional Severity Score–Head 3 or 4), but not the moderate or critical subgroups, survival to discharge significantly improved after guideline implementation (adjusted odds ratio = 8.42; 95% confidence interval 1.01 to 100+). The improvement in survival to discharge among patients with severe traumatic brain injury who received positive-pressure ventilation did not reach significance (adjusted odds ratio = 9.13; 95% confidence interval 0.79 to 100+). Conclusion Implementation of the pediatric out-of-hospital traumatic brain injury guidelines was not associated with improved survival when the entire spectrum of severity was analyzed as a whole (moderate, severe, and critical). However, both adjusted survival to hospital admission and discharge improved in children with severe traumatic brain injury, indicating a potential severity-based interventional opportunity for guideline effectiveness. These findings support the widespread implementation of the out-of-hospital pediatric traumatic brain injury guidelines.

Background Longitudinal randomized controlled trials (RCTs) often aim to test and measure the effect of treatment between arms at a single time point. A two-sample χ2 test is a common statistical approach when outcome data are binary. However, only complete outcomes are used in the analysis. Missing responses are common in longitudinal RCTs and by only analyzing complete data, power may be reduced and estimates could be biased. Generalized linear mixed models (GLMM) with a random intercept can be used to test and estimate the treatment effect, which may increase power and reduce bias. Methods We simulated longitudinal binary RCT data to compare the performance of a complete case χ2 test to a GLMM in terms of power, type I error, relative bias, and coverage under different missing data mechanisms (missing completely at random and missing at random). We considered how the baseline probability of the event, within subject correlation, and dropout rates under various missing mechanisms impacted each performance measure. Results When outcome data were missing completely at random, both χ2 and GLMM produced unbiased estimates; however, the GLMM returned an absolute power gain up to from 12.0% as compared to the χ2 test. When outcome data were missing at random, the GLMM yielded an absolute power gain up to 42.7% and estimates were unbiased or less biased compared to the χ2 test. Conclusions Investigators wishing to test for a treatment effect between treatment arms in longitudinal RCTs with binary outcome data in the presence of missing data should use a GLMM to gain power and produce minimally unbiased estimates instead of a complete case χ2 test.

Basidioma is the fruiting body of mushroom species. The deep understanding on the mechanism of basidioma development is valuable for mushroom breeding and cultivation. From winter mushroom (Flammulina velutipes), one of the top five industrially cultivated mushrooms, a novel putative Zn(II)2Cys6 transcription factor LFC1 with negative regulatory function in basidioma development was identified. The transcript level of lfc1 was dramatically decreased during basidioma development. Neither overexpression nor knockdown of lfc1 affected hyphal vegetative growth. However, knockdown of lfc1 could promote basidioma development and shorten cultivation time by 2 days, while overexpression of lfc1 delayed the optimal harvest time by 3 days. In the lfc1 knockdown strain, in which the lfc1 expression was reduced by 72%, mushroom yield and biological efficiency could be increased at least by 24%. Knockdown of lfc1 did not affect the shape of caps but significantly increased basidioma length and number, while its overexpression did not affect basidioma length but dramatically reduced basidioma number. In addition, rather than producing basidiomata with round caps as in wild type, the caps of basidiomata in the lfc1 overexpression mutants were significantly larger and the cap edge was wrinkled. RNA-seq analysis revealed that 455 genes had opposite transcriptional responses to lfc1 overexpression and knockdown. Some of them were previously reported as genes involved in basidioma development, including 3 hydrophobin encoding genes, 2 lectin encoding genes, FVFD16, an Eln2 ortholog encoding gene, and 3 genes encoding membrane components. As LFC1 homologs are widely present in mushroom species, lfc1 can be useful in mushroom breeding.Key Points• A novel transcription factor LFC1 negatively regulates fruiting in winter mushroom• LFC1 regulated transcription of more than 400 genes.• Reduction of LFC1 expression could shorten cultivation time and increase yield.• lfc1 could be a potentially useful reference gene for mushroom breeding.

There are a lot of Chinese news about the same topic on the Internet today. Many of them are similar or repetitive for readers. It is hard to find what are the readers needed exactly. Multi-document news summarization aim at extractioninformationfrommultiple news texts on sametopie to automatically generate summary report for readers. Our paper chooses the news of the Great Wall as an example to illustrate the method of automatic summary generation In ourmethod, combinedwiththe characteristies ofnews corpus, the HLDA topie importance calculation model is improved. Based on the abstractly characteristics of the model, news related features such as news headline words, topie sensitive words and TF-IDF are added. Abstract sentence extraction and sentence fusion, automatic generation of abstracts. Experimental results show that the proposed algorithm is higherin the index thanthe traditional method, indicatingthe accuracy of the corpus combined with news features and the improved HLDA algorithm.

Additional file 1. Supplemental SAS simulation and analysis.

Background/Aims To determine the accuracy of identifying ≥6-mm adenomatous polyps during colonoscopy and define its impact on subsequent interval screening. Methods We conducted a retrospective study of patients who underwent colonoscopies at Banner University Medical Center, Tucson from 2011 to 2015. All patients with ≥6-mm adenomatous polyps based on their colonoscopy report were included. Adenomatous polyps were excluded if they did not meet the criteria. Discrepancies in the polyp size were determined by calculating the percentage of size variation (SV). Clinical mis-sizing was defined as SV >33%. Results The polyps analyzed were predominantly

Objective High grade serous ovarian cancer (HGSC) remains one of the most lethal malignancies in females. We previously reported that γ-glutamyl cyclotransferase (GGCT) was significantly upregulated in serous ovarian cancer. The current study was aimed to explore the function and underlying mechanism of GGCT in HGSC. Methods GGCT expression was assessed by immunohistochemistry in 128 HGSC patients. Stable cell lines with GGCT gene overexpression or knockdown were established to investigate the function of GGCT in HGSC in vitro and in vivo . Results GGCT is highly upregulated in HGSC tissues and associated with FIGO stage, lymph node metastasis and ascitic fluid volume. High expression of GGCT is associated with poor survival in HGSC patients. The Harrell's c-indexes of the prognostic models for overall survival and progression-free survival prediction were 0.758 and 0.726, respectively. GGCT knockdown suppresses proliferation, clone formation, migration, and invasion of tumor cells in vitro while forced GGCT overexpression presents opposite results. Furthermore, GGCT silencing inhibits tumor growth and spread in vivo . Epithelial-mesenchymal transition (EMT) and PI3K/AKT/mTOR signaling pathway are suppressed in GGCT silenced cells and enhanced in GGCT overexpressed cells. Inactivation of PI3K/AKT/mTOR signaling pathway in GGCT overexpressed cells induces EMT inhibition. Conclusions Our data reveals an important role of GGCT in regulating EMT and progression of HGSC, providing a valuable prognostic marker and potential target for treatment of HGSC patients.

Continuous-time Markov models are commonly used to analyze longitudinal transitions between multiple disease states in panel data, where participants' disease states are only observed at multiple time points, and the exact state paths between observations are unknown. However, when covariate effects are incorporated and allowed to vary for different transitions, the number of potential parameters to estimate can become large even when the number of covariates is moderate, and traditional maximum likelihood estimation and subset model selection procedures can easily become unstable due to overfitting. We propose a novel regularized continuous-time Markov model with the elastic net penalty, which is capable of simultaneous variable selection and estimation for large number of parameters. We derive an efficient coordinate descent algorithm to solve the penalized optimization problem, which is fully automatic and data driven. We further consider an extension where one of the states is death, and time of death is exactly known but the state path leading to death is unknown. The proposed method is extensively evaluated in a simulation study, and demonstrated in an application to real-world data on airflow limitation state transitions.

Aim of study This study aims to quantify the relative impact of Dispatcher-Initiated Telephone cardiopulmonary resuscitation (TCPR) on survival and survival with favorable functional outcome after out-of-hospital cardiac arrest (OHCA) in a population of patients served by multiple emergency dispatch centers and more than 130 emergency medical services (EMS) agencies. Methods We conducted a retrospective, observational study of EMS-treated adult (≥18 years) patients with OHCA of presumed cardiac origin in Arizona, between January 1, 2011, and December 31, 2014. We compared survival and functional outcome among three distinct groups of OHCA patients: those who received no CPR before EMS arrival (no CPR group); those who received BCPR before EMS arrival and prior to or without telephone CPR instructions (BCPR group); and those who received TCPR (TCPR group). Results In this study, 2310 of 4391 patients met the study criteria (median age, 62 years; IQR 50, 74; 1540 male). 32.8% received no CPR, 23.8% received Bystander-Initiated CPR and 43.4% received TCPR. Overall survival was 11.5%. Using no CPR as the reference group, the multivariate adjusted odds ratio for survival at hospital discharge was 1.51 (95% confidence interval [CI], 1.04, 2.18) for BCPR and 1.64 (95% CI, 1.16, 2.30) for TCPR. The multivariate adjusted odds ratio of favorable functional outcome at discharge was 1.58 (95% CI 1.05, 2.39) for BCPR and 1.56 (95% CI, 1.06, 2.31) for TCPR. Conclusion TCPR is independently associated with improved survival and improved functional outcome after OHCA.

The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1. To elucidate the functional significance of VDR deacetylation, vitamin-d-responsive-element (VDRE)-based transcriptional assays were performed to determine if deacetylase overexpression affects VDR/VDRE-driven transcription. In HEK293 kidney and TE85 bone cells, co-transfection of low amounts (1-5ng) of a SIRT1-expression vector elicits a reproducible and statistically significant enhancement (1.3- to 2.6-fold) in transcription mediated by VDREs from the CYP3A4 and cyp24a1 genes, where the magnitude of response to 1,25D-ligand is 6- to 30-fold. Inhibition of SIRT1 via EX-527, or utilization of a SIRT1 loss-of-function mutant (H363Y), resulted in abrogation of SIRT1-mediated VDR potentiation. Studies with a novel, non-acetylatable VDR mutant (K413R) showed that the mutant VDR possesses enhanced responsiveness to 1,25D, in conjunction with reduced, but still significant, sensitivity to exogenous SIRT1, indicating that acetylation of lysine 413 is relevant, but that other acetylated residues in VDR contribute to modulation of its activity. We conclude that the acetylation of VDR comprises a negative feedback loop that attenuates 1,25D-VDR signaling. This regulatory loop is reversed by SIRT1-catalyzed deacetylation of VDR to amplify VDR signaling and 1,25D actions.

Objectives To determine whether the relationship between anthropometric measurements of obesity and mortality varies according to age, race, and ethnicity in older women. Design Prospective cohort study of multiethnic postmenopausal women. Setting Women's Health Initiative (WHI) observational study and clinical trials in 40 clinics. Participants Postmenopausal women aged 50–79 participating in WHI (N = 161,808). Measurements Baseline height, weight, and waist circumference (WC) were measured, and body mass index (BMI) was calculated based on height and weight. Demographic, health, and lifestyle data from a baseline questionnaire were used as covariates. The outcome was adjudicated death (n = 18,320) during a mean follow-up of 11.4 ± 3.2 years. Results Hazard ratios (HRs) and 95% confidence intervals (95% CIs) indicated that ethnicity and age modified (P < .01) the relationship between obesity and mortality. Underweight was associated with higher mortality, but overweight or slight obesity was not a risk factor for mortality in most ethnic groups except for Hispanic women in the obesity I category (HR = 1.42, 95% CI = 1.04–1.95). BMI was not or was only weakly associated with mortality in individuals aged 70–79 (HR = 0.90, 95% CI = 0.85–0.95 for overweight; HR = 0.98, 95 CI = 0.92–1.06 for obese I; HR = 1.11, 95% CI = 1.00–1.23 for obese II; HR = 1.08, 95% CI = 0.92–1.26 for obese III). In contrast, higher central obesity measured using WC was consistently associated with higher mortality in all groups. Conclusion Underweight is a significant risk factor for mortality in older women, and healthy BMI ranges may need to be specific for age, race, and ethnicity. The findings support a consistent relationship between central obesity and mortality.

Study objective Survival is significantly reduced by either hypotension or hypoxia during the out-of-hospital management of major traumatic brain injury. However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. In patients with major traumatic brain injury, we evaluate the associations between mortality and out-of-hospital hypotension and hypoxia separately and in combination. Methods All moderate or severe traumatic brain injury cases in the preimplementation cohort of the Excellence in Prehospital Injury Care study (a statewide, before/after, controlled study of the effect of implementing the out-of-hospital traumatic brain injury treatment guidelines) from January 1, 2007, to March 31, 2014, were evaluated (exclusions: 200 mm Hg). The relationship between mortality and hypotension (systolic blood pressure Results Among the 13,151 patients who met inclusion criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios for death within the cohorts, using the patients with neither hypotension nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects were additive on the log odds of death. Conclusion In this statewide analysis of major traumatic brain injury, combined out-of-hospital hypotension and hypoxia were associated with significantly increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death for patients with both hypotension and hypoxia were more than 2 times greater than for those with either hypotension or hypoxia alone. These findings seem supportive of the emphasis on aggressive prevention and treatment of hypotension and hypoxia reflected in the current emergency medical services traumatic brain injury treatment guidelines but clearly reveal the need for further study to determine their influence on outcome.

Emergency medical telecommunicators can play a key role in improving outcomes from out-of-hospital cardiac arrest (OHCA) by providing instructions for cardiopulmonary resuscitation (CPR) to callers. Telecommunicators, however, frequently encounter barriers that obstruct the Telephone CPR (TCPR) process. The nature and frequency of these barriers in public and residential locations have not been well investigated. The aim of this study is to identify the barriers to TCPR in public and residential locations.We conducted a retrospective study of audio recordings of EMS-confirmed OHCAs from eight regional 9-1-1 dispatch centers between January 2012 and December 2013.We reviewed 1850 eligible cases (public location OHCAs: N=223 and residential location OHCAs: N=1627). Telecommunicators less frequently encountered barriers such as inability to calm callers in public than in residential locations (2.1% vs 8.5%, p=0.002) or inability to place victims on a hard flat surface (13.9% vs 25.4%, p0.001). However, the barrier where callers were not with patients was more frequently observed in public than in residential locations (11.8% vs 2.7%, p0.001).This study revealed that barriers to TCPR are distributed differently across public and residential locations. Understanding these differences can aid in the development of strategies to enhance bystander CPR and improve overall patient outcomes.

Most of the edible mushrooms cannot be cultivated or have low yield under industrial conditions, partially due to the lack of knowledge on how basidioma (fruiting body) development is regulated. From winter mushroom (Flammulina velutipes), one of the most popular industrially cultivated mushrooms, a transcription factor, PDD1, with a high-mobility group (HMG)-box domain was identified based on its increased transcription during basidioma development. pdd1 knockdown by RNA interference affected vegetative growth and dramatically impaired basidioma development. A strain with an 89.9% reduction in the level of pdd1 transcription failed to produce primordia, while overexpression of pdd1 promoted basidioma development. When the transcriptional level of pdd1 was increased to 5 times the base level, the mushroom cultivation time was shortened by 9.8% and the yield was increased by at least 33%. RNA sequencing (RNA-seq) analysis revealed that pdd1 knockdown downregulated 331 genes and upregulated 463 genes. PDD1 positively regulated several genes related to fruiting, including 6 pheromone receptor-encoding genes, 3 jacalin-related lectin-encoding genes, FVFD16, and 2 FVFD16 homolog-encoding genes. PDD1 is a novel transcription factor with regulatory function in basidioma development found in industrially cultivated mushrooms. Since its orthologs are widely present in fungal species of the Basidiomycota phylum, PDD1 might have important application prospects in mushroom breeding. IMPORTANCE Mushrooms are sources of food and medicine and provide abundant nutrients and bioactive compounds. However, most of the edible mushrooms cannot be cultivated commercially due to the limited understanding of basidioma development. From winter mushroom (Flammulina velutipes; also known as Enokitake), one of the most commonly cultivated mushrooms, we identified a novel transcription factor, PDD1, positively regulating basidioma development. PDD1 increases expression during basidioma development. Artificially increasing its expression promoted basidioma formation and dramatically increased mushroom yield, while reducing its expression dramatically impaired its development. In its PDD1 overexpression mutants, mushroom number, height, yield, and biological efficiency were significantly increased. PDD1 regulates the expression of some genes that are important in or related to basidioma development. PDD1 is the first identified transcription factor with defined functions in mushroom development among commercially cultivated mushroom species, and it might be useful in mushroom breeding.

Objective: Little is known about End-Tidal CO 2 monitoring using nasal cannula sensors (NC-CO 2 ) in non-intubated patients. Objective: To describe the patterns of NC-CO 2 seen during the EMS care of spontaneously breathing major Traumatic Brain Injury (TBI) patients. Methods: Continuous NC-CO 2 data (Philips MRx™ monitors) were evaluated from non-intubated, major (moderate, severe, critical) TBI cases (4/13-5/17) in the EPIC TBI Study (NIH 1R01NS071049). Descriptive statistics were used to evaluate case and NC-CO 2 attributes. Results: Included were 92 cases [median age = 50 (range 10-91; 66% male)]. Median respiratory rate (RR) was >15/min in 87% of cases and >20/min in 53%. The highest median RR was 39. Sixteen cases (17%) had a median NC-CO 2 2 >50. Several common NC-CO 2 patterns emerged: 1) while the final level varied among patients, the vast majority of cases (79, 86%) attained a stable “plateau” with relatively small variation after that point; 2) ETCO 2 often “ramped up” from 2 plateaus. In 78% of the cases with normal CO 2 plateaus (35-45mmHg), these levels were maintained despite high RR and/or dramatic variations in RR. Conclusions: This initial work identifies that NC-CO 2 monitoring may provide useful information in non-intubated EMS patients. After initial “ramp up,” the vast majority achieved stable readings despite dramatic RR variations. Most patients (53%) were spontaneously hyperventilating at rates more than twice “normal.” Despite this, almost half of them (43%) had ETCO 2 plateaus that were normal/near normal throughout their course. It is unclear whether the “very low” readings ( 2 flow. Future studies comparing NC-CO 2 to measured arterial pCO 2 are needed to identify the correlation and accuracy of NC-CO 2 as a tool for evaluating ventilatory physiology.

Background: The EMS traumatic brain injury (TBI) guidelines encourage limiting prehospital intubation (ETI) to patients with profoundly depressed level of consciousness (LOC) and who cannot protect their airway or adequately ventilate without ETI. Thus, EMS providers may manage many TBI patients without intubating even when they have significant alterations in LOC. Monitoring End-Tidal CO2 by placing sensors in the nares (NC-CO2) of non-intubated patients may give providers valuable information about ventilatory status and trends. Study Objective: To evaluate the association between LOC and NC-CO2 in non-intubated TBI patients. Methods: Non-intubated cases from 6 EMS agencies reporting continuous monitor data (Philips MRx™) in the EPIC Study (NIH 1R01NS071049) were evaluated (4/13-3/17). Glasgow Coma Scale (GCS) was available from the EMS record in call cases. Comparisons in patient-level mean, median, lowest and highest NC-CO2 levels were made across GCS categories using clinically meaningful thresholds: Results: Included were 106 cases [median age: 47 (range: 9-91), 66% male]. The Table shows the NC-CO2 patterns and comparisons across the GCS categories. In no case was there a significant difference in NC-CO2 between the better vs. worse mental status cohort. Conclusion: We believe this is the first evaluation of the association between NC-CO2 and mental status in TBI. Patients that had significant (and even profound) decreases in LOC, but whom paramedics chose not to intubate, had remarkably similar NC-CO2 patterns compared to those with normal or near-normal mental status. This may support the overall approach of limiting ETI to those with airway/ventilatory compromise or impending hypoxia as there was no evidence of increasing NC-CO2, indicative of hypercapnia, in the non-intubated patients even when they had very depressed LOC.