The EGS Grading Scale For Skin And Soft Tissue Infections Is Predictive Of Poor Outcomes : A Multicenter Validation Study

Introduction: Over the last five years, the American Association for the Surgery of Trauma (AAST) has developed grading scales for Emergency General Surgery (EGS) diseases. In a prior validation study using diverticulitis, the grading scales were predictive of complications and length of stay. As EGS encompasses diverse diseases, the purpose of this study was to validate the grading scale concept against a different disease process with a higher associated mortality. We hypothesized that the grading scale would be predictive of complications, length of stay and mortality in skin and soft tissue infections (STI). Methods: This multi-institutional trial encompassed 12 centers. Data collected included demographic variables, disease characteristics and outcomes such as mortality, overall complications, hospital and ICU length of stay. The EGS scale for STI was used to grade each infection and two surgeons graded each case to evaluate inter-rater reliability. Results: 1170 patients were included in this study. Inter-rater reliability was moderate (kappa coefficient 0.472-0.642, with 64-76% agreement). Higher grades (IV and V) corresponded to significantly higher LRINEC scores when compared with lower EGS grades. Patients with grade IV and V STI had significantly increased odds of all complications, as well as ICU and overall length of stay. These associations remained significant in logistic regression controlling for age, gender, comorbidities, mental status and hospital-level volume. Grade V disease was significantly associated with mortality as well. Conclusion: This validation effort demonstrates that Grade IV and V STI are significantly predictive of complications, hospital length of stay and mortality. Though predictive ability does not improve linearly with STI grade, this is consistent with the clinical disease process, in which lower grades represent cellulitis and abscess and higher grades are invasive infections. This second validation study confirms the EGS grading scale as predictive, and easily used, in disparate disease processes

DESI Observations of the Andromeda Galaxy: Revealing the Immigration History of our Nearest Neighbor

We present DESI observations of the inner halo of M31, which reveal the kinematics of a recent merger - a galactic immigration event - in exquisite detail. Of the 11,416 sources studied in 3.75 hour of on-sky exposure time, 7,438 are M31 sources with well measured radial velocities. The observations reveal intricate coherent kinematic structure in the positions and velocities of individual stars: streams, wedges, and chevrons. While hints of coherent structures have been previously detected in M31, this is the first time they have been seen with such detail and clarity in a galaxy beyond the Milky Way. We find clear kinematic evidence for shell structures in the Giant Stellar Stream, the Northeast Shelf and Western Shelf regions. The kinematics are remarkably similar to the predictions of dynamical models constructed to explain the spatial morphology of the inner halo. The results are consistent with the interpretation that much of the substructure in the inner halo of M31 is produced by a single galactic immigration event 1 - 2 Gyr ago. Significant numbers of metal-rich stars ([Fe/H]$>-0.5$) are present in all of the detected substructures, suggesting that the immigrating galaxy had an extended star formation history. We also investigate the ability of the shells and Giant Stellar Stream to constrain the gravitational potential of M31, and estimate the mass within a projected radius of 125 kpc to be ${\rm log_{10}}\, M_{\rm NFW}(<125\,{\rm kpc})/M_\odot = 11.80_{-0.10}^{+0.12}$. The results herald a new era in our ability to study stars on a galactic scale and the immigration histories of galaxies.Comment: 45 pages, 22 figures, 8 tables; Astrophysical Journal in press; Data at https://zenodo.org/record/697749

Silencing, Positive Selection and Parallel Evolution: Busy History of Primate Cytochromes c

Cytochrome c (cyt c) participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i) loss of the paralogous testis isoform, (ii) an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii) atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection) occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics

Discerning Patterns and Quality of Neoadjuvant Chemotherapy Use Among Patients with Muscle-invasive Bladder Cancer

BackgroundNeoadjuvant chemotherapy is underutilized in bladder cancer patients who undergo radical cystectomy. However, the quality of regimens used in this setting remains largely unknown.ObjectiveTo determine utilization treatment patterns and survival outcomes according to regimens administered.Design, setting, and patientsWe used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify patients diagnosed with clinical stage TII-IV bladder cancer from January 1, 2001 to December 31, 2011.Outcome measurements and statistical analysisTemporal trends were assessed using the Cochran-Armitage test. Multivariable logistic regression models were used to identify predictors for neoadjuvant chemotherapy use. Cox proportional hazards models were used to compare overall survival according to regimens administered.Results and limitationsOf 2738 patients treated with radical cystectomy, 344 (12.6%) received neoadjuvant chemotherapy. The agents most commonly used were gemcitabine (72.3%), cisplatin (55.2%), and carboplatin (31.1%). The regimens most commonly used were gemcitabine-cisplatin (45.3%), gemcitabine-carboplatin (24.1%), and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC; 6.7%). Use of neoadjuvant chemotherapy more than tripled during the study period, from 5.7% in 2001 to 17.3% in 2011 (p&lt;0.001). The quality of the regimen administered impacted survival outcomes, as M-VAC use was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer (hazard ratio 0.24, 95% confidence interval 0.07-0.86; p=0.030]. Limitations include the limited ability of retrospective analysis to control for selection bias.ConclusionsNeoadjuvant chemotherapy was underused, and the quality of neoadjuvant chemotherapy regimens administered for bladder cancer was inconsistent with guideline recommendations. These findings are important when interpreting population-based data on the use of chemotherapy and extrapolating survival outcomes.Patient summaryIn a large population-based study, 12.6% of patients undergoing radical cystectomy for bladder cancer received neoadjuvant chemotherapy, half of whom received guideline-recommended regimens. The quality of the regimen impacted survival outcomes, as use of cisplatin-based chemotherapy was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer. However, &lt;1% of radical cystectomy patients received this regimen

Deconstructing dogma: Nonoperative management of small bowel obstruction in the virgin abdomen

Management of small bowel obstruction (SBO) has become more conservative, especially in those patients with previous abdominal surgery (PAS). However, surgical dogma continues to recommend operative exploration for SBO with no PAS. With the increased use of computed tomography imaging resulting in more SBO diagnoses, it is important to reevaluate the role of mandatory operative exploration. Gastrografin (GG) administration decreases the need for operative exploration and may be an option for SBO without PAS. We hypothesized that the use of GG for SBO without PAS will be equally effective in reducing the operative exploration rate compared with that for SBO with PAS. A post hoc analysis of prospectively collected data was conducted for patients with SBO from February 2015 through December 2016. Patients younger than 18 years, pregnant patients, and patients with evidence of hypotension, bowel strangulation, peritonitis, closed loop obstruction or pneumatosis intestinalis were excluded. The primary outcome was operative exploration rate for SBO with or without PAS. Rate adjustment was accomplished through multivariate logistic regression. Overall, 601 patients with SBO were included in the study, 500 with PAS and 101 patients without PAS. The two groups were similar except for age, sex, prior abdominal surgery including colon surgery, prior SBO admission, and history of cancer. Multivariate analysis showed that PAS (odds ratio [OR], 0.47; p = 0.03) and the use of GG (OR, 0.11; p < 0.01) were independent predictors of successful nonoperative management, whereas intensive care unit admission (OR, 16.0; p < 0.01) was associated with a higher likelihood of need for operation. The use of GG significantly decreased the need for operation in patients with and without PAS. Patients with and without PAS who received GG had lower rates of operative exploration for SBO compared with those who did not receive GG. Patients with a diagnosis of SBO without PAS should be considered for the nonoperative management approach using GG. Therapeutic, level IV