Closed surface bundles of least volume

Since the set of volumes of hyperbolic 3-manifolds is well ordered, for each fixed g there is a genus-g surface bundle over the circle of minimal volume. Here, we introduce an explicit family of genus-g bundles which we conjecture are the unique such manifolds of minimal volume. Conditional on a very plausible assumption, we prove that this is indeed the case when g is large. The proof combines a soft geometric limit argument with a detailed Neumann-Zagier asymptotic formula for the volumes of Dehn fillings. Our examples are all Dehn fillings on the sibling of the Whitehead manifold, and we also analyze the dilatations of all closed surface bundles obtained in this way, identifying those with minimal dilatation. This gives new families of pseudo-Anosovs with low dilatation, including a genus 7 example which minimizes dilatation among all those with orientable invariant foliations.Comment: 22 pages, 4 figures. V2: Corrected Table 1.9; V3: Added Table 1.10; V4: Minor edits; V5: Corrected Figure 2.1. To appear in AG&

Crystal structure of bis(μ2-di-n-butyldithiocarbamato-κ3S,S′:S;κ3S:S:S′)-hexacarbonyl-di-rhenium(I), C24H36N2O6Re2

C24H36N2O6Re2, triclinic, P¯1 (no. 2), a=10.3013(2) Å, b=11.3471(2) Å, c=14.5967(3) Å, α=72.540(2)°, β=73.074(2)°, γ=85.369(2)°, V =1557.05(6) Å3, Z =2, Rgt(F)=0.0214, wRref(F2)=0.0466, T =100(2) K

Development and structure of an accurate machine learning algorithm to predict inpatient mortality and hospice outcomes in the coronavirus disease 2019 era

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has challenged the accuracy and racial biases present in traditional mortality scores. An accurate prognostic model that can be applied to hospitalized patients irrespective of race or COVID-19 status may benefit patient care. RESEARCH DESIGN: This cohort study utilized historical and ongoing electronic health record features to develop and validate a deep-learning model applied on the second day of admission predicting a composite outcome of in-hospital mortality, discharge to hospice, or death within 30 days of admission. Model features included patient demographics, diagnoses, procedures, inpatient medications, laboratory values, vital signs, and substance use history. Conventional performance metrics were assessed, and subgroup analysis was performed based on race, COVID-19 status, and intensive care unit admission. SUBJECTS: A total of 35,521 patients hospitalized between April 2020 and October 2020 at a single health care system including a tertiary academic referral center and 9 community hospitals. RESULTS: Of 35,521 patients, including 9831 non-White patients and 2020 COVID-19 patients, 2838 (8.0%) met the composite outcome. Patients who experienced the composite outcome were older (73 vs. 61 y old) with similar sex and race distributions between groups. The model achieved an area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.88, 0.91) and an average positive predictive value of 0.46 (0.40, 0.52). Model performance did not differ significantly in White (0.89) and non-White (0.90) subgroups or when grouping by COVID-19 status and intensive care unit admission. CONCLUSION: A deep-learning model using large-volume, structured electronic health record data can effectively predict short-term mortality or hospice outcomes on the second day of admission in the general inpatient population without significant racial bias

The number of discharge medications predicts thirty-day hospital readmission: A cohort study

BACKGROUND: Hospital readmission occurs often and is difficult to predict. Polypharmacy has been identified as a potential risk factor for hospital readmission. However, the overall impact of the number of discharge medications on hospital readmission is still undefined. METHODS: To determine whether the number of discharge medications is predictive of thirty-day readmission using a retrospective cohort study design performed at Barnes-Jewish Hospital from January 15, 2013 to May 9, 2013. The primary outcome assessed was thirty-day hospital readmission. We also assessed potential predictors of thirty-day readmission to include the number of discharge medications. RESULTS: The final cohort had 5507 patients of which 1147 (20.8 %) were readmitted within thirty days of their hospital discharge date. The number of discharge medications was significantly greater for patients having a thirty-day readmission compared to those without a thirty-day readmission (7.2 ± 4.1 medications [7.0 medications (4.0 medications, 10.0 medications)] versus 6.0 ± 3.9 medications [6.0 medications (3.0 medications, 9.0 medications)]; P < 0.001). There was a statistically significant association between increasing numbers of discharge medications and the prevalence of thirty-day hospital readmission (P < 0.001). Multiple logistic regression identified more than six discharge medications to be independently associated with thirty-day readmission (OR, 1.26; 95 % CI, 1.17–1.36; P = 0.003). Other independent predictors of thirty-day readmission were: more than one emergency department visit in the previous six months, a minimum hemoglobin value less than or equal to 9 g/dL, presence of congestive heart failure, peripheral vascular disease, cirrhosis, and metastatic cancer. A risk score for thirty-day readmission derived from the logistic regression model had good predictive accuracy (AUROC = 0.661 [95 % CI, 0.643–0.679]). CONCLUSIONS: The number of discharge medications is associated with the prevalence of thirty-day hospital readmission. A risk score, that includes the number of discharge medications, accurately predicts patients at risk for thirty-day readmission. Our findings suggest that relatively simple and accessible parameters can identify patients at high risk for hospital readmission potentially distinguishing such individuals for interventions to minimize readmissions

Hydrodinamic Aspects of a High-Speed SWATH and New Hull Form

The main problems of high-speed ships operating in open seas are their insufficient seaworthiness and speed loss in high sea states. Small Water-plane Area Twin-Hulls (SWATH) are characterised by excellent seaworthiness, but the hull forms of a traditional SWATH are not suited for higher speeds. A new shape of underwater gondola has been developed for a semi-planing (S/P) SWATH. Additionally, hydrofoils can be applied to this ship to provide the optimal dynamic draught and trim, to mitigate motions in rough seas, and even to carry a part of the ship weight. The relative speed of this SWATH can be beneficially increased up to the displacement Froude number 3. Several concept designs addressing naval and civil transportation needs are outlined in this paper

Advanced care planning for hospitalized patients following clinician notification of patient mortality by a machine learning algorithm

IMPORTANCE: Goal-concordant care is an ongoing challenge in hospital settings. Identification of high mortality risk within 30 days may call attention to the need to have serious illness conversations, including the documentation of patient goals of care. OBJECTIVE: To examine goals of care discussions (GOCDs) in a community hospital setting with patients identified as having a high risk of mortality by a machine learning mortality prediction algorithm. DESIGN, SETTING, AND PARTICIPANTS: This cohort study took place at community hospitals within 1 health care system. Participants included adult patients with a high risk of 30-day mortality who were admitted to 1 of 4 hospitals between January 2 and July 15, 2021. Patient encounters of inpatients in the intervention hospital where physicians were notified of the computed high risk mortality score were compared with patient encounters of inpatients in 3 community hospitals without the intervention (ie, matched control). INTERVENTION: Physicians of patients with a high risk of mortality within 30 days received notification and were encouraged to arrange for GOCDs. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage change of documented GOCDs prior to discharge. Propensity-score matching was completed on a preintervention and postintervention period using age, sex, race, COVID-19 status, and machine learning-predicted mortality risk scores. A difference-in-difference analysis validated the results. RESULTS: Overall, 537 patients were included in this study with 201 in the preintervention period (94 in the intervention group; 104 in the control group) and 336 patients in the postintervention period. The intervention and control groups included 168 patients per group and were well-balanced in age (mean [SD], 79.3 [9.60] vs 79.6 [9.21] years; standardized mean difference [SMD], 0.03), sex (female, 85 [51%] vs 85 [51%]; SMD, 0), race (White patients, 145 [86%] vs 144 [86%]; SMD 0.006), and Charlson comorbidities (median [range], 8.00 [2.00-15.0] vs 9.00 [2.00 to 19.0]; SMD, 0.34). Patients in the intervention group from preintervention to postintervention period were associated with being 5 times more likely to have documented GOCDs (OR, 5.11 [95% CI, 1.93 to 13.42]; P = .001) by discharge compared with matched controls, and GOCD occurred significantly earlier in the hospitalization in the intervention patients as compared with matched controls (median, 4 [95% CI, 3 to 6] days vs 16 [95% CI, 15 to not applicable] days; P \u3c .001). Similar findings were observed for Black patient and White patient subgroups. CONCLUSIONS AND RELEVANCE: In this cohort study, patients whose physicians had knowledge of high-risk predictions from machine learning mortality algorithms were associated with being 5 times more likely to have documented GOCDs than matched controls. Additional external validation is needed to determine if similar interventions would be helpful at other institutions

Crystal structure of bis(mu(2)-di-n-butyldithio-carbamato-kappa S-3,S ':S;kappa S-3:S:S ')-hexacarbonyl-di-rhenium(I), C24H36N2O6Re2

C24H36N2O6Re2, triclinic, P (1) over bar (no. 2), a = 10.3013(2) angstrom, b = 11.3471(2) angstrom, c = 14.5967(3) angstrom, alpha = 72.540(2)degrees, beta = 73.074(2)degrees,gamma = 85.369(2)degrees, V = 1557.05(6) angstrom(3), Z = 2, R-gt(F) = 0.0214, wR(ref)(F-2) = 0.0466, T = 100(2) K

Antigen glycosylation regulates efficacy of CAR T cells targeting CD19

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported. Here we identify expression of the Golgi-resident intramembrane protease Signal peptide peptidase-like 3 (SPPL3) in malignant B cells as a potent regulator of resistance to CAR therapy. Loss of SPPL3 results in hyperglycosylation of CD19, an alteration that directly inhibits CAR T cell effector function and suppresses anti-tumor cytotoxicity. Alternatively, over-expression of SPPL3 drives loss of CD19 protein, also enabling resistance. In this pre-clinical model these findings identify post-translational modification of CD19 as a mechanism of antigen escape from CAR T cell therapy

Deleterious Heteroplasmic Mitochondrial Mutations are associated With an increased Risk of Overall and Cancer-Specific Mortality

Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia