The most common way to treat item nonresponse in surveys is to replace a missing value by a plausible value constructed on the basis of fully observed variables. Treating the imputed values as if they were observed may lead to invalid inferences. Bootstrap variance estimators for various finite population parameters are obtained using two pseudo-population bootstrap schemes. We establish the asymptotic properties of the resulting bootstrap variance estimators for population totals and population quantiles. A simulation study suggests that the methods perform well in terms of relative bias and coverage probability.
Objective To evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS). Methods A total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause. Results During 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers. Conclusions Our findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men.
Marfan syndrome is a mutation in the fibrillin-1 gene resulting in a connective tissue disorder primarily affecting musculoskeletal, cardiovascular and ocular systems. However, patients with Marfan’s rarely manifest gastrointestinal symptoms. Midgut volvulus is abnormal twisting of small bowel around its mesentery that can result in compromising blood flow to the bowel causing intestinal ischemia and obstruction. Primary midgut volvulus is a term used when there is no underlying cause for the volvulus. This case describes an 80-year-old female with Marfan syndrome presenting with primary midgut volvulus, which preoperatively was suspected based on imaging, and later confirmed upon operative exploration. The small bowel mesentery was long with a narrow base twisted around its mesentery 360°. The long narrow base and floppy mesentery likely contributed to hypermobility leading to volvulus and small bowel obstruction. To our knowledge, this is the first reported case of primary midgut volvulus associated with Marfan’s syndrome.
A 53-year-old man with previous history of sigmoid colon adenocarcinoma who had undergone surgical resection and adjuvant chemotherapy presented with slightly rising carcinoembryonic antigen (CEA), while anatomical imaging modalities were unremarkable. FDG PET-CT study did not identify residual tumoral disease; however, there were abnormalities in the gallbladder most likely suggestive of cholecystitis. Eight weeks after cholecystectomy, serum CEA concentration reached normal values. Final histopathology of the gallbladder was also consistent with acute on chronic cholecystitis.
The dark matter in or around the cosmic voids affects their shapes. Thethermodynamical properties of dark matter can alter the ellipticity of cosmicvoids. Here, applying the dark matter equation of state from thepseudo-isothermal density profile of galaxies, we explore the shapes of cosmicvoids with the non zero pressure dark matter in different cosmological models.For this purpose, the linear growth of density perturbation in the presence ofdark matter pressure is calculated. In addition, the matter transfer functionconsidering the dark matter pressure, as well as the linear matter powerspectrum in the presence of the dark matter pressure are presented. Employingthese results, the probability density distribution for the ellipticity ofcosmic voids with the non zero pressure dark matter is calculated. Ourcalculations verify that the dark matter pressure leads to more sphericalshapes for the cosmic voids.
We introduce our new code MYOSOTIS (Make Your Own Synthetic ObservaTIonS)which is designed to produce synthetic observations from simulated clusters.The code can synthesise observations from both ground- and spaced-basedobservatories, for a range of different filters, observational conditions andangular/spectral resolution. In this paper, we highlight some of the featuresof MYOSOTIS, creating synthetic observations from young massive star clusters.Our model clusters are simulated using nbody6 code and have different totalmasses, half-mass radii, and binary fractions. The synthetic observations aremade at the age of 2 Myr with Solar metallicity and under different extinctionconditions. For each cluster, we create synthetic images of the Hubble SpaceTelescope (HST) in the visible (WFPC2/F555W) as well as Very Large Telescopes(VLT) in the nearIR (SPHERE/IRDIS/Ks). We show how MYOSOTIS can be used to lookat mass function (MF) determinations. For this aim we re-estimate stellarmasses using a photometric analysis on the synthetic images. The synthetic MFslopes are compared to their actual values. Our photometric analysisdemonstrate that depending on the adopted filter, extinction, angularresolution and pixel sampling of the instruments, the power-law index of theunderlying MFs can be shallower than the observed ones by at least 0.25 dexwhich is in agreement with the observed discrepancies reported in theliterature, specially for young star clusters.
Background Mucormycosis is a serious infection caused by fungi of the order Mucorales. Rhizopus delemar is the most common etiologic agent of mucormycosis. Pathogenesis studies of mucormycosis have been hampered by poor genetic trackability of the organism, owing to rare chromosomal integration events and multinucleated nature of the cells. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) system has been widely used in genetic manipulation through efficient homologous and non-homologous break points in a variety of organisms including R. delemar. However, plasmid-free CRISPR/Cas9 system has not been previously described in the fungus. Here, we introduce a rapid plasmid-free system for inducing orotidine 5’-phosphate decarboxylase (pyrF) gene mutation in R. delemar. Methods Protoplasts of R. delemar 99–880 strain were transformed with 20 nucleotide gRNA targeting the N-terminus of pyrF gene and the Cas9 enzyme. Screening for pyrF auxotrophy was carried out by plating transformed protoplasts on potato dextrose agar (PDA) plates containing 1 mg/mL 5-fluoroorotic acid (5-FOA) and 100 µg/mL uracil. Putative mutant strains were selected for uracil auxotrophy by plating simultaneously on media with or without uracil. pyrF disruption was verified by using PCR and qRT–PCR. Results Approximately100 transformants were generated through plating on 5-FOA plates. Only three transformants did not grow on minimal medium lacking uracil, indicating that they were true pyrF null mutants. PCR analysis showed that these three transformants have undergone nucleotide deletion events within the pyrF gene. The lack of pyrF gene expression was further verified by using qRT–PCR relative to wild-type R. delemar 99–880. Conclusion Similar to the plasmid-based genome manipulation strategy, the plasmid-free CRISPR/Cas9 system can induce gene editing in R. delemar. This rapid and simple approach adds an additional tool in our conquest to understand pathogenesis of mucormycosis. Disclosures All authors: No reported disclosures.
Background In this prospective nation-wide survey of bloodstream isolates associated with first episode of FN in high-risk cancer patients from 14 US cancer centers (December 2016 and June 2018), viridans group Streptococci (VGS) were the most common Gram-positive isolate. We sought to clinically and microbiologically characterize VGS bloodstream infections (BSI). Methods Among 343 patients,we compared 90 with VGS vs 253 with non-VGS BSI. Minimum inhibitory concentrations for blood culture isolates were determined by broth dilution for selected agents at our reference microbiology laboratory (UNMC). Clinical data were electronically captured in RedCap, including local site isolate identification and confirmatory reference lab identification via MALDI. Categorical and continuous variables were assessed via chi-square and Mann–Whitney U tests, respectively. Results Ninety-two VGS isolates were identified among 90 FN patients, representing 27% of all BSI isolates. S. mitis or oralis comprised 64 (70%) of VGS. There were no differences between age, sex, and primary diagnosis (50% with AML) among the 2 groups; 1/3 were HSCT recipients. Fluoroquinolone prophylaxis was used in 64 (71%) vs. 139 (55%), P < 0.01, in VGS vs non-VGS groups. Critical illness composite (new need for pressor(s), mechanical ventilation or death within 30 days) was 6 (7%) vs. 44 (17%), P = 0.01, in the VGS vs non-VGS groups. Figure 1 displays an overview of antibiotic susceptibilities for 79 testable isolates. VGS susceptibilities to levofloxacin, penicillin, and ceftriaxone were 39%, 47%, and 94%, respectively. Conclusion VGS are common pathogens in FN patients. Prior fluoroquinolone prophylaxis use may be a risk factor. VGS BSI was not associated with increased critical illness compared with non-VGS. Finally, assuming ceftriaxone susceptibility confers that of cefepime, >90% of VGS are susceptible to empiric FN cefepime regimens. Disclosures All authors: No reported disclosures.
Background Invasive pulmonary aspergillosis (IPA) is a serious fungal infection afflicting immunocompromised patients. Galactomannan (GM) detection in biological samples using the Platelia ELISA has been shown to predict therapy response by azoles, and polyenes. We previously reported on the activity of APX001 (fosmanogepix) in treating murine IPA. Here, we investigated the potential use of GM as a biomarker of APX001 efficacy in an immunosuppressed murine model of IPA. Methods ICR mice (n = 8/group) were immunosuppressed with cyclophosphamide and cortisone acetate on days −2, and +3, relative to infection with Aspergillus fumigatus via inhalation. Treatment with placebo (diluent control), APX001 (104 mg/kg, PO, a human equivalent dose), or posaconazole (POSA, 30 mg/kg, BID [equivalent to 6× the humanized dose]) began 16-hour post-infection and continued daily. To extend the half-life of APX001, mice were administered 50 mg/kg of the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) 2 hours prior to APX001 administration. Mice were sacrificed 48-, 72-, or 96-hour post-infection and their lungs, bronchoalveolar lavage (BAL) and sera were collected. Lung fungal burden was determined by conidial equivalent (CE) using qPCR, while GM was determined using the Platelia ELISA. Results Compared with placebo, APX001 or POSA treatment resulted in a gradual decrease in tissue fungal burden over time with APX001 or POSA showing significant reduction as early as 96 and 72 hours, respectively (P < 0.005). Although the super-therapeutic dose of POSA resulted in faster reduction in lung fungal burden after 72 hours, both drugs resulted in similar reduction (~6–7 log) in lung CE vs. placebo after 96 hours. Changes in GM levels in BAL or serum samples mirrored reductions in lung CFU with significant decrease seen after 96 hours or 72 hours for APX001 or POSA, respectively, vs. placebo (P < 0.02) (figure). Conclusion A human equivalent dose of APX001 and a super humanized dose of POSA resulted in a time-dependent reduction of lung fungal burden and GM levels when compared with placebo. These results show that GM can be used as a biomarker of APX001 efficacy in immunosuppressed mice. Disclosures All authors: No reported disclosures.