High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a nonpolar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard ­reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto ester derived and an α-phenyl cyclohexanone-­derived enol carbonate

Patient and Provider Experience with Artificial Intelligence Screening Technology for Diabetic Retinopathy in a Rural Primary Care Setting

Introduction: The development of autonomous artificial intelligence for interpreting diabetic retinopathy (DR) images has allowed for point-of-care testing in the primary care setting. This study describes patient and provider experiences and perceptions of the artificial intelligence DR screening technology called EyeArt by EyeNuk during implementation of the tool at Western Maine Primary Care in Norway, Maine. Methods: This non-randomized, single-center, prospective observational study surveyed 102 patients and 13 primary care providers on their experience of the new screening intervention. Results: All surveyed providers agreed that the new screening tool would improve access and annual screening rates. Some providers also identified initial challenges in incorporating the tool into the primary care visit (31%). Patients expressed a favorable view of the service, sharing an openness to being screened more regularly (75%) and a desire to have screenings performed at Western Maine Primary Care going forward (81%). Discussion: Patients were generally favorable about their experience with the new DR screening technology. Providers indicated challenges due to the limited availability of trained medical assistant photographers during the initial implementation of DR screening, as well as timing issues in coordinating screening with regular office appointments. Conclusions: This study supports further investigation of this technology in primary care, particularly in areas with challenges to care access. The potential benefits of this innovative tool in caring for people with diabetes includes improving access to retinopathy screenings and supporting wider detection of vision-threatening retinopathy

A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B

A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B

Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides

Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing aryl bromides with electron-deficient secondary phosphine oxides is reported. The resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX ligands. The presented strategy is a useful alternative to known methods for constructing PHOX derivatives

A High Angular Resolution Survey of Massive Stars in Cygnus OB2: Results from the Hubble Space Telescope Fine Guidance Sensors

We present results of a high angular resolution survey of massive OB stars in the Cygnus OB2 association that we conducted with the Fine Guidance Sensor 1R (FGS1r) on the Hubble Space Telescope. FGS1r is able to resolve binary systems with a magnitude difference delta-V < 4 down to separations as small as 0.01 arcsec. The sample includes 58 of the brighter members of Cyg OB2, one of the closest examples of an environment containing a large number of very young and massive stars. We resolved binary companions for 12 targets and confirmed the triple nature of one other target, and we offer evidence of marginally resolved companions for two additional stars. We confirm the binary nature of 11 of these systems from complementary adaptive optics imaging observations. The overall binary frequency in our study is 22% to 26% corresponding to orbital periods ranging from 20 - 20,000 years. When combined with the known short-period spectroscopic binaries, the results supports the hypothesis that the binary fraction among massive stars is > 60%. One of the new discoveries is a companion to the hypergiant star MT 304 = Cyg OB2-12, and future measurements of orbital motion should provide mass estimates for this very luminous star.Comment: accepted for AJ, 84 pages, 61 figure

Sickle cell trait and priapism: a case report and review of the literature

Background A 32 year-old African-American man presented to our institution after attempting suicide via ingestion with quetiapine. He had reported a history of several days of substance abuse with alcohol, cocaine and marijuana related to a partying binge. Following this, his partner removed him from his residence resulting in a suicide attempt. During hospitalization the patient developed priapism, a condition he had not experienced before. Case presentation Given this was his first time with priapism, an extensive work-up revealed the patient had previously undiagnosed sickle cell trait, which we postulate to have been a significant factor in his development of acute priapism. Sickle cell trait is considered to be a generally benign condition except for a few rare complications under more demanding physical conditions. However, upon reviewing the literature on the association of sickle cell trait with priapism, we believe this may not be the case. Case reports and small series that appeared in the 1960s and 1970s indicated an association between priapism and sickle trait. Little has been reported recently, and the general teaching regarding sickle cell trait does not include this information. However, one case was reported with the use of phosphodiesterase-5 (PDE-5) inhibitors and the development of priapism in a patient with sickle cell trait. These medications are now first line treatment in erectile dysfunction. They act by enhancing nitric oxide (NO) production leading to relaxation of smooth muscle in the corpora cavernosa and penile arteries. Conclusion Priapism was not reported in the initial studies of these medications. Further review of the literature indicates this may be a complex relationship. Interestingly, PDE5 inhibitors also have been postulated to be protective in sickle cell disease and perhaps also sickle cell trait because priapism might be caused by reduced NO availability. In this article, we examine the evidence linking sickle cell trait to priapism, explore the implications of PDE5 use, particularly in the setting of sickle cell trait, and propose that teaching about sickle cell trait include a discussion of priapism risk

The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms

OBJECTIVE. Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS. The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS. A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23–1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70–6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07–1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71–2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17–2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22–2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS. Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients

First Case Start Times for Vascular Surgery

Problem/Impact Statement: 85% of first cases at Maine Medical Center for Vascular Surgery start late. According to one study done by Aurora Health Care; of 5,500 first case surgeries, 88% of them started late. The impact of this is far reaching. It is not in alignment with MMC value of Patient Centered Care because the patient becomes dissatisfied waiting to be brought in to surgery , they are fasting for longer than anticipated, and being away from their family while they wait causing anxiety. The financial impact is $1995 for each 1⁄2 hr. of O.R. time. Furthermore, this may result in elective cases being canceled, late cases create a back log of cases to be done, the hospital loses potential revenue, and staff stay later causing overtime accrual

A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries

Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol