Precedential Decisions at the PTAB: An Endangered Species?

This Article describes the USPTO’s practice of designating certain opinions as precedential, informative, or representative and compares it to the practice of issuing precedential opinions at other agencies that conduct quasi-judicial proceedings. The Article explores the impact of these agency practices on stare decisis. It concludes that the USPTO should simplify its designation process, increase the number of precedential opinions, and by doing so improve consistency and predictability

Prevalence and patterns of higher-order drug interactions in Escherichia coli.

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems

Design and Formation of a Large, Tetrahedral, Metal-ligand Cluster Using 1,1'-Binaphthyl Ligands

Many chemists have been fascinated with the development of discrete supramolecular structures that encapsulate guest molecules. These structures can be assembled through covalent or hydrogen bonds, electrostatic or metal-ligand interactions. These host structures have provided valuable insight into the forces involved in small molecule recognition. Our work has focused on the design and study of metal-ligand clusters of varying sizes. The naphthalene [M{sub 4}L{sub 6}]{sup 12-} cluster 1, shown in Figure 1, has demonstrated diastereoselective guest binding and chiral induction properties as well as the ability to catalyze reactions carried out inside the cavity in an enzyme-like manner. However, the size of the cavity (ca. 300-500 {angstrom}{sup 3}) has often limited the scope of substrates for these transformations

Association Between Public Reporting of Outcomes With Procedural Management and Mortality for Patients With Acute Myocardial Infarction

AbstractBackgroundPublic reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients.ObjectivesThis study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI).MethodsUsing the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting.ResultsAmong 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83).ConclusionsPublic reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI

Association between diagnosis code expansion and changes in 30-day risk-adjusted outcomes for cardiovascular diseases

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service beneficiaries aged ≥65 years. The acute myocardial infarction cohort and the heart failure cohort had 578 728 and 1 595 069 hospitalizations, respectively. We calculate comorbidities using (1) inpatient-only limited diagnoses, (2) inpatient-only unlimited diagnoses, (3) inpatient and outpatient limited diagnoses, and (4) inpatient and outpatient unlimited diagnoses. Across both cohorts

Screening and isolating eastern redcedar phytochemicals for creating economic opportunities in Missouri [abstract]

Eastern Redcedar (ERC) is one of the most widely distributed tree species in Missouri. The ERC is an important source of bioactive secondary metabolites, but very few of these biologically active compounds have been identified, purified or commercialized. An interdisciplinary collaboration between MU scientists was initiated in 2007 to identify and isolate biologically active phytochemicals from ERC tissues for possible commercial application. Our team has identified and purified biologically active compounds from leaves (needles) and fruit of the ERC. Many of these isolated diterpenoids not only have shown strong anti-microbial activities against a wide range of pathogenic bacteria, but also strong inhibitory activities against melanin biosynthesis. Recently, the isolated tricyclic diterpenoids have been recognized as promising anti-inflammatory, anti-microbial, and skin whitening agents by cosmetic and pharmaceutical industries. The objectives of the proposed study are to: 1) isolate and characterize the biologically active phytochemicals, and 2) elucidate chemical structures of active compounds and their associated mode of actions. The first of these compounds to be characterized is the purified bioactive diterpenoid. The purified bioactive diterpenoid was found to have a significant inhibitory effect on the growth of all Gram positive pathogens tested. This inhibition of Gram positive bacteria is likely due to action on the cell division machinery, for affected cells elongate without proper separation. Additional compounds have activity on fungal agents, as well as potential anti-melanin activities. The knowledge generated from our research will provide the opportunities to turn abundant, low-value, renewable materials from the ERC into a lucrative, high technology industry in Missouri. INVENTOR(S): Chun-Ho Lin; Brian M. Thompson; Hsin-Yeh Hsieh; Robert J. Kremer; Robert N. Lerch; Michael A. Gold and Harold E. Garrett CONTACT INFO: Harriet F. Francis, MS; J.D.; [email protected]; 573.884.0374 Per Stromhaug, Ph.D., MBA; [email protected]; 573.884.355

Andreev Reflection and Spin Injection into s−s- and d−d-wave Superconductors

We study the effect of spin injection into $s-$ and $d-$wave superconductors, with an emphasis on the interplay between boundary and bulk spin transport properties. The quantities of interest include the amount of non-equilibrium magnetization ($m$), as well as the induced spin-dependent current ($I_s$) and boundary voltage ($V_s$). In general, the Andreev reflection makes each of the three quantities depend on a different combination of the boundary and bulk contributions. The situation simplifies either for half-metallic ferromagnets or in the strong barrier limit, where both $V_s$ and $m$ depend solely on the bulk spin transport/relaxation properties. The implications of our results for the on-going spin injection experiments in high $T_c$ cuprates are discussed.Comment: 4 pages, REVTEX, 1 figure included; typos correcte

Arabidopsis BRUTUS-LIKE E3 ligases negatively regulate iron uptake by targeting transcription factor FIT for recycling

Organisms need to balance sufficient uptake of iron (Fe) with possible toxicity. In plant roots, a regulon of uptake genes is transcriptionally activated under Fe deficiency, but it is unknown how this response is inactivated when Fe becomes available. Here we describe the function of 2 partially redundant E3 ubiquitin ligases, BRUTUS-LIKE1 (BTSL1) and BTSL2, in Arabidopsis thaliana and provide evidence that they target the transcription factor FIT, a key regulator of Fe uptake, for degradation. The btsl double mutant failed to effectively down-regulate the transcription of genes controlled by FIT, and accumulated toxic levels of Fe in roots and leaves. The C-terminal domains of BTSL1 and BTSL2 exhibited E3 ligase activity, and interacted with FIT but not its dimeric partner bHLH39. The BTSL proteins were able to poly-ubiquitinate FIT in vitro and promote FIT degradation in vivo. Thus, posttranslational control of FIT is critical to prevent excess Fe uptake

Arabidopsis BRUTUS-LIKE E3 ligases negatively regulate iron uptake by targeting transcription factor FIT for recycling

Organisms need to balance sufficient uptake of iron (Fe) with possible toxicity. In plant roots, a regulon of uptake genes is transcriptionally activated under Fe deficiency, but it is unknown how this response is inactivated when Fe becomes available. Here we describe the function of 2 partially redundant E3 ubiquitin ligases, BRUTUS-LIKE1 (BTSL1) and BTSL2, in Arabidopsis thaliana and provide evidence that they target the transcription factor FIT, a key regulator of Fe uptake, for degradation. The btsl double mutant failed to effectively down-regulate the transcription of genes controlled by FIT, and accumulated toxic levels of Fe in roots and leaves. The C-terminal domains of BTSL1 and BTSL2 exhibited E3 ligase activity, and interacted with FIT but not its dimeric partner bHLH39. The BTSL proteins were able to poly-ubiquitinate FIT in vitro and promote FIT degradation in vivo. Thus, posttranslational control of FIT is critical to prevent excess Fe uptake

Risk‐Treatment Paradox in the Selection of Transradial Access for Percutaneous Coronary Intervention

Background: Access site complications contribute to morbidity and mortality during percutaneous coronary intervention (PCI). Transradial arterial access significantly lowers the risk of access site complications compared to transfemoral arteriotomy. We sought to develop a prediction model for access site complications in patients undergoing PCI with femoral arteriotomy, and assess whether transradial access was selectively used in patients at high risk for complications. Methods and Results: We analyzed 17 509 patients who underwent PCI without circulatory support from 2008 to 2011 at 5 institutions. Transradial arterial access was used in 17.8% of patients. In those who underwent transfemoral access, 177 (1.2%) patients had access site complications. Using preprocedural clinical and demographic data, a prediction model for femoral arteriotomy complications was generated. The variables retained in the model included: elevated age (P<0.001), female gender (P<0.001), elevated troponin (P<0.001), decreased renal function or dialysis (P=0.002), emergent PCI (P=0.01), prior PCI (P=0.005), diabetes (P=0.008), and peripheral artery disease (P=0.003). The model showed moderate discrimination (optimism‐adjusted c‐statistic=0.72) and was internally validated via bootstrap resampling. Patients with higher predicted risk of complications via transfemoral access were less likely to receive transradial access (P<0.001). Similar results were seen in patients presenting with and without ST‐segment myocardial infarction and when adjusting for individual physician operator. Conclusions: We generated and validated a model for transfemoral access site complications during PCI. Paradoxically, patients most likely to develop access site complications from transfemoral access, and therefore benefit from transradial access, were the least likely to receive transradial access