Activating Metal Sites for Biological Electron Transfer

This review focuses on the unique spectroscopic features of the blue copper active sites. These reflect a novel electronic structure that activates the site for rapid long-range electron transfer in its biological function. The role of the protein in determining the geometric and electronic structure of this site is defined, as is its contribution to function. This has been referred to as the entatic/rack-induced state. These concepts are then extended to cytochrome , which is also determined to be in an entatic state

Radiostereometric Analysis of Tantalum vs. Titanium Acetabular Shells in Young THR Patients

Introduction: In the active total hip replacement (THR) population, maintaining acetabular component stability and limiting polyethylene wear are crucial components to preventing premature implant failure. Titanium with Co/Cr/Mo fiber metal coating is among the most common materials used in cementless THR. Trabecular metal, composed of porous tantalum, has a metallic strut design resembling trabecular bone, designed to improve tissue infiltration and limit migration. This study assesses the stability and clinical outcomes of tantalum versus titanium acetabular shells using radiostereometric analysis (RSA) technology. Methods: In this IRB approved, prospective, randomized, blinded study, 46 patients received a primary THR by a single surgeon (DCA). Each patient was randomized to receive a titanium (23) (Trilogy, Zimmer) or tantalum (23) (Modular tantalum shell, Zimmer) uncemented hemispheric cup and either a highly-crosslinked or conventional polyethylene liner. Tantalum RSA markers were implanted around the liner periphery, femur, and periacetabular bone in each patient. RSA examinations, Harris Hip, UCLA, WOMAC, SF-36 scores were obtained at 10 days, 6 months, and annually with the furthest patients evaluated through 5 years. Results: Median translation was greater at all time points for the tantalum mesh cups except for the 3-year follow-up, however due to large standard errors, there was no significant difference between the two designs (p\u3e0.05). These large standard errors were predominantly caused by two outliers, neither of which had clinical evidence of loosening at 5 years follow-up. Mean UCLA, WOMAC, Harris Hip, and SF-36 PCS and MCS scores improved similarly in both groups. Conclusions: In this young THR population, both titanium and tantalum acetabular shells demonstrated excellent stability at five years follow up. Tantalum shells demonstrated slightly greater micromotion, but there was no statistically significant difference in shell migration. Outstanding clinical outcomes with statistically significant improvements in function and pain relief were observed in both groups

Radiostereometric Analysis of Femoral Head Penetration in Cross-Linked Polyethylene in THR Patients

Background: In the young total hip replacement (THR) population limiting polyethylene liner wear is crucial to preventing premature implant failure. Highly cross-linked ultra-high molecular weight polyethylene (HXLPE) liners were designed to improve wear resistance of polyethylene liners. Radiostereometric analysis (RSA) provides highly precise measurements of liner wear. This study utilized RSA to characterize wear of conventional versus HXLPE liners up to five years following THR. Methods: This IRB-approved, prospective, randomized, blinded study, involved 46 patients with a mean age of 58 and BMI of 30. Each patient was double randomized to receive a conventional or HXLPE liner with an uncemented titanium mesh or tantalum trabecular metal cup. Both liners were prepared from compression-molded GUR 1050 resin without calcium stearate, while HXLPE liners undergo further e-beam irradiation and annealing. At the time of surgery, 1mm tantalum RSA markers were implanted around the liner periphery, femur and periacetabular bone. RSA examinations, Harris Hip, UCLA, WOMAC, SF-36 scores were obtained pre-operatively, post-operatively, at six weeks, six months and annually through five years. Results: All patients had statistically significant improvement in Harris Hip, WOMAC and SF-36 PCS scores following THR with no difference between cohorts. On RSA examination, of titanium shells, HXLPE liners revealed significantly lower femoral head penetration at each follow up except six weeks and six months (p Conclusion: In this young THR population RSA shows significantly less femoral head penetration in the HXLPE liners compared to conventional liners. Novel RSA techniques have been developed to determine polyethylene wear in patients

FORCE-TJR: Innovative design for a national TJR comparative effectiveness research database

BACKGROUND: Joint replacement (TJR) registries have traditionnally focused on collecting implant data and analyzing time-to-revision. Sub-optimal outcomes short of revision are important to surgeons and patients. In 2010, the US federal Agency for Healthcare Research and Quality funded Function and Outcomes Research for Comparative Effectiveness in TJR (FORCE-TJR), a research consortium and database to collect comprehensive TJR outcomes, including patient-reported pain and function and post-operative sequelae. This $12 million research award will provide new information about post-TJR adverse events, patient-reported functional gain, and implant longevity. We developed novel methods to assure critical data collection and sustainability. METHODS: FORCE-TJR developed methods to (1) assemble a research consortium that includes a national sample of diverse surgeons and practices who agree to invite all patients to participate, (2) implement a virtual model for patient consent and data entry of consistent, validated patient-reported surveys, (3) conduct efficient screening for post-TJR sequelae and validated chart review and adjudication, and (4) document implant details. RESULTS: In the first 8 months, FORCE-TJR enrolled more than 90 surgeons in urban and rural settings, across 21 states; with academic, private, and HMO ownership; performing varied annual volumes of TJR surgery. Across practices, 80-95% of patients enrolled and more than 3250 patients consented to complete standardized surveys. More than 150 patients are enrolled each week, and enrollment rates will grow as additional surgeons join. CONCLUSION: FORCE-TJR employs innovative strategies to collect comprehensive post-TJR data from a national cohort of more than 30,000 patients. Comparative effectiveness research emerging from these data will include patient, implant, health system predictors of post-TJR adverse events, pain relief, functional gain, and revision. These TJR analyses will offer novel and important new evidence to guide patient and surgeon decisions, and are possible only because of this comprehensive research design

Modulational instability, solitons and beam propagation in spatially nonlocal nonlinear media

We present an overview of recent advances in the understanding of optical beams in nonlinear media with a spatially nonlocal nonlinear response. We discuss the impact of nonlocality on the modulational instability of plane waves, the collapse of finite-size beams, and the formation and interaction of spatial solitons.Comment: Review article, will be published in Journal of Optics B, special issue on Optical Solitons, 6 figure

Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites

A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates

Psilocybin desynchronizes the human brain

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trial

Political opportunity structures, democracy, and civil war

Theories of mobilization suggest that groups are more likely to resort to violence in the presence of political opportunity structures that afford greater prospects for extracting concessions from the government or better opportunities to topple ruling governments. However, existing efforts to consider the possible influences of political opportunity structures on incentives for violence and civil war empirically have almost invariably relied upon measures of democracy to proxy for the hypothesized mechanisms, most notably the argument that the opposing effects of political accommodation and repression will give rise to an inverted U-shaped relationship between democracy and the risk of civil war. The authors detail a number of problems with measures of democracy as proxies for political opportunity structures and develop alternative measures based on the likely risks that political leaders will lose power in irregular challenges and their implications for the incentives for resort to violence. The authors evaluate empirically how the security with which leaders hold office influences the prospects of violent civil conflict. The findings indicate that recent irregular leader entry and transitions indeed increase the risk of conflict onset, while democratic institutions are found to decrease the risk of civil war, after controlling for the new measures of state weakness. </jats:p