Unified Treatment of Asymptotic van der Waals Forces

In a framework for long-range density-functional theory we present a unified full-field treatment of the asymptotic van der Waals interaction for atoms, molecules, surfaces, and other objects. The only input needed consists of the electron densities of the interacting fragments and the static polarizability or the static image plane, which can be easily evaluated in a ground-state density-functional calculation for each fragment. Results for separated atoms, molecules, and for atoms/molecules outside surfaces are in agreement with those of other, more elaborate, calculations.Comment: 6 pages, 5 figure

Safety in Nonhuman Primates of Ocular AAV2-\u3cem\u3eRPE65\u3c/em\u3e, a Candidate Treatment for Blindness in Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is a molecularly heterogeneous disease group that leads to blindness. LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV- RPE65 vector. Human ocular gene transfer trials are being considered. Our safety studies of subretinal AAV-2/2. RPE65 in RPE65 -mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses. We now test the hypothesis that there can be vector-related toxicity to the normal monkey, with its human-like retina. Good Laboratory Practice safety studies following single intraocular injections of AAV-2/2. RPE65 in normal cynomolgus monkeys were performed for 1-week and 3-month durations. Systemic toxicity was not identified. Ocular-specific studies included clinical examinations, electroretinography, and retinal histopathology. Signs of ocular inflammation postinjection had almost disappeared by 1 week. At 3 months, electroretinography in vector-injected eyes was no different than in vehicle-injected control eyes or compared with presurgical recordings. Healed sites of retinal perforation from subretinal injections were noted clinically and by histopathology. Foveal architecture in subretinally injected eyes, vector or vehicle, could be abnormal. Morphometry of central retina showed no photoreceptor layer thickness abnormalities occurring in a dose-dependent manner. Vector sequences were present in the injected retina, vitreous, and optic nerve at 1 week but not consistently in the brain. At 3 months, there were no vector sequences in optic nerve and brain. The results allow for consideration of an upper range for no observed adverse effect level in future human trials of subretinal AAV-2/2. RPE65. The potential value of foveal treatment for LCA and other retinal degenerations warrants further research into how to achieve gene transfer without retinal injury from surgical detachment of the retina

Substance abuse treatment and psychiatric comorbidity: do benefits spill over? analysis of data from a prospective trial among cocaine-dependent homeless persons

BACKGROUND: Comorbid psychiatric illness can undermine outcomes among homeless persons undergoing addiction treatment, and psychiatric specialty care is not always readily available. The prognosis for nonsubstance abuse psychiatric diagnoses among homeless persons receiving behaviorally-based addiction treatment, however, is little studied. RESULTS: Data from an addiction treatment trial for 95 cocaine-dependent homeless persons (1996–1998) were used to profile psychiatric diagnoses at baseline and 6 months, including mood-related disorders (e.g. depression) and anxiety-related disorders (e.g. post-traumatic stress disorder). Treatment interventions, including systematic reinforcement for goal attainment, were behavioral in orientation. There was a 32% reduction in the prevalence of comorbid non-addiction psychiatric disorder from baseline to 6 months, with similar reductions in the prevalence of mood (-32%) and anxiety-related disorders (-20%) (p = 0.12). CONCLUSION: Among cocaine-dependent homeless persons with psychiatric comorbidity undergoing behavioral addiction treatment, a reduction in comorbid psychiatric disorder prevalence was observed over 6 months. Not all participants improved, suggesting that even evidence-based addiction treatment will prove insufficient for a meaningful proportion of the dually diagnosed homeless population

Barriers to Predicting the Mechanisms and Risk Factors of Non-Contact Anterior Cruciate Ligament Injury

High incidences of non-contact anterior cruciate ligament (ACL) injury, frequent requirements for ACL reconstruction, and limited understanding of ACL mechanics have engendered considerable interest in quantifying the ACL loading mechanisms. Although some progress has been made to better understand non-contact ACL injuries, information on how and why non-contact ACL injuries occur is still largely unavailable. In other words, research is yet to yield consensus on injury mechanisms and risk factors. Biomechanics, video analysis, and related study approaches have elucidated to some extent how ACL injuries occur. However, these approaches are limited because they provide estimates, rather than precise measurements of knee - and more specifically ACL - kinematics at the time of injury. These study approaches are also limited in their inability to simultaneously capture many of the contributing factors to injury

Ulnar-sided wrist pain. II. Clinical imaging and treatment

Pain at the ulnar aspect of the wrist is a diagnostic challenge for hand surgeons and radiologists due to the small and complex anatomical structures involved. In this article, imaging modalities including radiography, arthrography, ultrasound (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography are compared with regard to differential diagnosis. Clinical imaging findings are reviewed for a more comprehensive understanding of this disorder. Treatments for the common diseases that cause the ulnar-sided wrist pain including extensor carpi ulnaris (ECU) tendonitis, flexor carpi ulnaris (FCU) tendonitis, pisotriquetral arthritis, triangular fibrocartilage complex (TFCC) lesions, ulnar impaction, lunotriquetral (LT) instability, and distal radioulnar joint (DRUJ) instability are reviewed

Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease