Showing papers by "Tufts University published in 2006"
TL;DR: The MDRD Study equation has now been reexpressed for use with a standardized serum creatinine assay, allowing GFR estimates to be reported in clinical practice by using standardized serumcreatinine and overcoming this limitation to the current use of GFR estimating equations.
Abstract: Using standardized creatinine assays, the authors remeasured serum creatinine levels in 1628 patients whose glomerular filtration rate (GFR) had been measured by urinary clearance of 125I-isothalam...
5,115 citations
TL;DR: It is shown that viral-mediated, mesolimbic dopamine pathway–specific knockdown of brain-derived neurotrophic factor is required for the development of experience-dependent social aversion in mice experiencing repeated aggression.
Abstract: Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.
1,873 citations
16 Oct 2006
TL;DR: This paper recommends benchmarking selection and evaluation methodologies, and introduces the DaCapo benchmarks, a set of open source, client-side Java benchmarks that improve over SPEC Java in a variety of ways, including more complex code, richer object behaviors, and more demanding memory system requirements.
Abstract: Since benchmarks drive computer science research and industry product development, which ones we use and how we evaluate them are key questions for the community. Despite complex runtime tradeoffs due to dynamic compilation and garbage collection required for Java programs, many evaluations still use methodologies developed for C, C++, and Fortran. SPEC, the dominant purveyor of benchmarks, compounded this problem by institutionalizing these methodologies for their Java benchmark suite. This paper recommends benchmarking selection and evaluation methodologies, and introduces the DaCapo benchmarks, a set of open source, client-side Java benchmarks. We demonstrate that the complex interactions of (1) architecture, (2) compiler, (3) virtual machine, (4) memory management, and (5) application require more extensive evaluation than C, C++, and Fortran which stress (4) much less, and do not require (3). We use and introduce new value, time-series, and statistical metrics for static and dynamic properties such as code complexity, code size, heap composition, and pointer mutations. No benchmark suite is definitive, but these metrics show that DaCapo improves over SPEC Java in a variety of ways, including more complex code, richer object behaviors, and more demanding memory system requirements. This paper takes a step towards improving methodologies for choosing and evaluating benchmarks to foster innovation in system design and implementation for Java and other managed languages.
1,561 citations
TL;DR: The use of the 10 contemporary biomarkers that were studied adds only moderately to standard risk factors and only small increases in the ability to classify risk, as measured by the C statistic.
Abstract: BACKGROUND Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.
1,286 citations
TL;DR: It is proposed that posttraumatic stress disorder is characterized by exaggerated amygdala responses and deficient frontal cortical function and deficiencies in extinction and the capacity to suppress attention/response to trauma-related stimuli, as well as deficient hippocampal function.
1,247 citations
TL;DR: The NKDEP Laboratory Working Group has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum Creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study.
Abstract: Background: Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given.
Methods: The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement.
Results: The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study.
Conclusions: The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [<133 μmol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [<60 mL · min−1 · (1.73 m2)−1]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed.
1,140 citations
TL;DR: Electrospun silk-fibroin-based scaffolds are potential candidates for bone tissue engineering and the mild aqueous process required to spin the fibers offers an important option for delivery of labile cytokines and other components into the system.
1,115 citations
TL;DR: Cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib, where cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death.
Abstract: Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. Here we report ten individuals who developed severe congestive heart failure while on imatinib and we show that imatinib-treated mice develop left ventricular contractile dysfunction. Transmission electron micrographs from humans and mice treated with imatinib show mitochondrial abnormalities and accumulation of membrane whorls in both vacuoles and the sarco- (endo-) plasmic reticulum, findings suggestive of a toxic myopathy. With imatinib treatment, cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death. Retroviral gene transfer of an imatinib-resistant mutant of c-Abl, alleviation of ER stress or inhibition of Jun amino-terminal kinases, which are activated as a consequence of ER stress, largely rescues cardiomyocytes from imatinib-induced death. Thus, cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib.
1,091 citations
TL;DR: Neuroimaging research reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma‐unrelated affective information and suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD.
Abstract: The last decade of neuroimaging research has yielded important information concerning the structure, neurochemistry, and function of the amygdala, medial prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD). Neuroimaging research reviewed in this article reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma-unrelated affective information. Importantly, amygdala responsivity is positively associated with symptom severity in PTSD. In contrast, medial prefrontal cortex appears to be volumetrically smaller and is hyporesponsive during symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity. Lastly, the reviewed research suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD. Remaining research questions and related future directions are presented.
1,058 citations
TL;DR: Evidence suggests that increased consumption of n-3 FAs from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke.
996 citations
TL;DR: In this paper, B. mori silk fibroin films were studied thermally using temperature-modulated differential scanning calorimetry (TMDSC) to obtain the reversing heat capacity.
Abstract: We report a study of self-assembled beta-pleated sheets in B. mori silk fibroin films using thermal analysis and infrared spectroscopy. B. mori silk fibroin may stand as an exemplar of fibrous proteins containing crystalline beta-sheets. Materials were prepared from concentrated solutions (2−5 wt % fibroin in water) and then dried to achieve a less ordered state without beta-sheets. Crystallization of beta-pleated sheets was effected either by heating the films above the glass transition temperature (Tg) and holding isothermally or by exposure to methanol. The fractions of secondary structural components including random coils, alpha-helices, beta-pleated sheets, turns, and side chains were evaluated using Fourier self-deconvolution (FSD) of the infrared absorbance spectra. The silk fibroin films were studied thermally using temperature-modulated differential scanning calorimetry (TMDSC) to obtain the reversing heat capacity. The increment of the reversing heat capacity ΔCp0(Tg) at the glass transition fo...
TL;DR: Recent research into two fundamental bacterial small-molecule signaling pathways are reviewed, suggesting how these two pathways may converge to control complex processes including multicellularity, biofilm formation, and virulence.
Abstract: Bacteria use diverse small molecules for extra- and intracellular signaling. They scan small-molecule mixtures to access information about both their extracellular environment and their intracellular physiological status, and based on this information, they continuously interpret their circumstances and react rapidly to changes. Bacteria must integrate extra- and intracellular signaling information to mount appropriate responses to changes in their environment. We review recent research into two fundamental bacterial small-molecule signaling pathways: extracellular quorum-sensing signaling and intracellular cyclic dinucleotide signaling. We suggest how these two pathways may converge to control complex processes including multicellularity, biofilm formation, and virulence. We also outline new questions that have arisen from recent studies in these fields.
TL;DR: Stem cell-based tissue engineering using 3D silk fibroin scaffolds has expanded the use of silk-based biomaterials as promising scaffolds for engineering a range of skeletal tissues like bone, ligament, and cartilage, as well as connective tissues like skin.
TL;DR: Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy.
Abstract: Background— Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. Methods and Results— We prospectively analyzed 320 consecutive HCM patients (age, 47±17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients ≥50 mm Hg and were not exercised. Of the other 201 patients with gradients <50 mm Hg at rest (average, 4±9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve–septal contact after exercise (80±43 mm Hg), including 76 with marked gradients ≥50 mm Hg and 46 with ...
Book•
01 Jan 2006TL;DR: Dennett has never been one to shy away from big topics in philosophy as mentioned in this paper, and he is perhaps best known for his 1991 classic "The Self-Critique of Reason".
Abstract: By Daniel C. Dennett. New York: Viking, 2006. xvi + 448 pp., $25.95 cloth. Daniel Dennett has never been one to shy away from big topics in philosophy. He is perhaps best known for his 1991 classic...
TL;DR: It is suggested that obese people are more likely than people of normal weight to develop infections of various types including postoperative infections and other nosocomial infections, as well to develop serious complications of common infections.
Abstract: Obesity increases morbidity and mortality through its multiple effects on nearly every human system. However, the various aspects of the association between obesity and infection have not been reviewed. Thus, we reviewed the relevant literature focusing on clinical aspects of this association. Obesity has a clear but not yet precisely defined effect on the immune response through a variety of immune mediators, which leads to susceptibility to infections. Data on the incidence and outcome of specific infections, especially community-acquired infections, in obese people are so far limited. The available data suggest that obese people are more likely than people of normal weight to develop infections of various types including postoperative infections and other nosocomial infections, as well to develop serious complications of common infections. Large prospective studies are required to further define the burden of infectious morbidity and mortality conferred by obesity.
TL;DR: The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides, particularly among people with more elevated levels, and fish oil consumption also modestly improves HDL cholesterol, increases LDL cholesterol levels, but does not appear to adversely affect glucose homeostasis.
TL;DR: New evidence shows that polymyxins have less toxicity than previously reported, and the avoidance of concurrent administration of nephrotoxic and/or neurotoxic drugs, careful dosing, as well as more meticulous management of fluid and electrolyte abnormalities and use of critical care services may be some of the reasons for the discrepancy between data reported.
Abstract: The increasing problem of multidrug-resistant Gram-negative bacteria causing severe infections and the shortage of new antibiotics to combat them has led to the re-evaluation of polymyxins. These antibiotics were discovered from different species of Bacillus polymyxa in 1947; only two of them, polymyxin B and E (colistin), have been used in clinical practice. Their effectiveness in the treatment of infections due to susceptible Gram-negative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii, has not been generally questioned. However, their use was abandoned, except in patients with cystic fibrosis, because of concerns related to toxicity. We reviewed old and recent evidence regarding polymyxin-induced toxicity by searching Pubmed (from 1950 until May 2005). It was reported in the old literature that the use of polymyxins was associated with considerable toxicity, mainly nephrotoxicity and neurotoxicity, including neuromuscular blockade. However, recent studies showed that the incidence of nephrotoxicity is less common and severe compared to the old studies. In addition, neurotoxic effects of polymyxins are usually mild and resolve after prompt discontinuation of the antibiotics. Furthermore, cases of neuromuscular blockade and apnea have not been reported in the recent literature. New evidence shows that polymyxins have less toxicity than previously reported. The avoidance of concurrent administration of nephrotoxic and/or neurotoxic drugs, careful dosing, as well as more meticulous management of fluid and electrolyte abnormalities and use of critical care services may be some of the reasons for the discrepancy between data reported in the old and recent literature.
TL;DR: The notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation is supported, as well as the fact that PUFAs were independently associated with lower levels of proinflammatory markers and higher levels of antiinflammatory markers independent of confounders.
Abstract: Aims: Persons with high intake of polyunsaturated fatty acids (PUFAs) have lower cardiovascular morbidity and mortality. The protective effect of PUFAs is mediated by multiple mechanisms, including their antiinflammatory properties. The association of physiological PUFA levels with pro- and antiinflammatory markers has not been established. Methods and Results: In 1123 persons (aged 20–98 yr), we examined the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers. Adjusting for age, sex, and major confounders, lower arachidonic and docosahexaenoic acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGF. Lower -linolenic acid was associated with higherC-reactiveproteinandIL-1ra,andlowereicosapentaenoicacid was associated with higher IL-6 and lower TGF. Lower docosahexaenoic acid was strongly associated with lower IL-10. Total n-3 fatty acids were associated with lower IL-6 (P 0.005), IL-1ra (P 0.004), and TNF (P 0.040) and higher soluble IL-6r (P 0.001), IL-10 (P 0.024), and TGF (P 0.0012). Lower n-6 fatty acid levels weresignificantlyassociatedwithhigherIL-1ra(P0.026)andlower TGF(P0.014).Then-6ton-3ratiowasastrong,negativecorrelate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates. Conclusions: In this community-based sample, PUFAs, and especially total n-3 fatty acids, were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNF, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL6r, IL-10, TGF) independent of confounders. Our findings support the notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation. (J Clin Endocrinol Metab 91: 439–446, 2006)
TL;DR: The frequency of hyponatremia occurring in special clinical conditions--including congestive heart failure, cirrhosis, pneumonia, and acquired immunodeficiency syndrome--as well as in marathon runners will be reviewed.
TL;DR: It is shown that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions.
TL;DR: It is shown that ob/ob mice had diminished locomotor response to amphetamine and lacked locomotor sensitization to repeated amphetamine injections, both defects reversed by leptin infusion, and indicates that the mesoaccumbens DA pathway, critical to integrating motivated behavior, responds to this adipose-derived signal.
TL;DR: Evidence‐based information regarding the bioactivity of this herb is presented, and animal model studies indicate potent antiinflammatory action, some antimutagenic and cholesterol‐lowering activities, as well as antispasmotic and anxiolytic effects.
Abstract: Chamomile (Matricaria recutita L., Chamomilla recutita L., Matricaria chamomilla) is one of the most popular single ingredient herbal teas, or tisanes. Chamomile tea, brewed from dried flower heads, has been used traditionally for medicinal purposes. Evidence-based information regarding the bioactivity of this herb is presented. The main constituents of the flowers include several phenolic compounds, primarily the flavonoids apigenin, quercetin, patuletin, luteolin and their glucosides. The principal components of the essential oil extracted from the flowers are the terpenoids alpha-bisabolol and its oxides and azulenes, including chamazulene. Chamomile has moderate antioxidant and antimicrobial activities, and significant antiplatelet activity in vitro. Animal model studies indicate potent antiinflammatory action, some antimutagenic and cholesterol-lowering activities, as well as antispasmotic and anxiolytic effects. However, human studies are limited, and clinical trials examining the purported sedative properties of chamomile tea are absent. Adverse reactions to chamomile, consumed as a tisane or applied topically, have been reported among those with allergies to other plants in the daisy family, i.e. Asteraceae or Compositae.
TL;DR: The mechanisms used by homeothermic species to generate more heat and their regulation largely by thyroid hormone and the sympathetic nervous system are reviewed, finding that thyroid hormone plays a critical role in modulating the amount of the active TH, T(3), in BAT, thereby modulated the responses to SNS.
Abstract: Increased heat generation from biological processes is inherent to homeothermy. Homeothermic species produce more heat from sustaining a more active metabolism as well as from reducing fuel efficie...
TL;DR: Evidence‐based research regarding the bioactivity of this herb is reviewed and animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential.
Abstract: Peppermint (Mentha piperita L.) is one of the most widely consumed single ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant leaves, and the essential oil of peppermint are used in traditional medicines. Evidence-based research regarding the bioactivity of this herb is reviewed. The phenolic constituents of the leaves include rosmarinic acid and several flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile components of the essential oil are menthol and menthone. In vitro, peppermint has significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential. Human studies on the GI, respiratory tract and analgesic effects of peppermint oil and its constituents have been reported. Several clinical trials examining the effects of peppermint oil on irritable bowel syndrome (IBS) symptoms have been conducted. However, human studies of peppermint leaf are limited and clinical trials of peppermint tea are absent. Adverse reactions to peppermint tea have not been reported, although caution has been urged for peppermint oil therapy in patients with GI reflux, hiatal hernia or kidney stones.
TL;DR: Perinatal exposure to environmentally relevant BPA doses results in morphological and functional alterations of the male and female genital tract and Mammary glands that may predispose the tissue to earlier onset of disease, reduced fertility and mammary and prostate cancer.
TL;DR: The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.
Abstract: Background— Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. Methods and Results— This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treat...
TL;DR: The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.
Abstract: Purpose Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium) could improve the efficacy of systemic chemotherapy in patients with advanced melanoma. Patients and Methods We randomly assigned chemotherapy-naive patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival. Results Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (...
TL;DR: Self-reporting of adverse events after intravitreal bevacizumab injections did not show an increased rate of potential drug-related ocular or systemic events, and short-term results suggest that intrav itreal beVacIZumab seems to be safe.
Abstract: Aim: Off-label intravitreal injections of bevacizumab (Avastin) have been given for the treatment of neovascular and exudative ocular diseases since May 2005 Since then, the use of intravitreal bevacizumab has spread worldwide, but the drug-related adverse events associated with its use have been reported only in a few retrospective reviews The International Intravitreal Bevacizumab Safety Survey was initiated to gather timely information regarding adverse events from doctors around the world via the internet Methods: An internet-based survey was designed to identify adverse events associated with intravitreal bevacizumab treatment The survey web address was disseminated to the international vitreoretinal community via email Rates of adverse events were calculated from participant responses Results: 70 centres from 12 countries reported on 7113 injections given to 5228 patients Doctor-reported adverse events included corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation or uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal haemorrhage, retinal pigment epithelium tears, blood pressure elevation, transient ischaemic attack, cerebrovascular accident and death None of the adverse event rates exceeded 021% Conclusion: Intravitreal bevacizumab is being used globally for ocular diseases Self-reporting of adverse events after intravitreal bevacizumab injections did not show an increased rate of potential drug-related ocular or systemic events These short-term results suggest that intravitreal bevacizumab seems to be safe
TL;DR: The views expressed at the third session of the workshop "Tissue Engineering--The Next Generation," which was devoted to the engineering of complex tissue structures, included systems providing temporal and spatial regulation of growth factor availability and a clinician's perspective for functional tissue regeneration.
Abstract: This article summarizes the views expressed at the third session of the workshop "Tissue Engineering--The Next Generation," which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a "guided interplay" between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from "adult biology" of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician's perspective for functional tissue regeneration, and discussed new biomaterials that can be used to develop new regenerative technologies.