Viscosupplementation for the treatment of osteoarthritis of the knee (Review)

Background Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. Objectives To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). Search strategy MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched. Selection criteria RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). Data collection and analysis Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer. Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR). Main results Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. Authors' conclusions Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

Effect of gaze direction on neck muscle activity during cervical rotation

Control of the neck muscles is coordinated with the sensory organs of vision, hearing and balance. For instance, activity of splenius capitis (SC) is modified with gaze shift. This interaction between eye movement and neck muscle activity is likely to influence the control of neck movement. The aim of this study was to investigate the effect of eye position on neck muscle activity during cervical rotation. In eleven subjects we recorded electromyographic activity (EMG) of muscles that rotate the neck to the right [right obliquus capitis inferior (OI), multifides (MF), and SC, and left sternocleidomastoid (SCM)] with intramuscular or surface electrodes. In sitting, subjects rotated the neck in each direction to specific points in range that were held statically with gaze either fixed to a guide (at three different positions) that moved with the head to maintain a constant intra-orbit eye position or to a panel in front of the subject. Although right SC and left SCM EMG increased with rotation to the right, contrary to anatomical texts, OI EMG increased with both directions and MF EMG did not change from the activity recorded at rest. During neck rotation SCM and MF EMG was less when the eyes were maintained with a constant intra-orbit position that was opposite to the direction of rotation compared to trials in which the eyes were maintained in the same direction as the head movement. The inter-relationship between eye position and neck muscle activity may affect the control of neck posture and movement.

Cyclic MrIA: A stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the, beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

An integrated scheduling problem of PCB components on sequential pick-and-place machines:mathematical models and heuristic solutions

This paper formulates several mathematical models for determining the optimal sequence of component placements and assignment of component types to feeders simultaneously or the integrated scheduling problem for a type of surface mount technology placement machines, called the sequential pick-andplace (PAP) machine. A PAP machine has multiple stationary feeders storing components, a stationary working table holding a printed circuit board (PCB), and a movable placement head to pick up components from feeders and place them to a board. The objective of integrated problem is to minimize the total distance traveled by the placement head. Two integer nonlinear programming models are formulated first. Then, each of them is equivalently converted into an integer linear type. The models for the integrated problem are verified by two commercial packages. In addition, a hybrid genetic algorithm previously developed by the authors is adopted to solve the models. The algorithm not only generates the optimal solutions quickly for small-sized problems, but also outperforms the genetic algorithms developed by other researchers in terms of total traveling distance.

The tribology of linear tape recording systems

This thesis is devoted to the tribology at the head~to~tape interface of linear tape recording systems, OnStream ADRTM system being used as an experimental platform, Combining experimental characterisation with computer modelling, a comprehensive picture of the mechanisms involved in a tape recording system is drawn. The work is designed to isolate the mechanisms responsible for the physical spacing between head and tape with the aim of minimising spacing losses and errors and optimising signal output. Standard heads-used in ADR current products-and prototype heads- DLC and SPL coated and dummy heads built from a AI203-TiC and alternative single-phase ceramics intended to constitute the head tape-bearing surface-are tested in controlled environment for up to 500 hours (exceptionally 1000 hours), Evidences of wear on the standard head are mainly observable as a preferential wear of the TiC phase of the AI203-TiC ceramic, The TiC grains are believed to delaminate due to a fatigue wear mechanism, a hypothesis further confirmed via modelling, locating the maximum von Mises equivalent stress at a depth equivalent to the TiC recession (20 to 30 nm). Debris of TiC delaminated residues is moreover found trapped within the pole-tip recession, assumed therefore to provide three~body abrasive particles, thus increasing the pole-tip recession. Iron rich stain is found over the cycled standard head surface (preferentially over the pole-tip and to a lesser extent over the TiC grains) at any environment condition except high temperature/humidity, where mainly organic stain was apparent, Temperature (locally or globally) affects staining rate and aspect; stain transfer is generally promoted at high temperature. Humidity affects transfer rate and quantity; low humidity produces, thinner stains at higher rate. Stain generally targets preferentially head materials with high electrical conductivity, i.e. Permalloy and TiC. Stains are found to decrease the friction at the head-to-tape interface, delay the TiC recession hollow-out and act as a protective soft coating reducing the pole-tip recession. This is obviously at the expense of an additional spacing at the head-to-tape interface of the order of 20 nm. Two kinds of wear resistant coating are tested: diamond like carbon (DLC) and superprotective layer (SPL), 10 nm and 20 to 40 nm thick, respectively. DLC coating disappears within 100 hours due possibly to abrasive and fatigue wear. SPL coatings are generally more resistant, particularly at high temperature and low humidity, possibly in relation with stain transfer. 20 nm coatings are found to rely on the substrate wear behaviour whereas 40 nm coatings are found to rely on the adhesive strength at the coating/substrate interface. These observations seem to locate the wear-driving forces 40 nm below the surface, hence indicate that for coatings in the 10 nm thickness range-· i,e. compatible with high-density recording-the substrate resistance must be taken into account. Single-phase ceramic as candidate for wear-resistant tape-bearing surface are tested in form of full-contour dummy-heads. The absence of a second phase eliminates the preferential wear observed at the AI203-TiC surface; very low wear rates and no evidence of brittle fracture are observed.

Mechanisms of transfer film formation on data recording heads

The increasing demand for high capacity data storage requires decreasing the head-to-tape gap and reducing the track width. A problem very often encountered is the development of adhesive debris on the heads at low humidity and high temperatures that can lead to an increase of space between the head and media, and thus a decrease in the playback signal. The influence of stains on the playback signal of reading heads is studied using RAW (Read After Write) tests and their influence on the wear of the heads by using indentation technique. The playback signal has been found to vary and the errors to increase as stains form a patchy pattern and grow in size to form a continuous layer. The indentation technique shows that stains reduce the wear rate of the heads. In addition, the wear tends to be more pronounced at the leading edge of the head compared to the trailing one. Chemical analysis of the stains using ferrite samples in conjunction with MP (metal particulate) tapes shows that stains contain iron particles and polymeric binder transferred from the MP tape. The chemical anchors in the binder used to grip the iron particles now react with the ferrite surface to create strong chemical bonds. At high humidity, a thin layer of iron oxyhydroxide forms on the surface of the ferrite. This soft material increases the wear rate and so reduces the amount of stain present on the heads. The stability of the binder under high humidity and under high temperature as well as the chemical reactions that might occur on the ferrite poles of the heads influences the dynamic behaviour of stains. A model of stain formation taking into account the channels of binder degradation and evolution upon different environmental conditions is proposed.

A comparison of the estrous behavior of Holstein-Friesian cows when cubicle-housed and at pasture

This study compared estrous behavior of dairy cows kept in cubicle housing and fed a total mixed ration diet (HOUSED treatment) with that of cows kept at pasture with concentrate supplementation (PASTURE treatment). Behavior was compared both in the 48 h around standing estrus and during the standing estrus period. The 23 spring-calving Holstein-Friesians in each treatment were observed directly three times per day for nine weeks. The occurrence of nine selected behaviors associated with estrus was recorded during 20 min observation sessions. Twelve standing estrus events from each treatment were selected for analysis of the frequency of these nine behaviours over the 48 h around standing estrus. Milk progesterone profiles were used to confirm the dates of standing estrus events. Attempting to mount other cows, sniffing the anogenital region of other cows, resting the chin on other cows, receiving chin rests and head-to-head butts all showed significant changes in frequency in the 48 h around standing estrus in both treatments, reaching a peak during standing estrus (P ≤ 0.05). Mounting other cows increased significantly in the PASTURE treatment around standing estrus (P <0.001), but not in the HOUSED treatment. The frequency of ano-genital sniffs received by the animals in the PASTURE treatment also increased significantly around standing estrus (P <0.01) but not in the HOUSED treatment. When the animals were in standing estrus there was a significantly higher frequency of standing to be mounted in PASTURE than in HOUSED cows (median (q1, q3) PASTURE = 2.5 (1.0, 3.0), HOUSED = 0.0 (0.0, 1.0)) (P <0.01), but no difference in the frequency of the other eight sexual behaviors recorded. HOUSED cows did not exhibit the same increase in mounting during the standing estrus period as PASTURE cows and received fewer mounts in observation sessions during standing estrus. These results have implications for the use of estrus detection systems that rely solely on mounting behavior in cubicle-housed dairy cows. © 2012 Elsevier Inc.

The Impact of Motor Learning on Motor Behavior and Cortical Dynamics in a Complex Stressful Social Environment

An economy of effort is a core characteristic of highly skilled motor performance often described as being effortless or automatic. Electroencephalographic (EEG) evaluation of cortical activity in elite performers has consistently revealed a reduction in extraneous associative cortical activity and an enhancement of task-relevant cortical processes. However, this has only been demonstrated under what are essentially practice-like conditions. Recently it has been shown that cerebral cortical activity becomes less efficient when performance occurs in a stressful, complex social environment. This dissertation examines the impact of motor skill training or practice on the EEG cortical dynamics that underlie performance in a stressful, complex social environment. Sixteen ROTC cadets participated in head-to-head pistol shooting competitions before and after completing nine sessions of skill training over three weeks. Spectral power increased in the theta frequency band and decreased in the low alpha frequency band after skill training. EEG Coherence increased in the left frontal region and decreased in the left temporal region after the practice intervention. These suggest a refinement of cerebral cortical dynamics with a reduction of task extraneous processing in the left frontal region and an enhancement of task related processing in the left temporal region consistent with the skill level reached by participants. Partitioning performance into ‘best’ and ‘worst’ based on shot score revealed that deliberate practice appears to optimize cerebral cortical activity of ‘best’ performances which are accompanied by a reduction in task-specific processes reflected by increased high-alpha power, while ‘worst’ performances are characterized by an inappropriate reduction in task-specific processing resulting in a loss of focus reflected by higher high-alpha power after training when compared to ‘best’ performances. Together, these studies demonstrate the power of experience afforded by practice, as a controllable factor, to promote resilience of cerebral cortical efficiency in complex environments.

Essays on Financial Constraints, R&D Investments, and Competition

This dissertation consists of two chapters of theoretical studies that investigate the effect of financial constraints and market competition on research and development (R&D) investments. In the first chapter, I explore the impact of financial constraints on two different types of R&D investments. In the second chapter, I examine the impact of market competition on the relationship between financial constraints and R&D investments. In the first chapter, I develop a dynamic monopoly model to study a firm’s R&D strategy. Contrary to intuition, I show that a financially constrained firm may invest more aggressively in R&D projects than an unconstrained firm. Financial constraints introduce a risk that a firm may run out of money before its project bears fruit, which leads to involuntary termination on an otherwise positive-NPV project. For a company that relies on cash flow from assets in place to keep its R&D project alive, early success can be relatively important. I find that when the discovery process can be expedited by heavier investment (“accelerable” projects), a financially constrained company may find it optimal to “over”-invest in order to raise the probability of project survival. The over-investment will not happen if the project is only “scalable” (investment scales up payoffs). The model generates several testable implications regarding over-investment and project values. In the second chapter, I study the effects of competition on R&D investments in a duopoly framework. Using a homogeneous duopoly model where two unconstrained firms compete head to head in an R&D race, I find that competition has no effect on R&D investment if the project is not accelerable, and the competing firms are not constrained. In a heterogeneous duopoly model where a financially constrained firm competes against an unconstrained firm, I discover interesting strategic interactions that lead to preemption by the constrained firm in equilibrium. The unconstrained competitor responds to its constrained rival’s investment in an inverted-U shape fashion. When the constrained competitor has high cash flow risk, it accelerates the innovation in equilibrium, while the unconstrained firm invests less aggressively and waits for its rival to quit the race due to shortage of funds.

Lot production size problem and simulation of urban transport

OBJECTIVES AND STUDY METHOD: There are two subjects in this thesis: “Lot production size for a parallel machine scheduling problem with auxiliary equipment” and “Bus holding for a simulated traffic network”. Although these two themes seem unrelated, the main idea is the optimization of complex systems. The “Lot production size for a parallel machine scheduling problem with auxiliary equipment” deals with a manufacturing setting where sets of pieces form finished products. The aim is to maximize the profit of the finished products. Each piece may be processed in more than one mold. Molds must be mounted on machines with their corresponding installation setup times. The key point of our methodology is to solve the single period lot-sizing decisions for the finished products together with the piece-mold and the mold-machine assignments, relaxing the constraint that a single mold may not be used in two machines at the same time. For the “Bus holding for a simulated traffic network” we deal with One of the most annoying problems in urban bus operations is bus bunching, which happens when two or more buses arrive at a stop nose to tail. Bus bunching reflects an unreliable service that affects transit operations by increasing passenger-waiting times. This work proposes a linear mathematical programming model that establishes bus holding times at certain stops along a transit corridor to avoid bus bunching. Our approach needs real-time input, so we simulate a transit corridor and apply our mathematical model to the data generated. Thus, the inherent variability of a transit system is considered by the simulation, while the optimization model takes into account the key variables and constraints of the bus operation. CONTRIBUTIONS AND CONCLUSIONS: For the “Lot production size for a parallel machine scheduling problem with auxiliary equipment” the relaxation we propose able to find solutions more efficiently, moreover our experimental results show that most of the solutions verify that molds are non-overlapping even if they are installed on several machines. We propose an exact integer linear programming, a Relax&Fix heuristic, and a multistart greedy algorithm to solve this problem. Experimental results on instances based on real-world data show the efficiency of our approaches. The mathematical model and the algorithm for the lot production size problem, showed in this research, can be used for production planners to help in the scheduling of the manufacturing. For the “Bus holding for a simulated traffic network” most of the literature considers quadratic models that minimize passenger-waiting times, but they are harder to solve and therefore difficult to operate by real-time systems. On the other hand, our methodology reduces passenger-waiting times efficiently given our linear programming model, with the characteristic of applying control intervals just every 5 minutes.

Levantamento preliminar dos nemátodes anisaquídeos presentes no Gorz, Pagellus bogaraveo, (Br nnich, 1768), no estado selvagem na Região Autònoma da Madeira

Dissertação de mest. em Aquacultura, Faculdade de Ciências do Mar e do Ambiente, Univ. do Algarve, 2001

Head and eye movements and lane keeping in drivers with hemianopia and quadrantanopia compared to controls

Purpose: To compare the eye and head movements and lane-keeping of drivers with hemianopia and quadrantanopia with that of age-matched controls when driving under real world conditions. Methods: Participants included 22 hemianopes and 8 quadrantanopes (M age 53 yrs) and 30 persons with normal visual fields (M age 52 yrs) who were ≥ 6 months from the brain injury date and either a current driver or aiming to resume driving. All participants drove an instrumented dual-brake vehicle along a 14-mile route in traffic that included non-interstate city driving and interstate driving. Driving performance was scored using a standardised assessment system by two “backseat” raters and the Vigil Vanguard system which provides objective measures of speed, braking and acceleration, cornering, and video-based footage from which eye and head movements and lane-keeping can be derived. Results: As compared to drivers with normal visual fields, drivers with hemianopia or quadrantanopia on average were significantly more likely to drive slower, to exhibit less excessive cornering forces or acceleration, and to execute more shoulder movements off the seat. Those hemianopic and quadrantanopic drivers rated as safe to drive by the backseat evaluator made significantly more excursive eye movements, exhibited more stable lane positioning, less sudden braking events and drove at higher speeds than those rated as unsafe, while there was no difference between safe and unsafe drivers in head movements. Conclusions: Persons with hemianopic and quadrantanopic field defects rated as safe to drive have different driving characteristics compared to those rated as unsafe when assessed using objective measures of driving performance.