Frequency dynamics of gain-switched injection-locked semiconductor lasers

The frequency dynamics of gain-switched singlemode semiconductor lasers subject to optical injection is investigated. The requirements for low time jitter and reduced frequency chirp operation are studied as a function of the frequency mismatch between the master and slave lasers. Suppression of the power overshoot, typical during gain-switched operation, can be achieved for selected frequency detunings.

Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.

This clinical study was based on experimental results obtained in nude mice grafted with human colon carcinoma, showing that injected 131I-labeled F(ab')2 and Fab fragments from high affinity anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) gave markedly higher ratios of tumor to normal tissue localization than intact MAb. 31 patients with known colorectal carcinoma, including 10 primary tumors, 13 local tumor recurrences, and 21 metastatic involvements, were injected with 123I-labeled F(ab')2 (n = 14) or Fab (n = 17) fragments from MAb anti-CEA. The patients were examined by emission-computerized tomography (ECT) at 6, 24, and sometimes 48 h after injection using a rotating dual head scintillation camera. All 23 primary tumors and local recurrences except one were clearly visualized on at least two sections of different tomographic planes. Interestingly, nine of these patients had almost normal circulating CEA levels, and three of the visualized tumors weighed only 3-5 g. Among 19 known metastatic tumor involvements, 14 were correctly localized by ECT. Two additional liver and several bone metastases were discovered by immunoscintigraphy. Altogether, 86% of the tumor sites were detected, 82% with F(ab')2 and 89% with Fab fragments. The contrast of the tumor images obtained with Fab fragments suggests that this improved method of immunoscintigraphy has the potential to detect early tumor recurrences and thus to increase the survival of patients. The results of this retrospective study, however, should be confirmed in a prospective study before this method can be recommended for the routine diagnosis of cancer.

An improved method for measuring soil microbial activity by gas phase flow injection analysis

The rate of carbon dioxide production is commonly used as a measure of microbial activity in the soil. The traditional method of CO2 determination involves trapping CO2 in an alkali solution and then determining CO2 concentration indirectly by titration of the remaining alkali in the solution. This method is still commonly employed in laboratories throughout the world due to its relative simplicity and the fact that it does not require expensive, specific equipment. However, there are several drawbacks: the method is time-consuming, requires large amounts of chemicals and the consistency of results depends on the operator's skills. With this in mind, an improved method was developed to analyze CO2 captured in alkali traps, which is cheap and relatively simple, with a substantially shorter sample handling time and reproducibility equivalent to the traditional titration method. A comparison of the concentration values determined by gas phase flow injection analysis (GPFIA) and titration showed no significant difference (p > 0.05), but GPFIA has the advantage that only a tenth of the sample volume of the titration method is required. The GPFIA system does not require the purchase of new, costly equipment but the device was constructed from items commonly found in laboratories, with suggestions for alternative configurations for other detection units. Furthermore, GPFIA for CO2 analysis can be equally applied to samples obtained from either the headspace of microcosms or from a sampling chamber that allows CO2 to be released from alkali trapping solutions. The optimised GPFIA method was applied to analyse CO2 released from degrading hydrocarbons from a site contaminated by diesel spillage.

Intrathecal administration of Ziconotide: does single-shot injection predict efficacy?

Introduction: Though a trial of intrathecal (IT) therapy should always be performed before implantation of a definitive intrathecal pump, there is no agreement as to how this test should be performed. Ziconotide is trialed in most of cases with continuous IT administration using implanted catheters. Unlike other intrathecal drugs, there is little experience with single bolus IT injections of ziconotide. The aim of the study is to assess the feasibility of single-shot IT trialing with ziconotide. Patients and methods: Eleven consecutive patients with chronic neuropathic intractable pain were trialed with a single IT bolus of 2.5 mcg of ziconotide. Pain and side effects are monitored for at least 72 hours after the injection. Depending on the response, a second injection is given a week later, with either the same dose (if VAS decreased ≥50% without side effects), a higher dose of 3.75 mcg (if VAS decreased <50% without side effects) or a lower dose of 1.25 mcg (if VAS decreased ≥50% but with side effects). If VAS decreased less than 50% and side effects occurred, no further injection was performed. When VAS decreased >50% without side effects after the first or the second dose, the result is confirmed by one more injection of the same dose one week later. The trial is considered positive if two successive injections provide a VAS decreased more than 50% without side effects. Results: Eleven patients (6 females and 5 males) were included. Nine patients experienced modest or no pain relief. Four of these had significant side effects (dizziness, nausea, vomiting or abdominal pain) and had no further injection. In the others 5, one patient retired from study and four received a second injection of 3.75 mcg. The trial was negative in all 5 cases because of side effects (dizziness, drowsiness, weakness, muscle cramps), the pain decreased in only 2 patients. Two patients experienced profound pain relief with an IT injection of 2.5 mcg. One patient had no side effects and the other had dizziness and drowsiness that disappeared with an injection of 1.25 mcg. Pain relief without adverse effects was confirmed with the second injection. The trial was considered positive for those two patients. Discussion and conclusion: The response rate of 18% (2/11) is consistent with the success rate of a continuous infusion trialing with an implanted catheter. Single-shot injection of ziconotide may therefore predict efficacy.

Involvement of the RasGAP derived fragment N in the resistance of pancreatic beta cells towards apoptosis

RESUME DESTINE AUX NON SCIENTIFIQUESLe diabète est une maladie associée à un excès de glucose (sucre) dans le sang. Le taux de glucose sanguin augmente lorsque l'action d'une hormone, l'insuline, responsable du transport du glucose du sang vers les tissus de l'organisme diminue, ou lorsque les quantités d'insuline à disposition sont inadéquates.L'une des causes communes entre les deux grands types de diabète connus, le type 1 et le type 2, est la disparition des cellules beta du pancréas, spécialisées dans la sécrétion d'insuline, par mort cellulaire programmée aussi appelée apoptose. Alors que dans le diabète de type 1, la destruction des cellules beta est causée par notre propre système immunitaire, dans le diabète de type 2, la mort de ces cellules, est principalement causée par des concentrations élevées de graisses saturés ou de molécules impliquées dans l'inflammation que l'on rencontre en quantités augmentées chez les personnes obèses. Etant donné l'augmentation épidémique du nombre de personnes obèses de par le monde, on estime que le nombre de personnes diabétiques (dont une majorité sont des diabétiques de type 2), va passer de 171 million en l'an 2000, à 366 million en l'an 2030, expliquant la nécessité absolue de mettre au point de nouvelles stratégies thérapeutique pour combattre cette maladie.L'apoptose est un processus complexe dont la dérégulation induit de nombreuses affections allant du cancer jusqu'au diabète. L'activation de caspase 3, une protéine clé contrôlant la mort cellulaire, était connue pour systématiquement mener à la mort cellulaire programmée. Ces dernières années, notre laboratoire a décrit des mécanismes de survie qui sont activés par caspase 3 et qui expliquent sans doute pourquoi son activation ne mène pas systématiquement à la mort cellulaire. Lorsqu'elle est faiblement activée, caspase 3 clive une autre protéine appelée RasGAP en deux protéines plus courtes dont l'une, appelée le fragment Ν a la particularité de protéger les cellules contre l'apoptose.Durant ma thèse, j'ai été impliqué dans divers projets destinés à mieux comprendre comment le fragment Ν protégeait les cellules contre l'apoptose et à savoir s'il pouvait être utilisé comme outil thérapeutique dans les conditions de survenue d'un diabète expérimental. C'est dans ce but que nous avons créé une souris transgénique, appelée RIP-N, exprimant le fragment Ν spécifiquement dans les cellules beta. Comme attendu, les cellules beta de ces souris étaient plus résistantes à la mort induite par des composés connus pour induire le diabète, comme certaines molécules induisant l'inflammation ou les graisses saturées. Nous avons ensuite pu montrer que les souris RIP-N étaient plus résistantes à la survenue d'un diabète expérimental que ce soit par l'injection d'une drogue induisant l'apoptose des cellules beta, que ce soit dans un fond génétique caractérisé par une attaque spontanée des cellules beta par le système immunitaire ou dans le contexte d'un diabète de type 2 induit par l'obésité. Dans plusieurs des modèles animaux étudiés, nous avons pu montrer que le fragment Ν protégeait les cellules en activant une voie protectrice bien connue impliquant successivement les protéines Ras, PI3K et Akt ainsi qu'en bloquant la capacité d'Akt d'activer le facteur NFKB, connu pour être délétère pour la survie de la cellule beta. La capacité qu'a le fragment Ν d'activer Akt tout en prévenant l'activation de NFKB par Akt est par conséquent particulièrement intéressante dans l'intégration des signaux régulant la mort cellulaire dans le contexte de la survenue d'un diabète.La perspective d'utiliser le fragment Ν comme outil thérapeutique dépendra de notre capacité à activer les signaux protecteurs induits par le fragment Ν depuis l'extérieur de la cellule ou de dériver des peptides perméables aux cellules possédant les propriétés du fragment N.2 SUMMARYDiabetes mellitus is an illness associated with excess blood glucose. Blood glucose levels raise when the action of insulin decreases or when insulin is provided in inappropriate amounts. In type 1 diabetes (T1D) as well as in type 2 diabetes (T2D), the insulin secreting beta cells in the pancreas undergo controlled cell death also called apoptosis. Whereas in T1D, beta cells are killed by the immune system, in T2D, they are killed by several factors, among which are increased blood glucose levels, increased levels of harmful lipids or pro-inflammatory cytokines that are released by the dysfunctional fat tissue of obese people. Given the epidemic increase in the number of obese people throughout the world, the number of diabetic people (a majority of which are type 2 diabetes) is estimated to rise from 171 million affected people in the year 2000 to 366 million in 2030 explaining the absolute requirement for new therapies to fight the disease.Apoptosis is a very complex process whose deregulation leads to a wide range of diseases going from cancer to diabetes. Caspase 3 although known as a key molecule controlling apoptosis, has been shown to have various other functions. In the past few years, our laboratory has described a survival mechanism, that takes place at low caspase activity and that might explain how cells that activate their caspases for reasons other than apoptosis survive. In such conditions, caspase 3 cleaves another protein called RasGAP into two shorter proteins, one of which, called fragment N, protects cells from apoptosis.We decided to check whether fragment Ν could be used as a therapeutical tool in the context of diabetes inducing conditions. We thus derived a transgenic mouse line, called RIP-N, in which the expression of fragment Ν is restricted to beta cells. As expected, the beta cells of these mice were more resistant ex-vivo to cell death induced by diabetes inducing factors. We then showed that the RIP-N transgenic mice were resistant to streptozotocin induced diabetes, a mouse model mimicking type 1 diabetes, which correlated to fewer number of apoptotic beta cells in the pancreas of the transgenic mice compared to their controls. The RIP-N transgene also delayed overt diabetes development in the NOD background, a mouse model of autoimmune type 1 diabetes, and delayed the occurrence of obesity induced hyperglycemia in a mouse model of type 2-like diabetes. Interestingly, fragment Ν was mediating its protection by activating the protective Akt kinase, and by blocking the detrimental NFKB factor. Our future ability to activate the protective signals elicited by fragment Ν from the outside of cells or to derive cell permeable peptides bearing the protective properties of fragment Ν might condition our ability to use this protein as a therapeutic tool.3 RESUMELe diabète est une maladie associée à un excès de glucose plasmatique. La glycémie augmente lorsque l'action de l'insuline diminue ou lorsque les quantités d'insuline à disposition sont inadéquates. Dans le diabète de type 1 (D1) comme dans le diabète de type 2 (D2), les cellules beta du pancréas subissent la mort cellulaire programmée aussi appelée apoptose. Alors que dans le D1 les cellules beta sont tuées par le système immunitaire, dans le D2 elles sont tuées par divers facteurs parmi lesquels on trouve des concentrations élevées de glucose, d'acides gras saturés ou de cytokines pro-inflammatoires qui sont sécrétées en concentrations augmentées par le tissu adipeux dysfonctionnel des personnes obèses. Etant donné l'augmentation épidémique du nombre de personnes obèses de par le monde, on estime que le nombre de personnes diabétiques (dont une majorité sont des diabétiques de type 2), va passer de 171 million en l'an 2000, à 366 million en l'an 2030, justifiant la nécessité absolue de mettre au point de nouvelles stratégies thérapeutique pour combattre cette maladie.L'apoptose est un processus complexe dont la dérégulation induit de nombreuses affections allant du cancer jusqu'au diabète. Caspase 3, bien que connue comme étant une protéine clé contrôlant l'apoptose a bien d'autres fonctions démontrées. Ces dernières années, notre laboratoire a décrit un mécanisme de survie qui est activé lorsque caspase 3 est faiblement activée et qui explique probablement comment des cellules qui ont activé leurs caspases pour une autre raison que l'apoptose peuvent survivre. Dans ces conditions, caspase 3 clive une autre protéine appelée RasGAP en deux protéines plus courtes dont l'une, appelée le fragment Ν a la particularité de protéger les cellules contre l'apoptose.Nous avons donc décidé de vérifier si le fragment Ν pouvait être utilisé comme outil thérapeutique dans les conditions de survenue d'un diabète expérimental. Pour se faire, nous avons créé une souris transgénique, appelée RIP-N, exprimant le fragment Ν spécifiquement dans les cellules beta. Comme attendu, les cellules beta de ces souris étaient plus résistantes ex-vivo à la mort induite par des facteurs pro-diabétogènes. Nous avons ensuite pu montrer que les souris RIP-N étaient plus résistantes à la survenue d'un diabète induit par la streptozotocine, un drogue mimant la survenue d'un D1 et que ceci était corrélée à une diminution du nombre de cellules en apoptose dans le pancréas des souris transgéniques comparé à leurs contrôles. L'expression du transgène a aussi eu pour effet de retarder la survenue d'un diabète franc dans le fond génétique NOD, un modèle génétique de diabète de type 1 auto-immun, ainsi que de retarder la survenue d'une hyperglycémie dans un modèle murin de diabète de type 2 induit par l'obésité. Dans plusieurs des modèles animaux étudiés, nous avons pu montrer que le fragment Ν protégeait les cellules en activant la kinase protectrice Akt ainsi qu'en bloquant le facteur délétère NFKB. La perspective d'utiliser le fragment Ν comme outil thérapeutique dépendra de notre capacité à activer les signaux protecteurs induits par le fragment Ν depuis l'extérieur de la cellule ou de dériver des peptides perméables aux cellules possédant les propriétés du fragment

Treatment of velopharyngeal insufficiency by autologous fat injection.

Velopharyngeal insufficiency (VPI) is a structural or functional trouble, which causes hypernasal speech. Velopharyngeal flaps, speech therapy and augmentation pharyngoplasty, using different implants, have all been used to address this trouble. We hereby present our results following rhinopharyngeal autologous fat injection in 18 patients with mild velopharyngeal insufficiency (12 soft palate clefts, 4 functional VPI, 2 myopathy). 28 injections were carried out between 2004 and 2007. The degree of hypernasal speech was evaluated pre- and postoperatively by a speech therapist and an ENT specialist and quantified by an acoustic nasometry (Kay Elemetrics). All patients were exhaustively treated with preoperative speech therapy (average, 8 years). The mean value of the nasalance score was 37% preoperatively and 23% postoperatively (p = 0.015). The hypernasality was reduced postoperatively in all patients (1-3 degrees of the Borel-Maisonny score). There were no major complications, two minor complications (one hematoma, one cervical pain). The autologous fat injection is a simple, safe, minimally invasive procedure. It proves to be efficient in cases of mild velopharyngeal insufficiency or after a suboptimal velopharyngoplasty.

A role for altered TLR gene expression in association with increased expression of CD200R in the induction of mucosal tissue CD4(+) Treg in aged mice following gavage with a liver extract along with intramuscular monophosphoryl lipid A (MPLA) injection.

Previous studies showed a fetal sheep liver extract (FSLE), in association with LPS, injected into aged (>20 months) mice reversed the altered polarization (increased IL-4 and IL-10 with decreased IL-2 and IFN-gamma) in cytokine production seen from ConA stimulated lymphoid cells of those mice. Aged mice show a >60% decline in numbers and suppressive function of both CD4(+)CD25(+)Foxp3(+)Treg and so-called Tr3 (CD4(+)TGFbeta(+)). Their number/function is restored to levels seen in control (8-week-old) mice by FSLE. We have reported at length on the ability of a novel pair of immunoregulatory molecules, members of the TREM family, namely CD200:CD200R, to control development of dendritic cells (DCs) which themselves regulate production of Foxp3(+) Treg. The latter express a distinct subset of TLRs which control their function. We report that a feature of the altered Treg expression following combined treatment with FSLE and monophosphoryl lipid A, MPLA (a bioactive component of lipid A of LPS) is the altered gene expression both of distinct subsets of TLRs and of CD200Rs. We speculate that this may represent one of the mechanisms by which FSLE and MPLA alter immunity in aged mice.

Supervised injection services : what has been demonstrated? A systematic literature review

BACKGROUND: Supervised injection services (SISs) have been developed to promote safer drug injection practices, enhance health-related behaviors among people who inject drugs (PWID), and connect PWID with external health and social services. Nevertheless, SISs have also been accused of fostering drug use and drug trafficking. AIMS: To systematically collect and synthesize the currently available evidence regarding SIS-induced benefits and harm. METHODS: A systematic review was performed via the PubMed, Web of Science, and ScienceDirect databases using the keyword algorithm [("supervised" or "safer") and ("injection" or "injecting" or "shooting" or "consumption") and ("facility" or "facilities" or "room" or "gallery" or "centre" or "site")]. RESULTS: Seventy-five relevant articles were found. All studies converged to find that SISs were efficacious in attracting the most marginalized PWID, promoting safer injection conditions, enhancing access to primary health care, and reducing the overdose frequency. SISs were not found to increase drug injecting, drug trafficking or crime in the surrounding environments. SISs were found to be associated with reduced levels of public drug injections and dropped syringes. Of the articles, 85% originated from Vancouver or Sydney. CONCLUSION: SISs have largely fulfilled their initial objectives without enhancing drug use or drug trafficking. Almost all of the studies found in this review were performed in Canada or Australia, whereas the majority of SISs are located in Europe. The implementation of new SISs in places with high rates of injection drug use and associated harms appears to be supported by evidence.

CT-guided cervical foraminal injection: Is a direct foraminal approach still necessary?

Purpose: Cervical foraminal injection performed with a direct foraminal approach may induce serious neurologic complications. We describe a technique of CT-guided cervical facet joint (CFJ) injection as an indirect foraminal injection, including feasibility and diffusion pathways of the contrast agent. Methods and materials: Retrospective study included 84 punctures in 65 consecutive patients presenting neck pain and/or radiculopathy related to osteoarthritis or soft disc herniation. CT images were obtained from C2 to T1 in supine position, with a metallic landmark on the skin. CFJ punctures were performed by MSK senior radiologists with a lateral approach. CT control of the CFJ opacification was performed after injections of contrast agent (1 ml), followed by slow-acting corticosteroid (25 mg). CFJ opacification was considered as successful when joint space and/or capsular recess opacification occurred. The diffusion of contrast agent in foraminal and epidural spaces was recorded. We assessed the epidural diffusion both on axial and sagittal images, with a classification in two groups (small diffusion or large diffusion). Results: CFJ opacification was successful in 82% (69/84). An epidural and/or foraminal opacification was obtained in 74% (51/69). A foraminal opacification occurred in 92% (47/51) and an epidural opacification in 63% (32/51), with small diffusion in 47% (15/32) and large diffusion in 53% (17/32). No complication occurred. Conclusion: CT- guided CFJ injection is easy to perform and safe. It is most often successful, with a frequent epidural and/or foraminal diffusion of the contrast agent. This technique could be an interesting and safe alternative to foraminal cervical injection.

Biodistribution of anti-CEA F(ab')2 fragments after intra-arterial and intravenous injection in patients with liver metastases due to colorectal carcinoma.

The biodistribution of simultaneous intra-arterial and intravenous injections of a radiolabelled anti-CEA MAb F(ab')2 fragment was studied in three patients with liver metastases from colorectal cancer. Identical MAb fragments, labelled with either 125I or 131I, were injected over a period of 30 min into the hepatic artery and into a peripheral vein. After 1 or 2 days, biodistribution was measured in the surgically removed metastases, normal tissue samples and blood. By tissue radioactivity counting, tumour uptake in the range 6.3-9.1% of injected dose per gram was found. Superimposable metastasis-to-blood and metastasis-to-normal liver ratios were obtained for both iodine isotopes in all three patients. The results indicate that the intra-arterial injection of MAb F(ab')2 fragments gives no measurable advantage over more convenient injections into a peripheral vein.

Microcontroller-driven fluid-injection system for atomic force microscopy.

We present a programmable microcontroller-driven injection system for the exchange of imaging medium during atomic force microscopy. Using this low-noise system, high-resolution imaging can be performed during this process of injection without disturbance. This latter circumstance was exemplified by the online imaging of conformational changes in DNA molecules during the injection of anticancer drug into the fluid chamber.

Bridge Deck Rehabilitation Rebonding a Delaminated PCC Overlay By Epoxy Injection, HR-1036, 1989

The Iowa demonstration project to promote the rehabilitation of bridge deck concrete by rebonding delaminations with injected epoxy is a 150 ft x 150 ft high truss bridge on Iowa route No. 210 over Indian Creek near Maxwell in Story County (Service level D, AADT-730, Inventory Rating HS-16.9, Operating Rating HS-25). The objective of this study was to evaluate the effectiveness of repairing a delaminated bridge deck by epoxy injection, specifically a bridge deck with a delaminated portland cement concrete overlay. Observations noted during the project lead to the following conclusions: The delaminations rebonded with epoxy have remained solid through five years. The percentage of delamination has stayed essentially the same for both the epoxy injected and non-repaired areas. Epoxy injection appears to be a practical, cost effective alternative to other forms of deck rehabilitation when undertaken at the proper time. Cost effectiveness would reduce dramatically if delayed until breakouts have occurred. On the other hand it would be a slow, labor intensive process if undertaken too early when delaminations are small.

Cervical radiculopathy: Efficiency of CT-guided cervical facet joint corticosteroid injection : 47

Purpose: Cervical foraminal injection performed with a direct approach of the foramen may induce serious neurologic complications. Cervical facet joint (CFJ) injections are easier to perform and safe, and may diffuse in the epidural and foraminal spaces. We analyzed the efficiency and tolerance of CT-guided CFJ slow-acting corticosteroid injection in patients with radiculopathy related to disc herniation. Methods and materials: Pilot study included 17 patients presenting typical cervical radiculopathy related to disc herniation without relief of pain after medical treatment (one month duration). CFJ puncture was performed under CT guidance with a lateral approach. CT control of the CFJ opacification was performed after injections of contrast agent (1 ml), followed by slow-acting corticosteroid (25 mg). Main criteria for judgment was pain relief one month later (delta visual analogical scale VAS for 0 to 100 mm). Diffusion of iodinated contrast agent in the foramen was assessed by two radiologists in consensus. Results: Pain relief was significant at one month (delta VAS 22 ± 23 mm, p = 0.001) and 41% (7/17) of patients had pain relief more than 50%. In cases with foraminal diffusion, pain relief more than 50% occured in 5 patients (50%) and only in 2 patients (29%) in cases without foraminal diffusion. No complication occurred. Conclusion: CT-guided CFJ slow-acting corticosteroid injection is safe and provided good results at one month follow-up. It may be considered as an interesting percutaneous treatment in patients suffering from cervical radicular pain related to disc herniation.