U.S. Commission on Immigration Reform

The U.S. Commission on Immigration Reform was created by Congress to assess U.S. immigration policy and make recommendations regarding its implementation and effects. Mandated in the Immigration Act of 1990 to submit an interim report in 1994 and a final report in 1997, the Commission has undertaken public hearings, fact-finding missions, and expert consultations to identify the major immigration-related issues facing the United States today.LBJ School of Public Affair

Met het oog op wachttijd

Zonder een goed functionerend hoornvlies, hierna genoemd cornea, kunnen de ogen hun taak niet goed uitvoeren. Iets meer dan 100 jaar geleden, in 1905, werd de eerstes uccesvolle transplantatie van een cornea van een overleden donor uitgevoerd in Tsjechië, door oogarts Zirm. Mede door de ontwikkeling van operatiemicroscopen, extra dun hechtdraad en het gebruik van antibiotica worden vandaag de dag in Nederland ongeveer 900 corneatransplantaties per jaar uitgevoerd. In Nederland is de Nederlandse transplantatie Stichting (NTS) verantwoordelijk voor het toewijzen van cornea’s aan patiënten (Bokhorst et al., 2007).\ud De gemiddelde wachttijd voor een cornea in Nederland is ongeveer een half jaar, ofwel 175 dagen. (Zie figuur 1) De door de NTS en oogartsen meest genoemde oorzaken zijn een tekort aan operatiecapaciteit en cornea’s en de fluctuatie in zowel vraag als aanbod van cornea’s. Ons eerste doel was te onderzoeken in welke mate deze zaken de wachttijd beïnvloeden. Een tweede doel was mogelijke verbeteringen aan te dragen

Translational and Regulatory Challenges for Exon Skipping Therapies

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.status: publishe

Human Performance Models of Pilot Behavior

Five modeling teams from industry and academia were chosen by the NASA Aviation Safety and Security Program to develop human performance models (HPM) of pilots performing taxi operations and runway instrument approaches with and without advanced displays. One representative from each team will serve as a panelist to discuss their team s model architecture, augmentations and advancements to HPMs, and aviation-safety related lessons learned. Panelists will discuss how modeling results are influenced by a model s architecture and structure, the role of the external environment, specific modeling advances and future directions and challenges for human performance modeling in aviation

Direct gene transfer into cardiac myocytes in vivo

Recent studies have demonstrated that cardiac and skeletal myocytes share the ability to take up and stably express plasmid DNA injected directly into myocardium or skeletal muscle in vivo. Although this is a relatively inefficient process, with less than 1% of the myocytes expressing the injected recombinant DNA, expression in these cells is stable for periods of at least 6 months. The majority of the injected DNA is maintained in myocytes as an episome and apparently does not undergo DNA replication. The direct DNA injection approach has been used to map cardiac-specific transcriptional regulatory elements in cellular promoter/enhancers. Expression of recombinant proteins in the heart following direct DNA injection also holds promise for the treatment of a variety of acquired and inherited cardiovascular diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29917/1/0000274.pd

Rates of referable eye disease in the Scottish National Diabetic Retinopathy Screening Programme

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Peer reviewedPublisher PD

Two distinct mechanisms of interleukin-2 gene expression in human T lymphocytes

Interleukin-2 (IL-2) gene regulation was investigated in primary cultures of highly purified human peripheral blood CD28+T cells. Two discrete mechanisms for induction of T-cell proliferation could be distinguished by examining cell cycle progression and the expression of the IL-2 gene. Stimulation of cells by CD3 MoAb induced only transiently expressed, small amounts of IL-2 mRNA that was completely suppressed by cyclosporine. Costimulation of T cells with CD3 MoAb and either CD28 MoAb or PMA, but not calcium ionophore, induced a 50-100-fold increased in IL-2 gene expression and secretion. High levels of IL-2 gene expression could also be achieved by stimulation with calcium ionophore and PMA or CD28 MoAb and PMA, but not by CD28 MoAb plus calcium ionophore. IL-2 gene expression and T-cell proliferation induced by CD3 MoAb plus PMA or calcium ionophore plus PMA were completely suppressible by cyclosporine. In contrast, IL-2 gene expression and T-cell proliferation induced by CD28 MoAb plus PMA were unaffected by cyclosporine. The CD28 signal was dependent on new protein synthesis. Nuclear run-on transcription assays showed that anti-CD28 did not affect lymphokine transcription. A major effect of CD28 stimulation on mRNA stability was shown by studies using actinomycin D; CD28 stimulation substantially increased the half-life of IL-2 and TNF-alpha mRNA. The effects of anti-CD28 stimulation were specific for growth factors, and thus differ from previously described effects of cycloheximide on mRNA stability. These studies suggest the existence of two biochemical pathways for the induction of IL-2 production, one that occurs at the transcriptional level and is mediated by intracellular calcium release and protein kinase C and is cyclosporine-sensitive, and one that acts post-transcriptionally, is mediated by CD28 stimulation, and is cyclosporine-resistant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27894/1/0000314.pd

Three out of four working-age patients have fulfilled expectations towards paid employment six months after total hip or knee arthroplasty: a multicentre cohort study

To investigate factors associated with fulfilment of expectations towards paid employment after total hip/knee arthroplasty (THA/TKA). Cohort study including preoperatively employed patients aged 18-64 scheduled for THA/TKA. Expectations were collected preoperatively, and 6 and 12 months postoperatively with the paid employment item of the Hospitalfor-Special-Surgery Expectations Surveys (back-to-normal = 1; large improvement = 2; moderate improvement = 3; slight improvement = 4; not applicable = 5). Patients scoring not applicable were excluded. Fulfilment was calculated by subtracting preoperative from postoperative scores (< 0: unfulfilled; = 0: fulfilled). Multivariable logistic regression analyses were conducted separately for THA/TKA at 6 and 12 months postoperatively. Six months postoperatively, 75% of THA patients (n = 237/ n = 316) and 72% of TKA patients (n = 211/n = 294) had fulfilled expectations. Older age (TKA:OR 1.08, 95% CI 1.01-1.15) and better postoperative physical functioning (THA:OR 1.10, 95% CI 1.06-1.14; TKA:OR 1.03, 95% CI 1.01-1.06) increased the likelihood of fulfilment. Physical work tasks (THA:OR 0.12, 95% CI 0.03-0.44), preoperative sick leave (TKA:OR 0.33, 95% CI 0.17-0.65), and difficulties at work (THA:OR 0.10, 95% CI 0.03- 0.35; TKA:OR 0.41, 95% CI 0.17-0.98) decreased the likelihood of fulfilment. Twelve months postoperatively similar risk factors were found. Three out of four working-age THA/TKA patients had fulfilled expectations towards paid employment at 6 months postoperatively. Preoperative factors associated with fulfilment were older age, mental work tasks, no sick leave, postoperative factors were better physical functioning, and no perceived difficulties at work.Orthopaedics, Trauma Surgery and Rehabilitatio