The development test flight of the flight telerobotic servicer

The Development Test Flight (DTF-1) is the first of two shuttle flights to test operations of the Flight Telerobotic Servicer (FTS) in space and to demonstrate its capabilities in performing tasks for Space Station Freedom. The DTF-1 system, which Martin Marietta Astronautics Group is designing and building for the Goddard Space Flight Center, will be flown in December, 1991, as an attached payload on the shuttle. The design of the DTF-1 system, the tests to be performed, and the data to be gathered are discussed

Regulating Minors\u27 Access to Pornography Via the Internet: What Options Do Congress Have Left?, 23 J. Marshall J. Computer & Info. L. 453 (2005)

As with most innovations that have world-altering capabilities, the Internet is not without its very own dark side. This Internet\u27s ugly side represented by are the thousands of Web sites devoted to the procurement and dissemination of pornographic material. Although, undoubtedly, in a free society, people are entitled to have access to such material if they so desire it is also generally accepted there is not only a great need, but an uncompromisable duty to protect minors from, and prevent access to, this potentially harmful imagery. This Comment discusses the several recent attempts made by Congress to regulate the accessibility of pornography to minors via the Internet, specifically the Communications Decency Act ( CDA ), the Child Online Protection Act ( COPA ) and the Child Internet Protection Act ( CIPA ). The author discusses the background and reasoning of the cases dealing with CIPA, the CDA and COPA respectively. The only of the above mentioned Acts that Congress has been successful in enacting withstanding scrutiny under the First Amendment of the Constitution is CIPA. The analysis that follows reveals that the Supreme Court has left little, if any, room to manoeuvre with respect to Congress\u27 ability to regulate minors\u27 access to pornography via the Internet. Because only COPA\u27s definitions satisfied the stringent requirements of the First Amendment, the only remaining Constitutional conundrum for Congress to overcome is implementing a system that is the least restrictive means available, capable of achieving Congress\u27 stated goal in enacting COPA, this Comment suggests two alternatives to COPA\u27s age verification requirement that would be both capable of surviving strict scrutiny under the First Amendment as well as an effective means of protecting minors from the harmful effects of exposure to pornography. The two suggested alternatives, inspired by recent rules enacted prohibiting telemarketers from soliciting consumers telephonically, provided an individual consumer has affirmatively decided to be permanently removed from the telemarketers\u27 list, propose the creation of a similar “opt-out” system enabling access to Web sites that are deemed to fall under the purview of the controlling statute. Specifically the two alternatives suggested are a National Anti-Porn Internet Protocol Registry or a National Anti-Porn Cookie. Either of these suggestions is capable of withstanding strict scrutiny under the First Amendment while putting the onus on individual Internet users to determine for themselves whether they want to be able to access sexually explicit content available via the Internet

The Novel CFTR Mutation A457P in a Male with a Delayed Diagnosis of Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease that may be caused by more than 1000 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the case of a CF patient who was initially diagnosed at 16 years of age after presenting with mild respiratory compromise and pancreatic sufficiency. When genetic testing was first performed using a CF mutation panel, only a single F508del CFTR allele was identified. We subsequently performed testing, which revealed a previously unreported mutation: A457P (p.Ala457Pro, c.1369G>C). The patient's clinical course through adulthood is described, and genotype-phenotype correlation is discussed. The A457P mutation appears to confer a relatively mild phenotype, as is usually observed with CFTR class IV–VI defects. With the advent of more comprehensive and widely available genetic testing techniques, identification of CF genotypes in patients with milder disease variants may help stratify patients for targeted therapy and prevent late complications of the disease

Integrated orbital servicing study for low-cost payload programs. Volume 2: Technical and cost analysis

Orbital maintenance concepts were examined in an effort to determine a cost effective orbital maintenance system compatible with the space transportation system. An on-orbit servicer maintenance system is recommended as the most cost effective system. A pivoting arm on-orbit servicer was selected and a preliminary design was prepared. It is indicated that orbital maintenance does not have any significant impact on the space transportation system

Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.

OBJECTIVE: Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. STUDY DESIGN: To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. RESULTS: After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. CONCLUSIONS: It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included

Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation

Objective Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. Study design To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. Results After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. Conclusions It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis

Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation

Development of the CFQ-R-8D: estimating utilities from the cystic fibrosis questionnaire-revised

Objective Cystic fibrosis (CF) limits survival and negatively affects health-related quality of life (HRQOL). Cost-effectiveness analysis (CEA) may be used to make reimbursement decisions for new CF treatments; however, generic utility measures used in CEA, such as EQ-5D, are insensitive to meaningful changes in lung function and HRQOL in CF. Here we develop a new, CF disease–specific, preference-based utility measure based on the adolescent/adult version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely used, CF-specific, patient-reported measure of HRQOL. Methods Blinded CFQ-R data from 4 clinical trials (NCT02347657, NCT02392234, NCT01807923, and NCT01807949) were used to identify discriminating items for a classification system using psychometric (eg, factor and Rasch) analyses. Thirty-two health states were selected for a time-trade-off (TTO) exercise with a representative sample of the UK general population. TTO utilities were used to estimate a preference-based scoring algorithm by regression analysis (Tobit models with robust standard errors clustered on participants with censoring at −1). Results A classification system with 8 dimensions (CFQ-R-8D; Physical Functioning, Vitality, Emotion, Role Functioning, Breathing Difficulty, Cough, Abdominal Pain, and Body Image) was generated. TTO was completed by 400 participants (mean age, 47.3 years; 49.8% female). Among the regression models evaluated, the Tobit heteroscedastic–ordered model was preferred, with a predicted utility range from 0.236 to 1, no logical inconsistencies, and a mean absolute error of 0.032. Conclusion The CFQ-R-8D is the first disease-specific, preference-based scoring algorithm for CF, enabling estimation of disease-specific utilities for CEA based on the well-validated and widely used CFQ-R

Digenic inheritance and genetic modifiers

Digenic inheritance (DI) concerns pathologies with the simplest form of multigenic etiology, implicating more than 1 gene (and perhaps the environment). True DI is when biallelic or even triallelic mutations in 2 distinct genes, in cis or in trans, are necessary and sufficient to cause pathology with a defined diagnosis. In true DI, a heterozygous mutation in each of 2 genes alone is not associated with a recognizable phenotype. Well-documented diseases with true DI are so far rare and follow non-Mendelian inheritance. DI is also encountered when by serendipity, pathogenic mutations responsible for 2 distinct disease entities are co-inherited, leading to a mixed phenotype. Also, we can consider many true monogenic Mendelian conditions, which show impressively broad spectrum of phenotypes due to pseudo-DI, as a result of co-inheriting genetic modifiers (GMs). I am herewith reviewing examples of GM and embark on presenting some recent notable examples of true DI, with wider discussion of the literature. Undeniably, the advent of high throughput sequencing is bound to unravel more patients suffering with true DI conditions and elucidate many important GM, thus impacting precision medicine. - 2017 John Wiley & Sons A/S. Published by John Wiley & Sons LtdCyprus Research Promotion Foundation (co-funded by the European Regional Development Fund and the Republic of Cyprus), Grant/Award number: NEW INFRASTRUCTURE/STRATEGIC/0308/24 ; Republic of Cyprus; European Regional Development Fund. The work of Prof Deltas presented here was partly supported by the Cyprus Research Promotion Foundation through the grant NEW INFRASTRUCTURE/STRATEGIC/0308/24 (co-funded by the European Regional Development Fund and the Republic of Cyprus).Scopu

The improvement of the best practice guidelines for preimplantation genetic diagnosis of cystic fibrosis : toward an international consensus

Cystic fibrosis (CF) is one of the most common indications for preimplantation genetic diagnosis (PGD) for single gene disorders, giving couples the opportunity to conceive unaffected children without having to consider termination of pregnancy. However, there are no available standardized protocols, so that each center has to develop its own diagnostic strategies and procedures. Furthermore, reproductive decisions are complicated by the diversity of disease-causing variants in the CFTR (cystic fibrosis transmembrane conductance regulator) gene and the complexity of correlations between genotypes and associated phenotypes, so that attitudes and practices toward the risks for future offspring can vary greatly between countries. On behalf of the EuroGentest Network, eighteen experts in PGD and/or molecular diagnosis of CF from seven countries attended a workshop held in Montpellier, France, on 14 December 2011. Building on the best practice guidelines for amplification-based PGD established by ESHRE (European Society of Human Reproduction and Embryology), the goal of this meeting was to formulate specific guidelines for CF-PGD in order to contribute to a better harmonization of practices across Europe. Different topics were covered including variant nomenclature, inclusion criteria, genetic counseling, PGD strategy and reporting of results. The recommendations are summarized here, and updated information on the clinical significance of CFTR variants and associated phenotypes is presented