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Participation in supervised, laboratory-based aerobic exercise protocols holds promise in slowing the progression of Parkinson's disease (PD). Gaps remain regarding exercise adherence and effectiveness of laboratory protocols translated to community-based programs. The aim of the project was to monitor exercise behaviour and evaluate its effect on disease progression over a 6 month period in people with PD participating in a community-based Pedalling for Parkinson's (PFP) cycling program. A pragmatic, observational study design was utilised to monitor exercise behaviour at five community sites. The Movement Disorders Society-Unified Parkinson's disease Rating Scale Motor III (MDS-UPDRS-III) and other motor and non-motor outcomes were gathered at enrollment and following 6 months of exercise. Attendance, heart rate, and cadence data were collected for each exercise session. On average, people with PD (N = 41) attended nearly 65% of the offered PFP classes. Average percent of age-estimated maximum heart rate was 69.3 ± 11.9%; average cadence was 74.9 ± 9.0 rpms. The MDS-UPDRS III significantly decreased over the 6-month exercise period (37.2 ± 11.7 to 33.8 ± 11.7, p = 0.001) and immediate recall significantly improved (42.3 ± 12.4 to 47.1 ± 12.7, p = 0.02). Other motor and non-motor metrics did not exhibit significant improvement. Participants who attended ~74% or more of available PFP classes experienced the greatest improvement in MDS-UPDRS III scores; of those who attended less than 74% of classes, cycling greater than or equal to 76 rpms lead to improvement. Attendance and exercise intensity data indicated that a laboratory-based exercise protocol can be successfully translated to a community setting. Consistent attendance and pedalling at a relatively high cadence may be key variables to PD symptom mitigation. Improvement in clinical ratings coupled with lack of motor and non-motor symptom progression over 6 months provides rationale for further investigation of the real-world, disease-modifying potential of aerobic exercise for people with PD.

Aims GSK3640254, a novel, next-generation maturation inhibitor effective against a range of HIV polymorphisms with no cross-resistance to current antiretroviral therapy, could potentially be coadministered with dolutegravir as a 2-drug regimen. In this phase I study, pharmacokinetics and tolerability of GSK3640254 plus dolutegravir were assessed. Methods Healthy participants received dolutegravir 50 mg once daily (QD) on Days 1-5 in period 1, GSK3640254 200 mg QD on Days 1-7 in period 2, and dolutegravir 50 mg plus GSK3640254 200 mg QD on Days 1-7 in period 3. All treatments were administered with a moderate-fat meal 30 minutes prior to dosing. Pharmacokinetics parameters were derived by noncompartmental methods, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were derived using linear mixed effects models. Adverse events, laboratory measurements, electrocardiography and vital signs were monitored. Results Sixteen participants completed the study. GMRs (90% CIs) for dolutegravir area under the plasma concentration-time curve from time 0 to the end of the dosing interval at steady state, maximum observed concentration and plasma concentration at the end of the dosing interval were 1.17 (1.118-1.233), 1.09 (1.044-1.138) and 1.24 (1.160-1.315), respectively. The GMRs (90% CIs) for GSK3640254 were 1.04 (0.992-1.094), 0.99 (0.923-1.065) and 0.10 (0.939-1.056), respectively. Dolutegravir plus GSK3640254 coadministration did not meaningfully alter steady-state exposure to dolutegravir or GSK3640254. No clinically significant trends in tolerability or safety were observed. Conclusion Coadministration of GSK3640254 with dolutegravir did not result in clinically significant drug interaction and was well tolerated.

Background Deafness and hearing loss are common conditions that can be seen independently or as part of a syndrome and are often mediated by genetic causes. We sought to develop and validate a hereditary hearing loss panel (HHLP) to detect single nucleotide variants (SNVs), insertions and deletions (indels), and copy number variants (CNVs) in 166 genes related to nonsyndromic and syndromic hearing loss. Methods We developed a custom-capture next-generation sequencing (NGS) reagent to detect all coding regions, ±10 flanking bp, for the 166 genes related to nonsyndromic and syndromic hearing loss. Our validation consisted of testing 52 samples to establish accuracy, reproducibility, and analytical sensitivity. In addition to NGS, supplementary methods, including multiplex ligation-dependent probe amplification, long-range PCR, and Sanger sequencing, were used to ensure coverage of regions that had high complexity or homology. Results We observed 100% positive and negative percentage agreement for detection of SNVs (n = 362), small indels (1–22 bp, n = 25), and CNVs (gains, n = 8; losses, n = 17). Finally, we showed that this assay was able to detect variants with a variant allele frequency ≥20% for SNVs and indels and ≥30% to 35% for CNVs. Conclusions We validated an HHLP that detects SNVs, indels, and CNVs in 166 genes related to syndromic and nonsyndromic hearing loss. The results of this assay can be utilized to confirm a diagnosis of hearing loss and related syndromic disorders associated with known causal genes.

Aims GSK3640254 is a next-generation maturation inhibitor likely to be coadministered with combined oral contraceptives in HIV-positive women. Methods This phase I, open-label, 1-way study assessed pharmacokinetic and pharmacodynamic interactions of GSK3640254 200 mg and ethinyl oestradiol 0.03 mg/levonorgestrel 0.15 mg once daily in healthy female participants who received ethinyl oestradiol/levonorgestrel for 10 days with a moderate-fat meal after which GSK3640254 was added from Days 11 to 21. Primary endpoints were area under the plasma concentration-time curve to the end of the dosing interval (AUC0-t ), maximum observed concentration (Cmax ) and plasma concentration at the end of the dosing interval (Cτ ) for ethinyl oestradiol and levonorgestrel. Serum follicle-stimulating hormone, luteinizing hormone and progesterone concentrations were determined. Adverse events were monitored. Results Among 23 enrolled participants, 17 completed the study. Geometric least squares mean ratios (with vs. without GSK3640254) of AUC0-t , Cmax and Cτ were 0.974, 0.970 and 1.050 for ethinyl oestradiol and 1.069, 1.032 and 1.083 for levonorgestrel, respectively. Three participants had elevated progesterone levels, which occurred before GSK3640254 administration in 2 participants. No participants had elevated follicle-stimulating hormone or luteinizing hormone values. Fourteen participants (61%) reported adverse events. Four participants reported asymptomatic elevated transaminase levels meeting liver-stopping criteria; of these, 3 events occurred before GSK3640254 administration and led to study withdrawal. Conclusion Ethinyl oestradiol/levonorgestrel plus GSK3640254 coadministration did not affect steady-state pharmacokinetics or pharmacodynamics of ethinyl oestradiol and levonorgestrel in healthy female participants. No major tolerability findings were reported. Elevated liver transaminase levels were probably due to ethinyl oestradiol/levonorgestrel.

GSK3640254 is a next-generation maturation inhibitor that would likely be combined with standard antiretroviral agents to form a regimen of ≥2 fully active classes. This phase I, open-label, 2-period, 1-way study assessed potential pharmacokinetic (PK) interactions between GSK3640254 and tenofovir alafenamide/emtricitabine (TAF/FTC; including the metabolite tenofovir [TFV]) in healthy volunteers. Eligible participants received TAF/FTC 25/200 mg once daily (QD) on days 1 through 21 with a moderate-fat meal; GSK3640254 200 mg QD was added on days 15 through 21. Geometric least-squares mean ratios (GMRs) and 90% confidence intervals (CIs) were derived using linear mixed-effect models. Adverse events (AEs) and laboratory, electrocardiogram, and vital sign parameters were monitored. Sixteen participants, all male, received treatment; one withdrew because of treatment-related grade 1 urticaria. After TAF/FTC + GSK3640254 coadministration, TAF steady-state area under the plasma concentration-time curve from time zero to the end of the dosing interval and maximum observed concentration were 11% and 13% lower than when TAF/FTC was administered alone, with GMRs (90% CI) of 0.886 (0.75 to 1.04) and 0.874 (0.68 to 1.12), respectively. Steady-state PK of TFV and FTC was similar when TAF/FTC was administered alone or with GSK3640254. No clinically significant trends in tolerability or safety were observed. GSK3640254 200 mg QD did not meaningfully affect the steady-state PK of TAF, TFV, or FTC in healthy participants under fed conditions and was not associated with major tolerability or safety findings. These data support the further investigation of GSK3640254 for coadministration with TAF/FTC for the treatment of HIV. (This study has been registered at ClinicalTrials.gov under identifier NCT03836729.)

The L-type calcium channel gene, CACNA1C, is a validated risk gene for schizophrenia and the target of calcium channel blockers. Carriers of the risk-associated genotype (rs1006737 A allele) have increased frontal cortical activity during working memory and higher CACNA1C mRNA expression in the prefrontal cortex. The aim of this study was to determine how the brain-penetrant calcium channel blocker, nimodipine, changes brain activity during working memory and other cognitive and emotional processes. We conducted a double-blind randomized cross-over pharmacoMRI study of a single 60 mg dose of oral nimodipine solution and matching placebo in healthy men, prospectively genotyped for rs1006737. With performance unchanged, nimodipine significantly decreased frontal cortical activity by 39.1% and parietal cortical activity by 42.8% during the N-back task (2-back > 0-back contrast; PFWE n = 28). Higher peripheral nimodipine concentrations were correlated with a greater decrease in activation in the frontal cortex. Carriers of the risk-associated allele, A (n = 14), had a greater decrease in frontal cortical activation during working memory compared to non-risk allele carriers. No differences in brain activation were found between nimodipine and placebo for other tasks. Future studies should be conducted to test if the decreased cortical brain activity after nimodipine is associated with improved working memory performance in patients with schizophrenia, particularly those who carry the risk-associated genotype. Furthermore, changes in cortical activity during working memory may be a useful biomarker in future trials of L-type calcium channel blockers.

Eric Zimmerman assume à la fois les rôles de concepteur, d’artiste et de chercheur. Acteur majeur de l’industrie du jeu vidéo, il a dirigé Gamelab, un studio de développement de jeux vidéo influent dans les années 2000. À la fermeture de cette société en 2009, sa carrière a suivi une double direction : celle de chercheur et d’enseignant au sein du Game Center de l’université de New York d’une part, et celle de concepteur de jeu indépendant. Il travaille désormais sur des projets audacieux et ...

Retropharyngeal hematomas (RHs) represents a rare airway obstruction that requires timely intervention to avoid a fatal outcome. Further complicating this malady, RHs of massive proportions can complicate the decision of management selection. After comprehensive literature search, there has been no mention of pulmonary stenting as an intervention for RH. The following case presentation will demonstrate the importance of multidisciplinary management of a 60-year-old presenting with a RH causing airway obstruction, with the use of a novel approach. Airway stenting is a novel, conservative approach for successfully managing patients presenting with massive RH.

The 86 fields and discoveries in the central Mississippi Canyon, Atwater Valley, western DeSoto Canyon, and Lloyd Ridge protraction areas are summarized with production characteristics and representative seismic profiles and wire-line logs. Three trap styles are recognized: four-way closure, three-way closure, and stratigraphic. The reservoirs in nearly all of the fields areNeogene deepwater sandstones; four are in Upper Jurassic eolian sandstones. Development facilities include a variety of floating platforms and production units and subsea tiebacks. Copyright © 2017 The American Association of Petroleum Geologists. All rights reserved.

Objective: To evaluate whether assessment of calcification of aortic valves in standard transthoracic echocardiograms(TTE) correlates with actual calcium burden represented by aortic valve Agatston...

PurposeThe purpose of this paper is to look at measures of e‐mail use and e‐mail management among academic faculty in relation to research productivity. The aim is to report only on e‐mail use and management.Design/methodology/approachFor this quantitative study, productivity data were gathered from information management systems of Bar‐Ilan University in Israel and a survey questionnaire was distributed in order to measure e‐mail use. The scholarly community of Bar‐Ilan University was surveyed via a web‐form – of the 781 survey copies disseminated, 412 (52.8 per cent of the total) were received and the final usable number was 390 (49.9 per cent of the total).FindingsWith younger biological and/or professional age, there are correspondingly higher levels of e‐mail usage. It is clear that the younger a user is, the higher the perceived skill level and quantitative measures of e‐mail use, as well as a higher perception of one's capacity to use e‐mail. It would also seem that with older professional age, there is less perceived benefit to using e‐mail. With increased levels of perception as to the benefit of e‐mail to productivity, there is increased use of e‐mail.Originality/valueThis paper provides a depth of study (in its range of disciplines covered, in a single location, with a broad population) with a range of e‐mail measures not previously seen in this decade. While Israel is small in size, it accounts for 1 per cent of global scientific journal articles, emanating mainly from the universities and its achievements are such that the global community can indeed learn from the behaviour patterns of Israel's scholars, represented by the findings at one of the largest research universities.

This article reports on an unconventional collaborative event called Real-Time Research, a project that brought 25 participants together from radically divergent fields for a playful and somewhat improvisational investigation of what it means to do games and learning research. Real- Time Research took the form of a two-part workshop session at the 'Games, Learning & Society' (GLS) conference during the summer of 2008, in which attendees collaboratively designed and then conducted five research experiments that took place over the course of the two-day conference. The article reports on the results of those studies and the processes that generated them. Few models exist for the successful collaboration among research academics, let alone among research academics and game designers and practicing teachers and students. Traditional conferences are often unable to provide much time and space for genuinely substantive conversation within disciplines, let alone across disciplines. There is the occasional follow-up conversation after a particularly good PowerPoint presentation with the obligatory exchange of business cards (that rarely survive the trip home), perfunctory post-session discussions, and the chance run-in at the hotel bar, but beyond these mostly accidental exchanges, we wanted to create a context designed explicitly for productive collaboration. The Games Learning and Society Conference (GLS), held annually in Madison, Wisconsin, was the perfect occasion for such an experiment. GLS already straddles several domains: academics, industry designers, policy makers, practicing teachers, and gamers themselves. At GLS, conference designers place a premium on creating opportunities for different constituencies to congregate and share concerns through a number of design elements. This mix of participants can lead to entertaining and informative sessions; in one example from the first GLS, a gaming consultant suggested that games could one day replace teachers, and a bevy of objections shot up: Designers said it was too difficult to replace teacher practices with artificial intelligence; educational theorists raised the historical failure of such efforts, and teachers laughed and said, 'good luck with that'. These discussions are a good start, but we often learn best when we are engaged in meaningful activity working side by side with others (Vygotsky, 1978; Lave, 1988; Lave & Wenger, 1991). We need opportunities not just for cross-disciplinary conversation but cross-disciplinary collaboration. This kind of collaborative activity enables us to see how others view problems, to test our understandings against others, and to talk through key issues in a context grounded in specifics (rather than mired in the general). If it is true that we get to know each other and our world-views by actually engaging in activities with each other (Steinkuehler, 2004), then why not create a context within a conference in which this can happen? We hoped that such exercises, no matter how small, might seed future work not just among those who attend, but also among those disciplines/industries that the participants represent. A trick is how to enable such collaborations to happen on site and within the flow of a two-day conference program.

This paper introduces a dynamic perspective on institutional research performance that can be used for evaluative purposes. It combines four principles: importance of national situation; evolution data; multiple indicators and similar institutes. The perspective is applied to five Israeli research institutes and as such it also follows up earlier studies of Israel's changing research landscape. First several bibliometric indicators for Israel are presented. Then these institutes were classified according to their research profile and their scores over a publication period of 17 years are calculated. Their quintile rank position compared to European research institutes is presented. We conclude that the Israeli institutes publish papers that attract more citations than the field average. They also tend to publish in journals with a higher citation impact than the field. But because of their choice of journals it often difficult to reach the citation average set by this journal. Copyright , Beech Tree Publishing.

In this paper we examine various aspects of the scientific collaboration between Europe and Israel, and show that the traditional collaboration patterns of Israel (preference towards collaboration with the US) is changing, and the collaboration with the EU countries is growing.

This article is excerpted, with the permission of the editors and the publishers, from an edited book published by Peter Lang Publishing in conjunction with Eyebeam ( www.eyebeam.org ), a not-for-profit new media arts organization in New York City. It reproduces one of the book's four organizing ‘modules’ – Games as Exchange – which focuses on new kinds of social interaction made possible by digital gaming. The book grew out of an ideas exchange among participants involved in an online forum and live symposium discussing and debating game design and culture. The module reproduced in this article involves 15 of the 50 core contributors to the book as a whole, whose ideas were coordinated thematically and edited by Amy Scholder and Eric Zimmerman. The module is prefaced by Eric Zimmerman's Introduction to the book as a whole.

This chapter details using hash sets to identify, compare, and optionally hide files based on known hash values. You can save a considerable amount of time when thorough hash sets are available for certain types of investigations. X-Ways Forensics (XWF) contains robust hashing capabilities that allow for quickly finding items of interest or eliminating nonpertinent files in a case. There is virtually no limit to the number of individual hash sets that you can create in XWF.

X-Ways Forensics (XWF) is a versatile forensic application, effective in nearly every type of electronic evidence case from a basic level to the most advanced analysis. This includes civil cases involving electronic discovery and data collection. This chapter gives several methods and recommendations on using XWF in basic data collections in a manner that is better than nearly every other method.

This chapter explains case management, including creating a new case, working with existing cases, and creating and adding evidence to a case. After creating a case, a full explanation of X-Ways Forensics (XWF) capabilities in regard to imaging will be discussed including the imaging of hard drives and other medium in both running and “dead box” scenarios as well as physical memory. Finally, we discuss concepts such as creating and using XWF container files as well as rebuilding RAID arrays. We conclude this chapter by illustrating how we can use XWF with F-Response to interact fully with a wide variety of operating systems on an IP-based network.

Learning to navigate in any program is a prerequisite to using that program effectively, and X-Ways Forensics (XWF) is no different from any other program in that regard. Like the majority of Windows programs, XWF uses familiar concepts in its user interface including such things as main menus, tree views, grids, status bars, and context menus. While navigating the XWF interface is simple, understanding the depth of information exposed by XWF can take time to fully understand. Drilling down into each key component of the XWF interface will not only show you how much functionality is present in XWF, but more importantly it will demonstrate how to use this functionality to maximize productivity when conducting a forensic analysis.

You can install X-Ways Forensics (XWF) as you would any other program by using the provided setup program. However, XWF can simply be unzipped to a folder from which it can operate on nearly any source medium such as a compact disc or a flash drive.

X-Ways Forensics (XWF) includes functionality to add items of interest to one or more groups, or report tables (RTs). RTs are the core of XWF’s reporting functionality. In addition to adding an item to a RT, XWF also allows comments to be associated with objects in your case. When generating a report, XWF allows you to include essentially any piece of information available about a given item in your report, e.g., various dates and times, hash values, image thumbnails, etc.

A “triage,” or preview, of computer systems is an effective method of determining whether evidence exists on a computer system without conducting a complete, forensic analysis. Although X-Ways Forensics (XWF) is a full-featured forensic application, the design allows for previews of electronic media in as much detail as needed. Because the capabilities of XWF are not diminished when used in the field, you quickly can review many computers or conduct complete forensic analysis onsite as needed.

X-Ways Forensics (XWF) provides powerful, fast, and flexible search capabilities including ad hoc searches and highly configurable index-based searches. However, in almost every instance, a nonindexed or, in XWF terms, a Simultaneous Search will meet the needs of most examiners, even in cases with huge numbers of search terms and files. In cases where an indeterminate number of search terms are a possibility, using an index-based search will provide greater benefits. In addition to traditional string-based searches, XWF also supports GREP syntax .