How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Shocked monazite chronometry: integrating microstructural and in situ isotopic age data for determining precise impact ages

Monazite is a robust geochronometer and occurs in a wide range of rock types. Monazite also records shock deformation from meteorite impact but the effects of impact-related microstructures on the U–Th–Pb systematics remain poorly constrained. We have, therefore, analyzed shock-deformed monazite grains from the central uplift of the Vredefort impact structure, South Africa, and impact melt from the Araguainha impact structure, Brazil, using electron backscatter diffraction, electron microprobe elemental mapping, and secondary ion mass spectrometry (SIMS). Crystallographic orientation mapping of monazite grains from both impact structures reveals a similar combination of crystal-plastic deformation features, including shock twins, planar deformation bands and neoblasts. Shock twins were documented in up to four different orientations within individual monazite grains, occurring as compound and/or type one twins in (001), (100), (10 1 ¯) , {110}, { 212 } , and type two (irrational) twin planes with rational shear directions in [ 0 1 ¯ 1 ¯ ] and [ 1 ¯ 1 ¯ 0 ]. SIMS U–Th–Pb analyses of the plastically deformed parent domains reveal discordant age arrays, where discordance scales with increasing plastic strain. The correlation between discordance and strain is likely a result of the formation of fast diffusion pathways during the shock event. Neoblasts in granular monazite domains are strain-free, having grown during the impact events via consumption of strained parent grains. Neoblastic monazite from the Inlandsee leucogranofels at Vredefort records a 207Pb/206Pb age of 2010 ± 15 Ma (2σ, n = 9), consistent with previous impact age estimates of 2020 Ma. Neoblastic monazite from Araguainha impact melt yield a Concordia age of 259 ± 5 Ma (2σ, n = 7), which is consistent with previous impact age estimates of 255 ± 3 Ma. Our results demonstrate that targeting discrete microstructural domains in shocked monazite, as identified through orientation mapping, for in situ U–Th–Pb analysis can date impact-related deformation. Monazite is, therefore, one of the few high-temperature geochronometers that can be used for accurate and precise dating of meteorite impacts

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Letter Written by Aaron A. French, Jr. to the Bryant College Service Club Dated June 25, 1943

[Transcription begins]U S O June 25, 1943 Dear Friends: I wish to acknowledge receipt of two cartons of cigarettes for which I am very appreciative. I again thank you sincerely. My permanent address is: USS LST 208c/o Fleet Post OfficeNew York, N. Y. Sincerely,Aaron French Jr. ’28.[Transcription ends

Letter Written by Aaron A. French, Jr. to the Bryant College Service Club Dated April 4, 1943

[Transcription begins] Solomons, M. I. April 4, 1943 Dear Friends, It is with a feeling of pride that I acknowledge your remembrance of a gift of smokes received today. It was certainly a lift to show them and pass them around to my shipmates. They read the little card enclosed and thought it was pretty swell. Please accept my sincere thanks. My address is: Aaron French, Jr. SK—2/c Crew 4107—Brk. 13 U.S.N.—A.T.B. Solomons Branch Washington, D. C. Would also appreciate receiving the school paper. I am in the Amphibious Force and of the Class of 1928. Respectfully, Aaron French, Jr. [Transcription ends

Letter Written by Aaron A. French, Jr. to the Bryant College Service Club Dated April 20, 1945

[Transcription begins] Aaron A. French, Jr. SK A. T. B. N. O. B. Camp Bradford, Norfolk, 11, Va. April 20, 1945 Dear Friends, I have received your Easter news letter and a box of candy that went over seas. My sincere thanks. I returned from overseas and enjoyed a 30 day rehabilitation leave and now standing by at this Amphibious Training Base awaiting my new assignment. I surely appreciated all the favors you did for me and I’m glad to be back with you again; this is a swell country to come back to. Please keep me on your mailing list as I enjoy reading the news. Sincerely, A. French, Jr. [Transcription ends

Letter Written by Aaron A. French, Jr. to the Bryant College Service Club Dated April 19, 1943

[Transcription begins] Crew 4107 – Brk. 13 U.S.N. – A. T. B. Solomons Branch Washington, D.C. April 19, 1943. Dear Friends, Your mimeographed letter March 16th has finally caught up with me and it was certainly interesting and very much appreciated. Thanks very much again for the welcome gift of smokes which I received early this month. Many of us here enjoyed your remembrance. Sincerely, Aaron French, Jr. ‘28 SK-Yc [Transcription ends

Letter Written by Aaron A. French, Jr. to the Bryant College Service Club Dated May 12, 1944

[Transcription begins]UNITED STATES NAVY A. French, Jr. SK1cUSS LST 349c/o F.P.O. N.Y.C.North AfricaMay 12, 1944 Dear Friends, Your interesting V-Mail letter of 3/29 came in several days ago followed by a most welcome carton of Camel cigarettes received today. I sincerely thank you for your generous thoughtfulness and I appreciate it. My shipmates also appreciate your gift, you know what I mean!! I suggest the State of R.I. get on the ball, now, and appoint Mr. Ripley as State Director of Placements for Service Men. Vets would welcome such a move. We are resting-up here in North Africa. Was in at Anzio the first day, adding another star to my campaign bar. I am well and happy to say my five brothers in service (around the globe) are doing all right. Sincerely,Aaron French, Jr.\u2728[Transcription ends