Electrical stimulation to promote osseointegration of bone anchoring implants: a topical review

Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45\ua0years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments

Enhancing osteoblast survival through pulsed electrical stimulation and implications for osseointegration

Electrical stimulation has been suggested as a means for promoting the direct structural and functional bonding of bone tissue to an artificial implant, known as osseointegration. Previous work has investigated the impact of electrical stimulation in different models, both in vitro and in vivo, using various electrode configurations for inducing an electric field with a wide range of stimulation parameters. However, there is no consensus on optimal electrode configuration nor stimulation parameters. Here, we investigated a novel approach of delivering electrical stimulation to a titanium implant using parameters clinically tested in a different application, namely peripheral nerve stimulation. We propose an in vitro model comprising of Ti6Al4V implants precultured with MC3T3-E1 preosteoblasts, stimulated for 72\ua0h at two different pulse amplitudes (10\ua0\ub5A and 20\ua0\ub5A) and at two different frequencies (50\ua0Hz and 100\ua0Hz). We found that asymmetric charge-balanced pulsed electrical stimulation improved cell survival and collagen production in a dose-dependent manner. Our findings suggest that pulsed electrical stimulation with characteristics similar to peripheral nerve stimulation has the potential to improve cell survival and may provide a promising approach to improve peri-implant bone healing, particularly to neuromusculoskeletal interfaces in which implanted electrodes are readily available

Prediagnosis Leisure-Time Physical Activity and Lung Cancer Survival: A Pooled Analysis of 11 Cohorts

Background: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisuretime physical activity (LTPA) with all-cause and lung cancer–specific mortality among incident lung cancer patients. Methods: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer–specific mortality after adjustment for major prognostic factors and lifetime smoking history. Results: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate ¼ 20.9%, 95% CI ¼ 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR ¼ 0.93, 95% CI ¼ 0.88 to 0.99), but not with lung cancer–specific mortality (multivariable-adjusted HR ¼ 0.99, 95% CI ¼ 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction ¼ .008 for all-cause mortality and .003 for lung cancer–specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariableadjusted HRs were 0.80 (95% CI¼ 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI¼ 0.65 to 0.99) for lung cancer–specific mortality. Conclusions: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer

Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C)

Background: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected

Community First: A Study of how Digital Startups use Online Brand Communities to Rapidly Scale and Succeed in International Markets

Dagens digitale startups drar nytte av at internettet gjør det mulig å distribuere digitale produkter til kunder verden over, kun ved hjelp av et enkelt tastetrykk. Samtidig har det skjedd store fremskritt innen digitale kommunikasjonsplattformer, som gjør at disse startupene kan opprette og bygge aktive og engasjerte nettsamfunn. Noen digitale startups har dratt nytte av nettsamfunn for å forsterke egne verdiforslag, styrke markedsføringstiltak, oppmuntre og motivere til kundeengasjement, og få rask og direkte tilgang til kunder og deres tilbakemeldinger. Formålet med denne masteroppgaven er å undersøke hvordan nettsamfunn muliggjør digitale startups’ raske internasjonaliseringsprosesser. Oppgaven inneholder en omfattende litteraturstudie om internasjonaliseringen av digitale startups og nettsamfunn, åtte dybdeintervjuer med erfarne gründere av digitale startups, samt en utforskende casestudie på en digital startup i ferd med å internasjonalisere og bygge et aktivt nettsamfunn. Funnene fra litteraturstudiet, intervjuene og case-studiet brukes til å forme et praktisk rammeverk for å implementere en internasjonaliseringsstrategi som benytter nettsamfunn til å vokse fort og over landegrenser. Studiens funn viser at nettsamfunn kan være et svært effektivt verktøy for å oppnå rask og internasjonal vekst i en digital startup, ved å fasilitere for bruker-engasjement og positiv “word-of-mouth” spredning. I tillegg kan nettsamfunn benyttes som en kjernedel av en digital startups forretningsmodell, med diverse positive ringvirkninger for selskapet, kundene, og andre interessenter (f.eks. investorer og rådgivere). Studien viser viktigheten av å benytte nettsamfunn for digitale startups, og våre forskningsbidrag innebærer verdifull kunnskap og innsikt for videre forskning innen Internasjonalt Entreprenørskap. For gründere og ledere av digitale virksomheter, viser funnene våre derfor de potensielle gevinstene av å inkorporere nettsamfunn tidlig i kunde-strategien og nytten av lignende vekst-taktikker. Samt bidrar funnene våre til forståelsen rundt underliggende mekanismer i digitale startups’ internasjonaliseringsprosesser, og studien er blant de første som forsker på kombinasjonen av digital startup internasjonalisering og bruken av nettsamfunn

The Polarized Submillimeter Ice-Cloud Radiometer (PolSIR): Observing the diurnal cycle of ice clouds in the tropics and sub-tropics

International audienceIn May 2023 NASA has selected PolSIR as the latest addition to its Earth Venture Instrument class missions. This presentation will give an overview on PolSIR and its objectives. PolSIR addresses key research priorities related to uncertainties in our current understanding in high clouds and cloud feedbacks as formulated in NASA’s latest Decadal Survey and in the latest Intergovernmental Panel on Climate Change (IPCC) Assessment. In this context, PolSIR will address the following objectives: Constrain the seasonally influenced diurnal cycle amplitude, form, and timing of the ice water path (IWP) and particle diameter in tropical and sub-tropical ice clouds Determine the diurnal variability of ice clouds in the convective outflow areas and understand relation to deep convection Determine the relationship between shortwave and longwave radiative fluxes and the diurnal variability of ice clouds Enable improvement of climate models by providing novel observations of the diurnal cycle of ice clouds, ultimately leading to improved climate modeling skills and increased fidelity of climate forecasts in support of critical decision-making.The PolSIR mission consists of two 12U CubeSats, each equipped with a cross-track scanning polarized submillimeter radiometer in the spectral range of 325–680 GHz. The two PolSIR satellites fly in separate, 52-degree inclination, non-sun-synchronous orbits, taking science measurements between ±35 degrees latitude enabling monthly sampling of the diurnal cycle of ice clouds and their microphysical properties in the tropics and sub-tropics. PolSIR’s observation concept provides significant benefits over the Program of Record (PoR) as well as synergies with future missions which will either be in sun-synchronous orbits, thus not sampling the diurnal cycle, or lack the observation frequencies needed to fully observe ice water path (IWP)

Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial

Abstract Background Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation — commonly known as neuroma pain — and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP. Methods One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site. Discussion A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0–10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment. Trial registration ClincialTrials.gov NCT05009394

The Polarized Submillimeter Ice-Cloud Radiometer (PolSIR): Observing the diurnal cycle of ice clouds in the tropics and sub-tropics

International audienceIn May 2023 NASA has selected PolSIR as the latest addition to its Earth Venture Instrument class missions. This presentation will give an overview on PolSIR and its objectives. PolSIR addresses key research priorities related to uncertainties in our current understanding in high clouds and cloud feedbacks as formulated in NASA’s latest Decadal Survey and in the latest Intergovernmental Panel on Climate Change (IPCC) Assessment. In this context, PolSIR will address the following objectives: Constrain the seasonally influenced diurnal cycle amplitude, form, and timing of the ice water path (IWP) and particle diameter in tropical and sub-tropical ice clouds Determine the diurnal variability of ice clouds in the convective outflow areas and understand relation to deep convection Determine the relationship between shortwave and longwave radiative fluxes and the diurnal variability of ice clouds Enable improvement of climate models by providing novel observations of the diurnal cycle of ice clouds, ultimately leading to improved climate modeling skills and increased fidelity of climate forecasts in support of critical decision-making.The PolSIR mission consists of two 12U CubeSats, each equipped with a cross-track scanning polarized submillimeter radiometer in the spectral range of 325–680 GHz. The two PolSIR satellites fly in separate, 52-degree inclination, non-sun-synchronous orbits, taking science measurements between ±35 degrees latitude enabling monthly sampling of the diurnal cycle of ice clouds and their microphysical properties in the tropics and sub-tropics. PolSIR’s observation concept provides significant benefits over the Program of Record (PoR) as well as synergies with future missions which will either be in sun-synchronous orbits, thus not sampling the diurnal cycle, or lack the observation frequencies needed to fully observe ice water path (IWP)

Targeted muscle reinnervation: surgical protocol for a randomized controlled trial in postamputation pain

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated