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Introduction Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. Methods Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. Results Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). Conclusion EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control. Electronic supplementary material The online version of this article (10.1186/s12984-018-0452-1) contains supplementary material, which is available to authorized users.

© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Background: Relative to the oral contraceptive pill, uptake of long-acting reversible contraceptive methods (LARCs) in Australia continues to be lower than might be suggested by the evidence on their clinical and economic benefits. Aim: To undertake a critical appraisal of published economic evaluations of LARCs to assess the generalisability of their results to the Australian healthcare context. Materials and Methods: A search of the literature was conducted to identify studies of economic evaluations of LARCs using the Medline, Embase and PubMed databases. The quality of the studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: A total of 1009 citations were screened, from which 20 papers, typically reporting the cost per pregnancy avoided, were reviewed. The overall quality of the studies varied but was generally poor (average score of 62/100). To aid comparisons, results have been grouped under the headings IUS (all hormonal intrauterine systems), IUDs (all non-hormonal intrauterine devices), injectables (all contraceptive injections) and implants (all subdermal contraceptive implants). Overall, the results indicated that LARCs were more effective and less costly than oral contraceptives. Conclusions: Despite evidence that LARCs represent value for money, limitations in study quality and approaches must be taken into account when applying these results to Australia. Differences in healthcare settings aside, LARCs may also have benefits beyond their effect on pregnancy that might be captured in broader analyses, such as cost-benefit analyses using willingness to pay methods. These would capture benefits beyond health, which seem to be particularly relevant to contraception.

Globally, it is estimated that ~ 1500 Pg C of organic carbon is stored in the top meter of terrestrial soils. This represents the largest terrestrial pool of carbon. Appropriate management of soils, to maintain or increase the soil carbon pool, represents a significant climate change mitigation opportunity. To achieve this, appropriate tools and models are required in order to more accurately estimate soil carbon fluxes with a view to informing and developing more effective land use management strategies. Central to this is the evaluation of models currently in use to estimate soil carbon emissions. In the present study, we evaluate the ECOSSE (Estimating Carbon in Organic Soils – Sequestration and Emissions) model which has its origins in both SUNDIAL and RothC and has been widely used globally to model soil CO2 fluxes across different locations and land-use types on both organic and mineral soils. In contrast to previous studies, the model was found to poorly represent observed soil respiration at the study site, an arable cropland on mineral soil located in south-east Ireland. To isolate potential sources of error, the model was decomposed into its component rate equations or modifiers. This investigation highlighted a deficiency in the model simulated soil water, resulting in significant inhibition of the model simulated CO2 flux relative to the observed data. When measured values of soil water at the site were employed, the model simulated soil respiration improved significantly (r2 of 0.775 vs 0.154). This highlighted model deficiency remains to be evaluated at other sites; however, the research highlights the need for a more comprehensive evaluation of soil carbon models prior to their use in informing policy, particularly models which are employed at larger scales and for climate change projections.

Purpose Heart Transplant recipients previously exposed to CMV infection are considered intermediate risk for post-transplant CMV complications. Many centers therefore utilize "universal" prophylaxis for 3-6 months to mitigate this risk. However, it remains unclear how long prophylaxis should be continued post-transplant in this population. In the present analysis, we compared post-transplant CMV outcomes in patients receiving 3 vs. 6 months of valganciclovir prophylaxis in a multicenter, retrospective analysis. Methods Retrospective analysis of 321 intermediate risk (CMV R+) HTx recipients from 6 U.S. centers between 2010-2018 treated with universal prophylaxis with valganciclovir for either 3 months (n = 277) or 6 months (n = 44). The primary endpoint was the development of CMV viremia or end-organ disease resulting in the escalation of anti-CMV therapy. The secondary endpoint was hospitalization for CMV-related infection. Results Of the 321 patients in the analysis, 13.4% (n = 43) developed CMV viremia or end-organ infection requiring escalation of anti-CMV therapy, and 3.4% (n = 11) were hospitalized for CMV infection. Overall, there was no significant difference in the primary endpoint in patients treated with 3 months of valganciclovir compared to 6 months (12.6% vs. 18.2%, p = 0.316; Figure 1A). There was a trend toward reduction in CMV hospitalization in the 6-month treatment group (Figure 1B), but this did not achieve statistical significance (3.6% vs. 2.3%, p = 0.651), potentially due to a low number of events. Conclusion We found no difference in the risk of CMV viremia or hospitalization for CMV using either a 3-month or 6-month regimen for prophylaxis in HTx recipients at intermediate risk for CMV (R+).

Background:As medication non-adherence is a major risk factor for poor post-transplant outcomes, we explored how adherence is assessed, enhanced and integrated across the transplant continuum.Aim:The aim of this study was to study practice patterns regarding pre- and post-transplant medication adherence assessment and interventions in international heart transplant centres.Methods:We used data from the Building Research Initiative Group: chronic illness management and adherence in heart transplantation (BRIGHT) study, a cross-sectional study conducted in 36 heart transplant centres in 11 countries. On a 27-item questionnaire, 100 clinicians (range one to five per centre) reported their practice patterns regarding adherence assessment and intervention strategies pre-transplant, immediately post-transplant, less than one year, and one or more year post-transplant. Educational/cognitive, counselling/behavioural and psychosocial/affective strategies were assessed. Clinicians’ responses (intervention present vs. absent; or incongruence in reporting intervention) were aggregated at the centre level.Results:The adherence assessment method most commonly used along the transplant continuum was questioning patients (range 75–88.9%). Pre-transplant, all three categories of intervention strategy were applied. Providing reading materials (82.9%) or instructions (68.6%), involving family or support persons in education (91.4%), and establishing partnership (91.4%) were used most frequently. Post-transplant, strategies closely resembled those employed pre-transplant. Training patients (during recovery) and cueing were more often applied during hospitalisation (74.3%). After the first year post-transplant, except for motivational interviewing (25.7–28.6%), the number of strategies decreased.Conclusions:Across the transplant continuum, diverse adherence interventions are implemented; however, post-transplant, the frequency of adherence interventions decreases. Therefore, increased investment is necessary in long-term adherence interventions.

OBJECTIVES: The objectives of this study were to: (1) explore the proportion of HTx centers that have a multidisciplinary team and (2) assess the relationship between multidisciplinarity and the level of chronic illness management (CIM). BACKGROUND: The International Society for Heart and Lung Transplantation (ISHLT) recommends a multidisciplinary approach in heart transplant (HTx) follow-up care but little is known regarding the proportion of HTx centers that meet this recommendation and the impact on patient care. HTx centers with a multidisciplinary team may offer higher levels of CIM, a care model that has the potential to improve outcomes after HTx. METHODS: We conducted a secondary analysis of the BRIGHT study, a cross-sectional study in 11 countries. Multidisciplinarity in the 36 HTx centers was assessed through HTx director reports and was defined as having a team that was composed of physician(s), nurse(s), and another healthcare professional (either a social worker, psychiatrist, psychologist, pharmacist, dietician, physical therapist, or occupational therapist). CIM was assessed with the Patient Assessment of Chronic Illness Care (PACIC). Multiple linear regression assessed the relationship between multidisciplinarity and the level of CIM. RESULTS: Twenty-nine (80.6%) of the HTx centers had a multidisciplinary team. Furthermore, multidisciplinarity was significantly associated with higher levels of CIM (β = 5.2, P = 0.042). CONCLUSION: Majority of the HTx centers follows the ISHLT recommendation for a multidisciplinary approach. Multidisciplinarity was associated with CIM and point toward a structural factor that needs to be in place for moving toward CIM. ispartof: Heart & Lung vol:46 issue:5 pages:351-356 ispartof: location:United States status: published

We describe our optimization efforts to improve the physicochemical properties, solubility, and off-target profile of 1, an inhibitor of TarO, an early stage enzyme in the biosynthetic pathway for wall teichoic acid (WTA) synthesis. Compound 1 displayed a TarO IC50 of 125 nM in an enzyme assay and possessed very high lipophilicity (clogP = 7.1) with no measurable solubility in PBS buffer. Structure–activity relationship (SAR) studies resulted in a series of compounds with improved lipophilic ligand efficiency (LLE) consistent with the reduction of clogP. From these efforts, analog 9 was selected for our initial in vivo study, which in combination with subefficacious dose of imipenem (IPM) robustly lowered the bacterial burden in a neutropenic Staphylococci murine infection model. Concurrent with our in vivo optimization effort using 9, we further improved LLE as exemplified by a much more druglike analog 26.

Health literacy (HL) is a major determinant of health outcomes; however, there are few studies exploring the role of HL among heart transplant recipients. The objectives of this study were to: (1) explore and compare the prevalence of inadequate HL among heart transplant recipients internationally; (2) determine the correlates of HL; and (3) assess the relationship between HL and health-related behaviors.A secondary analysis was conducted using data of the 1,365 adult patients from the BRIGHT study, an international multicenter, cross-sectional study that surveyed heart transplant recipients across 11 countries and 4 continents. Using the Subjective Health Literacy Screener, inadequate HL was operationalized as being confident in filling out medical forms none/a little/some of the time (HL score of 0 to 2). Correlates of HL were determined using backward stepwise logistic regression. The relationship between HL and the health-related behaviors were examined using hierarchical logistic regression.Overall, 33.1% of the heart transplant recipients had inadequate HL. Lower education level (adjusted odds ratio [AOR] 0.24, p0.001), unemployment (AOR 0.69, p = 0.012) and country (residing in Brazil, AOR 0.25, p0.001) were shown to be associated with inadequate HL. Heart transplant recipients with adequate HL had higher odds of engaging in sufficient physical activity (AOR 1.6, p = 0.016). HL was not significantly associated with the other health behaviors.Clinicians should recognize that almost one third of heart transplant participants have inadequate health literacy. Furthermore, they should adopt communication strategies that could mitigate the potential negative impact of inadequate HL.

Background We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD). Methods and Results Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.0 U/mL. The median follow-up after transplant was 3.6 years (interquartile range, 2.2–5.6 years). After LVAD, AT1R-Ab levels increased from baseline and remained elevated until transplant. Freedom from adverse events at 5 years was lower in those with elevated AT1R-Ab levels at time of transplant. In an adjusted, multivariable Cox analysis, an AT1R-Ab level of >10 U/mL was associated with developing the primary end point (adjusted hazard ratio 3.4, 95% confidence interval 1.2–9.2, P = .017). Although C-reactive protein levels were high before and after LVAD placement, C-reactive protein did not correlate with AT1R-Ab. Conclusions In LVAD patients bridged to heart transplant, an increased AT1R-Ab level at time of transplant was associated with poor outcomes after heart transplant. Post-LVAD AT1R-Ab elevations were not correlated with serum markers of systemic inflammation. Larger studies are needed to examine the pathologic role of AT1R-Ab in heart transplant.

To compare the objective and subjective efficacy of three treatments on acute hip-flexion range of motion (ROM).Assessor-blind, randomized within-subject cross-over.University athletic training clinic.Twenty-two female collegiate lacrosse and soccer athletes.The passive straight-leg-raise (PSLR) was used to measure acute hip-flexion ROM pre- and post foam rolling (FR), superficial heating (SH), combination (SH + FR) and control treatments. A seven-point Likert scale statement measured the perceived effectiveness of each treatment.Superficial heat (+10.4%, ES = 0.78), FR (+7.26%, ES = 0.52), and SH + FR treatment (+12.9%, ES = 1.26) improved hip ROM when compared to the control (+2.4%, ES = 0.24) (all p 0.001). The SH + FR treatment resulted in a greater improvement in hip ROM compared to FR (p = 0.001, ES = 0.95), whereas no significant difference was observed between the SH and FR (p = 0.083, ES = 0.68) or SH and SH + FR treatment (p = 0.270, ES = 0.43). SH + FR was perceived as more effective than FR (p = 0.033, ES = 1.21), but not SH (p = 0.193, ES = 0.63). However, only a moderately positive correlation (r = 0.508) between objective and subjective measures of hamstring flexibility was found.All treatments significantly improve hamstring flexibility with SH + FR being the most effective. Rehabilitation professionals should practice caution when relying on athlete perception and should prescribe treatments on an individual basis.

OBJECTIVE We sought to describe a technique for ultra-low-contrast angiography (ULCA) in patients with advanced chronic kidney disease (CKD) and previous coronary artery bypass surgery (CABG). BACKGROUND Patients with advanced CKD and previous CABG are at high risk of developing contrast-induced nephropathy (CIN) because of the additional contrast often required to identify bypass grafts. Apart from hydration, reduced contrast administration is the only established method to minimize the risk of CIN. PATIENTS AND METHODS Ten patients underwent ULCA, whereby an intracoronary injection of saline and coronary guidewires were used instead of test injections of contrast for engagement of bypass grafts with catheters. Estimated glomerular filtration rate (eGFR) before and 30 days following angiography were recorded as was the need for renal replacement therapy 1 year after the procedure. RESULTS All patients completed a diagnostic angiogram without complications. The median volume of contrast delivered was 13.5 ml (interquartile range: 10.5-17.8). The median eGFR was 18.3 ml/min/1.73 m (interquartile range: 16.5-28.2). There was no statistically significant difference in eGFR before the procedure and 30 days after the procedure (P=0.79). No patient required dialysis 30 days after the procedure. Two patients required initiation of dialysis at 1 year after the procedure. CONCLUSION In patients with advanced CKD and previous CABG, ULCA may be performed with high procedural success and without complications, minimizing the risk of CIN in these high-risk patients.

Tedizolid phosphate, the prodrug of the active antibiotic tedizolid, is an oxazolidinone for the treatment of acute bacterial skin and skin structure infections. Studies in a mouse thigh infection model demonstrated that tedizolid has improved potency and pharmacokinetics/pharmacodynamics (PK/PD) compared with those of linezolid. Subsequent studies showed that the efficacy of tedizolid was enhanced in immunocompetent (IC) mice compared with neutropenic (immunosuppressed [IS]) mice, with stasis at clinically relevant doses being achieved only in the presence of granulocytes. The tedizolid label therefore contains a warning about its use in neutropenic patients. This study reevaluated the PK/PD of tedizolid and linezolid in the mouse thigh infection model in IC and IS mice using a methicillin-resistant Staphylococcus aureus (MRSA) strain (ATCC 33591) and a methicillin-susceptible S. aureus (MSSA) strain (ATCC 29213). The antistaphylococcal effect of doses ranging from 1 to 150 mg/kg of body weight tedizolid (once daily) or linezolid (twice daily) was determined at 24, 48, and 72 h after initiating treatment. In IC mice, stasis was achieved in the absence of antibiotics, and both tedizolid and linezolid reduced the burden further beyond a static effect. In IS mice, tedizolid achieved stasis against MRSA ATCC 33591 and MSSA ATCC 29213 at 72 h at a human clinical dose of 200 mg, severalfold lower than that in earlier studies. Linezolid achieved a static effect against MRSA ATCC 33591 in IS mice at a dose lower than that used clinically. This study demonstrates that, with time, both tedizolid and linezolid at clinically relevant exposures achieve stasis in neutropenic mice with an MRSA or MSSA thigh infection.

Soil is a complex material capable of storing and releasing large amounts of carbon, making it an integral part of the global carbon cycle. As soil is included in national inventory assessments where countries quantify their emissions, it is important that estimates of the soil carbon flux are as accurate as possible. Measuring the flux of carbon from every surface on the planet is unrealistic, therefore modelling emissions is the next best method of emissions assessment. Among modelling approaches, process-based modelling allows for the highest specificity of input data. Process-based models split soil carbon into pools with different decay rates influenced by environmental (biotic and abiotic) factors and management. The Estimation of Carbon in Organic Soils – Sequestration and Emissions (ECOSSE) model has previously been recommended as the optimum process-based model for simulating greenhouse gas (GHG) emissions from Irish soils. Results from the site-specific evaluation of the ECOSSE model for an Irish arable site showed a temporal offset between measurements and model outputs which could not be explained by model parameters, motivating further in-depth analysis of the model. This subsequent analysis indicated that the rate modifiers, which control the release of carbon from different pools in the soil, were functioning as intended, but highlighted issues with the model simulation of soil water. The modelled soil dried out fully when in reality it was above field capacity, attributable to erroneous simulation of evaporation on this well-drained sandy soil. In parallel, a spatial process-based model (GlobalECOSSE) was employed to derive national emissions estimates for multiple GHGs and CO2 equivalents for designated agricultural land uses on the island of Ireland. The justification for using the spatial process-based model was to provide an assessment of a model that had fewer input requirements and operated on a monthly timescale to simulate areal emissions. Results showed soil carbon emissions are enhanced during warmer months and lessened during colder ones, and showed cropland and grassland to be CO2 sources on an annual timeframe. The importance of examining emissions holistically is emphasised as some Irish grasslands are GHG sinks when other GHGs such as methane and nitrous oxide are included, and all croplands are GHG sources. To assess the susceptibility of Irish soils to unusual or extreme weather events, statistical sampling of past weather events was employed to generate inputs for GlobalECOSSE. The response of Irish soils to extreme weather events shows warmer temperatures enhance respiration, while drought conditions restrict it. Warm and wet conditions enhance respiration most as respiration increases with temperature and is not limited by moisture availability in this scenario. Including all GHGs produces similar patterns with most Irish soils being C sinks under normal climate and hydrological conditions, and more areas becoming sources during hot, very hot and hot & wet conditions (derived from extremes in the observed record). These results are presented in the context of the uncertainties in observations (large ranges across datasets and methods of partitioning fluxes) and in modelling (different models giving different magnitudes and even directions of change). More observations, experiments and modelling studies across land-use and climate types are needed before confident projections can be given. Observational networks should be placed strategically to determine responses from common soil and land-use types, and moisture regimes. Current action should focus on maintaining the carbon already in soils by avoiding disturbance, and promoting sensible sequestration practices such as cover-cropping, minimum/no tillage and incorporation of straw/manure.

Purpose Heart transplant recipients with prior exposure to CMV (R+) are considered intermediate risk for CMV-related complications, and current guidelines allow for either universal prophylaxis or a pre-emptive approach to prophylaxis. Some centers prefer a preemptive approach to mitigate the cost and risks of prophylaxis, most notably the risk of leukopenia. In the present study, we evaluate the risks of leukopenia with each prophylaxis approach. Methods Retrospective analysis of 440 intermediate risk (CMV R+) HTx recipients from 6 U.S. centers between 2010-2018, treated with either universal prophylaxis (73%, n = 323) or preemptive therapy (27%, n = 117). The primary endpoint was the development of leukopenia (WBC Results Of the 440 patients in the analysis, 177 (40%) developed leukopenia (WBC Conclusion Leukopenia occurs in 40% of heart transplant recipients. Although CMV prophylaxis has been associated with leukopenia, there is no difference in this risk when comparing a universal vs. preemptive prophylaxis strategy for CMV.

Purpose Currently, there are patients who meet criteria for lung transplant who are denied listing because of underlying heart disease. Likewise, there are patients who meet criteria for heart transplant but are denied listing because of lung disease. In addition, end-stage pulmonary hypertension has become more commonly treated with bilateral lung transplantation. From 2006 to 2018, no adult heart-lung transplantation (HLT) was performed in New York State. Given this unmet need our center has renewed interest in HLT. Methods All patients who underwent HLT from 06/2019 to 09/2020 were reviewed. Patients were listed per standard UNOS guidelines. The primary outcome was hospital and 1year survival. Results 10 patients (50% male; mean age 54±8 years) underwent HLT during this period. All patients had been deemed not appropriate candidates for isolated heart or lung transplant at more than one transplant center. The indication for HLT was interstitial lung disease (ILD) with ischemic cardiomyopathy (n=4), nonischemic cardiomyopathy with PAH (n=2), PAH with RV failure (n=2), and ILD with RV failure (n=2). Median lung allocation score and heart waitlist status were 71 (IQR: 41-85) and 2 (IQR: 1-3) respectively. Three patients had re-operative sternotomies. Two patients bridged to transplant with VA-ECMO, two with VV-ECMO and three patients required IABP. One patient received a DCD donor heart-lung block utilizing normothermic regional perfusion, and two patients received Hep C+ donor organs. One patient was left on central VA-ECMO postoperatively for early lung PGD. No lung PGD grade 3 at 72 hours or significant heart PGD at any time point were observed. At a median follow up of 287 (IQR: 108-401 days), all patients are alive at home. Conclusion Our initial center experience demonstrates that appropriately selected patients with end stage heart and lung disease who would otherwise die without transplantation can be offered HLT with excellent short-term outcomes.