Bone-to-bone and implant-to-bone impingement : a novel graphical representation for hip replacement planning

Bone-to-bone impingement (BTBI) and implant-to-bone impingement (ITBI) risk assessment is generally performed intra-operatively by surgeons, which is entirely subjective and qualitative, and therefore, lead to sub-optimal results and recurrent dislocation in some cases. Therefore, a method was developed for identifying subject-specific BTBI and ITBI, and subsequently, visualising the impingement area on native bone anatomy to highlight where prominent bone should be resected. Activity definitions and subject-specific bone geometries, with planned implants were used as inputs for the method. The ITBI and BTBI boundary and area were automatically identified using ray intersection and region growing algorithm respectively to retain the same ‘conical clearance angle’ obtained to avoid prosthetic impingement (PI). The ITBI and BTBI area was then presented with different colours to highlight the risk of impingement, and importance of resection. A clinical study with five patients after 2 years of THA was performed to validate the method. The results supported the study hypothesis, in that the predicted highest risk area (red coloured zone) was completely/majorly resected during the surgery. Therefore, this method could potentially be used to examine the effect of different pre-operative plans and hip motions on BTBI, ITBI, and PI, and to guide bony resection during THA surgery

Prediction and visualisation of bony impingement for subject specific total hip arthroplasty

Bony impingement (BI) may contribute to restricted hip joint motion, and recurrent dislocation after total hip arthroplasty (THA), and therefore, should be avoided where possible. However, BI risk assessment is generally performed intra-operatively by surgeons, which is partially subjective and qualitative. Therefore, the aim of the study was to develop a method for identifying subject-specific BI, and subsequently, visualising BI area on native bone anatomy to highlight the amount of bone should be resected. Activity definitions and subject-specific bone geometries, constructed from CT scans, with planned implants were used as inputs for the method. For each activity, a conical clearance angle (CCA) was checked between femur and pelvis through simulation. Simultaneously, BI boundary and area were automatically calculated using ray intersection and region growing algorithm respectively. The potential use of the developed method was explained through a case study using an anonymised pre-THA patient data. Two pure (flexion, and extension) and two combined hip joint motions (internal and external rotation at flexion and extension respectively) were considered as activities. BI area were represented in two ways: (a) CCA specific where BI area for each activity with different CCAs was highlighted, (b) activity specific where BI area for all activities with a particular CCA was presented. Result showed that BI area between the femoral and pelvic parts was clearly identified so that the pre-operative surgical plan could be adjusted to minimise impingement. Therefore, this method could potentially be used to examine the effect of different preoperative plans and hip motion on BI, and to guide bony resection during THA surgery

Inhaled Corticosteroids Alone and in Combination With Long-Acting beta(2) Receptor Agonists to Treat Reduced Lung Function in Preterm-Born Children A Randomized Clinical Trial:A Randomized Clinical Trial

IMPORTANCE: Decreases in future lung function are a hallmark of preterm birth, but studies for management of decreased lung function are limited. OBJECTIVE: To determine whether 12 weeks of treatment with inhaled corticosteroids (ICS) alone or in combination with long-acting β(2) agonists (LABA) improves spirometry and exercise capacity in school-aged preterm-born children who had percent predicted forced expiratory volume in 1 second (%FEV(1)) less than or equal to 85% compared with inhaled placebo treatment. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, placebo-controlled trial was conducted to evaluate ICS and ICS/LABA against placebo. Preterm-born children (age, 7-12 years; gestation ≤34 weeks at birth) who did not have clinically significant congenital, cardiopulmonary, or neurodevelopmental abnormalities underwent spirometry, exercise testing, and measurement of fractional exhaled nitric oxide before and after treatment. A total of 144 preterm-born children at the Children’s Hospital for Wales in Cardiff, UK, were identified and enrolled between July 1, 2017, and August 31, 2019. INTERVENTIONS: Each child was randomized to 1 of 3 cohorts: fluticasone propionate, 50 μg, with placebo; fluticasone propionate, 50 μg, with salmeterol, 25 μg; or placebo inhalers, all given as 2 puffs twice daily for 12 weeks. Children receiving preexisting ICS treatment underwent washout prior to randomization to ICS or ICS/LABA. MAIN OUTCOMES AND MEASURES: The primary outcome was between-group differences assessed by adjusted pretreatment and posttreatment differences of %FEV(1) using analysis of covariance. Intention-to-treat analysis was conducted. RESULTS: Of 144 preterm-born children who were identified with %FEV(1) less than or equal to 85%, 53 were randomized. Treatment allocation was 20 children receiving ICS (including 5 with prerandomization ICS), 19 children receiving ICS/LABA (including 4 with prerandomization ICS), and 14 children receiving placebo. The mean (SD) age of children was 10.8 (1.2) years, and 29 of the randomized children (55%) were female. The posttreatment %FEV(1) was adjusted for sex, gestation, bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, and pretreatment values. Posttreatment adjusted means for %FEV(1), using analysis of covariance, were 7.7% (95% CI, −0.27% to 15.72%; P = .16) higher in the ICS group and 14.1% (95% CI, 7.3% to 21.0%; P = .002) higher in the ICS/LABA group compared with the placebo group. Active treatment decreased the fractional exhaled nitric oxide and improved postexercise bronchodilator response but did not improve exercise capacity. One child developed cough when starting inhaler treatment; no other adverse events reported during the trial could be attributed to the inhaler treatment. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial suggest that combined ICS/LABA treatment is beneficial for prematurity-associated lung disease in children. TRIAL REGISTRATION: EudraCT number: 2015-003712-2

Implementation of a web-based resilience enhancement training for nurses : pilot randomized controlled trial

Background: Global workforce challenges faced by health care providers are linked to low levels of job satisfaction, recruitment, retention, and well-being, with detrimental impacts on patient care outcomes. Resilience-building programs can provide support for staff who endure highly stressful environments, enhance resilience, and support recruitment and retention, with web-based formats being key to increasing accessibility. Objective: We aimed to examine participants’ engagement with a newly developed Resilience Enhancement Online Training for Nurses (REsOluTioN), explore its acceptability, and compare levels of resilience and psychological well-being in nurses who completed REsOluTioN with those who did not. Methods: We carried out a pilot randomized trial (1:1), conducted at a single site (mental health and community trust in South England) between August 2021 and May 2022. Local research ethics approvals were obtained. Nurses were invited to participate and were randomly assigned to a waitlist group or REsOluTioN group. Training lasted for 4 weeks, consisting of prereading, web-based facilitated sessions, and mentorship support. We evaluated trial engagement, acceptability of training, and pre-post changes in resilience, measured by the Brief Resilience Scale, and psychological well-being, measured by the Warwick Edinburgh Mental Wellbeing Scale. Qualitative participant feedback was collected. Consolidated Standards of Reporting Trials 2010 extension guidelines for reporting pilot and feasibility trials were used. Results: Of 108 participants recruited, 93 completed the study. Participants’ mean age was 44 (SD 10.85) years. Most participants were female (n=95, 88.8%), White (n=95, 88.8%), and worked in community settings (n=91, 85.0%). Sixteen facilitated and 150 mentoring sessions took place. Most REsOluTioN program participants reported the sessions helped improve their resilience (n=24, 72.8%), self-confidence (n=24, 72.7%), ability to provide good patient care (n=25, 75.8%), relationships with colleagues (n=24, 72.7%), and communication skills (n=25, 75.8%). No statistically significant differences between training and control groups and time on well-being (F1,91=1.44, P=.23, partial η2=0.02) and resilience scores (F1,91=0.33, P=.57, partial η2=0.004) were revealed; however, there were positive trends toward improvement in both. Nurse participants engaged with the REsOluTioN program and found it acceptable. Most found web-based training and mentoring useful and enjoyed learning, reflection, networking, and participatory sessions. Conclusions: The REsOluTioN program was acceptable, engaging, perceived as useful, and nurses were keen for it to be implemented to optimize resilience, psychological health, communication, and workplace environments. The study has evidenced that it is acceptable to implement web-based resilience programs with similar design features within busy health care settings, indicating a need for similar programs to be carefully evaluated. Mentorship support may also be a key in optimizing resilience. Trial limitations include small sample size and reduced statistical power; a multicenter randomized controlled trial could test effectiveness of the training on a larger scale

Sympathetic-transduction in untreated hypertension

Transduction of muscle sympathetic nerve activity (MSNA) into vascular tone varies with age and sex. Older normotensive men have reduced sympathetic transduction so that a given level of MSNA causes less arteriole vasoconstriction. Whether sympathetic transduction is altered in hypertension (HTN) is not known. We investigated whether sympathetic transduction is impaired in untreated hypertensive men compared to normotensive controls. Eight untreated hypertensive men and 10 normotensive men (age 50 ± 15 years vs. 45 ± 12 years (mean ± SD); p = 0.19, body mass index (BMI) 24.7 ± 2.7 kg/m(2) vs. 26.0 ± 4.2 kg/m(2); p = 0.21) were recruited. MSNA was recorded from the peroneal nerve using microneurography; beat-to-beat blood pressure (BP; Finapres) and heart rate (ECG) were recorded simultaneously at rest for 10 min. Sympathetic-transduction was quantified using a previously described method. The relationship between MSNA burst area and subsequent diastolic BP was measured for each participant with the slope of the regression indicating sympathetic transduction. MSNA was higher in the hypertensive group compared to normotensives (73 ± 17 bursts/100 heartbeats vs. 49 ± 19 bursts/100 heart bursts; p = 0.007). Sympathetic-transduction was lower in the hypertensive versus normotensive group (0.04%/mmHg/s vs. 0.11%/mmHg/s, respectively; R = 0.622; p = 0.006). In summary, hypertensive men had lower sympathetic transduction compared to normotensive individuals suggesting that higher levels of MSNA are needed to cause the same level of vasoconstrictor tone

Is High Blood Pressure Self-Protection for the Brain?

Rationale: Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular abnormalities of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the etiology of essential hypertension, which remains enigmatic in 95% of patients. Objective: To evaluate the role of the cerebral circulation in the pathophysiology of hypertension. Methods and Results: We completed a series of retrospective and mechanistic case-control magnetic resonance imaging and physiological studies, in normotensive and hypertensive humans (n=259). Interestingly, in humans with hypertension, we report a higher prevalence of congenital cerebrovascular variants; vertebral artery hypoplasia and an incomplete posterior circle of Willis, which were coupled with increased cerebral vascular resistance, reduced cerebral blood flow and a higher incidence of lacunar type infarcts. Causally, cerebral vascular resistance was elevated before the onset of hypertension and elevated sympathetic nerve activity (n=126). Interestingly, untreated hypertensive patients (n=20) had a cerebral blood flow similar to age-matched controls (n=28). However, participants receiving anti-hypertensive therapy (with blood pressure controlled below target levels) had reduced cerebral perfusion (n=19). Finally, elevated cerebral vascular resistance was a predictor of hypertension suggesting it may be a novel prognostic and/or diagnostic marker (n=126). < Conclusions: Our data indicate that congenital cerebrovascular variants in the posterior circulation and the associated cerebral hypoperfusion may be a factor in triggering hypertension. Therefore lowering blood pressure may worsen cerebral perfusion in susceptible individuals

Repeated administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) modulates neuroinflammation and amyloid plaque load in mice bearing amyloid precursor protein and presenilin-1 mutant transgenes

BACKGROUND: Data indicates anti-oxidant, anti-inflammatory and pro-cognitive properties of noradrenaline and analyses of post-mortem brain of Alzheimer's disease (AD) patients reveal major neuronal loss in the noradrenergic locus coeruleus (LC), the main source of CNS noradrenaline (NA). The LC has projections to brain regions vulnerable to amyloid deposition and lack of LC derived NA could play a role in the progression of neuroinflammation in AD. Previous studies reveal that intraperitoneal (IP) injection of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) can modulate neuroinflammation in amyloid over-expressing mice and in one study, DSP-4 exacerbated existing neurodegeneration. METHODS: TASTPM mice over-express human APP and beta amyloid protein and show age related cognitive decline and neuroinflammation. In the present studies, 5 month old C57/BL6 and TASTPM mice were injected once monthly for 6 months with a low dose of DSP-4 (5 mg kg(-1)) or vehicle. At 8 and 11 months of age, mice were tested for cognitive ability and brains were examined for amyloid load and neuroinflammation. RESULTS: At 8 months of age there was no difference in LC tyrosine hydroxylase (TH) across all groups and cortical NA levels of TASTPM/DSP-4, WT/Vehicle and WT/DSP-4 were similar. NA levels were lowest in TASTPM/Vehicle. Messenger ribonucleic acid (mRNA) for various inflammatory markers were significantly increased in TASTPM/Vehicle compared with WT/Vehicle and by 8 months of age DSP-4 treatment modified this by reducing the levels of some of these markers in TASTPM. TASTPM/Vehicle showed increased astrocytosis and a significantly larger area of cortical amyloid plaque compared with TASTPM/DSP-4. However, by 11 months, NA levels were lowest in TASTPM/DSP-4 and there was a significant reduction in LC TH of TASTPM/DSP-4 only. Both TASTPM groups had comparable levels of amyloid, microglial activation and astrocytosis and mRNA for inflammatory markers was similar except for interleukin-1 beta which was increased by DSP-4. TASTPM mice were cognitively impaired at 8 and 11 months but DSP-4 did not modify this. CONCLUSION: These data reveal that a low dose of DSP-4 can have varied effects on the modulation of amyloid plaque deposition and neuroinflammation in TASTPM mice dependent on the duration of dosing

Robotics and Automated Systems for Environmental Sustainability: Monitoring Terrestrial Biodiversity

It is critical to protect Earth’s biodiversity, not just for its own intrinsic value, but also for the ecosystem services it underpins. Yet biodiversity is in crisis, with up to 1 million animal and plant species at risk of extinction, many within decades. This dire projection has captured world attention and triggered major mitigation efforts, but we are faced with problems in assessing global trends in biodiversity – which species, taxa, habitats and ecosystems are suffering the greatest declines? Are current mitigation measures having any positive impact? To answer key questions such as these, ecologists are seeking the help of robotics and automated systems (RAS) experts in the monumental task of attempting to monitor the state of biodiversity.In this White Paper, we have surveyed recent literature and consulted more than 120 international expert ecologists and engineers working in the fields of biodiversity and robotics. We have done this to evaluate the potential for developing robotic and autonomous systems that could massively extend the scope of terrestrial biodiversity monitoring across habitats globally. The complexities of biodiversity itself, and the many barriers and challenges that must be overcome in monitoring it, are formidable. We assess each of these barriers in turn, highlighting currently available RAS solutions, as well as nascent technologies that may be relevant to future RAS for biodiversity (RAS-BD) monitoring. Using this information, we have drawn up a roadmap of actions needed to address the barriers that should be easiest to overcome. Encouragingly, we find that a variety of existing RAS capabilities may be transferable to a biodiversity monitoring context. Beyond these are the harder barriers, where promising novel ideas being researched at UK universities and research institutes may, in time, become integral parts of future RAS-BD monitoring technology. We believe that RAS-BD technology has great potential to complement and considerably extend the field survey work undertaken by expert human observers. In the UK, we are fortunate in having particular strengths in both biodiversity and robotics research; as a nation we are in an ideal position to integrate them and become a leading force in the development and application of RAS-BD monitoring. To this end, we propose these recommendations that we hope will guide future government strategy in an area that is vital to the future of humanity:● The creation and funding of an integrated multidisciplinary task force, including academics and industry specialists with expertise in RAS and biodiversity, to support technological research and development.● Future UK funding and focus should be prioritised to utilise existing RAS capabilities to develop first generation RAS-BD technology for monitoring biodiversity.● Relevant nascent technologies being researched by numerous UK academic teams need increased and accelerated research and development funding to turn pioneering concepts into enhanced RAS-BD technology suited to overcoming the hardest monitoring barriers that ecologists encounter.● Education strategies should be developed to foster links between aspiring engineers, biologists andcomputer technologists, both in the curriculum of schools, and at later stages in universities and research facilities

Aging in females is associated with changes in respiratory modulation of sympathetic nerve activity and blood pressure

Sympathetic nerve activity (SNA) is tightly coupled with the respiratory cycle. In healthy human males, respiratory modulation of SNA does not change with age. However, it is unclear how this modulation is affected by age in females. We investigated whether respiratory sympathetic modulation is altered in healthy postmenopausal (PMF) versus premenopausal female (YF), and younger male (YM) adults, and determined its relationship to resting blood pressure. Muscle SNA (MSNA; microneurography), respiration (transducer belt), ECG, and continuous blood pressure were measured in 12 YF, 13 PMF, and 12 YM healthy volunteers. Respiratory modulation of MSNA was quantified during two phases of the respiratory cycle: mid-late expiration and inspiration/postinspiration. All groups showed respiratory modulation of MSNA (P < 0.0005). There was an interaction between the respiratory phase and group for MSNA [bursts/100 heartbeats (HB) (P ¼ 0.004) and bursts/min (P ¼ 0.029)], with smaller reductions in MSNA during inspiration observed in PMF versus the other groups. Respiratory modulation of blood pressure was also reduced in PMF versus YF (6 [2] vs. 12 [9] mmHg, P ¼ 0.008) and YM (13 [13] mmHg, P ¼ 0.001, median [interquartile range]). The magnitude of respiratory sympathetic modulation was related to resting blood pressure in PMF only, such that individuals with less modulation had greater resting blood pressure. The data indicate that aging in postmenopausal females is associated with less inspiratory inhibition of MSNA. This correlated with a higher resting blood pressure in PMF only. Thus, the reduced modulation of MSNA could contribute to the age-related rise in blood pressure that occurs in females. NEW & NOTEWORTHY The current study demonstrates that respiratory modulation of sympathetic nerve activity (SNA) is reduced in healthy postmenopausal (PMF) versus premenopausal females (YF). Furthermore, respiratory sympathetic modulation was negatively related to resting blood pressure in postmenopausal females, such that blood pressure was greater in individual with less modulation. Reduced respiratory sympathetic modulation may have implications for the autonomic control of blood pressure in aging postmenopausal females, by contributing to age-related sympathetic activation and reducing acute, respiratory-linked blood pressure variation