Neural Interface-Based Motor Neuroprosthesis in Poststroke Upper Limb Neurorehabilitation: An Individual Patient Data Meta-analysis.

OBJECTIVE: To determine the efficacy of neural interface-based neurorehabilitation, including brain-computer interface, through conventional and individual patient data (IPD) meta-analysis and to assess clinical parameters associated with positive response to neural interface-based neurorehabilitation. DATA SOURCES: PubMed, EMBASE, and Cochrane Library databases up to February 2022 were reviewed. STUDY SELECTION: Studies using neural interface-controlled physical effectors (functional electrical stimulation and/or powered exoskeletons) and reported Fugl-Meyer Assessment-upper-extremity (FMA-UE) scores were identified. This meta-analysis was prospectively registered on PROSPERO (#CRD42022312428). PRISMA guidelines were followed. DATA EXTRACTION: Changes in FMA-UE scores were pooled to estimate the mean effect size. Subgroup analyses were performed on clinical parameters and neural interface parameters with both study-level variables and IPD. DATA SYNTHESIS: Forty-six studies containing 617 patients were included. Twenty-nine studies involving 214 patients reported IPD. FMA-UE scores increased by a mean of 5.23 (95% confidence interval [CI]: 3.85-6.61). Systems that used motor attempt resulted in greater FMA-UE gain than motor imagery, as did training lasting >4 vs ≤4 weeks. On IPD analysis, the mean time-to-improvement above minimal clinically important difference (MCID) was 12 weeks (95% CI: 7 to not reached). At 6 months, 58% improved above MCID (95% CI: 41%-70%). Patients with severe impairment (P=.042) and age >50 years (P=.0022) correlated with the failure to improve above the MCID on univariate log-rank tests. However, these factors were only borderline significant on multivariate Cox analysis (hazard ratio [HR] 0.15, P=.08 and HR 0.47, P=.06, respectively). CONCLUSION: Neural interface-based motor rehabilitation resulted in significant, although modest, reductions in poststroke impairment and should be considered for wider applications in stroke neurorehabilitation.

Character Traits Predict Health and Well-Being beyond Personality.

We examined the incremental validity of character in predicting health outcomes and well-being beyond personality traits and investigated the extent to which health-related behaviors mediate the relationship between character and well-being. Findings indicate that several character cores (e.g., transcendence, fortitude) predict well-being, health behaviors, and health outcomes beyond different measures of personality traits, indicating that character is discriminable from personality as indicated by incremental prediction. In particular, fortitude, temperance, transcendence, and sincerity appear to be key players. Implications for character research are discussed.

Experience Using Adjuvant Bacteriophage Therapy for the Treatment of 10 Recalcitrant Periprosthetic Joint Infections: A Case Series.

Periprosthetic joint infections are a devastating complication of joint replacement surgery. One novel therapeutic that has potential to change the current treatment paradigm is bacteriophage therapy. Herein, we discuss our experiences with bacteriophage therapy for 10 recalcitrant periprosthetic joint infections and review the treatment protocols utilized to achieve successful outcomes.

Wideband multimode optical parametric oscillation in a Kerr microresonator.

Parametric oscillation in Kerr microresonators provides an attractive pathway for the generation of new optical frequencies in a low-power, small-footprint device. The frequency shift of the newly generated parametric sidebands is set by the phasematching of the underlying four-wave-mixing process, with the generation of large frequency shift sidebands typically placing exacting requirements on a resonator's dispersion profile. In practice, this limits the range of viable pump wavelengths, and ultimately the range of output frequencies. In this paper, we consider a multimode four-wave-mixing process in which the pump and sidebands propagate in different mode families of the resonator. We show that this multimode configuration yields a considerable relaxation in the phasematching requirements needed to generate large frequency shift parametric sidebands, allowing their formation even in resonators with strong second-order dispersion. Experimentally we use a magnesium-fluoride micro-disk resonator to demonstrate this multimode phasematching. By accessing different pump and sideband modes, four distinct multimode parametric processes generating frequency shifts between 118 and 216 THz are reported. The resulting separation between the two sidebands is almost three octaves.

Kerr microresonator dual-comb source with adjustable line-spacing.

Optical microresonators offer a highly-attractive new platform for the generation of optical frequency combs. Recently, several groups have been able to demonstrate the generation of dual-frequency combs in a single microresonator driven by two optical pumps. This opens the possibility for microresonator-based dual-comb systems suitable for measurement applications such as spectroscopy, ranging and imaging. Key to the performance of these systems are the parameters of the radio-frequency comb spectrum that arises from the interference of the two optical combs. In this work, we present a simple mechanism to enable the discrete fine-tuning of these parameters by driving the two optical combs with optical pumps with different azimuthal mode numbers. The mechanism consists of tuning the difference in azimuthal mode number between the two pumps by selection of the pumps' frequencies. We are able to implement this technique when the two counter-propagating pumps are set to drive resonances of the same spatial mode family, as well as different mode families. In each case, we experimentally observe ∼1 MHz of discrete tunability in the line-spacing of the radio-frequency comb as the frequency offset between the two pumps is scanned between 0 to 80 free-spectral-ranges.

Conceptualizing "positive attributes" across psychological perspectives.

BACKGROUND: The growth of positive psychology has birthed debate on the nature of what "positive" really means. Conceptualizations of positive attributes vary across psychological perspectives, and it appears these definitional differences stem from standards for "positive" espoused by three normative ethical frameworks: consequentialism, deontology, and virtue ethics. When definitions of "positive" do not align with one of these ethical schools, it appears researchers rely on preference to distinguish positive attributes. In either case, issues arise when researchers do not make their theoretical alignment explicit, leading to value-laden, often subjective criteria being smuggled into science as a description of what is positive. OBJECTIVE: To foster a deeper critical understanding of the different approaches, we examine how these conceptual definitions of positive attributes (mis)align with their ethical traditions or fail to align with an ethical school. METHOD: We review several positive attribute theories across psychological disciplines that serve as examples of the ethical and non-ethical sources of "positivity." Through this, we assess the conceptual criteria for what each approach considers "positive," note the degree of alignment between definition and ethical school, and draw attention to potential issues. CONCLUSION: We advance the conceptual assessment of positive attributes by considering the implications of failing to explicitly address the theoretical foundation from which a construct is defined.

Enhancing medical students` confidence and performance in integrated structured clinical examinations (ISCE) through a novel near-peer, mixed model approach during the COVID-19 pandemic.

BACKGROUND: Near-peer medical education serves as an important method of delivering education to junior students by senior students. Due to the reduced clinical exposure because of the COVID-19 pandemic, we developed a mentorship scheme to help medical students with their Integrated Structured Clinical Examinations (ISCEs) by providing a combination of near-peer mentorship together with lecture-based teaching on a weekly basis for a 12-week period. Students attended a specialty-focused lecture every Tuesday followed by a small group teaching session organised by their tutor. METHODS: A longitudinal evaluative interventional study was undertaken by the international student led medical education organisation, OSCEazy. The teaching programme was organised and conducted by third year medical students to a recruited cohort of second year medical students. Students' perceptions of ISCEs (confidence, anxiety, and overall performance) were evaluated using 5-point Likert scales while their knowledge of the specialty was assessed using 10 single best answer questions which were distributed via Google® forms at the start and end of each week. In addition, we assessed tutor perceptions of their teaching and learning experience. RESULTS: Seventy-two tutees were enrolled in the programme (mean age: 24.4, female: 77.8%). 88.9% of the participants had not attended any online ISCE teaching prior to this. They preferred in-person ISCE teaching as compared to virtual sessions [median 4.5 (IQR 4-5) vs 3 (IQR 3-4), p <  0.0001), respectively]. There was a significant overall increase in knowledge when comparing pre-session and post-session performance [mean 53.7% vs 70.7%, p <  0.0001)]. There was a significant increase in student confidence [Confidence: median 3 (IQR:3-4) vs 4 (IQR 3-4), p <  0.0001] while no change was seen in the anxiety and perception of their overall performance in an ISCE. [Anxiety: median 3 (IQR 2-4) vs 3 (IQR 3-4), p = 0.37, Performance: median 3 (IQR 3-4) vs median 3 (IQR 3-4), p <  0.0001]. The tutors reported an increase in their confidence in teaching ISCEs online [median 3 (IQR 2-3.25) vs median 4 (IQR 4-5), p <  0.0001)]. CONCLUSION: Online near-peer teaching increases the confidence of both tutees and tutors involved while enhancing the tutees' knowledge of the specialty. Thus, medical schools should incorporate near-peer teaching in their curriculum to enhance the student learning experience.

Osteochondroma Pathogenesis: Mouse Models and Mechanistic Insights into Interactions with Retinoid Signaling.

Osteochondromas are cartilage-capped tumors that arise near growing physes and are the most common benign bone tumor in children. Osteochondromas can lead to skeletal deformity, pain, loss of motion, and neurovascular compression. Currently, surgery is the only available treatment for symptomatic osteochondromas. Osteochondroma mouse models have been developed to understand the pathology and the origin of osteochondromas and develop therapeutic drugs. Several cartilage regulatory pathways have been implicated in the development of osteochondromas, such as bone morphogenetic protein, hedgehog, and WNT/ß-catenin signaling. Retinoic acid receptor-γ is an important regulator of endochondral bone formation. Selective agonists for retinoic acid receptor-γ, such as palovarotene, have been investigated as drugs for inhibition of ectopic endochondral ossification, including osteochondromas. This review discusses the signaling pathways involved in osteochondroma pathogenesis and their possible interactions with the retinoid pathway.

Relevance of presenting risks of frailty, sarcopaenia and osteopaenia to outcomes from aneurysmal subarachnoid haemorrhage.

INTRODUCTION: Aneurysmal subarachnoid haemorrhage (aSAH) is a condition with significant morbidity and mortality. Traditional markers of aSAH have established their utility in the prediction of aSAH outcomes while frailty markers have been validated in other surgical specialties. We aimed to compare the predictive value of frailty indices and markers of sarcopaenia and osteopaenia, against the traditional markers for aSAH outcomes. METHODS: An observational study in a tertiary neurosurgical unit on 51 consecutive patients with ruptured aSAH was performed. The best performing marker in predicting the modified Rankin scale (mRS) on discharge was selected and an appropriate threshold for the definition of frail and non-frail was derived. We compared various frailty indices (modified frailty index 11, and 5, and the National Surgical Quality Improvement Program score [NSQIP]) and markers of sarcopaenia and osteopaenia (temporalis [TMT] and zygoma thickness), against traditional markers (age, World Federation of Neurological Surgery and modified Fisher scale [MFS]) for aSAH outcomes. Univariable and multivariable analysis was then performed for various inpatient and long-term outcomes. RESULTS: TMT was the best performing marker in our cohort with an AUC of 0.82, Somers' D statistic of 0.63 and Tau statistic 0.25. Of the frailty scores, the NSQIP performed the best (AUC 0.69), at levels comparable to traditional markers of aSAH, such as MFS (AUC 0.68). The threshold of 5.5 mm in TMT thickness was found to have a specificity of 0.93, sensitivity of 0.51, positive predictive value of 0.95 and negative predictive value of 0.42. After multivariate analysis, patients with TMT ≥ 5.5 mm (defined as non-frail), were less likely to experience delayed cerebral ischaemia (OR 0.11 [0.01 - 0.93], p = 0.042), any complications (OR 0.20 [0.06 - 0.069], p = 0.011), and had a larger proportion of favourable mRS on discharge (95.0% vs. 58.1%, p = 0.024) and at 3-months (95.0% vs. 64.5%, p = 0.048). However, the gap between unfavourable and favourable mRS was insignificant at the comparison of 1-year outcomes. CONCLUSION: TMT, as a marker of sarcopaenia, correlated well with the presenting status, and outcomes of aSAH. Frailty, as defined by NSQIP, performed at levels equivalent to aSAH scores of clinical relevance, suggesting that, in patients presenting with acute brain injury, both non-neurological and neurological factors were complementary in the determination of eventual clinical outcomes. Further validation of these markers, in addition to exploration of other relevant frailty indices, may help to better prognosticate aSAH outcomes and allow for a precision medicine approach to decision making and optimization of best outcomes.

The Development and Validation of a Multidimensional Forced-Choice Format Character Measure: Testing the Thurstonian IRT Approach.

There has been reemerging interest within psychology in the construct of character, yet assessing it can be difficult due to social desirability of character traits. Forced-choice formats offer one way to address response bias, but traditional scoring methods (i.e., ipsative) associated with this format makes comparing scores between people problematic. Nevertheless, recent advances in modeling item responding (Thurstonian IRT) enable scoring that recovers absolute standing on latent traits and allows for score comparisons between people. Based on recent work in character measurement (CIVIC), we developed a multidimensional forced-choice measure of character (CIVIC-MFC) and scored it using Thurstonian IRT. Initial validation using a sample of 798 participants demonstrated good support for factorial, convergent, and concurrent validity for scores on the CIVIC-MFC, although they did not demonstrate more faking resistance than scores on a Likert-type format version. Potential explanations are discussed.

Beyond the dermis-high-risk invasive squamous cell carcinoma: a retrospective review.

OBJECTIVE: Most cutaneous squamous cell carcinomas (cSCC) are low risk and can be treated with simple excision or ablation. High-risk cSCC require invasive treatment, including radical surgery. We present our experience in treating invasive cSCC of the pelvis and extremities. METHOD: A retrospective review of the data of patients with invasive cSCC, indicated for surgery between 2014 and 2018, from a single institution was carried out. RESULTS: A total of 19 patients (nine men, 10 women) were included in the study. Mean age was 62 years; mean tumour size was 8.6cm). Of the 19 patients, five patients with paraplegia with cSCC arising from hard-to-heal ulcers died of infection or bleeding after surgery or systemic therapy. Also, nine patients with localised cSCC underwent margin-negative resection with or without radiation; one patient experienced disease relapse. Of the participants, two patients with previous transplants and multifocal aggressive cSCC underwent numerous resections but succumbed to disease, and two patients who presented with locally recurrent disease after previous positive margin resection and radiation underwent re-resection but developed recurrent disease. CONCLUSIONS: Prognosis for invasive cSCC largely depends on clinical setting. Tumours arising from ulcers in patients with paraplegia have a poor prognosis regardless of treatment. Invasive cSCC in transplant patients are often multifocal and often recur. Debulking procedures are associated with local recurrence despite radiation. Patients presenting with localised disease have a favourable prognosis with wide resection, flap coverage and adjuvant therapy.

Understanding the Action of RARγ Agonists on Human Osteochondroma Explants.

Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.

Origins of clustered frequency combs in Kerr microresonators.

Recent experiments have demonstrated the generation of widely spaced parametric sidebands that can evolve into "clustered" optical frequency combs in Kerr microresonators. Here we describe the physics that underpins the formation of such clustered comb states. In particular, we show that the phase matching required for the initial sideband generation is such that (at least) one of the sidebands experiences anomalous dispersion, enabling the sideband to drive frequency comb formation via degenerate and non-degenerate four-wave mixing. We validate our proposal through a combination of experimental observations made in a magnesium-fluoride microresonator and corresponding numerical simulations. We also investigate the coherence properties of the resulting clustered frequency combs. Our findings provide valuable insights on the generation and dynamics of widely spaced parametric sidebands and clustered frequency combs in Kerr microresonators.

Digital waveguide adiabatic passage part 2: experiment.

Using a femtosecond laser writing technique, we fabricate and characterise three-waveguide digital adiabatic passage devices, with the central waveguide digitised into five discrete waveguidelets. Strongly asymmetric behaviour was observed, devices operated with high fidelity in the counter-intuitive scheme while strongly suppressing transmission in the intuitive. The low differential loss of the digital adiabatic passage designs potentially offers additional functionality for adiabatic passage based devices. These devices operate with a high contrast (>90%) over a 60 nm bandwidth, centered at ∼ 823 nm.

Comparative effectiveness research: what to do when experts disagree about risks.

BACKGROUND: Ethical issues related to comparative effectiveness research, or research that compares existing standards of care, have recently received considerable attention. In this paper we focus on how Ethics Review Committees (ERCs) should evaluate the risks of comparative effectiveness research. MAIN TEXT: We discuss what has been a prominent focus in the debate about comparative effectiveness research, namely that it is justified when "nothing is known" about the comparative effectiveness of the available alternatives. We argue that this focus may be misleading. Rather, we should focus on the fact that some experts believe that the evidence points in favor of one intervention, whereas other experts believe that the evidence favors the alternative(s). We will then introduce a case that illustrates this point, and based on that, discuss how ERCs should deal with such cases of expert disagreement. CONCLUSION: We argue that ERCs have a duty to assess the range of expert opinions and based on that assessment arrive at a risk judgment about the study under consideration. We also argue that assessment of expert disagreement is important for the assignment of risk level to a clinical trial: what is the basis for expert opinions, how strong is the evidence appealed to by various experts, and how can clinical trial monitoring affect the possible increased risk of clinical trial participation.

Increased Femoral Component Size Options Improves Manipulation Rate in Females and Knee Society Clinical Scores in Males.

INTRODUCTION: The gender-specific total knee arthroplasty (TKA) debate focuses on differences in distal femoral mediolateral to anteroposterior aspect ratio between males and females. However, randomized studies have been unable to demonstrate significant differences in outcomes utilizing gender-specific implants. No studies have examined the effect of intermediate femoral component sizes on outcome. We compared outcomes before and after intermediate sizing availability. MATERIALS AND METHODS: We identified 331 patients (413 knees) who underwent primary TKA between 2003 and 2004 with a single complete knee system. There were 121 males and 210 females. Three intermediate femoral sizes were added in March 2004 to the six initial options. Patients before March 2004 were assigned to group 1 (n=178), and after to group 2 (n=235). RESULTS: Follow-up averaged 8.5 years. Preoperative demographics and clinical scores were similar between groups. Knee Society (KS) clinical and functional scores improved in females in both groups, but there was no significant difference. Male patients in group 2 had a significant improvement in KS clinical scores compared to male patients in group 1 (group 1: 33.9, group 2: 41.1; p=0.01). Females in group 2 had significantly less need for manipulation, 1.9%, versus females in group 1, 8.7% (p=0.01). MUA rates were similar for men between groups. Overall, there were 19 revisions (4.6%) with no differences between groups or by genders. Once intermediate sizes were available, they were used in 48% of females and 13% of males. The average femoral component size for females in group 1 was 65 mm and decreased in group 2 to 62.5 mm. The average size of femoral components in males was 70 mm in both groups. CONCLUSIONS: Availability of intermediate size femoral component sizes was associated with a lower rate of manipulation in female patients. Greater KS clinical score improvement was observed in men after availability of additional femoral sizes.

No ethical divide between China and the West in human embryo research.

This is a discussion of the reaction to the recent research article publication in the journal Protein & Cell by a group of scientists at Sun Yat-sen University using the CRISPR/Cas9 technique on editing non-viable human zygotes. Many commentators condemned the Chinese scientists for overstepping ethical boundaries long accepted in Western countries and accused China of having lax regulations on genomic research in general. We argue that not only did this research follow strict ethical standards and fully comply with current regulations, but China also has a well-developed regulatory framework governing such research comparable to many developed countries. We see the reactions among Western commentators as a misunderstanding of the current situation and an expression of a lack of willingness to acknowledge China as an equal partner in the international debate about proper limits to the development of new biotechnologies.

Eugenics and Mandatory Informed Prenatal Genetic Testing: A Unique Perspective from China.

The application of genetic technologies in China, especially in the area of prenatal genetic testing, is rapidly increasing in China. In the wealthy regions of China, prenatal genetic testing is already very widely adopted. We argue that the government should actively promote prenatal genetic testing to the poor areas of the country. In fact, the government should prioritize resources first to make prenatal genetic testing a standard routine care with an opt-out model in these area. Healthcare professions would be required to inform pregnant women about the availability of genetic testing and provide free testing on a routine basis unless the parents choose not to do so. We argue that this proposal will allow parents to make a more informed decision about their reproductive choices. Secondarily, this proposal will attract more healthcare professionals and other healthcare resources to improve the healthcare infrastructures in the less-developed regions of the country. This will help to reduce the inequity of accessing healthcare services between in different regions of China. We further argue that this policy proposal is not practicing eugenics.