A new patient-specific helical maxillary distractor: a cadaver test.

The primary objective of this cadaver study was to assess the feasibility of a novel custom helical distraction system and a patient-specific antral maxillary distractor. The study involved two fresh cadaver heads and followed a systematic procedure. First, virtual planning was conducted for an asymmetric maxillomandibular advancement. Custom patient-specific hardware was then fabricated to enable sequential mandibular advancement and gradual maxillary distraction. The mandibular lengthening procedures were found to be highly accurate, with only minor deviations from the planned results. In terms of maxillary distraction, the patient-specific antral distractors demonstrated favorable outcomes, with two noteworthy exceptions. Ideal forward maxillary advancement was short by a modest 2-3 mm in both cadavers. Additionally, cadaver 2 exhibited an unplanned pitch malrotation. However, an excellent occlusion was achieved in cadaver 1 and an acceptable anterior occlusion in cadaver 2, albeit with bilateral posterior open bites that could be readily corrected with interdental elastics in a clinical setting. This cadaver model study provides compelling evidence for the feasibility of patient-specific antral helical distractors, highlighting their potential to yield positive outcomes. Importantly, the study results suggest that patient-specific antral distractors may offer superior results compared to the current standard of linear distractors.

Novel patient-specific helical maxillary distractor: an in vitro feasibility study.

At present, stock linear distractors are used for internal maxillary distraction osteogenesis. However, the authors' research group has demonstrated, through an in silico analysis, that linear distraction leads to bone deformities and malocclusion, whereas helical distraction can yield ideal outcomes. A system for designing and manufacturing custom helical distractors has recently been developed, and the feasibility of these appliances now needs to be assessed. This study was, therefore, conducted to gain an initial insight into their feasibility. The study had two goals. First, it aimed to demonstrate, in an in vitro model, that the novel system of custom helical distraction can produce appropriate clinical outcomes. The second aim was to compare the performance of custom helical distractors with that of stock devices and hybrid devices (i.e., linear appliances that feature patient-specific footplates). Interpreting the results as trends, this study showed that the system of custom helical distraction resulted in in vitro outcomes that were superior to those obtained with stock and hybrid devices.

Helical distraction is superior to linear and circular distraction in mandibular distraction osteogenesis: an in silico study.

Helical mandibular distraction is theoretically better than linear or circular distraction. However, it is not known whether this more complex treatment will result in unquestionably better outcomes. Therefore, the best attainable outcomes of mandibular distraction osteogenesis were evaluated in silico, given the constraints of linear, circular, and helical motion. This cross-sectional kinematic study included 30 patients with mandibular hypoplasia who had been treated with distraction, or to whom this treatment had been recommended. Demographic information and the computed tomography (CT) scans showing the baseline deformity were collected. The CT scans of each patient were segmented and three-dimensional models of the face created. Then, the ideal distraction outcomes were simulated. Next, the most favorable helical, circular, and linear distraction movements were calculated. Finally, errors were measured: misalignment of key mandibular landmarks, misalignment of the occlusion, and changes in intercondylar distance. Helical distraction produced trivial errors. In contrast, circular and linear distractions resulted in errors that were statistically and clinically significant. Helical distraction also preserved the planned intercondylar distance, while circular and linear distractions led to unwanted changes in the intercondylar distance. It is now evident that helical distraction offers a new strategy to improve the outcomes of mandibular distraction osteogenesis.

Workplace oral health promotion activities among community-aged care workers: A qualitative exploration.

BACKGROUND: The workplace is an ideal-and priority-setting for health promotion activities. Developing and implementing workplace health promotion interventions, including oral health promotion activities, can help create health-supporting workplace environments. OBJECTIVE: To pilot workplace oral health promotion activities among staff working in the aged care sector, report their impact and explore participants' views on the factors that contribute to participation and effectiveness. METHODS: This study comprised three phases: (i) the development and face validation of the resources, (ii) a 3-h educational session and (iii) five interview sessions with participants 4-6 weeks following the education session. The recorded interviews were transcribed verbatim and analysed thematically. RESULTS: Eleven community-aged care workforce were invited to five feedback sessions. Ten participants were female and ranged in age from 18 to 64. All participants gave favourable comments about the content and delivery of the training session and accompanying resources. The participants felt that the benefits of WOHP include improved staff knowledge, awareness and oral care routine, the ability to share (and put into practice) the gained knowledge and information with their dependants, a lower risk of having poor oral health that adversely affects their well-being and work tasks, and potentially beneficial impacts on the organization's staff roster. Their attendance in the WOHP was facilitated by being paid to attend and scheduling the sessions during work time. Future WOHP suggestions include the possibility of a one-stop dental check-up at the workplace or staff dental care discounts from local dental practitioners and combining oral health with other health promotion activities. CONCLUSIONS: Planning and implementing WOHP was deemed acceptable and feasible in this study context and successfully achieved short-term impacts among community-aged care workers. Appropriate times and locations, organizational arrangements and a variety of delivery options contributed to successful programme planning and implementation.

Helical distraction is superior to linear distraction in maxillary distraction osteogenesis: an in silico study.

This in silico kinematic study was performed to evaluate the best attainable outcomes of maxillary distraction osteogenesis given the constraints of linear and helical motion. The study sample included the retrospective records of 30 patients with maxillary retrusion who had been treated with distraction or had been recommended this treatment. The primary outcomes were the errors of linear and helical distraction. The study measured two types of error: misalignment of key upper jaw landmarks and misalignment of the occlusion. Concerning the misalignment of key landmarks, the median misalignments resulting from helical distraction were minimal; the interquartile ranges were also minimal. The median misalignments and interquartile ranges that resulted from linear distraction were significantly larger. Regarding the occlusal misalignments, helical distraction produced minor occlusal misalignments, while linear distraction produced significantly larger errors. The results of this study confirmed that helical motion is the ideal motion for LeFort I distraction.

Parametric longitudinal coupling between a high-impedance superconducting resonator and a semiconductor quantum dot singlet-triplet spin qubit.

Coupling qubits to a superconducting resonator provides a mechanism to enable long-distance entangling operations in a quantum computer based on spins in semiconducting materials. Here, we demonstrate a controllable spin-photon coupling based on a longitudinal interaction between a spin qubit and a resonator. We show that coupling a singlet-triplet qubit to a high-impedance superconducting resonator can produce the desired longitudinal coupling when the qubit is driven near the resonator's frequency. We measure the energy splitting of the qubit as a function of the drive amplitude and frequency of a microwave signal applied near the resonator antinode, revealing pronounced effects close to the resonator frequency due to longitudinal coupling. By tuning the amplitude of the drive, we reach a regime with longitudinal coupling exceeding 1 MHz. This mechanism for qubit-resonator coupling represents a stepping stone towards producing high-fidelity two-qubit gates mediated by a superconducting resonator.

Coherent spin qubit transport in silicon.

A fault-tolerant quantum processor may be configured using stationary qubits interacting only with their nearest neighbours, but at the cost of significant overheads in physical qubits per logical qubit. Such overheads could be reduced by coherently transporting qubits across the chip, allowing connectivity beyond immediate neighbours. Here we demonstrate high-fidelity coherent transport of an electron spin qubit between quantum dots in isotopically-enriched silicon. We observe qubit precession in the inter-site tunnelling regime and assess the impact of qubit transport using Ramsey interferometry and quantum state tomography techniques. We report a polarization transfer fidelity of 99.97% and an average coherent transfer fidelity of 99.4%. Our results provide key elements for high-fidelity, on-chip quantum information distribution, as long envisaged, reinforcing the scaling prospects of silicon-based spin qubits.

Health Assessment Questionnaire at One Year Predicts All-Cause Mortality in Patients With Early Rheumatoid Arthritis.

OBJECTIVE: Higher self-reported disability (high Health Assessment Questionnaire [HAQ] score) has been associated with hospitalizations and mortality in established rheumatoid arthritis (RA), but associations in early RA are unknown. METHODS: Patients with early RA (symptom duration <1 year) enrolled in the Canadian Early Arthritis Cohort who initiated disease-modifying antirheumatic drugs and had completed HAQ data at baseline and 1 year were included in the study. Discrete-time proportional hazards models were used to estimate crude and multi-adjusted associations of baseline HAQ and HAQ at 1 year with all-cause mortality in each year of follow-up. RESULTS: A total of 1,724 patients with early RA were included. The mean age was 55 years, and 72% were women. Over 10 years, 62 deaths (3.6%) were recorded. Deceased patients had higher HAQ scores at baseline (mean ± SD 1.2 ± 0.7) and at 1 year (0.9 ± 0.7) than living patients (1.0 ± 0.7 and 0.5 ± 0.6, respectively; P < 0.001). Disease Activity Score in 28 joints (DAS28) was higher in deceased versus living patients at baseline (mean ± SD 5.4 ± 1.3 versus 4.9 ± 1.4) and at 1 year (mean ± SD 3.6 ± 1.4 versus 2.8 ± 1.4) (P < 0.001). Older age, male sex, lower education level, smoking, more comorbidities, higher baseline DAS28, and glucocorticoid use were associated with mortality. Contrary to HAQ score at baseline, the association between all-cause mortality and HAQ score at 1 year remained significant even after adjustment for confounders. For baseline HAQ score, the unadjusted hazard ratio (HR) was 1.46 (95% confidence interval [95% CI] 1.02-2.09), and the adjusted HR was 1.25 (95% CI 0.81-1.94). For HAQ score at 1 year, the unadjusted HR was 2.58 (95% CI 1.78-3.72), and the adjusted HR was 1.75 (95% CI 1.10-2.77). CONCLUSION: Our findings indicate that higher HAQ score and DAS28 at 1 year are significantly associated with all-cause mortality in a large early RA cohort.

An evaluation of a new practice-based small group learning (PBSGL) initiative in Wales.

In 2018, a new practice-based small group learning (PBSGL) pilot initiative was launched in Wales to promote interprofessional learning among different primary care professionals. The aim of this study was to evaluate the initiative in order to identify its strengths and areas for improvement. Data were collected through focus groups with PBSGL groups in Wales and analysed thematically. Participants generally held positive views of PBSGL and were impressed with the variety and overall relevance of the learning materials, although concern was raised about the relevance of all learning materials to the Welsh context. The interprofessional component was valued for reducing feelings of isolation and all participants were able to contribute to discussions, an outcome helped by existing relationships among group members. Many participants reflected on occasions where they had made changes to their practice as a result of PBSGL activity. Time and funding were cited as potential barriers to continuing participation in PBSGL and there is scope to tailor material more to the context of the healthcare system in Wales.

A catalyst for transforming health systems and person-centred care: Canadian national position statement on patient-reported outcomes.

Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.

Palindromic Rheumatism Frequently Precedes Early Rheumatoid Arthritis: Results From an Incident Cohort.

BACKGROUND: This multicenter incident cohort aimed to characterize how often early rheumatoid arthritis (ERA) patients self-report episodic joint inflammation (palindromic rheumatism) preceding ERA diagnosis and which characteristics differentiate these patients from those without prior episodic symptoms. METHODS: Data were from patients with early confirmed or suspected RA (more than 6 weeks and less than 12 months) enrolled in the Canadian Early ArThritis CoHort (CATCH) between April 2017 to March 2018 who completed study case report forms assessing joint pain and swelling prior to ERA diagnosis. Chi-square and t tests were used to compare characteristics of patients with and without self-reported episodic joint inflammation prior to ERA diagnosis. Multivariable logistic regression was used to identify sociodemographic and clinical measures associated with past episodic joint inflammation around the time of ERA diagnosis. RESULTS: A total of 154 ERA patients were included; 66% were female, and mean (SD) age and RA symptom duration were 54 (15) years and 141 (118) days. Sixty-five (42%) ERA patients reported a history of episodic joint pain and swelling, half of whom reported that these symptoms preceded ERA diagnosis by over 6 months. ERA patients with past episodic joint inflammation were more often female, had higher income, were seropositive, had more comorbidities, fewer swollen joints, and lower Clinical Disease Activity Index (CDAI) around the time of ERA diagnosis (P < 0.05). These associations remained significant in multivariable regression adjusting for other sociodemographic and RA clinical measures. CONCLUSION: Almost half of ERA patients experienced episodic joint inflammation prior to ERA diagnosis. These patients were more often female, had higher income, and presented with milder disease activity at ERA diagnosis.

Prevalence and Characteristics of Metabolic Syndrome Differ in Men and Women with Early Rheumatoid Arthritis.

Objective: Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods: A cross-sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex-stratified logistic regression identified baseline variables associated with MetS. Results: The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high-density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion: The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

Boolean logic by convective obstacle flows.

We present a potential new mode of natural computing in which simple, heat-driven fluid flows perform Boolean logic operations. The system comprises a two-dimensional single-phase fluid that is heated from below and cooled from above, with two obstacles placed on the horizontal mid-plane. The obstacles remove all vertical momentum that flows into them. The horizontal momentum extraction of the obstacles is controlled in a binary fashion, and constitutes the 2-bit input. The output of the system is a thresholded measure of the energy extracted by the obstacles. Due to the existence of multiple attractors in the phase space of this system, the input-output relationships are equivalent to those of the OR, XOR or NAND gates, depending on the threshold and obstacle separation. The ability to reproduce these logical operations suggests that convective flows might have the potential to perform more general computations, despite the fact that they do not involve electronics, chemistry or multiple fluid phases.

Convective flow in the presence of a small obstacle: Symmetry breaking, attractors, hysteresis, and information.

This work explores the stability and hysteresis effects that occur when a small sink of momentum is introduced into a heat-driven, two-dimensional convective flow. As per standard fluid mechanical intuition, the system minimizes work generation and dissipation when one component of momentum is extracted. However, when the sink absorbs all incoming momentum, the system configures itself such that one of the convection plumes aligns directly with the sink. This state is the most hydrodynamically stable, but it maximizes, rather than minimizes extracted mechanical work. Furthermore, in the case of only vertical momentum extraction, there are two attractors, with different stabilities. Numerical experiments involving slow variations of the horizontal momentum extraction show a clear history dependence. This hysteresis preserves information about the system's past states, and hence represents a primitive memory. The momentum sink can also be used to manipulate the horizontal position of the flow field, with potential applications in microfluidics and laminar convection systems. This simple system exhibits the phenomena of autocatalysis (during the initial growth of the convection plumes), negative feedback (the attractors are either fully or quasistable), memory, and elementary computation.

Localization of Contextual and Context Removed Auditory Fear Memory within the Basolateral Amygdala Complex.

Debilitating and persistent fear memories can rapidly form in humans following exposure to traumatic events. Fear memories can also be generated and studied in animals via Pavlovian fear conditioning. The current study was designed to evaluate basolateral amygdala complex (BLC) involvement following the formation of different fear memories (two contextual fear memories and one adjusted auditory fear memory). Fear memories were created in the same context with five 1.0 mA (0.50 s) foot-shocks and, where necessary, five auditory tones (5 kHz, 75 dB, 20 s). The adjusted auditory fear conditioning protocol was employed to remove background contextual fear and produce isolated auditory fear memories. Immunofluorescent labeling was utilized to identify neurons expressing immediate early genes (IEGs). We found the two contextual fear conditioning (CFC) procedures to produce similar levels of fear-related freezing to context. Contextual fear memories produced increases in BLC IEG expression with distinct and separate patterns of expression. These data suggest contextual fear memories created in slightly altered contexts, can produce unique patterns of amygdala activation. The adjusted auditory fear conditioning procedure produced memories to a tone, but not to a context. This group, where no contextual fear was present, had a significant reduction in BLC IEG expression. These data suggest background contextual fear memories, created in standard auditory fear conditioning protocols, contribute significantly to increases in amygdala activation.

Molecular Adsorbent Recirculating System Support Followed by Liver Transplantation for Multiorgan Failure From Heatstroke.

BACKGROUND: Exertional heatstroke is an extremely rare cause of fulminant hepatic failure. Maximal supportive care has failed to provide adequate survival in earlier studies. This is particularly true in cases accompanied by multiorgan failure. METHODS AND MATERIALS: Our prospectively collected transplant database was retrospectively reviewed to identify patients undergoing liver transplantation for heatstroke between January 1, 2012, and December 31, 2016. We report 3 consecutive cases of male patients with fulminant hepatic failure from exertional heatstroke. RESULTS: All patients developed multiorgan failure and required intubation, vasopressor support, and renal replacement therapy. All patients were listed urgently for liver transplantation and were supported with the molecular adsorbent recirculating system while awaiting transplantation. All patients underwent liver transplantation alone and are alive and well, with recovered renal function, normal liver allograft function, and no chronic sequelae of their multiorgan failure at more than one year. CONCLUSION: Extreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that may benefit from therapy using the Molecular Adsorbent Recirculating System while waiting for liver transplantation as a component of a multidisciplinary, multiorgan system approach.

Combining online and in-person methods to evaluate the content validity of PROMIS fatigue short forms in rheumatoid arthritis.

PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p ≥ .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r ≥ 0.82; p < .000) and moderately with patient assessments of disease activity (r ≥ 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥ 94%) could distinguish general fatigue from RA fatigue. Most (≥ 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.

Defining the role of corticotropin releasing factor binding protein in alcohol consumption.

The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP), and has been implicated in alcohol use disorder (AUD). Therefore, identification of the exact contribution of each protein that mediates CRF effects is necessary to design effective therapeutic strategies for AUD. A series of in vitro/in vivo experiments across different species were performed to define the biological discrete role of CRFBP in AUD. First, to establish the CRFBP role in receptor signaling, we developed a novel chimeric cell-based assay and showed that CFRBP full length can stably be expressed on the plasma membrane. We discovered that only CRFBP(10 kD) fragment is able to potentiate CRF-intracellular Ca2+ release. We provide evidence that CRHBP gene loss increased ethanol consumption in mice. Then, we demonstrate that selective reduction of CRHBP expression in the center nucleus of the amygdala (CeA) decreases ethanol consumption in ethanol-dependent rats. CRFBP amygdalar downregulation, however, does not attenuate yohimbine-induced ethanol self-administration. This effect was associated with decreased hemodynamic brain activity in the CRFBP-downregulated CeA and increased hemodynamic activity in the caudate putamen during yohimbine administration. Finally, in alcohol-dependent patients, genetic variants related to the CRFBP(10 kD) fragment were associated with greater risk for alcoholism and anxiety, while other genetic variants were associated with reduced risk for anxiety. Taken together, our data provide evidence that CRFBP may possess both inhibitory and excitatory roles and may represent a novel pharmacological target for the treatment of AUD.

Patient-reported outcomes: pathways to better health, better services, and better societies.

While the use of PROs in research is well established, many challenges lie ahead as their use is extended to other applications. There is consensus that health outcome evaluations that include PROs along with clinician-reported outcomes and administrative data are necessary to inform clinical and policy decisions. The initiatives presented in this paper underline evolving recognition that PROs play a unique role in adding the patient perspective alongside clinical (e.g., blood pressure) and organizational (e.g., admission rates) indicators for evaluating the effects of new products, selecting treatments, evaluating quality of care, and monitoring the health of the population. In this paper, we first explore the use of PRO measures to support drug approval and labeling claims. We critically evaluate the evidence and challenges associated with using PRO measures to improve healthcare delivery at individual and population levels. We further discuss the challenges associated with selecting from the abundance of measures available, opportunities afforded by agreeing on common metrics for constructs of interest, and the importance of establishing an evidence base that supports integrating PRO measures across the healthcare system to improve outcomes. We conclude that the integration of PROs as a key end point within individual patient care, healthcare organization and program performance evaluations, and population surveillance will be essential for evaluating whether increased healthcare expenditure is translating into better health outcomes.