The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

The temporal structure of REM sleep shows minute-scale fluctuations across brain and body in mice and humans.

Rapid eye movement sleep (REM) is believed to have a binary temporal structure with "phasic" and "tonic" microstates, characterized by motoric activity versus quiescence, respectively. However, we observed in mice that the frequency of theta activity (a marker of rodent REM) fluctuates in a nonbinary fashion, with the extremes of that fluctuation correlating with phasic-type and tonic-type facial motricity. Thus, phasic and tonic REM may instead represent ends of a continuum. These cycles of brain physiology and facial movement occurred at 0.01 to 0.06 Hz, or infraslow frequencies, and affected cross-frequency coupling and neuronal activity in the neocortex, suggesting network functional impact. We then analyzed human data and observed that humans also demonstrate nonbinary phasic/tonic microstates, with continuous 0.01 to 0.04-Hz respiratory rate cycles matching the incidence of eye movements. These fundamental properties of REM can yield insights into our understanding of sleep health.

Substrate dependence of transport coupling and phenotype of a small multidrug resistance transporter in Pseudomonas aeruginosa.

Small multidrug resistance (SMR) transporters are key players in the defense of multidrug-resistant pathogens to toxins and other homeostasis-perturbing compounds. However, recent evidence demonstrates that EmrE, an SMR from Escherichia coli and a model for understanding transport, can also induce susceptibility to some compounds by drug-gated proton leak. This runs down the ∆pH component of the proton-motive force (PMF), reducing the viability of the affected bacteria. Proton leak may provide an unexplored drug target distinct from the targets of most known antibiotics. Activating proton leak requires an SMR to be merely present, rather than be the primary resistance mechanism, and dissipates the energy source for many other efflux pumps. PAsmr, an EmrE homolog from Pseudomonas aeruginosa, transports many EmrE substrates in cells and purified systems. We hypothesized that PAsmr, like EmrE, may confer susceptibility to some compounds via drug-gated proton leak. Growth assays of E. coli expressing PAsmr displayed substrate-dependent resistance and susceptibility phenotypes, and in vitro solid-supported membrane electrophysiology experiments revealed that PAsmr performs both antiport and substrate-gated proton uniport, demonstrating the same functional promiscuity observed in EmrE. Growth assays of P. aeruginosa strain PA14 demonstrated that PAsmr contributes resistance to some antimicrobial compounds, but no growth defect is observed with susceptibility substrates, suggesting P. aeruginosa can compensate for the proton leak occurring through PAsmr. These phenotypic differences between P. aeruginosa and E. coli advance our understanding of the underlying resistance mechanisms in P. aeruginosa and prompt further investigation into the role that SMRs play in antibiotic resistance in pathogens. IMPORTANCE: Small multidrug resistance (SMR) transporters are a class of efflux pumps found in many pathogens, although their contributions to antibiotic resistance are not fully understood. We hypothesize that these transporters may confer not only resistance but also susceptibility, by dissipating the proton-motive force. This means to use an SMR transporter as a target; it merely needs to be present (as opposed to being the primary resistance mechanism). Here, we test this hypothesis with an SMR transporter found in Pseudomonas aeruginosa and find that it can perform both antiport (conferring resistance) and substrate-gated proton leak. Proton leak is detrimental to growth in Escherichia coli but not P. aeruginosa, suggesting that P. aeruginosa responds differently to or can altogether prevent ∆pH dissipation.

Slipping Away: Slippage in hazard ratios over datacuts and its impact on immuno-oncology combination economic evaluations.

OBJECTIVES: This study examines the impact of slippage in hazard ratios (tending towards the null over subsequent datacuts) for overall survival for combination treatment with a PD-(L)-1 inhibitor and a tyrosine kinase inhibitor (TKI) in advanced renal cell carcinoma (RCC). METHODS: Four trials' Kaplan Meier curves were digitized over several datacuts and fitted with standard parametric curves. Accuracy and consistency of early data projections were calculated versus observed restricted mean survival time (RMST) and fitted lifetime survival from the longest follow-up datacut. The change in economically justifiable price (eJP) was calculated fitting the same curve to both arms, using an assumed average utility of 0.7 and willingness-to-pay threshold of £30,000 per QALY. The eJP represents the lifetime justifiable price increment for the new treatment, including differences in drug, administration and disease-related costs. RESULTS: Slippage in hazard ratios was observed in trials with longer follow-up, potentially influenced by subsequent PD-(L)-1 use after TKI monotherapy, early stoppage of PD-(L)-1 and development of resistance. Lognormal and log-logistic curves were more likely to over-predict the observed result; Gompertz and gamma under-predicted. Statistical measures for goodness of fit did not reliably predict the RMST. Large differences in incremental mean life years were observed between even the penultimate and final datacuts for the majority of the fitted curves, meaningfully impacting the eJP. CONCLUSIONS: This work demonstrates the challenge in predicting treatment benefits with novel therapies using immature data. Incorporating information on the impact of subsequent treatment is likely to play a key role in improving predictions.

Public Health Dashboards in Overdose Prevention: The Rhode Island Approach to Public Health Data Literacy, Partnerships, and Action.

As the field of public health rises to the demands of real-time surveillance and rapid data-sharing needs in a postpandemic world, it is time to examine our approaches to the dissemination and accessibility of such data. Distinct challenges exist when working to develop a shared public health language and narratives based on data. It requires that we assess our understanding of public health data literacy, revisit our approach to communication and engagement, and continuously evaluate our impact and relevance. Key stakeholders and cocreators are critical to this process and include people with lived experience, community organizations, governmental partners, and research institutions. In this viewpoint paper, we offer an instructive approach to the tools we used, assessed, and adapted across 3 unique overdose data dashboard projects in Rhode Island, United States. We are calling this model the "Rhode Island Approach to Public Health Data Literacy, Partnerships, and Action." This approach reflects the iterative lessons learned about the improvement of data dashboards through collaboration and strong partnerships across community members, state agencies, and an academic research team. We will highlight key tools and approaches that are accessible and engaging and allow developers and stakeholders to self-assess their goals for their data dashboards and evaluate engagement with these tools by their desired audiences and users.

C-N Bond Formation at Discrete CuIII-Aryl Complexes.

Copper(III) aryl species are widely proposed as intermediates in Cu-catalyzed C-C and C-heteroatom bond formation reactions. Despite their wide utility, mechanistic aspects of C-heteroatom formation at CuIII centers as well as factors that lead to byproducts, e.g., Ar-H, Ar-Ar, remain elusive due to the rarity of discrete CuIII-Ar complexes. Herein, we report the synthesis and reactivity of a series of CuII and CuIII aryl complexes that closely mimic the intermediates in Cu-catalyzed C-N coupling reactions. Copper(II) aryl complexes [TBA][LCuII-ArR] were synthesized via the treatment of CuII with a range of aryl donors, such as ZnAr2R, TMS-ArR, and ArR-Bpin. Oxidation of [TBA][LCuII-ArR] produces formal copper(III) aryl complexes LCuIII-ArR. Treatment of copper(III) aryl complexes with neutral nitrogen nucleophiles produces the C-N coupling product in up to 64% yield, along with commonly observed byproducts, such as Ar-H and Ar-Ar. Hammett analysis of the C-N bond formation performed with various N-nucleophiles shows a ρ value of -1.66, consistent with the electrophilic character of LCuIII-ArR. We propose mechanisms for common side reactions in Cu-catalyzed coupling reactions that lead to the formation of Ar-Ar and Ar-H.

Molecular Network Approach to Anisotropic Ising Lattices: Parsing Magnetization Dynamics in Er3+ Systems with 0-3-Dimensional Spin Interactivity.

We present a wide-ranging interrogation of the border between single-molecule and solid-state magnetism through a study of erbium-based Ising-type magnetic compounds with a fixed magnetic unit, using three different charge-balancing cations as the means to modulate the crystal packing environment. Properties rooted in the isolated spin Hamiltonian remain fixed, yet careful observation of the dynamics reveals the breakdown of this approximation in a number of interesting ways. First, differences in crystal packing lead to a striking 3 orders of magnitude suppression in magnetic relaxation rates, indicating a rich interplay between intermolecular interactions governed by the anisotropic Ising lattice stabilization and localized slow magnetic relaxation driven by the spin-forbidden nature of quantum tunneling of the f-electron-based magnetization. By means of diverse and rigorous physical methods, including temperature-dependent X-ray crystallography, field, temperature, and time-dependent magnetometry, and the application of a new magnetization fitting technique to quantify the magnetic susceptibility peakshape, we are able to construct a more nuanced view of the role nonzero-dimensional interactions can play in what are predominantly considered zero-dimensional magnetic materials. Specifically, we use low field susceptibility and virgin-curve analysis to isolate metamagnetic spin-flip transitions in each system with a field strength corresponding to the expected strength of the internal dipole-dipole lattice. This behavior is vital to a complete interpretation of the dynamics and is likely common for systems with such high anisotropy. This collective interactivity opens a new realm of possibility for molecular magnetic materials, where their unprecedented localized anisotropy is the determining factor in building higher dimensionality.

Intraoperative bowel perfusion assessment methods and their effects on anastomotic leak rates: meta-analysis.

BACKGROUND: Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies have been described for intraoperative assessment of bowel perfusion. This systematic review and meta-analysis aimed to evaluate the most frequently used bowel perfusion assessment modalities in elective colorectal procedures, and to assess their associated risk of anastomotic leak. Technologies included indocyanine green fluorescence angiography, diffuse reflectance spectroscopy, laser speckle contrast imaging, and hyperspectral imaging. METHODS: The review was preregistered with PROSPERO (CRD42021297299). A comprehensive literature search was performed using Embase, MEDLINE, Cochrane Library, Scopus, and Web of Science. The final search was undertaken on 29 July 2022. Data were extracted by two reviewers and the MINORS criteria were applied to assess the risk of bias. RESULTS: Some 66 eligible studies involving 11 560 participants were included. Indocyanine green fluorescence angiography was most used with 10 789 participants, followed by diffuse reflectance spectroscopy with 321, hyperspectral imaging with 265, and laser speckle contrast imaging with 185. In the meta-analysis, the total pooled effect of an intervention on anastomotic leak was 0.05 (95 per cent c.i. 0.04 to 0.07) in comparison with 0.10 (0.08 to 0.12) without. Use of indocyanine green fluorescence angiography, hyperspectral imaging, or laser speckle contrast imaging was associated with a significant reduction in anastomotic leak. CONCLUSION: Bowel perfusion assessment reduced the incidence of anastomotic leak, with intraoperative indocyanine green fluorescence angiography, hyperspectral imaging, and laser speckle contrast imaging all demonstrating comparable results.

Early access schemes for innovative health technologies: the views of international stakeholders.

OBJECTIVES: Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation. METHODS: Two virtual workshops were convened including (i) UK-based policy experts (England, Wales, and Scotland) and (ii) representatives from multiple healthcare systems (England, France, Sweden, Canada, Poland, and Norway). Participants were encouraged to share their experiences with EASs in their healthcare system and highlight key challenges for policy makers. Discussions were transcribed and analyzed using framework analysis. RESULTS: Participants agreed that EASs have value when targeted toward innovative technologies with the potential for significant clinical benefit in an area of high unmet need. Participants discussed potential solutions to the challenges faced by payers implementing EASs, including defining eligibility criteria, supporting evidence generation, and approaches to reimbursement. CONCLUSIONS: Participants agreed that EASs are one possible solution for their healthcare systems and have the potential to deliver significant clinical value to patients. However, widespread adoption of EASs is limited due to concerns about the risks for patients and healthcare budgets, further solutions are needed to deliver EASs for targeted therapies.

An evaluation of managed access agreements in England based on stakeholder experience.

OBJECTIVES: The objective of this research was to evaluate managed access policy in England, drawing upon the expertise of a range of stakeholders involved in its implementation. METHODS: Seven focus groups were conducted with payer and health technology assessment representatives, clinicians, and representatives from industry and patient/carer organizations within England. Transcripts were analyzed using framework analysis to identify stakeholders' views on the successes and challenges of managed access policy. RESULTS: Stakeholders discussed the many aims of managed access within the National Health Service in England, and how competing aims had affected decision making. While stakeholders highlighted a number of priorities within eligibility criteria for managed access agreements (MAAs), stakeholders agreed that strict eligibility criteria would be challenging to implement due to the highly variable nature of innovative technologies and their indications. Participants highlighted challenges faced with implementing MAAs, including evidence generation, supporting patients during and after the end of MAAs, and agreeing and reinforcing contractual agreements with industry. CONCLUSIONS: Managed access is one strategy that can be used by payers to resolve uncertainty for innovative technologies that present challenges for reimbursement and can also deliver earlier access to promising technologies for patients. However, participants cautioned that managed access is not a "silver bullet," and there is a need for greater clarity about the aims of managed access and how these should be prioritized in decision making. Discussions between key stakeholders involved in managed access identified challenges with implementing MAAs and these experiences should be used to inform future managed access policy.

Vanadium Electronic Configuration Determination From L2,3 Transition in V-oxide Compounds and Roscoelite.

We report on the electronic structure of vanadium in synthetic V-oxides and in natural roscoelite (V-rich phyllosilicate). This study applied electron energy-loss spectroscopy (EELS) in the scanning transmission electron microscope (STEM), combined with first-principle calculations, to (1) establish relationships between the V oxidation state and EELS L2,3 features and (2) better constrain the oxidation state and crystallographic siting of V in roscoelite, with implications for other V-bearing phyllosilicates. Both EELS measurements and band structure calculations show that the EELS L2/L3 ratio increases as the oxidation state of V increases. We establish a quantitative relationship between the V L2,3 near-edge structure and the V oxidation state by normalizing the L2 maximum peak intensity to the L3 peak intensity. By applying this method to roscoelite, we find that it hosts a mix of trivalent and tetravalent V distributed between the octahedral and tetrahedral sites with a V4+/ΣV = 0.6 ± 0.1. This relationship is applicable to measurements of V oxidation states in oxide and phyllosilicate minerals, which is useful for constraining the conditions of rock and mineral formation and has potential implications for metal extraction from phyllosilicate ores.

Describing the landscape of integrated clinical educational programs for PAs and NPs.

PURPOSE: Postgraduate clinical training (PCT) has been available to PAs since the 1970s and to NPs since at least 2007. Some programs now enroll PAs and NPs. Although this new training model appears to be expanding, little data about integrated PA/NP programs are available. METHODS: This study examined the PA/NP PCT landscape in the United States. Programs were identified from membership rosters of the Association of Postgraduate Physician Assistant Programs and the Association of Post Graduate APRN Programs. Data (program name, sponsoring institution, location, specialty, accreditation status) were identified from programs' websites. RESULTS: We identified 106 programs at 42 sponsoring institutions. Various specialties, most commonly in emergency medicine, critical care, and surgery, were represented. Few were accredited. CONCLUSIONS: PA/NP PCT is now common, with about half of the programs accepting PAs and NPs. These programs represent a unique form of interprofessional education involving full integration of two professions in the same program and are worthy of further investigation.

Identifying Predictors of Opioid Overdose Death at a Neighborhood Level With Machine Learning.

Predictors of opioid overdose death in neighborhoods are important to identify, both to understand characteristics of high-risk areas and to prioritize limited prevention and intervention resources. Machine learning methods could serve as a valuable tool for identifying neighborhood-level predictors. We examined statewide data on opioid overdose death from Rhode Island (log-transformed rates for 2016-2019) and 203 covariates from the American Community Survey for 742 US Census block groups. The analysis included a least absolute shrinkage and selection operator (LASSO) algorithm followed by variable importance rankings from a random forest algorithm. We employed double cross-validation, with 10 folds in the inner loop to train the model and 4 outer folds to assess predictive performance. The ranked variables included a range of dimensions of socioeconomic status, including education, income and wealth, residential stability, race/ethnicity, social isolation, and occupational status. The R2 value of the model on testing data was 0.17. While many predictors of overdose death were in established domains (education, income, occupation), we also identified novel domains (residential stability, racial/ethnic distribution, and social isolation). Predictive modeling with machine learning can identify new neighborhood-level predictors of overdose in the continually evolving opioid epidemic and anticipate the neighborhoods at high risk of overdose mortality.

Soil Invertebrates Generate Microplastics From Polystyrene Foam Debris.

To fully understand microplastics' impact on soil ecosystems, one must recognize soil organisms as not just passively enduring their negative effects, but potentially contributing to microplastics' formation, distribution, and dynamics in soil. We investigated the ability of four soil invertebrates, the cricket Acheta domesticus L. (Orthoptera: Gryllidae), the isopod Oniscus asellus L. (Isopoda: Oniscidae), larvae of the beetle Zophobas morio Fabricius (Coleoptera: Tenebrionidae), and the snail Cornu aspersum Müller (Stylommatophora: Helicidae) to fragment macroscopic pieces of weathered or pristine polystyrene (PS) foam. We placed invertebrates into arenas with single PS foam pieces for 24 h, then collected and assessed the microplastic content of each invertebrate's fecal material, its cadaver, and the sand substrate of its arena via hydrogen peroxide digestion, filtration, and fluorescent staining. All taxa excreted PS particles, though snails only to a tiny extent. Beetle larvae produced significantly more microplastics than snails, and crickets and isopods fragmented the weathered PS foam pieces more than the pristine pieces, which they left untouched. A follow-up experiment with pristine PS foam assessed the effect of different treatments mimicking exposure to the elements on fragmentation by isopods. PS foam pieces soaked in a soil suspension were significantly more fragmented than untreated pieces or pieces exposed to UV light alone. These findings indicate that soil invertebrates may represent a source of microplastics to the environment in places polluted with PS foam trash, and that the condition of macroplastic debris likely affects its palatability to these organisms.

Feasibility of non-invasive neuromonitoring in general intensive care patients using a multi-parameter transcranial Doppler approach.

PURPOSE: To assess the feasibility of Transcranial Doppler ultrasonography (TCD) neuromonitoring in a general intensive care environment, in the prognosis and outcome prediction of patients who are in coma due to a variety of critical conditions. METHODS: The prospective trial was performed between March 2017 and March 2019 Addenbrooke's Hospital, Cambridge, UK. Forty adult patients who failed to awake appropriately after resuscitation from cardiac arrest or were in coma due to conditions such as meningitis, seizures, sepsis, metabolic encephalopathies, overdose, multiorgan failure or transplant were eligible for inclusion. Gathered data included admission diagnosis, duration of ventilation, length of stay in the ICU, length of stay in hospital, discharge status using Cerebral Performance Categories (CPC). All patients received intermittent extended TCD monitoring following inclusion in the study. Parameters of interest included TCD-based indices of cerebral autoregulation, non-invasive intracranial pressure, autonomic system parameters (based on heart rate variability), critical closing pressure, the cerebrovascular time constant and indices describing the shape of the TCD pulse waveform. RESULTS: Thirty-seven patients were included in the final analysis, with 21 patients classified as good outcome (CPC 1-2) and 16 as poor neurological outcomes (CPC 3-5). Three patients were excluded due to inadequacies identified in the TCD acquisition. The results indicated that irrespective of the primary diagnosis, non-survivors had significantly disturbed cerebral autoregulation, a shorter cerebrovascular time constant and a more distorted TCD pulse waveform (all p<0.05). CONCLUSIONS: Preliminary results from the trial indicate that multi-parameter TCD neuromonitoring increases outcome-predictive power and TCD-based indices can be applied to general intensive care monitoring.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE). DESIGN: Retrospective, multicenter, comparative cohort study. PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers. METHODS: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity (VA). RESULTS: Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51-1.18; P = 0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the "universal face mask" group (OR, 0.46; 95% CI, 0.22-0.99; P = 0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the "universal face mask" group (P = 0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for "no face mask" group compared with 1.65 (~20/900) for the "universal face mask" group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764). CONCLUSIONS: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

REFRACTIVE OUTCOMES AFTER SUTURELESS INTRASCLERAL FIXATION OF INTRAOCULAR LENS WITH PARS PLANA VITRECTOMY.

PURPOSE: To evaluate the refractive outcomes of sutureless intrascleral fixation of intraocular lens with pars plana vitrectomy. METHOD: A retrospective, consecutive cohort from multiple surgeons of a single center. Primary outcomes included spherical equivalent (SEQ) and change in SEQ (ΔSEQ) from preoperative intraocular lens power calculations. Secondary outcomes included refractive outcomes of fixation at 1.5 mm, 2 mm, and 2.5 mm posterior to the limbus. RESULTS: In total, 84 eyes of 80 patients were included. Preoperative logarithm of the minimum angle of resolution visual acuity was 1.21 ± 0.68 (20/320). The mean follow-up time was 2.33 ± 1.36 years. At 3 months, SEQ was -0.50 ± 1.59 D and ΔSEQ was 0.58 ± 1.49 D. At 1 year, SEQ was -0.55 ± 1.32 D and ΔSEQ was 0.39 ± 1.42 D. At the last follow-up, logarithm of the minimum angle of resolution visual acuity was 0.34 ± 0.34 (20/40), SEQ was -0.51 ± 1.44 D, and ΔSEQ was 0.57 ± 1.27 D. There was no difference between SEQ or ΔSEQ throughout follow-up (P = 0.97 and P = 0.96, respectively). At fixation distances more posterior to the limbus, mean ΔSEQ was more hyperopic at 3 months, 1-year, and the last follow-up (P = 0.02, P = 0.01, and P = 0.006, respectively). CONCLUSION: Refractive outcomes for sutureless intrascleral fixation of intraocular lens with pars plana vitrectomy were favorable and showed stability postoperatively. These results may aid surgeons achieve better desired refractive outcomes for this technique.

Linking political exposures to child and maternal health outcomes: a realist review.

BACKGROUND: Conceptual and theoretical links between politics and public health are longstanding. Internationally comparative systematic review evidence has shown links between four key political exposures - the welfare state, political tradition, democracy and globalisation - on population health outcomes. However, the pathways through which these influences may operate have not been systematically appraised. Therefore, focusing on child and maternal health outcomes, we present a realist re-analysis of the dataset from a recent systematic review. METHODS: The database from a recent systematic review on the political determinants of health was used as the data source for this realist review. Included studies from the systematic review were re-evaluated and those relating to child and/or maternal health outcomes were included in the realist synthesis. Initial programme theories were generated through realist engagement with the prior systematic review. These programme theories were adjudicated and refined through detailed engagement with the evidence base using a realist re-synthesis involving two independent reviewers. The revised theories that best corresponded to the evidence base formed the final programme theories. RESULTS: Out of the 176 included studies from the systematic review, a total of 67 included child and/or maternal health outcomes and were included in the realist re-analysis. Sixty-three of these studies were ecological and data were collected between 1950 and 2014. Six initial programme theories were generated. Following theory adjudication, three theories in revised form were supported and formed the final programme theories. These related to a more generous welfare state leading to better child and maternal health especially in developed countries through progressive social welfare policies, left-of-centre political tradition leading to lower child mortality and low birth weight especially in developed countries through greater focus on welfare measures, and increased globalisation leading to greater child and infant mortality and youth smoking rates in LMECs through greater influence of multinational corporations and neoliberal trade organisations. CONCLUSION: We present a realist re-analysis of a large systematically identified body of evidence on how four key political exposures - the welfare state, democracy, political tradition and globalisation - relate to child and maternal health outcomes. Three final programme theories were supported.

Infraorbital Nerve Decompression for Chronic Post Traumatic Neuralgia: A Novel Approach and Review of the Safety and Efficacy of Piezoelectric Surgery on Soft Tissues and Nerves.

ABSTRACT: Chronic post traumatic infraorbital nerve (ION) hyperesthesia is a rare complication of orbital floor fractures. Surgical decompression of the ION has been reported to relieve chronic post traumatic infraorbital neuralgia. This case report describes a novel approach for ION decompression in a patient who suffered from chronic infraorbital neuralgia associated with a healed displaced orbital floor fracture. We used an intraoperative 3D image-guided navigation system to accurately localize the fracture site and employed piezoelectric surgery for nerve decompression. We further review the literature on the safety and efficacy of piezoelectric surgery on soft tissue and nerves.

The dominant limb preferentially stabilizes posture in a bimanual task with physical coupling.

Humans are endowed with an ability to skillfully handle objects, like when holding a jar with the nondominant hand while opening the lid with the dominant hand. Dynamic dominance, a prevailing theory in handedness research, proposes that the nondominant hand is specialized for postural stability, which would explain why right-handed people hold the jar steady using the left hand. However, the underlying specialization of the nondominant hand has only been tested unimanually, or in a bimanual task where the two hands had different functions. Using a dedicated dual-wrist robotic interface, we tested the dynamic dominance hypothesis in a bimanual task where both hands carry out the same function. We examined how left- and right-handed subjects held onto a vibrating virtual object using their wrists, which were physically coupled by the object. Muscular activity of the wrist flexors and extensors revealed a preference for cocontracting the dominant hand during both holding and transport of the object, which suggests proficiency in the dominant hand for stabilization, contradicting the dynamic dominance hypothesis. While the reliance on the dominant hand was partially explained by its greater strength, the Edinburgh inventory was a better predictor of the difference in the cocontraction between the dominant and nondominant hands. When provided with redundancy to stabilize the task, the dominant hand preferentially cocontracts to absorb perturbing forces.NEW & NOTEWORTHY We found that subjects prefer to stabilize a bimanually held object by cocontracting their dominant limb, contradicting the established view that the nondominant limb is specialized toward stabilization.