Lower Limb Malrotation following Minimally Invasive Plating in Distal Tibia Fractures.

Introduction: Minimally invasive percutaneousosteosynthesis (MIPO) plating techniques havedemonstrated good outcomes in the treatment of distal tibia fractures. Early arthritis and functional impairment mayoccur if length and rotation are not restored. This study aims to determine the incidence and severity of tibia malrotation following MIPO plating of isolated unilateral distal tibia fractures, defined as torsional difference of greater than 10° as compared to the contralateral limb and whether the degree of malrotation affects functional outcomes scores. Materials and methods: This was a level 2 prospective cohort study. All patients with fractures of the distal tibia who underwent surgical fixation with the exclusion ofpatients with polytrauma, neurovascular injuries or pre-existing disabilities were recruited. Patients underwent MIPO plating followed by a post-operative ComputedTomography (CT) scan of bilateral lower limbs. AOFAS ankle-hindfoot score was recorded at six months and one year follow-up. Results: A total of 24 patients (28 to 83 years old) were recruited. Nineteen patients obtained CT scans. Nine of the 19 patients (47.3%) had tibia malrotation. The mean tibia malrotation angle was 10.3° (0° - 45°). The average AOFAS scores was 82.4 and 84.3 at 6 months and 1 year follow-up. Degree of CT malrotation was not significantly associated with AOFAS scores at 6 month (spearman rho -0.386) and 1 year (spearman rho -0.343). Conclusions: Tibia malrotation following MIPO plating of distal tibia fractures is common, with an incidence of 47.3% and an average malrotation angle of 10.3°. The degree of malrotation does not appear to have significant mid-term functional impact on the patient.

Behavioral, metabolic, and lipidomic characterization of the 5xFADxTg30 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is associated with both extracellular amyloid-ß (Aß) plaques and intracellular tau-containing neurofibrillary tangles (NFT). We characterized the behavioral, metabolic and lipidomic phenotype of the 5xFADxTg30 mouse model which contains overexpression of both Aß and tau. Our results independently reproduce several phenotypic traits described previously for this model, while providing additional characterization. This model develops many aspects associated with AD including frailty, decreased survival, initiation of aspects of cognitive decline and alterations to specific lipid classes and molecular lipid species in the plasma and brain. Notably, some sex-specific differences exist in this model and motor impairment with aging in this model does compromise the utility of the model for some movement-based behavioral assessments of cognitive function. These findings provide a reference for individuals interested in using this model to understand the pathology associated with elevated Aß and tau or for testing potential therapeutics for the treatment of AD.

Laboratory Study of Collisionless Magnetic Reconnection.

A concise review is given on the past two decades' results from laboratory experiments on collisionless magnetic reconnection in direct relation with space measurements, especially by the Magnetospheric Multiscale (MMS) mission. Highlights include spatial structures of electromagnetic fields in ion and electron diffusion regions as a function of upstream symmetry and guide field strength, energy conversion and partitioning from magnetic field to ions and electrons including particle acceleration, electrostatic and electromagnetic kinetic plasma waves with various wavelengths, and plasmoid-mediated multiscale reconnection. Combined with the progress in theoretical, numerical, and observational studies, the physics foundation of fast reconnection in collisionless plasmas has been largely established, at least within the parameter ranges and spatial scales that were studied. Immediate and long-term future opportunities based on multiscale experiments and space missions supported by exascale computation are discussed, including dissipation by kinetic plasma waves, particle heating and acceleration, and multiscale physics across fluid and kinetic scales.

The application of epiphenotyping approaches to DNA methylation array studies of the human placenta.

BACKGROUND: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. RESULTS: Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry-informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, as well as over very long placental processing times. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. CONCLUSIONS: This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. We further demonstrate the specific utility of epiphenotyping tools developed for use with placental DNAme data, and show that these variables (i) provide an independent check of clinically obtained data and (ii) provide a robust approach to compare variables across different datasets. Finally, we present a general framework for the processing and analysis of placental DNAme data, integrating the epiphenotype variables discussed here.

Sex and pubertal influences on the neurodevelopmental underpinnings of schizophrenia: A case for longitudinal research on adolescents.

Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.

Establishment of CT diagnostic reference levels (DRLs) for a Singapore healthcare cluster.

INTRODUCTION: The use of computed tomography (CT) in healthcare institutions has increased rapidly in recent years. The Singapore Health Services (SingHealth) cluster of healthcare institutions has taken the first step in establishing a local cluster-wide CT Diagnostic Reference Levels (DRL) in Singapore. CT dose data from each institution were collected through two primary dosimetry metrics: volume CT dose index (CTDIvol measured in mGy) and dose-length product (DLP measured in mGy.cm). METHODS: Data from 19 CT scanners in seven institutions under one of Singapore healthcare cluster were retrospectively collected and analysed. The five common adult CT examinations analysed were CT Brain (non-contrast enhanced), CT Chest (IV contrast enhanced), CT Kidney-Ureter-Bladder (CT KUB, non-contrast enhanced), CT Pulmonary Angiogram (CT PA, IV contrast enhanced) and CT Abdomen-Pelvis (CT AP, IV contrast enhanced, single phase). Median CTDIvol and DLP values for the five CT examinations from each institution were derived, with the cluster DRLs determined as the 75th percentile of the distribution of the institution median dose values. RESULTS: A total of 2413 dose data points were collected over a six-month period from June to November 2020. The cluster CT DRLs for the five CT examinations were determined to be 47 mGy and 820 mGy.cm for CT Brain, 5.4 mGy and 225 mGy.cm for CT Chest, 6.7 mGy and 248 mGy.cm for CT PA, 4.6 mGy and 190 mGy.cm for CT KUB and 6.9 mGy and 349 mGy.cm for CT AP. CONCLUSION: The establishment of the cluster CT DRLs provided individual institutions with a better understanding if their CT doses are unusually high or low, while emphasising that these DRLs are not meant as hard dose limits or constraints to follow strictly.

Comparison of Aortobifemoral Bypass and Endovascular Treatment for Chronic Infrarenal Abdominal Aortic Occlusion From the CHAOS (CHronic Abdominal Aortic Occlusion, ASian Multicenter) Registry.

PURPOSE: To directly compare the clinical outcomes of aortobifemoral bypass surgery (ABF) and endovascular treatment (EVT) for chronic total occlusion (CTO) of the infrarenal abdominal aorta (IAA). MATERIALS AND METHODS: In this retrospective, multicenter study, we used an international database of 436 patients who underwent revascularization for CTO of the IAA between 2007 and 2017 at 30 Asian cardiovascular centers. After excluding 52 patients who underwent axillobifemoral bypass surgery, 384 patients (139 ABFs and 245 EVTs) were included in the analysis. Propensity score-matched analysis was performed to compare clinical results in the periprocedural period and the long-term. RESULTS: Propensity score matching extracted 88 pairs. Procedure time (ABF; 288 [240-345] minutes vs EVT; 159 [100-205] minutes, p<0.001) and length of hospital stay (17 [12-23] days vs 5 [4-13] days, p<0.001) were significantly shorter in the EVT group than in the ABF group, while the proportions of procedural success (98.9% versus 96.6%, p=0.620), complications (9.1% versus 12.3%, p=0.550), and mortality (2.3% versus 3.8%, p=1.000) were not different between the groups. At 1 months, ABI significantly increased more in the ABF group for both in a limb with the lower (0.56 versus 0.50, p=0.018) and the higher (0.49 versus 0.34, p=0.001) baseline ABI, while the change of the Rutherford category was not significantly different between the groups (p=0.590). At 5 years, compared with the EVT group, the ABF group had significantly better primary patency (89.4±4.3% versus 74.8±4.3%, p=0.035) and survival rates (86.9±4.5% versus 66.2±7.5%, p=0.007). However, there was no significant difference between the groups for secondary patency (100.0%±0.0% versus 93.5%±3.9%, p=0.160) and freedom from target lesion revascularization (TLR) (89.3±4.3% vs 77.3±7.3%, p=0.096). CONCLUSION: Even with recent advancements in EVT, primary patency was still significantly better for ABF in CTO of the IAA. However, there was no difference between the groups in terms of secondary patency and freedom from TLR at 5 years. Furthermore, there was no difference in procedural success, complications, mortality, and improvement in the Rutherford classification during the periprocedural period, with significantly shorter procedure time and hospital stay in the EVT group.

Polypharmacy Predicts Onset and Transition of Frailty, Malnutrition, and Adverse Outcomes in Peritoneal Dialysis Patient.

BACKGROUND: Polypharmacy, frailty and malnutrition are known predictors of adverse outcomes in dialysis patients. Little has reported about their interaction and composite prognostic values. We aimed to describe the interaction between polypharmacy, frailty, nutrition, hospitalization, and survival in peritoneal dialysis patients. METHODS: In this prospective cohort study, we recruited 573 peritoneal dialysis patients. Drug burden was measured by medication number and daily pill load. Frailty and nutrition were assessed by the validated Frailty Score (FQ) and Subjective Global Assessment (SGA) respectively. All patients were followed for two years. Primary outcome was all-cause mortality. Secondary outcomes were fall and fracture episodes, hospitalization, change in FQ and SGA. RESULTS: At baseline, each patient took 7.5 ± 2.6 medications with 15.5 ± 8.5 tablets per day. Medication number, but not daily pill load predicted baseline FQ (p = 0.004) and SGA (p = 0.03). Over 2 years, there were 69 fall and 1,606 hospitalization episodes. In addition, 148 (25.8%) patients died, while FQ and SGA changed by 0.73 ± 4.23 and -0.07 ± 1.06 respectively in survivors. Medication number (hospitalization: p = 0.02, survival: p = 0.005), FQ (hospitalization: p < 0.001; survival: p = 0.01) predicted hospitalization and survival. Medication number also predicted fall episodes (p = 0.02) and frailty progression (p = 0.002). Daily pill load did not predict any of these outcomes. CONCLUSIONS: Drug burden is high in peritoneal dialysis patients, and it carries important prognostic implication. Medication number but not pill load significantly predicted onset and progression of frailty, malnutrition, fall, hospitalization, and mortality.

Fabrication of infrared linear arrays of InAs planar avalanche photodiodes.

We report a, to the best of our knowledge, new device fabrication process for 128-pixel linear arrays of InAs planar avalanche photodiodes, utilizing selective area implantation of Beryllium ions into epitaxially-grown InAs wafers. The pixels exhibited uniform avalanche gain and responsivity. Room temperature responsivity values at 1550 and 2004 nm wavelengths are 0.49 ± 0.017 and 0.89 ± 0.024 A/W, respectively. Reverse dark current-voltage and avalanche gain measurements were carried out at different temperatures (from room temperature to 150 K). At 200 K at -15 V reverse bias, the pixels exhibited an avalanche gain of 22.5 ± 1.18 and dark current density of 0.68 ± 0.48 A/cm2.

Simulation of Al0.85Ga0.15As0.56Sb0.44 avalanche photodiodes.

Al0.85Ga0.15As0.56Sb0.44 is a promising avalanche material for near infrared avalanche photodiodes (APDs) because they exhibit very low excess noise factors. However electric field dependence of ionization coefficients in this material have not been reported. We report a Simple Monte Carlo model for Al0.85Ga0.15As0.56Sb0.44, which was validated using reported experimental results of capacitance-voltage, avalanche multiplication and excess noise factors from five APDs. The model was used to produce effective ionization coefficients and threshold energies between 400-1200 kV.cm-1 at room temperature, which are suitable for use with less complex APD simulation models.

Electron-Scale Reconnection in Three-Dimensional Shock Turbulence.

Magnetic reconnection has been observed in the transition region of quasi-parallel shocks. In this work, the particle-in-cell method is used to simulate three-dimensional reconnection in a quasi-parallel shock. The shock transition region is turbulent, leading to the formation of reconnecting current sheets with various orientations. Two reconnection sites with weak and strong guide fields are studied, and it is shown that reconnection is fast and transient. Reconnection sites are characterized using diagnostics including electron flows and magnetic flux transport. In contrast to two-dimensional simulations, weak guide field reconnection is realized. Furthermore, the current sheets in these events form in a direction almost perpendicular to those found in two-dimensional simulations, where the reconnection geometry is constrained.

Wound healing complications following folded flap palatoplasty in brachycephalic dogs.

OBJECTIVE: To determine the incidence and characteristics of wound healing complications after folded flap palatoplasty (FFP). METHODS: Prospective study of 25 dogs that underwent FFP as a component of corrective multilevel surgery for brachycephalic obstructive airway syndrome. Oropharyngeal re-examination was conducted after a minimum of 28 days post-operatively, unless indicated earlier by the onset of clinical signs. RESULTS: Wound healing complications occurred in nine dogs (36%). Minor and major wound complications were diagnosed at a median of 36 days (1.5-51 days) post-operatively. Eight dogs had major wound complications, four of which showed no associated clinical signs. Two patterns of major wound complications were observed: incisional dehiscence (ID) with caudal retraction of the soft palate mucosa and development of a full-thickness defect (FTD) in the centre of the soft palate. Revision of the soft palate surgery was performed in five dogs, failing again in one dog with ID. Clinical signs resolved in symptomatic dogs after revision surgery to close FTD. CONCLUSION: In this study, wound healing complications were common after FFP and were not associated with significant clinical deterioration. Further research is necessary to determine the value and timing of routine post-operative oropharyngeal examination for assessment of soft palate healing after FFP as well as the indication for and success of approaches to the management of wound healing complications. The two distinct patterns of FFP failure recognised may provide insight into the underlying causes and lead to refinements in folded flap palatoplasty technique.

A balancing act: changing the referral pathway following remote consultations for dizziness during the coronavirus disease 2019 pandemic.

BACKGROUND: This paper reports our experience in managing dizzy patients remotely during the coronavirus disease 2019 pandemic, and explored its safety as an alternative to face-to-face consultations. METHODS: Dizzy patients referred by their general practitioner were contacted to answer a validated questionnaire. Clinicians recorded the time needed for consultations, and the diagnosis at each of the following assessment stages: after review of the electronic general practitioner letter; following completion of the questionnaire; following the telephone consultation; and/or at follow up. Patients were telephoned no earlier than three months later to determine satisfaction with the service and symptom resolution. Electronic patient records were checked for presentation to hospital because of dizziness. RESULTS: Seventy patients had telephone consultations. None presented to the emergency department or were admitted. The majority of consultations took 15-30 minutes. The most diagnosed condition was benign positional paroxysmal vertigo. Seventy-nine per cent of patients were satisfied with the service. The questionnaire and telephone consultations demonstrated the greatest diagnosis agreement (κ = 0.40). CONCLUSION: Validated questionnaire and telephone consultations are a safe alternative to face-to-face consultations. Our patient referral pathway has now changed to include elements of the questionnaire.

Calorimeter with Bayesian unfolding of spectra of high-flux broadband x rays.

We report the development of a multipurpose differential x-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high energy x-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5% for electron temperatures from 1 to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56 ± 0.04 MeV for a 700 µm Ti titanium target and 0.53 ± 0.03 MeV for a 50 µm target. We investigate bremsstrahlung from a target irradiated by laser-wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated x rays with a peak energy of 1.1 MeV, and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

The management of penile intraepithelial neoplasia (PeIN): clinical and histological features and treatment of 345 patients and a review of the literature.

INTRODUCTION: Penile intraepithelial neoplasia (PeIN) is a histological term for precancerous penile lesions. PeIN is important due to the high morbidity and mortality associated with progression to penile squamous cell carcinoma (PSSC). But PeIN is rare, contributing to a limited evidence-base for the relative efficacy of available treatment options. OBJECTIVES & METHODS: To consolidate and expand knowledge about PeIN and its treatment, we describe the clinical and histological characteristics, treatments and outcomes of 345 patients with PeIN, managed by our multidisciplinary team. Our results are compared and contrasted with those in the literature, following comprehensive review. RESULTS: 8.7% of patients had concomitant, invasive PSCC, whilst 91.3% demonstrated PeIN alone. 84% had undifferentiated PeIN, and 10.7% differentiated PeIN (5.2%, not specified). Clinical or histological evidence of HPV alone was present in 58%; features of lichen sclerosus alone in 12%; features of both in 29.4%. Only 14.4% of patients could be treated solely with topical agents or cryotherapy, whereas the remaining 85.6% underwent some form of surgical intervention, circumcision being the mainstay. Just 2.6% progressed to PSCC. CONCLUSIONS: Clinical management of PeIN can be rationally optimized with excellent outcomes. Circumcision is important. Topical treatments alone are disappointing.

Hybrid Simulations of the Cusp and Dayside Magnetosheath Dynamics Under Quasi-Radial Interplanetary Magnetic Fields.

Under quasi-radial interplanetary magnetic fields (IMF), foreshock turbulence can have an impact on the magnetosheath and cusps depending on the location of the quasi-parallel shock. We perform three-dimensional simulations of Earth's dayside magnetosphere using the hybrid code HYPERS, and compare northward and southward quasi-radial IMF configurations. We study the magnetic field configuration, fluctuations in the magnetosheath and the plasma in the regions around the northern cusp. Under northward IMF with Earthward B x , there is a time-varying plasma depletion layer immediately outside the northern cusp. In the southward IMF case, the impact of foreshock turbulence and high-speed jets, together with magnetopause reconnection, can lead to strong density enhancements in the cusp.

Clinician perspectives on a culturally adapted patient decision aid concerning maintenance therapy for asthma.

BACKGROUND AND OBJECTIVE: Patients with persistent asthma often show poor adherence to inhaled corticosteroids (ICS). Shared decision-making can improve adherence rates in this population. Patient decision aids (PDAs) are tools to facilitate shared decision-making. To date, only one PDA, developed in a Canadian French-speaking population, exists for patients considering ICS maintenance therapy. This PDA has been culturally adapted in this study to contextualize to the needs of multi-ethnic Asian patients in Singapore. This study explored the views of local clinicians on the content, design and implementation of this newly-adapted PDA. METHODS: 24 clinicians, who were purposively sampled from polyclinics and a tertiary institution, were interviewed on the content, design and implementation of the PDA. The interviews were audio-recorded, transcribed and analyzed via thematic analysis. RESULTS: Clinicians generally accepted the design of the PDA. They suggested for the target users to be patients on Step 2 of GINA guidelines and the number of options to be reduced from four to two (do nothing or start inhaled corticosteroids). Moreover, they supported including a list of values for patients to select from given that Asian patients often do not articulate their values readily. The addition of more visual aids, the production of multilingual Asian editions and the involvement of nurses to administer the PDA was also suggested. CONCLUSION: The PDA was culturally-adapted with local clinicians' perspectives to target multi-ethnic Asian patients with persistent asthma (Step 2 GINA guidelines). The main changes include a list of values and addition of visual aids.