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1.
J Bone Joint Surg Am ; 101(19): 1750-1760, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577680

RESUMO

BACKGROUND: Treatment outcomes and risk factors for neurological deficits in pediatric patients with an os odontoideum are unclear. METHODS: We reviewed the data for 102 children with os odontoideum who were managed at 11 centers between 2000 and 2016 and had a minimum duration of follow-up of 2 years. Thirty-one children had nonoperative treatment, and 71 underwent instrumented posterior cervical spinal arthrodesis for the treatment of C1-C2 instability. Nonoperative treatment consisted of observation (n = 29) or immobilization with a cervical collar (n = 1) or halo body jacket (n = 1). Surgical treatment consisted of atlantoaxial (n = 50) or occipitocervical (n = 21) arthrodesis. One patient also underwent transoral odontoidectomy. RESULTS: Thirty children (29%) presented with neurological deficits, 28 of whom had radiographic atlantoaxial instability (atlantoaxial distance >5 mm) or limited space (≤13 mm) available for the spinal cord (risk ratio, 7.8 [95% confidence interval, 2.0 to 31] compared with children with no radiographic risk factors). The 27 children without neurological deficits or atlantoaxial instability at presentation underwent nonoperative treatment and remained asymptomatic. Of the initial nonoperative cohort, one child developed atlantoaxial instability, and another had a persistent neurological deficit; both children underwent spinal arthrodesis during the study period. One child with cervical instability declined surgery and remained asymptomatic. Spinal fusion occurred in 68 patients in the surgical group by the end of the study period (mean, 3.7 years; range, 2.0 to 11.8 years). Surgical complications occurred in 21 children, including nonunion in 12, new neurological deficits in 4, cerebrospinal fluid leak in 2, symptomatic instrumentation requiring removal 2, and vertebral artery injury in 1. Nine children underwent revision surgery. In the surgical group, Japanese Orthopaedic Association neurological function scores improved significantly from preoperatively to the latest follow-up for the upper extremities (p = 0.026) and lower extremities (p = 0.007). CONCLUSIONS: The risk of developing a neurological deficit was strongly associated with atlantoaxial instability and limited space available for the spinal cord in children with os odontoideum. Nonoperative treatment was safe for asymptomatic patients without atlantoaxial instability. Spinal arthrodesis resolved the neurological deficits of children with symptomatic os odontoideum. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31596132

RESUMO

An alarming proportion of individuals with diabetes are not achieving their individualized goals. Several recent randomized controlled trials and real-world observational studies have demonstrated that use of continuous glucose monitoring (CGM) improves clinical and psychosocial outcomes individuals with type 1 and type 2 diabetes. However, CGM use is denied to many individuals who could benefit from this technology due to eligibility criteria that require a documented history of frequent self-monitoring of blood glucose (SMBG). In this article, we discuss the absence of evidence supporting coverage policies and present data demonstrating that prior frequency of SMBG is not predictive of successful CGM use.

3.
Eur J Cancer ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31543384

RESUMO

BACKGROUND: For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed. METHODS: We have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)-specific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings. RESULTS: A total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma. CONCLUSION: We demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panel-based approach can identify actionable genetic alterations in a high proportion of patients.

4.
J Clin Pathol ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554679

RESUMO

OBJECTIVE: To describe and investigate the potential causes of the isolated caecal patch lesion, a previously undescribed endoscopic phenomenon of a lesion fulfilling endoscopic and histopathological criteria for chronic inflammatory bowel disease but without evidence of similar inflammatory pathology elsewhere at colonoscopy. METHODS: Cases were collected prospectively by one specialist gastrointestinal pathologist over a 10-year period. Full endoscopic and histopathological analysis was undertaken and follow-up sought to understand the likely cause(s) of the lesions. RESULTS: Six cases are described. Two had very close links with ulcerative colitis, one predating the onset of classical distal disease and the other occurring after previous demonstration of classical distal ulcerative colitis. Two occurred in younger patients and we postulate that these lesions may predict the subsequent onset of chronic inflammatory bowel disease. Finally two can be reasonably attributed to the effects of non-steroidal inflammatory agent therapy. CONCLUSIONS: Caecal patch lesions can be demonstrated in isolation. Despite the strong association of caecal patch lesions with ulcerative colitis, solitary lesions may well have disparate causes but nevertheless possess a close relationship with chronic inflammatory bowel disease.

5.
Sci Signal ; 12(598)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506382

RESUMO

Despite the benefits of chimeric antigen receptor (CAR)-T cell therapies against lymphoid malignancies, responses in solid tumors have been more limited and off-target toxicities have been more marked. Among the possible design limitations of CAR-T cells for cancer are unwanted tonic (antigen-independent) signaling and off-target activation. Efforts to overcome these hurdles have been blunted by a lack of mechanistic understanding. Here, we showed that single-cell analysis with time course mass cytometry provided a rapid means of assessing CAR-T cell activation. We compared signal transduction in expanded T cells to that in T cells transduced to express second-generation CARs and found that cell expansion enhanced the response to stimulation. However, expansion also induced tonic signaling and reduced network plasticity, which were associated with expression of the T cell exhaustion markers PD-1 and TIM-3. Because this was most evident in pathways downstream of CD3ζ, we performed similar analyses on γδT cells that expressed chimeric costimulatory receptors (CCRs) lacking CD3ζ but containing DAP10 stimulatory domains. These CCR-γδT cells did not exhibit tonic signaling but were efficiently activated and mounted cytotoxic responses in the presence of CCR-specific stimuli or cognate leukemic cells. Single-cell signaling analysis enabled detailed characterization of CAR-T and CCR-T cell activation to better understand their functional activities. Furthermore, we demonstrated that CCR-γδT cells may offer the potential to avoid on-target, off-tumor toxicity and allo-reactivity in the context of myeloid malignancies.

6.
J Biol Chem ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519749

RESUMO

Insect-borne flaviviruses produce a 300-500 base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5'-3' exoribonuclease 1 (XRN1) via structures located in their 3' UTRs.  In this study, we demonstrate that sfRNA production by Zika virus represses XRN1 analogous to what we have previously shown for other flaviviruses.  Using protein-RNA reconstitution and a stringent RNA pulldown assay with human choriocarcinoma (JAR) cells, we demonstrate that the sfRNAs from both dengue type 2 and Zika viruses interact with a common set of 21 RNA-binding proteins that contribute to the regulation of post-transcriptional processes in the cell, including splicing, RNA stability and translation.  We found that four of these sfRNA-interacting host proteins - DEAD-box helicase 6 (DDX6) and enhancer of mRNA decapping 3 (EDC3) (two RNA decay factors), phosphorylated adaptor for RNA export (PHAX, a regulator of the biogenesis of the splicing machinery), and apolipoprotein B mRNA-editing enzyme catalytic subunit 3C (APOBEC3C, a nucleic acid editing deaminase) inherently restrict Zika virus infection.  Furthermore, we demonstrate that the regulation of cellular mRNA decay and RNA splicing are compromised by Zika virus infection as well as by sfRNA alone.  Collectively, these results reveal the large extent to which Zika virus-derived sfRNAs interact with cellular RNA-binding proteins and highlight the potential for widespread dysregulation of post-transcriptional control which likely limits the effective response of these cells to viral infection.

7.
BMJ Case Rep ; 12(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434663

RESUMO

A 53-year-old woman was admitted with thyroid storm and severe behavioural problems. She had longstanding bipolar affective disorder. She was psychotic and obstructed in-patient medical management for thyroid storm. She required one-to-one psychiatric nursing and was placed under section 3 of the Mental Health Act meaning she could be detained in hospital for psychiatric treatment for up to 6 months. She underwent a total thyroidectomy. Due to her paranoid mental state, she refused treatment and the administration of thyroid hormone replacement was difficult. Postoperatively, intramuscular levothyroxine was used effectively to stabilise her thyroid function. There are no consensus guidelines on the use of parenteral levothyroxine and intramuscular levothyroxine is rarely used. This case uniquely illustrates its utility with bi-weekly blood tests showing a fast and stable response to intramuscular hormone replacement.

8.
J Bone Joint Surg Am ; 101(16): 1485-1494, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31436657

RESUMO

BACKGROUND: Newer designs and techniques of total ankle arthroplasty (TAA) have challenged the assumption of ankle arthrodesis (AA) as the primary treatment for end-stage ankle arthritis. The objective of this study was to compare physical and mental function, ankle-specific function, pain intensity, and rates of revision surgery and minor complications between these 2 procedures and to explore heterogeneous treatment effects due to age, body mass index (BMI), patient sex, comorbidities, and employment on patients treated by 1 of these 2 methods. METHODS: This was a multisite prospective cohort study comparing outcomes of surgical treatment of ankle arthritis. Subjects who presented after nonoperative management had failed received either TAA or AA using standard-of-treatment care and rehabilitation. Outcomes included the Foot and Ankle Ability Measure (FAAM), Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) scores, pain, ankle-related adverse events, and treatment success. RESULTS: Five hundred and seventeen participants underwent surgery and completed a baseline assessment. At 24 months, the mean improvement in FAAM activities of daily living (ADL) and SF-36 PCS scores was significantly greater in the TAA group than in the AA group, with a difference between groups of 9 points (95% confidence interval [CI] = 3, 15) and 4 points (95% CI = 1, 7), respectively. The crude incidence risks of revision surgery and complications were greater in the AA group; however, these differences were no longer significant after adjusting for age, sex, BMI, and Functional Comorbidity Index (FCI). The treatment success rate was greater after TAA than after AA for those with an FCI of 4 (80% versus 62%) and not fully employed (81% versus 58%) but similar for those with an FCI score of 2 (81% versus 77%) and full-time employment (79% versus 78%). CONCLUSIONS: At 2-year follow-up, both AA and TAA were effective. Improvement in several patient-reported outcomes was greater after TAA than after AA, without a significant difference in the rates of revision surgery and complications. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

9.
Cancer Res ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405846

RESUMO

Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant in vivo models has limited our insight into the development of aggressive disease. The Th-MYCN genetically-engineered mouse model develops rapidly-progressive chemosensitive neuroblastoma and lacks clinically-relevant metastases. To study tumor progression in a context more reflective of clinical therapy, we delivered multi-cycle treatment with cyclophosphamide to Th-MYCN mice, individualizing therapy using MRI, to generate the Th-MYCNCPM32 model. These mice developed chemoresistance and spontaneous bone-marrow metastases. Tumors exhibited an altered immune microenvironment with increased stroma and tumor-associated fibroblasts. Analysis of copy number aberrations (CNAs) revealed genomic changes characteristic of human MYCN-amplified neuroblastoma, specifically copy number gains at mouse chromosome 11, syntenic with gains on human chromosome 17q. RNA sequencing revealed enriched expression of genes associated with 17q gain and upregulation of genes associated with high-risk neuroblastoma, such as the cell-cycle regulator Cyclin B1-interacting protein 1 (Ccnb1ip1) and Thymidine Kinase (TK1). The anti-apoptotic, pro-metastatic JAK-STAT3 pathway was activated in chemoresistant tumors, and treatment with the JAK1/JAK2 inhibitor CYT387 reduced progression of chemoresistant tumors and increased survival. Our results highlight that under treatment conditions which mimic chemotherapy in human patients, Th-MYCN mice develop genomic, microenvironmental and clinical features reminiscent of human chemorefractory disease. The Th-MYCNCPM32 model therefore is a useful tool to dissect in detail mechanisms that drive metastasis and chemoresistance, and highlights dysregulation of signaling pathways such as JAK-STAT3 that could be targeted to improve treatment of aggressive disease.

10.
Dig Endosc ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365756

RESUMO

BACKGROUND AND AIM: Acute gastrointestinal bleeding carries poor outcomes unless prompt endoscopic hemostasis is achieved. Mortality in these patients remains significant. Hemospray is a novel intervention that creates a mechanical barrier over bleeding sites. We report the largest dataset of patient outcomes after treatment with Hemospray from an international multicenter registry. PATIENTS AND METHODS: Prospective data (Jan 2016-May 2018) from 12 centers across Europe were collected. Immediate hemostasis was defined as endoscopic cessation of bleeding within 5 min after application of Hemospray. Rebleeding was defined as subsequent drop in hemoglobin, hematemesis, persistent melena with hemodynamic compromise post-therapy. RESULTS: Three hundred and fourteen cases were recruited worldwide (231 males, 83 females). Median pretreatment Blatchford score was 11 (IQR: 8-14) and median complete Rockall score (RS) was 7 (IQR: 6-8) for all patients. Peptic ulcer disease (PUD) was the most common pathology (167/314 = 53%) and Forrest Ib the most common bleed type in PUD (100/167 = 60%). 281 patients (89.5%) achieved immediate hemostasis after successful endoscopic therapy with Hemospray. Rebleeding occurred in 29 (10.3%) of the 281 patients who achieved immediate hemostasis. Seven-day and 30-day all-cause mortality were 11.5% (36/314) and 20.1% (63/314), respectively (lower than the predicted rates as per the RS). Similar hemostasis rates were noted in the Hemospray monotherapy (92.4%), combination therapy (88.7%) and rescue therapy (85.5%) groups. CONCLUSIONS: These data show high rates of immediate hemostasis overall and in all subgroups. Rebleeding and mortality rates were in keeping/lower than predicted rates.

11.
Proc Natl Acad Sci U S A ; 116(36): 17867-17873, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31427510

RESUMO

Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity-ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.

12.
PLoS One ; 14(8): e0216373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398192

RESUMO

Adoptive transfer of ex vivo expanded tumor infiltrating lymphocytes (TILs) has led to clinical benefit in some patients with melanoma but has not demonstrated convincing efficacy in other solid cancers. Whilst the presence of TILs in many types of cancer is often associated with better clinical prognosis, their function has not been systematically evaluated across cancer types. Responses to immunological checkpoint inhibitors in a wide range of cancers, including those for which adoptive transfer of expanded TILs has not shown clinical benefit, has clearly delineated a number of tumor type associated with tumor-reactive lymphocytes capable of effecting tumor remissions. Neuroblastoma is an aggressive childhood solid cancer in which immunotherapy with GD2-directed antibodies confers a proven survival advantage through incompletely understood mechanisms. We therefore evaluated the feasibility of ex vivo expansion of TILs from freshly resected neuroblastoma tumors and the potential therapeutic utility of TIL expansions. TILs were successfully expanded from both tumor biopsies or resections. Significant numbers of NKT and γδT cells were identified alongside the mixed population of cytotoxic (CD8+) and helper (CD4+) T cells of both effector and central memory phenotypes. Isolated TILs were broadly non-reactive against autologous tumor and neuroblastoma cell lines, so enhancement of neuroblastoma killing was attained by transducing TILs with a second-generation chimeric antigen receptor (CAR) targeting GD2. CAR-TILs demonstrated antigen-specific cytotoxicity against tumor cell lines. This study is the first to show reproducible expansion of TILs from pediatric neuroblastoma, the high proportion of innate-like lymphocytes, and the feasibility to use CAR-TILs therapeutically.

13.
JBJS Case Connect ; 9(3): e0159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31390335

RESUMO

CASE: This report describes a 7-year-old girl with Langerhans cell histiocytosis (LCH) of the thoracic spine who developed neurological deterioration during nonsurgical management. She was treated with decompression and instrumented fusion followed by chemotherapy, recovered completely after surgery, and was doing well at 6-year follow-up. CONCLUSIONS: The best treatment of LCH of the spine is not clear, but in the setting of neurologic compromise after failing conservative management, surgical decompression with adjuvant chemotherapy should be considered.

14.
F1000Res ; 8: 823, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316758

RESUMO

Background: Primary cell culture using serum free media supplemented with growth factors has been used in a number of cancers to propagate primary cells with stem like properties, which form as spherical cellular aggregates. Methods: We systematically evaluated the capacity of freshly disaggregated neuroblastoma tumors to become established as neurospheres in stem cell media using a uniform protocol. 67 primary neuroblastoma samples from patients treated at a single institution were prospectively evaluated for their ability to become established in culture. Samples, either solid tissue or cells from surgical transit fluid both post chemotherapy and chemotherapy naïve, were evaluated from diagnostic needle biopsies or surgical resections. Results: Overall 37 neurosphere cultures were successfully established from 67 samples. In 11 out of 14 cases investigated by flow cytometry, uniform staining for neuroblastoma markers CD56 and GD2 was demonstrated in CD45 negative non-hemopoietic cells, confirming neuroblastoma origin. Conclusion: We present a simple and reproducible approach for producing primary neurospheres from neuroblastoma samples, which provides a reliable resource for future work including genetic analysis, stem cell research and models for therapeutics.

15.
BMC Med Educ ; 19(1): 277, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340792

RESUMO

BACKGROUND: The term 'dyslexia' refers to a condition that impacts upon reading and writing abilities whilst not altering intelligence. Individuals with dyslexia may have difficulties with the speed and accuracy and their reading and writing, amongst other issues. Dyslexia is not automatically considered a disability but is a protected characteristic under the UK Equality Act (2010), and therefore employers and educational institutions are required to provide 'reasonable adjustments' in order to allow individuals to reach their full potential. There is a lack of research on this issue, but what little there is suggests that doctors feel as though any support they received ended when they graduated from medical school. MAIN BODY: A core distinction between medical school and medical practice is the requirement to prescribe medicines as registered medical practitioners. Junior doctors have to master this complex and potentially hazardous skill "on the job", with a perceived lack of support. Here, we open up a debate about the potential impact of dyslexia on prescribing, and the need to find supports that may be effective in enabling doctors with dyslexia prescribe medicines safely and effectively - and thus reach their full potential as medical practitioners and promote patient safety. CONCLUSION: We argue that medical schools and hospitals could immediately provide dyslexia awareness training in both undergraduate and postgraduate settings. We discuss electronic prescribing systems, and conclude that research is required to identify effective supports for junior doctors with dyslexia.

16.
J Bone Joint Surg Am ; 101(13): 1177-1184, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31274719

RESUMO

BACKGROUND: Ambulatory activity is reduced in patients with ankle arthritis. In this study, we measured step activity over time in 2 treatment groups and secondarily compared step activity with results of patient-reported outcome measures (PROMs). METHODS: Patients who were treated with either ankle arthrodesis or ankle arthroplasty wore a step activity monitor preoperatively and at 6, 12, 24, and 36 months postoperatively. Changes from preoperative baseline in total steps per day and per-day metrics of low, medium, and high-activity step counts were measured in both treatment groups. Step activity was compared with each subject's PROM scores as reported on the Musculoskeletal Function Assessment (MFA) and the Short Form-36 (SF-36) physical function and bodily pain subscales. RESULTS: Of the 3 activity levels, combined group high-activity step counts showed the greatest increase (mean of 278 steps [95% confidence interval (CI), 150 to 407 steps], a 46% improvement from preoperatively). At 6 months, the mean high-activity step improvement for the arthroplasty group was 194 steps compared with a mean decline of 44 steps for the arthrodesis group (mean 238-step difference [95% CI, -60 to 536 steps]). By 36 months postoperatively, the greater improvement in high-activity steps for the arthroplasty versus the arthrodesis group was no longer present. There were no significant pairwise differences in improvement based on surgical treatment method at any individual follow-up time point. For a within-patient increase of 1,000 total steps, there was a mean change in the MFA, SF-36 physical function, and SF-36 bodily pain scores of -1.8 (95% CI, -2.4 to -1.2), 3.8 (95% CI, 2.8 to 4.8), and 2.8 (95% CI, 1.8 to 3.9), respectively (p < 0.0001 for all associations). There was no evidence that the association differed by study visit, or by study visit and surgical procedure interaction (p > 0.10). CONCLUSIONS: Surgical treatment of ankle arthritis significantly improves ambulatory activity, with greater change occurring at high activity levels. Improvement may occur more quickly following arthroplasty than arthrodesis, but at 3 years, we detected no significant difference between the 2 procedures. Step counts, while associated with PROMs, do not parallel them, and thus may be a useful supplementary measure, particularly in longitudinal studies. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

17.
Phys Rev Lett ; 122(21): 217702, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31283344

RESUMO

Spin-orbit coupling is relatively weak for electrons in bulk silicon, but enhanced interactions are reported in nanostructures such as the quantum dots used for spin qubits. These interactions have been attributed to various dissimilar interface effects, including disorder or broken crystal symmetries. In this Letter, we use a double-quantum-dot qubit to probe these interactions by comparing the spins of separated singlet-triplet electron pairs. We observe both intravalley and intervalley mechanisms, each dominant for [110] and [100] magnetic field orientations, respectively, that are consistent with a broken crystal symmetry model. We also observe a third spin-flip mechanism caused by tunneling between the quantum dots. This improved understanding is important for qubit uniformity, spin control and decoherence, and two-qubit gates.

18.
Telemed J E Health ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31161968

RESUMO

Introduction: Widespread screening for cognitive decline is an important challenge to address as the aging population grows, but there is currently a shortage of clinical infrastructure to meet the demand for in-person evaluation. Remotely delivered assessments that utilize eye-tracking data from webcams, such as visual paired comparison (VPC) tasks, could increase access to remote, asynchronous neuropsychological screening for cognitive decline but further validation against clinical-grade eye trackers is required. Methods: To demonstrate equivalence between a novel automated scoring system for eye-tracking metrics acquired through a laptop-embedded camera and a gold-standard eye tracker, we analyzed VPC data from 18 subjects aged 50+ with normal cognitive function across three visits. The eye tracker data were scored by the manufacturer's software, and the webcam data were scored by a novel algorithm. Results: Automated scoring of webcam-based VPC data revealed strong correlations with the clinical-grade eye-tracking camera. Correlation of mean VPC performance across all time points was robust: r = 0.95 (T1 r = 0.97; T2 r = 0.88; T3 r = 0.97; p's < 0.001). Correlation of per-trial performance across time points was also robust: r = 0.88 (T1 r = 0.85; T2 r = 0.89; T3 r = 0.92; p's < 0.001). Mean differences between performance data acquired by each device were 0.00. Conclusion: These results suggest that device-embedded cameras are a valid and scalable alternative to traditional laboratory-based equipment for gaze-based tasks measuring cognitive function. The validation of this technique represents an important technical advance for the field of teleneuropsychology.

19.
Foot Ankle Int ; 40(9): 1068-1078, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31170812

RESUMO

BACKGROUND: Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (ß-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/ß-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. METHODS: Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/ß-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/ß-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. RESULTS: In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/ß-TCP-collagen to autograft. Safety-related outcomes were equivalent. CONCLUSION: PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/ß-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. LEVEL OF EVIDENCE: Level I, prospective randomized study.

20.
Inorg Chem ; 58(14): 9057-9066, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31247828

RESUMO

A family of bis(neocuproine) complexes of Fe2+ and Co2+ have been investigated for neocuproine redox noninnocence. A series of redox isomers of M(neocuproine)2n+ (where n = 2, 1, 0 for Co and n = 2, 0 for Fe) have been synthesized and thoroughly characterized. The electronic structure of these complexes has been rigorously investigated using a variety of techniques, including X-ray absorption spectroscopy, Mössbauer spectroscopy, X-ray diffraction, electron paramagnetic resonance spectroscopy, and magnetic measurements. All of these techniques are consistent with ligand-based reduction events to generate radical neocuproine complexes. Thus, neocuproine adds to a growing family of chelating N-donor type ligands that participate in redox noninnocence and may be useful for future catalyst and reaction design.

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