Atomic and Electronic Structure in MgO-SiO2.

Understanding disordered structure is difficult due to insufficient information in experimental data. Here, we overcome this issue by using a combination of diffraction and simulation to investigate oxygen packing and network topology in glassy (g-) and liquid (l-) MgO-SiO2 based on a comparison with the crystalline topology. We find that packing of oxygen atoms in Mg2SiO4 is larger than that in MgSiO3, and that of the glasses is larger than that of the liquids. Moreover, topological analysis suggests that topological similarity between crystalline (c)- and g-(l-) Mg2SiO4 is the signature of low glass-forming ability (GFA), and high GFA g-(l-) MgSiO3 shows a unique glass topology, which is different from c-MgSiO3. We also find that the lowest unoccupied molecular orbital (LUMO) is a free electron-like state at a void site of magnesium atom arising from decreased oxygen coordination, which is far away from crystalline oxides in which LUMO is occupied by oxygen's 3s orbital state in g- and l-MgO-SiO2, suggesting that electronic structure does not play an important role to determine GFA. We finally concluded the GFA of MgO-SiO2 binary is dominated by the atomic structure in terms of network topology.

Comparative efficacy of stannous fluoride and copper sulfate footbath solutions for the treatment and prevention of digital dermatitis in lactating dairy cows.

The objective of this study was to determine whether a novel footbath solution containing stannous fluoride (SnF2) was superior to 5% copper sulfate solution for the treatment and prevention of digital dermatitis (DD) in dairy cattle. Study 1 was conducted over 4 weeks in Missouri and involved 34 lactating Holstein-Friesian cows with hind feet DD lesions. Cows in group SF walked through a footbath containing a proprietary formulation of SnF2 once weekly, whereas cows in group CS walked through a 5% CuSO4 footbath once daily for 5 d each week. Study 2 was conducted over 8 weeks in California and involved 40 lactating Holstein-Friesian cows with hind feet DD lesions. Cows in group SF walked through a SnF2 footbath for 3 consecutive days then once a week for the following 7 weeks. Cows in group CS walked through a 5% CuSO4 footbath 3 times each week for 8 weeks. Data collection included lesion type, lesion area, locomotion score, and pain score. Digital dermatitis was actively transmitted in study 1, and lesion area and locomotion scores were lower in group SF than group CS. In contrast, DD was not actively transmitted in study 2, and lesion area and locomotion scores were similar in groups SF and CS. Stannous fluoride delayed the development of active DD lesions in study 1 compared with copper sulfate, with a lower relative risk (0.57, P < 0.001) of a hind foot developing an active DD lesion over 28 d. However, SnF2 decreased the rate that active DD lesions transitioned to M3, M4, or M0 lesions compared with 5% copper sulfate in both studies, with the relative risk of a hind foot with an active DD lesion transitioning to M3, M4, or M0 in group SF being slightly lower in study 1 (0.83, P = 0.042) and study 2 (0.90, P = 0.020) than group CS. Our findings demonstrated that walking cows through a stannous fluoride footbath once per week in a herd undergoing active transmission of infection was more effective in preventing active DD lesions, but less effective in treating active DD lesions, than walking cows through a copper sulfate footbath 4 times per week. The novel SnF2 footbath solution shows promise for controlling DD in dairy herds that want an alternative footbath solution to CuSO4 and are interested in limiting the environmental accumulation of copper.

Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

BACKGROUND: Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. OBJECTIVE: Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. METHODS: We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. DISCUSSION: The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Intermolecular correlations of liquid and glassy CS2 studied by synchrotron radiation x-ray diffraction.

How is the orientation of molecular liquids ordered on cooling? What are the basic structures of molecular glasses, e.g., close to the crystalline structure or some special structures such as icosahedral cluster? These are long-standing questions in liquid and glass physics. We have constructed a novel cryostat to prepare simple molecular glasses by vapor deposition and performed in situ synchrotron radiation x-ray diffraction experiments. The glassy state of a simple molecule CS2, which cannot be vitrified by normal liquid quenching, was successfully prepared with this instrument, and its diffraction data were collected in a wide Q-range of 0.16-25.7 Å-1 with a high-energy diffractometer at BL04B2, SPring-8. The diffraction data of liquid CS2 were also recorded in a wide temperature range of 160-300 K. These diffraction data were analyzed with molecular dynamics simulations and reverse Monte Carlo modelings to investigate orientational correlation. From the obtained 3D structure models, the orientational correlation between neighboring CS2 molecules was investigated quantitatively as a function of temperature. At room temperature, the parallel and T-shaped arrangements are preferred for the nearest neighbor correlation. On cooling, these arrangements are developed gradually, and its rate became prominent below the melting temperature (162 K). In the glassy state, the slipped-parallel arrangement is dominant as well as the T-shaped arrangement. Both arrangements appear in the CS2 crystal, indicating that the structure of glassy CS2 is close to that of crystalline CS2.

Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.

Targeting both CD20 and phosphatidylinositol 3-kinase (PI3K), a protein that is critically involved in B-cell maturation, could be an efficacious strategy for treating B-cell malignancies. The safety of the next-generation compounds umbralisib, a PI3K-δ inhibitor, plus ublituximab, an anti-CD20 monoclonal antibody (combination referred to as U2), was evaluated in patients with chronic lymphocytic lymphoma (CLL) or non-Hodgkin lymphoma (NHL) in this phase 1/1b study. Phase 1 dose escalation was performed with a 3 + 3 design to establish the maximum tolerated dose. In this portion, ublituximab was given intravenously (NHL, 900 mg; CLL, 600 or 900 mg) for 12 cycles. Umbralisib was given orally once daily at 800 or 1200 mg (initial formulation) or 400 to 1200 mg (micronized formulation) in the phase 1 dose escalation portion, and at 800 to 1200 mg in the phase 1b portion until progression, toxicity, or study removal. The maximum tolerated dose was not reached in either the CLL or NHL cohort, and only 1 dose-limiting toxicity was observed. U2 had low instances of grade 3 or higher diarrhea (8%), pneumonia (8%), or hepatic toxicity (4%). Treatment discontinuation due to adverse events occurred in 13% of patients, and umbralisib dose reductions occurred in 15% of patients. The overall response rate for all patients was 46% with 17% complete responses. The median duration of response was 20 months (95% confidence interval, 11.3-not reached). U2 was well tolerated, and no new safety signals were observed over single-agent umbralisib. Preliminary efficacy with this combination is promising and warrants further investigation. This study was registered at www.clinicaltrials.gov as #NCT02006485.

The nature of night eating syndrome: Using network analysis to understand unique symptomological relationships.

OBJECTIVES: Despite the initial characterization of night eating syndrome (NES) in 1955, the definition and operationalization of its symptoms has varied considerably. To standardize the definition of NES and its symptoms, Allison et al. developed research diagnostic criteria. Even so, conceptualization and intervention of NES remains guided by medical models, which assume that pathology is driven by a distinct, underlying causal mechanism. Conversely, recent work on other eating disorders (EDs) has used network analysis to reconceptualize ED psychopathology and treatment by identifying (a) unique relationships between key symptoms, and (b) the symptoms most central to specific EDs. The present study examined NES symptoms through network analysis to identify the most central symptoms within the NES network. METHOD: Regularized partial correlation networks were estimated using 144 individuals in a community sample diagnosed with NES. Participants completed semi-structured interviews, self-report measures, and food/sleep diaries to measure NES symptoms, nonspecific health domains (e.g., sleep disturbance, overall mood, stress, and circadian rhythm functioning), and transdiagnostic ED symptoms. RESULTS: Depressed mood, poor sleep quality, and a strong urge to eat upon awakening at night were highly central to the psychopathology network for NES and were significantly more central than most other NES symptoms and nonspecific health domains. DISCUSSION: This study provides insight on the unique symptomological relationships of NES and sets the stage for future work that can identify causal linkages among NES symptoms. These symptoms represent key elements of the core psychopathology of NES and should represent primary targets for intervention.

Dissociation between reduced pain and arterial blood pressure following epidural spinal cord stimulation in patients with chronic pain: A retrospective study.

PURPOSE: Acute pain and resting arterial blood pressure (BP) are positively correlated in patients with chronic pain. However, it remains unclear whether treatment for chronic pain reduces BP. Therefore, in a retrospective study design, we tested the hypothesis that implantation of an epidural spinal cord stimulator (SCS) device to treat chronic pain would significantly reduce clinic pain ratings and BP and that these reductions would be significantly correlated. METHODS: Pain ratings and BP in medical records were collected before and after surgical implantation of a SCS device at the University of Iowa Hospitals and Clinics between 2008 and 2018 (n = 213). RESULTS: Reductions in pain rating [6.3 ± 2.0 vs. 5.0 ± 1.9 (scale: 0-10), P < 0.001] and BP [mean arterial pressure (MAP) 95 ± 10 vs. 89 ± 10 mmHg, P < 0.001] were statistically significant within 30 days of SCS. Interestingly, BP returned toward baseline within 60 days following SCS implantation. Multiple linear regression analysis showed that sex (P = 0.007), baseline MAP (P < 0.001), and taking hypertension (HTN) medications (P < 0.001) were significant determinants of change in MAP from baseline (Δ MAP) (model R2 = 0.33). After statistical adjustments, Δ MAP was significantly greater among women than among men ( - 7.2 ± 8.5 vs. - 3.9 ± 8.5 mmHg, P = 0.007) and among patients taking HTN medications than among those not taking hypertension medications ( - 10.1 ± 8.7 vs. - 3.9 ± 8.5 mmHg, P < 0.001), despite no group differences in change in pain ratings. CONCLUSIONS: Together, these findings suggest that SCS for chronic pain independently produces clinically meaningful, albeit transient, reductions in BP and may provide a rationale for studies aimed at reducing HTN medication burden among this patient population.

Hidden Error in Optical Stereotactic Navigation Systems and Strategy to Maximize Accuracy.

BACKGROUND: Optical neuronavigation has been established as a reliable and effective adjunct to many neurosurgical procedures. Operations such as asleep deep brain stimulation (aDBS) benefit from the potential increase in accuracy that these systems offer. Built into these technologies is a degree of tolerated error that may exceed the presumed accuracy resulting in suboptimal outcomes. OBJECTIVE: The objective of this study was to identify an underlying source of error in neuronavigation and determine strategies to maximize accuracy. METHODS: A Medtronic Stealth system (Stealth Station 7 hardware, S8 software, version 3.1.1) was used to simulate an aDBS procedure with the Medtronic Nexframe system. Multiple configurations and orientations of the Nexframe-Nexprobe system components were examined to determine potential sources of, and to quantify navigational error, in the optical navigation system. Virtual entry point and target variations were recorded and analyzed. Finally, off-plan error was recorded with the AxiEM system and visual observation on a phantom head. RESULTS: The most significant source of error was found to be the orientation of the reference marker plate configurations to the camera system, with the presentation of the markers perpendicular to the camera line of site being the most accurate position. Entry point errors ranged between 0.134 ± 0.048 and 1.271 ± 0.0986 mm in a complex, reproducible pattern dependent on the orientation of the Nexprobe reference plate. Target errors ranged between 0.311 ± 0.094 and 2.159 ± 0.190 mm with a similarly complex, repeatable pattern. Representative configurations were tested for physical error at target with errors ranging from 1.2 mm to 1.4 mm. Throughout data acquisition, no orientation was indicated as outside the acceptable tolerance by the Stealth software. CONCLUSIONS: Use of optical neuronavigation is expected to increase in frequency and variety of indications. Successful implementation of this technology depends on understanding the tolerances built into the system. In situations that depend on extremely high precision, surgeons should familiarize themselves with potential sources of error so that systems may be optimized beyond the manufacturer's built-in tolerances. We recommend that surgeons align the navigation reference plate and any optical instrument's reference plate spheres in the plane perpendicular to the line of site of the camera to maximize accuracy.

Entropy Pair Functional Theory: Direct Entropy Evaluation Spanning Phase Transitions.

We prove that, within the class of pair potential Hamiltonians, the excess entropy is a universal, temperature-independent functional of the density and pair correlation function. This result extends Henderson's theorem, which states that the free energy is a temperature dependent functional of the density and pair correlation. The stationarity and concavity of the excess entropy functional are discussed and related to the Gibbs-Bugoliubov inequality and to the free energy. We apply the Kirkwood approximation, which is commonly used for fluids, to both fluids and solids. Approximate excess entropy functionals are developed and compared to results from thermodynamic integration. The pair functional approach gives the absolute entropy and free energy based on simulation output at a single temperature without thermodynamic integration. We argue that a functional of the type, which is strictly applicable to pair potentials, is also suitable for first principles calculation of free energies from Born-Oppenheimer molecular dynamics performed at a single temperature. This advancement has the potential to reduce the evaluation the free energy to a simple modification to any procedure that evaluates the energy and the pair correlation function.

Buried Liquid Interfaces as a Form of Chemistry in Confinement: The Case of 4-Dimethylaminobenzonitrile at the Silica-Aqueous Interface.

Time-resolved fluorescence emission and resonance-enhanced second harmonic generation (SHG) spectra were collected from 4-dimethylaminobenzonitrile (DMABN) adsorbed to the aqueous-silica interface in order to identify how strongly associating solvent-substrate interactions change DMABN's photoisomerization properties. In bulk polar solution, DMABN forms an excited twisted intramolecular charge-transfer (TICT) state that emits with a distinctive, solvatochromic fluorescent signature. At the silica-aqueous interface, the TICT fluorescence disappears, similar to DMABN's behavior in nonpolar environments. SHG spectra confirm that the interface is, in fact, polar, and DMABN's unusual fluorescence emission acquired from the interface is attributed to strong hydrogen bonding associations between the water molecules and the silica surface that prevent adsorbate isomerization. Additionally, SHG spectra show a strong resonance at long wavelengths that is unexpected based on bulk absorbance spectra and selection rules for nonlinear hyperpolarizabilities. Using both Zerner's INDO semiempirical and TD-DFT calculations, this spectroscopic behavior is attributed to a combination of strong electric fields present at the aqueous-silica interface and surface-induced changes to DMABN's ground-state molecular structure.

Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study.

Community-based screening and treatment of women aged 70-85 years at high fracture risk reduced fractures; moreover, the screening programme was cost-saving. The results support a case for a screening programme of fracture risk in older women in the UK. INTRODUCTION: The SCOOP (screening for prevention of fractures in older women) randomized controlled trial investigated whether community-based screening could reduce fractures in women aged 70-85 years. The objective of this study was to estimate the long-term cost-effectiveness of screening for fracture risk in a UK primary care setting compared with usual management, based on the SCOOP study. METHODS: A health economic Markov model was used to predict the life-time consequences in terms of costs and quality of life of the screening programme compared with the control arm. The model was populated with costs related to drugs, administration and screening intervention derived from the SCOOP study. Fracture risk reduction in the screening arm compared with the usual management arm was derived from SCOOP. Modelled fracture risk corresponded to the risk observed in SCOOP. RESULTS: Screening of 1000 patients saved 9 hip fractures and 20 non-hip fractures over the remaining lifetime (mean 14 years) compared with usual management. In total, the screening arm saved costs (£286) and gained 0.015 QALYs/patient in comparison with usual management arm. CONCLUSIONS: This analysis suggests that a screening programme of fracture risk in older women in the UK would gain quality of life and life years, and reduce fracture costs to more than offset the cost of running the programme.

Systematic screening using FRAX® leads to increased use of, and adherence to, anti-osteoporosis medications: an analysis of the UK SCOOP trial.

In the large community-based SCOOP trial, systematic fracture risk screening using FRAX® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. INTRODUCTION: In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM). METHODS: SCOOP was a primary care-based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70-85 years) were randomised to either usual NHS care, or assessment using the FRAX® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%). RESULTS: The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01). CONCLUSIONS: Systematic fracture risk screening using FRAX® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care.

Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study.

A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. INTRODUCTION: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. METHODS: The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. RESULTS: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. CONCLUSION: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.

Impact of the Diabetes Inpatient Care and Education (DICE) project on length of stay and mortality.

AIM: To determine whether the Diabetes Inpatient Care and Education (DICE) programme, a whole-systems approach to managing inpatient diabetes, reduces length of stay, in-hospital mortality and readmissions. RESEARCH DESIGN AND METHODS: Diabetes Inpatient Care and Education initiatives included identification of all diabetes admissions, a novel DICE care-pathway, an online system for prioritizing referrals, use of web-linked glucose meters, an enhanced diabetes team, and novel diabetes training for doctors. Patient administration system data were extracted for people admitted to Ipswich Hospital from January 2008 to June 2016. Logistic regression was used to compare binary outcomes (mortality, 30-day readmissions) 6 months before and after the intervention; generalized estimating equations were used to compare lengths of stay. Interrupted time series analysis was performed over the full 7.5-year period to account for secular trends. RESULTS: Before-and-after analysis revealed a significant reduction in lengths of stay for people with and without diabetes: relative ratios 0.89 (95% CI 0.83, 0.97) and 0.93 (95% CI 0.90, 0.96), respectively; however, in interrupted time series analysis the change in long-term trend for length of stay following the intervention was significant only for people with diabetes (P=0.017 vs P=0.48). Odds ratios for mortality were 0.63 (0.48, 0.82) and 0.81 (0.70, 0.93) in people with and without diabetes, respectively; however, the change in trend was not significant in people with diabetes, while there was an apparent increase in those without diabetes. There was no significant change in 30-day readmissions, but interrupted time series analysis showed a rising trend in both groups. CONCLUSION: The DICE programme was associated with a shorter length of stay in inpatients with diabetes beyond that observed in people without diabetes.

Spinal Cord Stimulation for Visceral Pain: Present Approaches and Future Strategies.

INTRODUCTION: The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges. METHODS: A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain. RESULTS: To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative. CONCLUSIONS: Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy.

Walking School Bus Programs: Implementation Factors, Implementation Outcomes, and Student Outcomes, 2017-2018.

PURPOSE AND OBJECTIVES: Walking school bus programs increase children's physical activity through active travel to school; however, research to inform large-scale implementation of such programs is limited. We investigated contextual factors, implementation outcomes, and student outcomes in existing walking school bus programs in the United States and internationally. INTERVENTION APPROACH: Walking school bus programs involve a group of children walking to school together with an adult leader. On the trip to school, these adults provide social support, address potential traffic and interpersonal safety, and serve as role models to the children while children increase their physical activity levels. EVALUATION METHODS: We conducted surveys with existing walking school bus programs identified through internet searches, referrals, and relevant email listservs. Leaders from 184 programs that operated at least 1 trip per week completed the survey. We used regression analyses to compare differences in contextual factors by area income and location, associations between contextual factors and implementation outcomes, and associations between implementation outcomes and student outcomes. RESULTS: Walking school bus programs in low-income communities had more route leaders and engaged in more active travel to school-related activities of being sustained than those in higher income. Programs that had no external funding, multiple route leaders, and coordination by a school or district staff member (as opposed to a parent) had greater student participation than other programs. Providing more trips than other programs per week was associated with reduced tardiness, reduced bullying, and improved neighborhood walkability. The greatest barriers to implementation were recruiting and maintaining students and identifying and maintaining route leaders. IMPLICATIONS FOR PUBLIC HEALTH: Walking school bus programs can be implemented successfully in many contexts using various models. The involvement of several people in leadership roles is critical for sustainability. Evidence-based implementation strategies that overcome barriers can improve reach, implementation, and sustainability of walking school bus programs and can increase children's physical activity.

Weight change before and after adenotonsillectomy in children: An analysis based upon pre-surgery body mass category.

OBJECTIVES: To determine the standardised body mass index (BMIz) trajectory before and after adenotonsillectomy/tonsillectomy between children in different weight classifications in a larger sample than has been studied previously, and to identify which patient factors would explain the difference in these outcomes. DESIGN: We used a retrospective chart review and leveraged data of weight status pre- and post-adenotonsillectomy/tonsillectomy from a cohort of paediatric patients seen between May 2004 and April 2017. SETTING: Data were collected from an electronic medical record at a single Midwest paediatric health system. PARTICIPANTS: The study population included a convenience sample of 1,751 paediatric patients who underwent adenotonsillectomy or tonsillectomy and had at least two height and weight measurements recorded on the same date both before and after surgery. MAIN OUTCOME MEASURES: Change in BMIz trajectories before and after surgery. RESULTS: Of 1751 paediatric patients (ages 3-11) underwent adenotonsillectomy/tonsillectomy procedures. Age at time of surgery and gender were not significant predictors. Children in different weight classifications demonstrated differences in BMIz trajectory after surgery. Children with overweight/obesity experience a decrease in BMIz, whereas children with underweight or normal weight experience an increase in BMIz. CONCLUSIONS: Improvement in weight status is seen after surgery: increased BMI for those underweight and decreased BMI for those with overweight/obesity. We advocate for behavioural strategies as a first-line treatment in children with underweight or overweight/obesity, and results suggest that coordinating these efforts alongside adenotonsillectomy/tonsillectomy when indicated for medical reasons may be warranted. However, further research is needed to confirm these findings due to the observational nature of this study.

Durotomy Surrogate and Seals for Intradural Spinal Cord Stimulators: Apparatus and Review of Clinical Methods and Materials.

INTRODUCTION: We are developing a novel intradural spinal cord stimulator for treatment of neuropathic pain and spasticity. A key feature is the means by which it seals the dura mater to prevent leakage of cerebrospinal fluid (CSF). We have built and employed a test rig that enables evaluation of candidate seal materials. METHODS: To guide the design of the test rig, we reviewed the literature on neurosurgical durotomies. The test rig has a mock durotomy slot with a dural substitute serving as the surrogate dura mater and water as the CSF. The primary experimental goal was to evaluate the effectiveness of candidate gasket materials as seals against CSF leakage in an implanted prototype device, at both normal and super-physiologic pressures. A secondary goal was to measure the transmembrane flows in a representative dural substitute material, to establish its baseline aqueous transport properties. RESULTS: The seals prevented leakage of water at the implantation site over periods of ≈ ten days, long enough for the scar tissue to form in the clinical situation. The seals also held at water pressure transients approaching 250 mm Hg. The residual volumetric flux of water through the dura substitute membrane (Durepair®) was δVT /A ≈ 0.24 mm3 /min/cm2 , consistent with expectations for transport through the porous membrane prior to closure and equalization of internal/external pressures. CONCLUSIONS: We have demonstrated the workability of obtaining robust seal against leakage at the implantation site of a novel intradural stimulator using a custom-designed test rig. Extension of the method to in vivo testing in a large animal model will be the next step.

Temporal and external validation of a prediction model for adverse outcomes among inpatients with diabetes.

AIM: To temporally and externally validate our previously developed prediction model, which used data from University Hospitals Birmingham to identify inpatients with diabetes at high risk of adverse outcome (mortality or excessive length of stay), in order to demonstrate its applicability to other hospital populations within the UK. METHODS: Temporal validation was performed using data from University Hospitals Birmingham and external validation was performed using data from both the Heart of England NHS Foundation Trust and Ipswich Hospital. All adult inpatients with diabetes were included. Variables included in the model were age, gender, ethnicity, admission type, intensive therapy unit admission, insulin therapy, albumin, sodium, potassium, haemoglobin, C-reactive protein, estimated GFR and neutrophil count. Adverse outcome was defined as excessive length of stay or death. RESULTS: Model discrimination in the temporal and external validation datasets was good. In temporal validation using data from University Hospitals Birmingham, the area under the curve was 0.797 (95% CI 0.785-0.810), sensitivity was 70% (95% CI 67-72) and specificity was 75% (95% CI 74-76). In external validation using data from Heart of England NHS Foundation Trust, the area under the curve was 0.758 (95% CI 0.747-0.768), sensitivity was 73% (95% CI 71-74) and specificity was 66% (95% CI 65-67). In external validation using data from Ipswich, the area under the curve was 0.736 (95% CI 0.711-0.761), sensitivity was 63% (95% CI 59-68) and specificity was 69% (95% CI 67-72). These results were similar to those for the internally validated model derived from University Hospitals Birmingham. CONCLUSIONS: The prediction model to identify patients with diabetes at high risk of developing an adverse event while in hospital performed well in temporal and external validation. The externally validated prediction model is a novel tool that can be used to improve care pathways for inpatients with diabetes. Further research to assess clinical utility is needed.

Femoral vascular conductance and peroneal muscle sympathetic nerve activity responses to acute epidural spinal cord stimulation in humans.

NEW FINDINGS: What is the central question of this research? Does acute spinal cord stimulation increase vascular conductance and decrease muscle sympathetic nerve activity in the lower limbs of humans? What is the main finding and its importance? Acute spinal cord stimulation led to a rapid rise in femoral vascular conductance, and peroneal muscle sympathetic nerve activity demonstrated a delayed reduction that was not associated with the initial increase in femoral vascular conductance. These findings suggest that neural mechanisms in addition to attenuated muscle sympathetic nerve activity might be involved in the initial increase in femoral vascular conductance during acute spinal cord stimulation. ABSTRACT: Clinical cases have indicated an increase in peripheral blood flow after continuous epidural spinal cord stimulation (SCS) and that reduced muscle sympathetic nerve activity (MSNA) might be a potential mechanism. However, no studies in humans have directly examined the effects of acute SCS (<60 min) on vascular conductance and MSNA. In study 1, we tested the hypothesis that acute SCS (<60 min) of the thoracic spine would lead to increased common femoral vascular conductance, but not brachial vascular conductance, in 11 patients who previously underwent surgical SCS implantation for management of neuropathic pain. Throughout 60 min of SCS, common femoral artery conductance was elevated and significantly different from brachial artery conductance [in millilitres per minute: 15 min, change (Δ) 26 ± 37 versus Δ-2 ± 19%; 30 min, Δ28 ± 45 versus Δ0 ± 26%; 45 min, Δ48 ± 43 versus Δ2 ± 21%; 60 min, Δ36 ± 61 versus Δ1 ± 24%; and 15 min post-SCS, Δ51 ± 64 versus Δ6 ± 33%; P = 0.013]. A similar examination in a patient with cervical SCS revealed minimal changes in vascular conductance. In study 2, we examined whether acute SCS reduces peroneal MSNA in a subset of SCS patients (n = 5). The MSNA burst incidence in response to acute SCS gradually declined and was significantly reduced at 45 and 60 min of SCS (in bursts per 100 heart beats: 15 min, Δ-1 ± 12%; 30 min, Δ-14 ± 12%; 45 min, Δ-19 ± 16%; 60 min, Δ-24 ± 18%; and 15 min post-SCS: Δ-11 ± 7%; P = 0.015). These data demonstrate that acute SCS rapidly increases femoral vascular conductance and reduces peroneal MSNA. The gradual reduction in peroneal MSNA observed during acute SCS suggests that neural mechanisms in addition to attenuated MSNA might be involved in the acute increase in femoral vascular conductance.