Design and Preliminary Testing of Demand-Responsive Transverse Rumble Strips

Transverse rumble strips are common practice to alert drivers by engaging their auditory and tactile senses in addition to visual senses by traffic signals. However, continuous exposure to noise and vibration by transverse rumble strips often results in diminished effectiveness and erratic behaviors, leading to additional safety challenges. In response, demand-responsive transverse rumble strips were developed as traffic safety countermeasures that reduce unnecessary noise and vibration associated with transverse rumble strips by incorporating active control of the rumble strips. Rather than staying static, demand-responsive transverse rumble strips are activated based on the presence of pedestrians, at predesignated times, or in response to abrupt changes in traffic flow. To evaluate the effectiveness of demand-responsive transverse rumble strips, the research team assessed noise and vibration data, both inside the vehicles and on the roadside, for various types of vehicles traveling at different speeds. The test data indicate that demand-responsive transverse rumble strips produced noticeable in-vehicle noise and vibration that could alert drivers to downstream events. Furthermore, demand-responsive transverse rumble strips generated sufficient noise to alert roadside pedestrians to vehicle presence but at low enough level to be considered as acceptable for a residential neighborhood use. Accordingly, demand-responsive transverse rumble strips could address the challenges that static transverse rumble strips face, by providing a design with relatively limited noise while enhancing safety

Pattern of access to cafeteria-style diet determines fat mass and degree of spatial memory impairments in rats.

Repeated 'cycling' between healthy and unhealthy eating is increasingly common but the effects of such cycling on cognitive function are unknown. Here we tested the effects of cycling between chow and a cafeteria diet (CAF) rich in saturated fat and refined carbohydrates on fat mass and place recognition memory in rats. Rats fed the chow diet (control group) were compared with groups fed CAF for either: 3 consecutive days per week followed by 4 days of chow, (3CAF:4CHOW group); 5 consecutive days per week followed by 2 days of chow (5CAF:2CHOW group); or 7 days per week (7CAF group). Total days of exposure to CAF were matched between the latter groups by staggering the introduction of CAF diet. After 16-18 days of CAF, spatial recognition memory was significantly worse in the 7CAF group relative to controls. After 23-25 days of CAF, both the 7CAF and 5CAF:2CHOW groups, but not the 3CAF:4CHOW group, were impaired relative to controls, mirroring changes in fat mass measured by EchoMRI. CAF feeding did not affect object recognition memory or total exploration time. These results indicate that even when matching total exposure, the pattern of access to unhealthy diets impairs spatial memory in a graded fashion

Association between obesity and infarct size: insight into the obesity paradox.

Abstract: Background: In patients with coronary heart disease, being overweight or obese is associated with better outcomes, a phenomenon known as the \u27obesity paradox\u27. Despite the high prevalence of obesity in the United Sates, its effects on infarct size are largely unexplored. Methods: Prospective cross-sectional study of 102 consecutive patients admitted with acute myocardial infarction (MI). Standardized forms were used to collect data on body mass index (BMI), waist circumference (WC), cardiovascular risk factors, and medications. Peak troponin I and creatinine phosphokinase (CPK) were used to estimate infarct size. Epicardial and pericardial fat were measured by echocardiography. We used univariate and multivariate analyses to assess whether obesity was associated with infarct size. Correlations between BMI, WC and cardiac fat with cardiac biomarkers were also performed. Results: Mean age was 62±12 years, and 55% were men. Obesity was diagnosed in 69%. On multivariate analysis, obesity was associated with greater infarct size in non-ST elevation MI (p=0.02). A positive correlation was observed between BMI and peak troponin I (rho=0.24, p=0.03), and both, BMI and WC had a positive correlations with CPK levels (rho=0.28, & rho=0.28, both p=0.02). However, in ST elevation MI, obesity was associated with smaller infarct size (p=0.05). Epicardial fat + pericardial fat had a negative correlation with peak CPK levels (rho=-0.36, p=0.05). Conclusions: We observed an opposite association between obesity and infarct size depending on the type of MI. These results were unexpected and may provide insight into the pathophysiology of the obesity paradox

Continuous-flow left ventricular assist device outflow graft stenting: Indications and outcomes

Introduction: Stenosis in the continuous-flow left ventricular assist device (CF-LVAD) outflow graft can be caused by various mechanical and anatomical factors. Increasingly, percutaneous management has been utilized to re-establish adequate CF-LVAD flow. We sought to evaluate indications for such interventions and their outcomes. Methods: An electronic search was performed to identify all studies in the English literature reporting CF-LVAD outflow graft stenting for various etiologies. Twenty-one studies consisting of 26 patients were included in the analysis. Results: Median patient age was 59 years [45.8-67.0] and 65.4% (17/26) were male. 58.3% (14/24) of patients had HeartWare HVAD, 37.5% (9/24) had HeartMate II LVAD, and 4.2% (1/24) had HeartMate III LVAS. Median time from device placement to outflow graft stenting was 24.0 months [7.8-30.4]. 76.9% of patients (20/26) presented with heart failure. 34.6% (9/26) had outflow graft thrombosis, 34.6% (9/26) stenosis, 11.5% (3/26) kinking, 11.5% (3/26) pseudoaneurysm, 3.8% (1/26) external graft compression, and 3.8% (1/26) had a bronchialarterial fistula. 88.5% (23/26) procedures led to immediate flow improvement with the remaining 11.5% (3/26) receiving additional stenting. Post-intervention flows were significantly improved (4.7 L/min [4.1-4.8] post-intervention vs 2.9 L/min [2.0-3.5] initial, p=0.01). 96.2% (25/26) patients were discharged from the hospital. The 30-day mortality was 6.7% (1/15). Overall mortality during the median follow-up of 90 days [7.0-240.0] was 9.5% (2/21). Discussion: Outflow graft stenting appears to effectively alleviate CF-LVAD outflow graft obstruction with low mortality. Longer-term follow up is necessary to determine the longevity of such an intervention but early results are promising

Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development

Male Rat Offspring Are More Impacted by Maternal Obesity Induced by Cafeteria Diet than Females-Additive Effect of Postweaning Diet.

Maternal obesity increases the risk of health complications in offspring, but whether these effects are exacerbated by offspring exposure to unhealthy diets warrants further investigation. Female Sprague-Dawley rats were fed either standard chow (n = 15) or 'cafeteria' (Caf, n = 21) diets across pre-pregnancy, gestation, and lactation. Male and female offspring were weaned onto chow or Caf diet (2-3/sex/litter), forming four groups; behavioural and metabolic parameters were assessed. At weaning, offspring from Caf dams were smaller and lighter, but had more retroperitoneal (RP) fat, with a larger effect in males. Maternal Caf diet significantly increased relative expression of ACACA and Fasn in male and female weanling liver, but not CPT-1, SREBP and PGC1; PPARα was increased in males from Caf dams. Maternal obesity enhanced the impact of postweaning Caf exposure on adult body weight, RP fat, liver mass, and plasma leptin in males but not females. Offspring from Caf dams appeared to exhibit reduced anxiety-like behaviour on the elevated plus maze. Hepatic CPT-1 expression was reduced only in adult males from Caf fed dams. Post weaning Caf diet consumption did not alter liver gene expression in the adult offspring. Maternal obesity exacerbated the obesogenic phenotype produced by postweaning Caf diet in male, but not female offspring. Thus, the impact of maternal obesity on adiposity and liver gene expression appeared more marked in males. Our data underline the sex-specific detrimental effects of maternal obesity on offspring

Association of maternal serum PAPP-A levels, nuchal translucency and crown rump length in first trimester with adverse pregnancy outcomes: Retrospective cohort study.

OBJECTIVE: Are first trimester serum pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency (NT) and crown rump length (CRL) prognostic factors for adverse pregnancy outcomes? METHOD: Retrospective cohort women, singleton pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression, outcomes: small for gestational age (SGA), pre-eclampsia (PE), pre-term birth (PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND). RESULTS: 12,592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824 (14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths (0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91 (95% CI 0.85,0.97)] and stillbirth [ 0.71 (95% CI 0.52,0.98)] as PAPP-A increases. Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage [aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b) PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. CONCLUSIONS: PAPP-A, NT and CRL independent prognostic factor for adverse pregnancy outcomes, especially PAPP-A and SGA with lower PAPP-A associated with increased risk

Evidence of Altered Peripheral Nerve Function in a Rodent Model of Diet-Induced Prediabetes.

Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of prediabetes induced by a cafeteria (CAF) diet in Sprague-Dawley rats (n = 15 CAF versus n = 15 control). Neuropathy phenotyping included nerve conduction, tactile sensitivity, intraepidermal nerve fiber density (IENFD) and nerve excitability testing, an in vivo measure of ion channel function and membrane potential. Metabolic phenotyping included body composition, blood glucose and lipids, plasma hormones and inflammatory cytokines. After 13 weeks diet, CAF-fed rats demonstrated prediabetes with significantly elevated fasting blood glucose, insulin and impaired glucose tolerance as well as obesity and dyslipidemia. Nerve conduction, tactile sensitivity and IENFD did not differ; however, superexcitability was significantly increased in CAF-fed rats. Mathematical modeling demonstrated this was consistent with a reduction in sodium-potassium pump current. Moreover, superexcitability correlated positively with insulin resistance and adiposity, and negatively with fasting high-density lipoprotein cholesterol. In conclusion, prediabetic rats over-consuming processed, palatable foods demonstrated altered nerve function that preceded overt PN. This work provides a relevant model for pathophysiological investigation of diabetic complications

The Use of Calcium Sulfate and Calcium Phosphate Composite Graft to Augment Screw Purchase in Osteoporotic Ankles

ABSTRACT Background: Screws placed in the distal fibula may not have satisfactory purchase during internal fixation of an osteoporotic ankle fracture. Tibia-pro-fibula screws that extend from the fibula into the distal tibial metaphysis provide additional purchase. The purpose of this study was to investigate if purchase of these screws can be enhanced further by injecting calcium sulfate and calcium phosphate composite graft into the drill holes prior to insertion of the screws. Materials and Methods: Bone density was quantified using a DEXA scan in paired cadaver legs. One leg from each pair was randomly selected for injection of composite graft into the screw holes before insertion of the screws. Two screws were inserted through the fibula into the distal tibial metaphysis in each leg, at the level of the syndesmosis under fluoroscopy in a standardized fashion in an MTS machine. Results: After testing 4 pairs of cadaver legs, a statistically significant difference was noted in displacement (p = 0.018 distal, p = 0.0093 proximal), failure load, (p = 0.0185 distal, p = 0.0238 proximal), and failure energy (p = 0.0071 distal, p = 0.0115 proximal) between augmented and non-augmented screws, with the augmented screws being considerably stronger. Conclusion: Screws augmented with composite graft provide significantly greater purchase in an osteoporotic fibular fracture model. Clinical relevance: Composite graft augmented screws inserted into the distal tibia from the fibula may enhance the stability of internal fixation of an osteoporotic ankle fracture. This may enable earlier weightbearing and return to function which is important in elderly patients