Laser Welding of a Stent

We consider the problem of modelling the manufacture of a cylindrical Stent, in which layers of a plastic material are welded together by a Laser beam. We firstly set up the equations for this system and solve them by using a Finite Element method. We then look at various scalings which allow the equations to be simplified. The resulting equations are then solved analytically to obtain approximate solutions to the radial temperature profile and the averaged axial temperature profile

Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass

Type 2 diabetes (T2D) is characterized by β cell dysfunction and loss. Single nucleotide polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide association studies, lead to impaired β cell function. While deletion of the homologous murine Tcf7l2 gene throughout the developing pancreas leads to impaired glucose tolerance, deletion in the β cell in adult mice reportedly has more modest effects. To inactivate Tcf7l2 highly selectively in β cells from the earliest expression of the Ins1 gene (∼E11.5) we have therefore used a Cre recombinase introduced at the Ins1 locus. Tcfl2fl/fl::Ins1Cre mice display impaired oral and intraperitoneal glucose tolerance by 8 and 16 weeks, respectively, and defective responses to the GLP-1 analogue liraglutide at 8 weeks. Tcfl2fl/fl::Ins1Cre islets displayed defective glucose- and GLP-1-stimulated insulin secretion and the expression of both the Ins2 (∼20%) and Glp1r (∼40%) genes were significantly reduced. Glucose- and GLP-1-induced intracellular free Ca2+ increases, and connectivity between individual β cells, were both lowered by Tcf7l2 deletion in islets from mice maintained on a high (60%) fat diet. Finally, analysis by optical projection tomography revealed ∼30% decrease in β cell mass in pancreata from Tcfl2fl/fl::Ins1Cre mice. These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of β cell function and mass, serving as an important regulator of gene expression and islet cell coordination. The possible relevance of these findings for the action of TCF7L2 polymorphisms associated with Type 2 diabetes in man is discusse

A Novel Drill Set for the Enhancement and Assessment of Robotic Surgical Performance

Background: There currently exist several training modules to improve performance during video-assisted surgery. The unique characteristics of robotic surgery make these platforms an inadequate environment for the development and assessment of robotic surgical performance. Methods: Expert surgeons (n=4) (greater than 50 clinical robotic procedures and greater than 2 years of clinical robotic experience) were compared to novice surgeons (n=17) (less than 5 clinical cases and limited laboratory experience) using the da Vinci Surgical System. Seven drills were designed to simulate clinical robotic surgical tasks. Performance score was calculated by the equation Time to Completion + (minor error) x 5 + (major error) x 10. The Robotic Learning Curve (RLC) was expressed as a trend line of the performance scores corresponding to each repeated drill. Results: Performance scores for experts were better than novices in all 7 drills (p less than 0.05). The RLC for novices reflected an improvement in scores (p less than 0.05). In contrast, experts demonstrated a flat RLC for 6 drills and an improvement in one drill (p=0.027). Conclusion: This new drill set provides a framework for performance assessment during robotic surgery. The inclusion of particular drills and their role in training robotic surgeons of the future awaits larger validation studies

Structural basis of paralog-specific KDM2A/B nucleosome recognition

The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic patch recognition proteome wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. Despite fundamental roles in transcriptional repression in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any related JumonjiC (JmjC) domain lysine demethylase, remain unclear. We used a covalent conjugate between H3K36 and a demethylase inhibitor to solve cryogenic electron microscopy structures of KDM2A and KDM2B trapped in action on a nucleosome substrate. Our structures show that KDM2-nucleosome binding is paralog specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation

FLIM FRET Technology for Drug Discovery: Automated Multiwell-Plate High-Content Analysis, Multiplexed Readouts and Application in Situ**

A fluorescence lifetime imaging (FLIM) technology platform intended to read out changes in Förster resonance energy transfer (FRET) efficiency is presented for the study of protein interactions across the drug-discovery pipeline. FLIM provides a robust, inherently ratiometric imaging modality for drug discovery that could allow the same sensor constructs to be translated from automated cell-based assays through small transparent organisms such as zebrafish to mammals. To this end, an automated FLIM multiwell-plate reader is described for high content analysis of fixed and live cells, tomographic FLIM in zebrafish and FLIM FRET of live cells via confocal endomicroscopy. For cell-based assays, an exemplar application reading out protein aggregation using FLIM FRET is presented, and the potential for multiple simultaneous FLIM (FRET) readouts in microscopy is illustrated

The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium

BACKGROUND: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes. HYPOTHESIS: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018. RESULTS: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without (P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days (P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) (P = .592). CONCLUSION: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery

Training Programmes Can Change Behaviour and Encourage the Cultivation of Over-Harvested Plant Species

Cultivation of wild-harvested plant species has been proposed as a way of reducing over-exploitation of wild populations but lack of technical knowledge is thought to be a barrier preventing people from cultivating a new species. Training programmes are therefore used to increase technical knowledge to encourage people to adopt cultivation. We assessed the impact of a training programme aiming to encourage cultivation of xaté (Chamaedorea ernesti-augusti), an over-harvested palm from Central America. Five years after the training programme ended, we surveyed untrained and trained individuals focusing on four potential predictors of behaviour: technical knowledge, attitudes (what individuals think about a behaviour), subjective norms (what individuals perceive others to think of a behaviour) and perceived behavioural control (self assessment of whether individuals can enact the behaviour successfully). Whilst accounting for socioeconomic variables, we investigate the influence of training upon these behavioural predictors and examine the factors that determine whether people adopt cultivation of a novel species. Those who had been trained had higher levels of technical knowledge about xaté cultivation and higher belief in their ability to cultivate it while training was not associated with differences in attitudes or subjective norms. Technical knowledge and perceived behavioural control (along with socio-economic variables such as forest ownership and age) were predictors of whether individuals cultivate xaté. We suggest that training programmes can have a long lasting effect on individuals and can change behaviour. However, in many situations other barriers to cultivation, such as access to seeds or appropriate markets, will need to be addressed

Integrated continuous process design for crystallisation, spherical agglomeration, and filtration of lovastatin

Purpose This work seeks to improve the particle processability of needle-like lovastatin crystals and develop a small-footprint continuous MicroFactory for its production. Methods General conditions for optimal spherical agglomeration of lovastatin crystals and subsequent product isolation are developed, first as batch processes, and then transferred to continuous MicroFactory operation. Results Methyl isobutyl ketone is a suitable bridging liquid for the spherical agglomeration of lovastatin. Practical challenges including coupling unit operations and solvent systems; mismatched flow rates and inconsistent suspension solid loading were resolved. The successful continuous production of lovastatin spherical agglomerates (D50 = 336 µm) was achieved. Spherical agglomeration increased the density of the bulk lovastatin powder and improved product flowability from poor to good, whilst maintaining lovastatin tablet performance. Conclusion A continuous, integrated MicroFactory for the crystallisation, spherical agglomeration, and filtration of lovastatin is presented with improved product particle processability. Up to 16,800 doses of lovastatin (60 mg) can be produced per day using a footprint of 23 m2

Hippocampus Shape Analysis and Late-Life Depression

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F1,103 = 5.26; p = 0.0240) but not right hippocampus volume (F1,103 = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms

Detailed description of Division I ice hockey concussions: Findings from the NCAA and Department of Defense CARE Consortium

Objective: Since concussion is the most common injury in ice hockey, the objective of the current study was to elucidate risk factors, specific mechanisms, and clinical presentations of concussion in men's and women's ice hockey. Methods: Ice hockey players from 5 institutions participating in the Concussion Assessment, Research, and Education Consortium were eligible for the current study. Participants who sustained a concussion outside of this sport were excluded. There were 332 (250 males, 82 females) athletes who participated in ice hockey, and 47 (36 males, 11 females) who sustained a concussion. Results: Previous concussion (odds ratio (OR) = 2.00; 95% confidence interval (95% CI): 1.02‒3.91) was associated with increased incident concussion odds, while wearing a mouthguard was protective against incident concussion (OR = 0.43; 95%CI: 0.22‒0.85). Overall, concussion mechanisms did not significantly differ between sexes. There were specific differences in how concussions presented clinically across male and female ice hockey players, however. Females (9.09%) were less likely than males (41.67%) to have a delayed symptom onset (p = 0.045). Additionally, females took significantly longer to reach asymptomatic (p = 0.015) and return-to-play clearance (p = 0.005). Within the first 2 weeks post-concussion, 86.11% of males reached asymptomatic, while only 45.50% of females reached the same phase of recovery. Most males (91.67%) were cleared for return to play within 3 weeks of their concussion, compared to less than half (45.50%) of females. Conclusion: The current study proposes possible risk factors, mechanisms, and clinical profiles to be validated in future concussions studies with larger female sample sizes. Understanding specific risk factors, concussion mechanisms, and clinical profiles of concussion in collegiate ice hockey may generate ideas for future concussion prevention or intervention studies