Clinical applications of custom-made vaginal cylinders constructed using three-dimensional printing technology.

PurposeThree-dimensional (3D) printing technology allows physicians to rapidly create customized devices for patients. We report our initial clinical experience using this technology to create custom applicators for vaginal brachytherapy.Material and methodsThree brachytherapy patients with unique clinical needs were identified as likely to benefit from a customized vaginal applicator. Patient 1 underwent intracavitary vaginal cuff brachytherapy after hysterectomy and chemotherapy for stage IA papillary serous endometrial cancer using a custom printed 2.75 cm diameter segmented vaginal cylinder with a central channel. Patient 2 underwent interstitial brachytherapy for a vaginal cuff recurrence of endometrial cancer after prior hysterectomy, whole pelvis radiotherapy, and brachytherapy boost. We printed a 2 cm diameter vaginal cylinder with one central and six peripheral catheter channels to fit a narrow vaginal canal. Patient 3 underwent interstitial brachytherapy boost for stage IIIA vulvar cancer with vaginal extension. For more secure applicator fit within a wide vaginal canal, we printed a 3.5 cm diameter solid cylinder with one central tandem channel and ten peripheral catheter channels. The applicators were printed in a biocompatible, sterilizable thermoplastic.ResultsPatient 1 received 31.5 Gy to the surface in three fractions over two weeks. Patient 2 received 36 Gy to the CTV in six fractions over two implants one week apart, with interstitial hyperthermia once per implant. Patient 3 received 18 Gy in three fractions over one implant after 45 Gy external beam radiotherapy. Brachytherapy was tolerated well with no grade 3 or higher toxicity and no local recurrences.ConclusionsWe established a workflow to rapidly manufacture and implement customized vaginal applicators that can be sterilized and are made of biocompatible material, resulting in high-quality brachytherapy for patients whose anatomy is not ideally suited for standard, commercially available applicators

HELPING TEACHERS UN-STRUCTURE: A PROMISING APPROACH

The amount of overt structure in the presentation of a task affects students’ engagement, creativity, and willingness to tolerate frustration. In a professional development project, with algebra teachers from nine American schools, we tried to help teachers make judicious decisions in their use of structure by having them facilitate low-structure tasks, remove structure from overly structured tasks, and observe “at-risk” students engaged in learning through low-structure tasks. Project schools that worked on structuring generally improved their algebra passing rates, both overall and for African-American students

The epidemiology of chronic kidney disease (CKD) in rural East Africa: A population-based study.

BackgroundChronic kidney disease (CKD) may be common among individuals living in sub-Saharan Africa due to the confluence of CKD risk factors and genetic predisposition.MethodsWe ascertained the prevalence of CKD and its risk factors among a sample of 3,686 participants of a population-based HIV trial in rural Uganda and Kenya. Prevalent CKD was defined as a serum creatinine-based estimated glomerular filtration rate <60 mL/min/1.73m2 or proteinuria (urine dipstick ≥1+). We used inverse-weighting to estimate the population prevalence of CKD, and multivariable log-link Poisson models to assess the associations of potential risk factors with CKD.ResultsThe estimated CKD prevalence was 6.8% (95% CI 5.7-8.1%) overall and varied by region, being 12.5% (10.1-15.4%) in eastern Uganda, 3.9% (2.2-6.8%) in southwestern Uganda and 3.7% (2.7-5.1%) in western Kenya. Risk factors associated with greater CKD prevalence included age ≥60 years (adjusted prevalence ratio [aPR] 3.5 [95% CI 1.9-6.5] compared with age 18-29 years), HIV infection (aPR 1.6 [1.1-2.2]), and residence in eastern Uganda (aPR 3.9 [2.6-5.9]). However, two-thirds of individuals with CKD did not have HIV, diabetes, or hypertension as risk factors. Furthermore, we noted many individuals who did not have proteinuria had dipstick positive leukocyturia or hematuria.ConclusionThe prevalence of CKD is appreciable in rural East Africa and there are considerable regional differences. Conventional risk factors appear to only explain a minority of cases, and leukocyturia and hematuria were common, highlighting the need for further research into understanding the nature of CKD in sub-Saharan Africa

Growing a list

It is easy to find expert knowledge on the Internet on almost any topic, but obtaining a complete overview of a given topic is not always easy: Information can be scattered across many sources and must be aggregated to be useful. We introduce a method for intelligently growing a list of relevant items, starting from a small seed of examples. Our algorithm takes advantage of the wisdom of the crowd, in the sense that there are many experts who post lists of things on the Internet. We use a collection of simple machine learning components to find these experts and aggregate their lists to produce a single complete and meaningful list. We use experiments with gold standards and open-ended experiments without gold standards to show that our method significantly outperforms the state of the art. Our method uses the clustering algorithm Bayesian Sets even when its underlying independence assumption is violated, and we provide a theoretical generalization bound to motivate its use.

Analysis of Neptune's 2017 Bright Equatorial Storm

We report the discovery of a large ($\sim$8500 km diameter) infrared-bright storm at Neptune's equator in June 2017. We tracked the storm over a period of 7 months with high-cadence infrared snapshot imaging, carried out on 14 nights at the 10 meter Keck II telescope and 17 nights at the Shane 120 inch reflector at Lick Observatory. The cloud feature was larger and more persistent than any equatorial clouds seen before on Neptune, remaining intermittently active from at least 10 June to 31 December 2017. Our Keck and Lick observations were augmented by very high-cadence images from the amateur community, which permitted the determination of accurate drift rates for the cloud feature. Its zonal drift speed was variable from 10 June to at least 25 July, but remained a constant $237.4 \pm 0.2$ m s$^{-1}$ from 30 September until at least 15 November. The pressure of the cloud top was determined from radiative transfer calculations to be 0.3-0.6 bar; this value remained constant over the course of the observations. Multiple cloud break-up events, in which a bright cloud band wrapped around Neptune's equator, were observed over the course of our observations. No "dark spot" vortices were seen near the equator in HST imaging on 6 and 7 October. The size and pressure of the storm are consistent with moist convection or a planetary-scale wave as the energy source of convective upwelling, but more modeling is required to determine the driver of this equatorial disturbance as well as the triggers for and dynamics of the observed cloud break-up events.Comment: 42 pages, 14 figures, 6 tables; Accepted to Icaru

Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders

Mechanics of the tricuspid valve: from clinical diagnosis/treatment, in vivo and in vitro investigations, to patient-specific biomechanical modeling

Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent undesired backflow of blood from the right ventricle into the right atrium during systole. Various treatment options are currently available for FTR; however, research for the tricuspid heart valve, functional tricuspid regurgitation, and the relevant treatment methodologies are limited due to the pervasive expectation among cardiac surgeons and cardiologists that FTR will naturally regress after repair of left-sided heart valve lesions. Recent studies have focused on (i) understanding the function of the TV and the initiation or progression of FTR using both in-vivo and in-vitro methods, (ii) quantifying the biomechanical properties of the tricuspid valve apparatus as well as its surrounding heart tissue, and (iii) performing computational modeling of the TV to provide new insight into its biomechanical and physiological function. This review paper focuses on these advances and summarizes recent research relevant to the TV within the scope of FTR. Moreover, this review also provides future perspectives and extensions critical to enhancing the current understanding of the functioning and remodeling tricuspid valve in both the healthy and pathophysiological states