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Tay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 × 10

The Global Alliance for Surgical, Obstetric, Trauma and Anaesthesia Care (G4 Alliance, http://www.theg4alliance.org/) is thepreeminent global surgery advocacy organization (1) dedicated to eliminating disparities in surgical care around the world. A coalitionof over 60 non-profit organizations, professional societies, academic centers, and other groups, the G4 Alliance represents civil societyinterests in global surgery from the grassroots to the international level. The organization convenes its membership to address commoninterests and concerns, facilitates knowledge and resource sharing, builds consensus and alignment, and conducts outreach withmultilateral organizations, donors, and other global health programs and advocacy initiatives. In a sector characterized by diverseactors and fragmentation of care delivery, scholarship, and funding (2,3), the G4 Alliance provides communication and coordinationaround a common surgical and health system strengthening agenda. The purpose of this paper is to highlight the multiple organizationsthat specifically contribute to neurosurgical advocacy within the G4 Alliance.

BACKGROUND: The Health Information National Trends Survey (HINTS) is a probability-based, nationally representative survey conducted routinely to gather information about the American public’s cancer-related beliefs and behaviors, including the use of cancer-related information. HINTS was created to produce national estimates and has lacked the ability to create accurate and precise state and regional estimates. The motivation for this current work was to create state- and regional-level estimates using a national sample (HINTS) through standard calibration methods. Health estimates at a local level can inform policy decisions that better target the cancer needs within a community. Local-level data allow researchers an opportunity to examine local populations in finer detail without additional costly data collection. METHODS: By combining seven cycles of HINTS data from 2012–2018 and then raking the previously created person-level weights, we were able to create tables and maps of HINTS subnational survey estimates for key outcomes that have small variances and little potential bias. RESULTS AND CONCLUSION: This paper describes the methods used to harmonize and aggregate data across cycles, create state- and regional-level estimates from the pooled data, and produce survey weights for the pooled datasets. It demonstrates both the opportunities and the challenges of pooled data analysis.

Conventional aluminum nitride (AlN) template fabrication techniques, like hydride vapour phase epitaxy or AlN growth on patterned sapphire substrates, usually lead to step-bunched template surfaces. The resulting macrosteps cause emission broadening or even multiple-peak characteristics of ultraviolet light-emitting diodes (UV LEDs) fabricated on such AlN templates. In order to reduce these macrosteps and to provide a smoother surface, even without the need of a thick AlN deposition, a two-layer growth procedure is reported here. A three-dimensional (3D) – twodimensional (2D) sequential growth initiates a significant modification of the previous AlN surface morphology and simultaneously limits the evolving tensile strain. A primarily step-bunched surface with a surface roughness root mean square of 1.8 nm is successfully reduced by the two-layer growth procedure down to 0.8 nm, without any film cracking. This distinct roughness reduction of more than 50% is achieved within an AlN thickness of only 1.3 µm. With a smoother surface, the electroluminescence characteristic of a UV LED structure is substantially improved. Instead of a double-peak emission, typical for LEDs grown on step-bunched templates, a single-peak emission and lower spectral width were achieved, indicating the high potential of the suggested two-layer technique for improving performance.

Purpose: Despite the large impact heart disease has on morbidity and mortality, many are unaware of the risk factors and the steps they can take to reduce their own risk. Participation in clinical trials for discovering new approaches for the prevention and treatment of heart disease is important. This study sought to determine interest in participation in clinical trials of those diagnosed with heart disease and hypertension as compared to those without such diagnoses, and to assess associated sociodemographic characteristics of interest in participation Methods: Analyses were conducted using data from the 2014 administration of the National Cancer Institute's Health Information National Trends Survey . HINTS is a nationally-representative survey of the US adult (18+) population. The primary outcome of interest was whether respondents expressed interest in participating in research. Bivariate analyses were conducted initially to explore potential associations between sociodemographic factors and having had a diagnosis of hypertension or heart disease. Multivariate logistic regression was used to assess relationships between sociodemographic factors and outcomes, controlling for relevant sociodemographic characteristics and prior diagnosis of hypertension or heart attack. Weighted analyses were done to obtain population-level estimates. Findings: Of the 3,498 respondents, 1,569 (33.3%,) reported having a prior diagnosis of hypertension; 362 of 3,493 (7.0%,) respondents indicated that they had a previously diagnosed heart condition. Logistic regression showed that younger hypertensive participants had higher odds of being interested in participating in clinical trials as compared to those aged 75 years and older (OR = 3.62, 95% CI = 1.94-6.78). Those with regular care providers had higher odds of being interested in clinical trial participation compared to those without regular providers (OR = 1.51, 95% CI = 1.07-2.11). Likewise, younger participants aged 18-34 reporting heart conditions (OR = 3.58, 95% CI = 1.79-7.16) had higher odds of being interested in clinical trial participation compared to those aged 75 and older. No statistical differences were seen in clinical trial awareness, participation, or interest across race or gender. Conclusions: Participants who have a diagnosis of heart disease or hypertension and report being interested in engaging in clinical trial research are generally younger and have a regular health care provider. Therefore, behavioral intervention efforts should focus on translating clinical trial participation interest to participation in younger adults. Clinical trial recruitment efforts should also focus on unique methods to increase interest and subsequent trial enrollment in older adults and those without regularly provided care.

Students and teachers have much in common. The possibility for solidarity and an activist alliance between students and contingent faculty is possible because of their shared position of exploitation by corporate-style management. In order to create a strategic alliance between students and faculty certain conditions must be present: visionary proposals such as free higher education and the abolition of contingency must replace concessions and “fine-tuning”; political equality between students and teachers must replace paternalism and patronage; aggressive rhetorical strategies that place our struggles with the frameworks of corporatization and austerity should replace status-quo unionism. Participatory democracy and organizing must be taken seriously as the only way to revive representative structures. In order to realize our goals and principles, we need an action plan and a counter-narrative. We can build our political capacity by knitting together existing political forces into an effective community of interest dedicated to the public good.

After decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced-based argument for the fundamental role of surgery and anaesthesia within cost-effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.

A strategy for bonding water-rich hydrogels to diverse materials for electronic skins, energy storage, and soft optics is reported., Introducing methods for instant tough bonding between hydrogels and antagonistic materials—from soft to hard—allows us to demonstrate elastic yet tough biomimetic devices and machines with a high level of complexity. Tough hydrogels strongly attach, within seconds, to plastics, elastomers, leather, bone, and metals, reaching unprecedented interfacial toughness exceeding 2000 J/m2. Healing of severed ionic hydrogel conductors becomes feasible and restores function instantly. Soft, transparent multilayered hybrids of elastomers and ionic hydrogels endure biaxial strain with more than 2000% increase in area, facilitating soft transducers, generators, and adaptive lenses. We demonstrate soft electronic devices, from stretchable batteries, self-powered compliant circuits, and autonomous electronic skin for triggered drug delivery. Our approach is applicable in rapid prototyping and in delicate environments inaccessible for extended curing and cross-linking.

In article number 1500396, R. Moser and co‐workers free toy brinks from the playroom! The bricks form the basis of a tensile tester with a measurement accuracy on par with standard laboratory equipment. The tensile tester is found to be a powerful characterization tool for stretchable and flexible electronics for foldable and bendable smart appliances.

Toy bricks are an ideal platform for the cost-effective rapid prototyping of a tabletop tensile tester with measurement accuracy on par with expensive, commercially available laboratory equipment. Here, a tester is presented that is not only a versatile demonstration device in mechanics, electronics, and physics education and an eye-catcher on exhibitions, but also a powerful tool for stretchable electronics research. Following the "open-source movement" the build-up of the tester is described and all the details for easy reproduction are disclosed. A a new design of highly conformable all-elastomer based graded rigid island printed circuit boards is developed. Tough bonded to this elastomer substrate are imperceptible electronic foils bearing conductors and off-the-shelf microelectronics, paving the way for next generation smart electronic appliances.

Now that the necessary theory is clear, this chapter gives an overview of the measurement method and the actual build-up of the setup used. The approaches for the sample deformation along with the measurement and acquisition methods of the needed quantities for recording stress-strain and resistance-strain data are presented in detail.

This chapter provides an overview on the fundamental nature and the common methods to describe the behaviour of elastic materials, in particular rubber-like materials. First the term elasticity along with different simple forms of elastic deformation is illustrated. Secondly, mathematical models and different approaches for the description of elastic characteristics of materials are shown with the focus on rubber-like materials, being capable of large elastic deformations. The last part will deal with the experimental determination of fundamental elastic properties.

Now that the necessary theory of rubber-elasticty and the measurement method along with the design of the measurement setup was laid out, a few example measurements are shown in the following chapter. In particular the Young’s Modulus of polydimethylsiloxane (PDMS) with different degree of cross-linking and its dependence on the stretching velocity is determined with the methods explained in Section 2. The second part focusses on the electromechanical characterization of stretchable electrode films on PDMS.

Bolivia, one of the poorest countries in the world, ranks 108th on the 2013 Human Development Index. With approximately 1 neurosurgeon per 200,000 people, access to neurosurgery in Bolivia is a growing health concern. Furthermore, neurosurgery in nonindustrialized countries has been considered both cost-prohibitive and lacking in outcomes evaluation. A non-governmental organization (NGO) supports spinal procedures in Bolivia (Solidarity Bridge), and the authors sought to determine its impact and cost-effectiveness.In a retrospective review of prospectively collected data, 19 patients were identified prior to spinal instrumentation and followed over 12 months. For inclusion, patients required interviewing prior to surgery and during at least 2 follow-up visits. All causes of spinal pathology were included. Sixteen patients met inclusion criteria and were therefore part of the analysis. Outcomes measured included assessment of activities of daily living, pain, ambulation, return to work/school, and satisfaction. Cost-effectiveness was determined by cost-utility analysis. Utilities were derived using the Health Utilities Index. Complications were incorporated into an expected value decision tree.Median (± SD) preoperative satisfaction was 2.0 ± 0.3 (on a scale of 0-10), while 6-month postoperative satisfaction was 7 ± 1.4 (p0.0001). Ambulation, pain, and emotional disability data suggested marked improvement (56%, 69%, and 63%, respectively; p = 0.035, 0.003, and 0.006). Total discounted incremental quality-adjusted life year (QALY) gain was 0.771. The total discounted cost equaled $9036 (95% CI $8561-$10,740) at 2 years. Computing the incremental cost-effectiveness ratio resulted in a value of $11,720/QALY, ranging from $9220 to $15,473/QALY in a univariate sensitivity analysis.This NGO-supported spinal instrumentation program in Bolivia appears to be cost-effective, especially when compared with the conventional $50,000/QALY benchmark and the WHO endorsed country-specific threshold of $16,026/QALY. However, with a gross domestic product per capita in Bolivia equaling $4800 per year and 30.3% of the population living on less than $2 per day, this cost continues to appear unrealistic. Additionally, the study has several significant limitations, namely its limited sample size, follow-up period, the assumption that patients not receiving surgical intervention would not make any clinical improvement, the reliance on the NGO for patient selection and sustainable practices such as follow-up care and ancillary services, and the lack of a randomized prospective design. These limitations, as well as an unclear understanding of Bolivian willingness-to-pay data, affect the generalizability of the study findings and impede widespread economic policy reform. Because cost-effectiveness research may inevitably direct care decisions and prove that an effort such as this can be cost saving, a prospective, properly controlled investigation is now warranted.

Generally tritiated homoharringtonine ([3H]HHT, 150 microCi, 430 micrograms) was administered intravenously to seven patients at varying times before surgical resection of malignant brain tumor. Plasma, urine, cerebrospinal fluid (CSF), and tumor specimens were obtained during surgery, and the concentrations of HHT, its major metabolite, and [3H]HHT equivalent were determined chromatographically and radiochemically. For [3H]HHT equivalent, the concentration in tumor ranged from 0.6 to 4.3 ng/g and the ratio of tumor to plasma concentration from 0.5 to 1.8. In one patient who had CSF available for drug determination, the CSF to plasma ratio of total [3H]HHT was 0.3 at 45 minutes after drug administration and less than 0.2 ng/ml was unchanged HHT. For unchanged HHT, drug concentration in tumor ranged from undetectable (4 patients) to 1.8 ng/g. A major metabolite of HHT was detectable in the tumor specimens of all the patients. These results indicate that homoharringtonine can penetrate into brain tumors; in 3 patients with brain tumors, the ratios of HHT concentration in the tumor to that in the concurrent plasma were greater than one.