Contemporary and Future Approaches to Precision Medicine in Inherited Cardiomyopathies: JACC Focus Seminar 3/5

Inherited cardiomyopathies are commonly occurring myocardial disorders that are associated with substantial morbidity and mortality. Clinical management strategies have focused on treatment of heart failure and arrhythmic complications in symptomatic patients according to standardized guidelines. Clinicians are now being urged to implement precision medicine, but what does this involve? Advances in understanding of the genetic underpinnings of inherited cardiomyopathies have brought new possibilities for interventions that are tailored to genes, specific variants, or downstream mechanisms. However, the phenotypic variability that can occur with any given pathogenic variant suggests that factors other than single driver gene mutations are often involved. This is propelling a new imperative to elucidate the nuanced ways in which individual combinations of genetic variation, comorbidities, and lifestyle may influence cardiomyopathy phenotypes. Here, Part 3 of a 5-part precision medicine Focus Seminar series reviews the current status and future opportunities for precision medicine in the inherited cardiomyopathies

Remotely Accessible Testbed for Software Defined Radio Development

Previous development testbeds have assumed that the developer was physically present in front of the hardware being used. No provision for remote operation of basic functions (power on/off or reset) was made, because the developer/operator was sitting in front of the hardware, and could just push the button manually. In this innovation, a completely remotely accessible testbed has been created, with all diagnostic equipment and tools set up for remote access, and using standardized interfaces so that failed equipment can be quickly replaced. In this testbed, over 95% of the operating hours were used for testing without the developer being physically present. The testbed includes a pair of personal computers, one running Linux and one running Windows. A variety of peripherals is connected via Ethernet and USB (universal serial bus) interfaces. A private internal Ethernet is used to connect to test instruments and other devices, so that the sole connection to the outside world is via the two PCs. An important design consideration was that all of the instruments and interfaces used stable, long-lived industry standards, such as Ethernet, USB, and GPIB (general purpose interface bus). There are no plug-in cards for the two PCs, so there are no problems with finding replacement computers with matching interfaces, device drivers, and installation. The only thing unique to the two PCs is the locally developed software, which is not specific to computer or operating system version. If a device (including one of the computers) were to fail or become unavailable (e.g., a test instrument needed to be recalibrated), replacing it is a straightforward process with a standard, off-the-shelf device

S-Band POSIX Device Drivers for RTEMS

This is a set of POSIX device driver level abstractions in the RTEMS RTOS (Real-Time Executive for Multiprocessor Systems real-time operating system) to SBand radio hardware devices that have been instantiated in an FPGA (field-programmable gate array). These include A/D (analog-to-digital) sample capture, D/A (digital-to-analog) sample playback, PLL (phase-locked-loop) tuning, and PWM (pulse-width-modulation)-controlled gain. This software interfaces to Sband radio hardware in an attached Xilinx Virtex-2 FPGA. It uses plug-and-play device discovery to map memory to device IDs. Instead of interacting with hardware devices directly, using direct-memory mapped access at the application level, this driver provides an application programming interface (API) offering that easily uses standard POSIX function calls. This simplifies application programming, enables portability, and offers an additional level of protection to the hardware. There are three separate device drivers included in this package: sband_device (ADC capture and DAC playback), pll_device (RF front end PLL tuning), and pwm_device (RF front end AGC control)

Integrated demultiplexing and amplification of coherent optical combs

The explosive growth of the internet during the last few decades has been enabled by two complementary innovations in optical communications: the use of multiple optical channels within a single optical fibre, and the increase in the bandwidth of individual channels to hundreds of Gbps. Further increases in overall bandwidth look to be provided by more spectrally efficient optical superchannels that use coherent sub-carriers generated using optical orthogonal frequency division multiplexing (OFDM). Yet, a cost effective way of generating these signals has not been demonstrated. One crucial, but missing piece is an effective means to separate the closely frequency spaced optical sub-carriers from the coherent optical comb before placing information on each sub-carrier, and thus creating the OFDM signal. Here, we demonstrate a flexible strategy implemented in a compact photonic integrated circuit (PIC) that is used to separate and amplify these sub-carriers using on-chip injection locking

Allocating the Burdens of Climate Action: Consumption-Based Carbon Accounting and the Polluter-Pays Principle

Action must be taken to combat climate change. Yet, how the costs of climate action should be allocated among states remains a question. One popular answer—the polluter-pays principle (PPP)—stipulates that those responsible for causing the problem should pay to address it. While intuitively plausible, the PPP has been subjected to withering criticism in recent years. It is timely, following the Paris Agreement, to develop a new version: one that does not focus on historical production-based emissions but rather allocates climate burdens in proportion to each state’s annual consumption-based emissions. This change in carbon accounting results in a fairer and more environmentally effective principle for distributing climate duties

Delivering HIV services in partnership: factors affecting collaborative working in a South African HIV programme

Abstract Background The involvement of Global Health Initiatives (GHIs) in delivering health services in low and middle income countries (LMICs) depends on effective collaborative working at scales from the local to the international, and a single GHI is effectively constructed of multiple collaborations. Research is needed focusing on how collaboration functions in GHIs at the level of health service management. Here, collaboration between local implementing agencies and departments of health involves distinct power dynamics and tensions. Using qualitative data from an evaluation of a health partnership in South Africa, this article examines how organisational power dynamics affected the operation of the partnership across five dimensions of collaboration: governance, administration, organisational autonomy, mutuality, and norms of trust and reciprocity. Results Managing the tension between the power to provide resources held by the implementing agency and the local Departments’ of Health power to access the populations in need of these resources proved critical to ensuring that the collaboration achieved its aims and shaped the way that each domain of collaboration functioned in the partnership. Conclusions These findings suggest that it is important for public health practitioners to critically examine the ways in which collaboration functions across the scales in which they work and to pay particular attention to how local power dynamics between partner organisations affect programme implementation

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Infant feeding knowledge, perceptions and practices among women with and without HIV in Johannesburg, South Africa: a survey in healthcare facilities

BACKGROUND: South Africa has a history of low breastfeeding rates among women with and without Human Immunodeficiency Virus (HIV). In this study, we assessed infant feeding knowledge, perceptions and practices among pregnant and postpartum women with and without HIV, in the context of changes in infant feeding and Prevention of Mother-to-Child Transmission of HIV (PMTCT) guidelines. METHODS: This was a cross-sectional survey conducted from April 2014 to March 2015 in 10 healthcare facilities in Johannesburg, South Africa. A total of 190 pregnant and 180 postpartum women (74 and 67, respectively, were HIV positive) were interviewed using a semi-structured questionnaire. Multiple regression analyses assessed factors associated with an intention to exclusively breastfeed, and exclusive breastfeeding of infants less than six months of age. RESULTS: Women with HIV had better overall knowledge on safe infant feeding practices, both in general and in the context of HIV infection. There were however gaps in knowledge among women with and without HIV. Information from healthcare facilities was the main source of information for all groups of women in the study. A greater percentage of women without HIV 80.9% (93/115), reported an intention to exclusively breastfeed, compared to 64.9% (48/74) of women with HIV, p = 0.014. Not having HIV was positively associated with a reported intention to breastfeed, Adjusted Odds Ratio (AOR) 3.60, 95% CI 1.50, 8.62. Other factors associated with a reported intention to exclusively breastfeed were prior breastfeeding experience and higher knowledge scores on safe infant feeding practices in the context of HIV infection. Among postpartum women, higher scores on general knowledge of safe infant feeding practices were positively associated with reported exclusive breastfeeding, AOR 2.18, 95% CI 1.52, 3.12. Most women perceived that it was difficult to exclusively breastfeed and that cultural factors were a barrier to exclusive breastfeeding. CONCLUSIONS: While a greater proportion of women are electing to breastfeed, HIV infection and cultural factors remain an important influence on safe infant feeding practices. Healthcare workers are the main source of information, and highlight the need for accurate and consistent messaging for both women with and without HIV