A natural history study of X-linked myotubular myopathy

Objective: To define the natural history of X-linked myotubular myopathy (MTM). Methods: We performed a cross-sectional study that included an online survey (n = 35) and a prospective, 1-year longitudinal investigation using a phone survey (n = 33). Results: We ascertained data from 50 male patients with MTM and performed longitudinal assessments on 33 affected individuals. Consistent with existing knowledge, we found that MTM is a disorder associated with extensive morbidities, including wheelchair (86.7% nonambulant) and ventilator (75% requiring >16 hours of support) dependence. However, unlike previous reports and despite the high burden of disease, mortality was lower than anticipated (approximate rate 10%/y). Seventy-six percent of patients with MTM enrolled (mean age 10 years 11 months) were alive at the end of the study. Nearly all deaths in the study were associated with respiratory failure. In addition, the disease course was more stable than expected, with few adverse events reported during the prospective survey. Few non–muscle-related morbidities were identified, although an unexpectedly high incidence of learning disability (43%) was noted. Conversely, MTM was associated with substantial burdens on patient and caregiver daily living, reflected by missed days of school and lost workdays. Conclusions: MTM is one of the most severe neuromuscular disorders, with affected individuals requiring extensive mechanical interventions for survival. However, among study participants, the disease course was more stable than predicted, with more individuals surviving infancy and early childhood. These data reflect the disease burden of MTM but offer hope in terms of future therapeutic intervention

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI

Do smallholder farmer-led seed systems have the capacity to supply good-quality, fungal-free sorghum seed?

Local seed systems that are developed, managed and maintained by farmers are a fundamental practice in smallholder crop production, supporting more than 80% of farmers in sub-Saharan Africa and feeding more than 70% of its population. The resilience of such systems is under threat from poverty, climate change, drought, increased pests and diseases, over-promotion of modern crop varieties, change of lifestyles and restrictive seed policies. The system continues to be maligned as having inferior quality, yet few studies support this assertion. This study aims to fll this research gap by evaluating 60 sorghum seed samples collected from smallholder farmers in Uzumba-MarambaPfungwe and Chimanimani districts of Zimbabwe. We investigated the efect of farmer-led seed management practices (e.g. seed acquisition and seed storage practices) on farm-derived sorghum seed quality (moisture, germination and fungal incidences). We found farmers using diverse seed sources and seed storage practices. Seeds were typically of good quality in that their storage moisture content was low, their germination was high, and fungal incidences were low. Seed sourced from local markets, non-governmental organizations and other farmers had germination and moisture standards that met the sorghum certifcation standards in Zimbabwe. However, few samples obtained from the relatives and government failed to meet the germination and/or moisture certifcation standards. We detected low incidences of fungi (Aspergillus favus, Aspergillus niger, Curvularia lunata, Fusarium sp. and Penicillium sp.) in sorghum seed samples tested and in particular Fusarium sp., which is the most economic important fungus in sorghum production. We conclude that farmer-led seed systems have the capacity to supply seeds of good quality and recommend that such systems should be recognized and promoted to meet the ever-evolving needs of smallholder farmers in sub-Saharan Africa

Impact of Firm Heterogeneity on Direct and Spillover Effects of FDI: Micro Evidence from Ten Transition Countries

This paper presents a comparative study of the importance of direct technology transfer and spillovers through FDI on a set of ten transition countries, using a common methodology and appropriate methods to account for selection and simultaneity correction. This paper considers by far the largest firm level dataset (more than 90,000 firms) used by any study on the spillover effects of FDI. The main novelty of the paper is the explicit control for various sources of firm heterogeneity when accounting for different effects of FDI on firm perfirmance. Controlling for these variables leads to some interesting results which contrast with the previous empirical work in the field. We find that horizontal spillovers have become increasingly important over the last decade, and they may even become more important than vertical spillovers. Furthfirmore, this work shows that the heterogeneity of firms in tfirms of absorptive capacity, size, productivity and technology levels affect the results. These findings suggest that both direct effects from foreign ownership as well as the spillovers from foreign firms substantially depend on the absorptive capacity and productivity level of individual firms. Only more productive firms and firms with higher absorptive capacities are able to both compete with foreign affiliates in the same sector and benefit from the increased upstream demand for intfirmediates generated by foreign affiliates. In addition, these results show that foreign presence may also affect smaller firms to a larger extent than larger firms, but this impact may be in either direction

Promotionalism, motivationalism and reasons to perform physically impossible actions

In this paper I grant the Humean premise that some reasons for action are grounded in the desires of the agents whose reasons they are. I then consider the question of the relation between the reasons and the desires that ground them. According to promotionalism, a desire that p grounds a reason to φ insofar as A’s φing helps promote p. According to motivationalism a desire that p grounds a reason to φ insofar as it explains why, in certain circumstances, A would be motivated to φ. I then give an argument favouring motivationalism, namely that promotionalism entails that agents have reasons to perform physically impossible actions, whereas motivationalism entails that there are no such reasons. Although this is a version of the ‘Too Many Reasons’ objection to promotionalism, I show that existing responses to that problem do not transfer to the case of reasons to perform physically impossible actions. In the penultimate section I consider and reject some objections to motivationalism made by promotionalists. The conclusion is that Humeans about reasons for action should prefer motivationalism