Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations

Hominin reactions to herbivore distribution in the Lower Palaeolithic of the Southern Levant

We explore the relationship between the edaphic potential of soils and the mineral properties of the underlying geology as a means of mapping the differential productivity of different areas of the Pleistocene landscape for large herbivores. These factors strongly control the health of grazing animals irrespective of the particular types of vegetation growing on them, but they have generally been neglected in palaeoanthropological studies in favour of a more general emphasis on water and vegetation, which provide an incomplete picture. Taking the Carmel-Galilee-Golan region as an example, we show how an understanding of edaphic potential provides insight into how animals might have exploited the environment. In order to simplify the analysis, we concentrate on the Lower Palaeolithic period and the very large animals that dominate the archaeofaunal assemblages of this period. Topography and the ability of soils to retain water also contribute to the differential productivity and accessibility of different regions and to patterns of seasonal movements of the animals, which are essential to ensure a supply of healthy fodder throughout the year, especially for large animals such as elephants, which require substantial regions of good grazing and browsing. Other animals migrating in groups have similar needs. The complex topography of the Southern Levant with frequent sudden and severe changes in gradient, and a wide variety of landforms including rocky outcrops, cliffs, gorges, and ridges, places major limits on these patterns of seasonal movements. We develop methods of mapping these variables, based on the geology and our substantial field experience, in order to create a framework of landscape variation that can be compared with the locations and contents of archaeological sites to suggest ways in which early hominins used the variable features of the landscape to target animal prey, and we extend the analysis to the consideration of smaller mammals that were exploited more intensively after the disappearance of the elephants. We consider some of the ways in which this regional-scale approach can be further tested and refined, and advocate the development of such studies as an essential contribution to understanding the wider pattern of hominin dispersal

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH)

Development of LEU-based targets for radiopharmaceutical manufacturing: A review

Mo is an essential medical isotope that comprises of at least 70% of radioactive procedures globally. Currently an essential component of 99 Mo manufacturing is the uranium target from which 99 Mo is produced by fission. As the world moves towards low enriched uranium (LEU) targets due to non-proliferation concerns it is becoming of interest to find methods to increase the efficiency of the LEU targets in order to reduce the ever increasing nuclear waste levels of which a long term solution for disposal or treatment has yet to be satisfactorily found. Advantages and disadvantages of various target designs are investigated and discussed along current disposal and reprocessing methods. The idea of a reusable target is introduced as a way forward in reducing the nuclear waste burden for future generations