Impact of the English Directly Enhanced Service (DES) for Learning Disability

Final Report to the Department of Healt

Re-engineering the Multimission Command System at the Jet Propulsion Laboratory

The Operations Engineering Lab (OEL) at JPL has developed the multimission command system as part of JPL's Advanced Multimission Operations System. The command system provides an advanced multimission environment for secure, concurrent commanding of multiple spacecraft. The command functions include real-time command generation, command translation and radiation, status reporting, some remote control of Deep Space Network antenna functions, and command file management. The mission-independent architecture has allowed easy adaptation to new flight projects and the system currently supports all JPL planetary missions (Voyager, Galileo, Magellan, Ulysses, Mars Pathfinder, and CASSINI). This paper will discuss the design and implementation of the command software, especially trade-offs and lessons learned from practical operational use. The lessons learned have resulted in a re-engineering of the command system, especially in its user interface and new automation capabilities. The redesign has allowed streamlining of command operations with significant improvements in productivity and ease of use. In addition, the new system has provided a command capability that works equally well for real-time operations and within a spacecraft testbed. This paper will also discuss new development work including a multimission command database toolkit, a universal command translator for sequencing and real-time commands, and incorporation of telecommand capabilities for new missions

Selective hydrogenation of nitro compounds to amines by coupled redox reactions over a heterogeneous biocatalyst

Cleaner synthesis of amines remains a key challenge in organic chemistry because of their prevalence in pharmaceuticals, agrochemicals and synthetic building blocks. Here, we report a different paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. The hydrogenase enzyme releases electrons from H2 to a carbon black support which facilitates nitro-group reduction. For 30 nitroarenes we demonstrate full conversion (isolated yields 78 – 96%), with products including pharmaceuticals benzocaine, procainamide and mesalazine, and 4-aminophenol – precursor to paracetamol (acetaminophen). We also showcase gram-scale synthesis of procainamide with 90% isolated yield. We demonstrate potential for extension to aliphatic substrates. The catalyst is highly selective for reduction of the nitro group over other unsaturated bonds, tolerant to a wide range of functional groups, and exhibits excellent stability in reactions lasting up to 72 hours and full reusability over 5 cycles with a total turnover number over 1 million, indicating scope for direct translation to fine chemical manufacturing

Improving the Reporting of Primary Care Research: An International Survey of Researchers

PURPOSE: To assess opportunities to improve reporting of primary care (PC) research to better meet the needs of its varied users. METHODS: International, interprofessional online survey of PC researchers and users, 2018 to 2019. Respondents used Likert scales to rate frequency of difficulties in interpreting, synthesizing, and applying PC research reports. Free-text short answers were categorized by template analysis to record experiences, concerns, and suggestions. Areas of need were checked across existing reporting guidelines. RESULTS: Survey yielded 255 respondents across 24 nations, including 138 women (54.1%), 169 physicians (60%), 32 scientists (11%), 20 educators (7%), and 18 public health professionals (6%). Overall, 37.4% indicated difficulties using PC research reports "50% or more of the time." The most common problems were synthesizing findings (58%) and assessing generalizability (42%). Difficulty was reported by 49% for qualitative, 46% for mixed methods, and 38% for observational research. Most users wanted richer reporting of theoretical foundation (53.7%); teams, roles, and organization of care (53.4%); and patient involvement in the research process (52.7%). Few reported difficulties with ethics or disclosure of funding or conflicts. Free-text answers described special challenges in reporting PC research: context of clinical care and setting; practical details of interventions; patient-clinician and team relationships; and generalizability, applicability and impact in the great variety of PC settings. Cross-check showed that few current reporting guidelines focus on these needs. CONCLUSIONS: Opportunities exist to improve the reporting of PC research to make it more useful for its many users, suggesting a role for a PC research reporting guideline

Where there is no hospital: improving the notification of community deaths

Globally, an estimated two-thirds of all deaths occur in the community, the majority of which are not attended by a physician and remain unregistered. Identifying and registering these deaths in civil registration and vital statistics (CRVS) systems, and ascertaining the cause of death, is thus a critical challenge to ensure that policy benefits from reliable evidence on mortality levels and patterns in populations. In contrast to traditional processes for registration, death notification can be faster and more efficient at informing responsible government agencies about the event and at triggering a verbal autopsy for ascertaining cause of death. Thus, innovative approaches to death notification, tailored to suit the setting, can improve the availability and quality of information on community deaths in CRVS systems.; Here, we present case studies in four countries (Bangladesh, Colombia, Myanmar and Papua New Guinea) that were part of the initial phases of the Bloomberg Data for Health Initiative at the University of Melbourne, each of which faces unique challenges to community death registration. The approaches taken promote improved notification of community deaths through a combination of interventions, including integration with the health sector, using various notifying agents and methods, and the application of information and communication technologies. One key factor for success has been the smoothing of processes linking notification, registration and initiation of a verbal autopsy interview. The processes implemented champion more active notification systems in relation to the passive systems commonly in place in these countries.; The case studies demonstrate the significant potential for improving death reporting through the implementation of notification practices tailored to a country's specific circumstances, including geography, cultural factors, structure of the existing CRVS system, and available human, information and communication technology resources. Strategic deployment of some, or all, of these innovations can result in rapid improvements to death notification systems and should be trialled in other settings

Is there sufficient Ensifer and Rhizobium species diversity in UK farmland soils to support red clover (Trifolium pratense), white clover (T. repens), lucerne (Medicago sativa) and black medic (M. lupulina)?

Rhizobia play important roles in agriculture owing to their ability to fix nitrogen through a symbiosis with legumes. The specificity of rhizobia-legume associations means that underused legume species may depend on seed inoculation with their rhizobial partners. For black medic (Medicago lupulina) and lucerne (Medicago sativa) little is known about the natural prevalence of their rhizobial partner Ensifer meliloti in UK soils, so that the need for inoculating them is unclear. We analysed the site-dependence of rhizobial seed inoculation effects on the subsequent ability of rhizobial communities to form symbioses with four legume species (Medicago lupulina, M. sativa, Trifolium repens and T. pratense). At ten organic farms across the UK, a species-diverse legume based mixture (LBM) which included these four species was grown. The LBM seed was inoculated with a mix of commercial inocula specific for clover and lucerne. At each site, soil from the LBM treatment was compared to the soil sampled prior to the sowing of the LBM (the control). From each site and each of the two treatments, a suspension of soils was applied to seedlings of the four legume species and grown in axenic conditions for six weeks. Root nodules were counted and their rhizobia isolated. PCR and sequencing of a fragment of the gyrB gene from rhizobial isolates allowed identification of strains. The number of nodules on each of the four legume species was significantly increased when inoculated with soil from the LBM treatment compared to the control. Both the proportion of plants forming nodules and the number of nodules formed varied significantly by site, with sites significantly affecting the Medicago species but not the Trifolium species. These differences in nodulation were broadly reflected in plant biomass where site and treatment interacted; at some sites there was a significant advantage from inoculation with the commercial inoculum but not at others. In particular, this study has demonstrated the commercial merit of inoculation of lucerne with compatible rhizobia

Diversity of epidemiological transition in the Pacific: Findings from the application of verbal autopsy in Papua New Guinea and the Solomon Islands.

BACKGROUND: Cause of death data are essential for rational health planning yet are not routinely available in Papua New Guinea (PNG) and Solomon Islands. Indirect estimation of cause of death patterns suggests these populations are epidemiologically similar, but such assessments are not based on direct evidence. METHODS: Verbal autopsy (VA) interviews were conducted at three sites in PNG and nationwide in Solomon Islands. Training courses were also facilitated to improve data from medical certificates of cause of death (MCCODs) in both countries. Data were categorised into broad groups of endemic and emerging conditions to aid assessment of the epidemiological transition. FINDINGS: Between 2017 and 2020, VAs were collected for 1,814 adult deaths in PNG and 819 adult deaths in Solomon Islands. MCCODs were analysed for 662 deaths in PNG and 1,408 deaths in Solomon Islands. The VA data suggest lower NCD mortality (48.8% versus 70.3%); higher infectious mortality (27.0% versus 18.3%) and higher injury mortality (24.5% versus 11.4%) in PNG compared to Solomon Islands. Higher infectious mortality in PNG was evident for both endemic and emerging infections. Higher NCD mortality in Solomon Islands reflected much higher emerging NCDs (43.6% vs 21.4% in PNG). A similar pattern was evident from the MCCOD data. INTERPRETATION: The cause of death patterns suggested by VA and MCCOD indicate that PNG is earlier in its epidemiological transition than Solomon Islands, with relatively higher infectious mortality and lower NCD mortality. Injury mortality was also particularly high in PNG.This study was funded by Bloomberg Philanthropies

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

BACKGROUND: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown. METHODS: We performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm(2), n = 319) and high (> 1.11 g/cm(2), n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections. RESULTS: Based on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm(2)) and 138 females with high (>1.04 g/cm(2)) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD. CONCLUSION: This study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18