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Replacing sedentary behaviors during leisure time with active video gaming has been shown to be an enjoyable option for increasing physical activity. However, most off-the-shelf active video gaming controllers are not accessible or usable for individuals with mobility impairments. To address this requirement, a universal video game controller (called the GAIMplank) was designed and developed. This study aimed to assess the usability of the GAIMplank video game controller for playing PC video games among individuals with mobility impairments. Measures of enjoyment, perceived exertion, and qualitative data on the user experience were also examined. Adults (aged 18-75 years) with a mobility impairment were recruited to participate in a single testing session in the laboratory. Before testing began, basic demographic information, along with minutes of weekday and weekend physical activity, minutes of weekday and weekend video game play, and video game play experience were collected. The GAIMplank was mapped to operate as a typical joystick controller. Depending on their comfort and functional ability, participants chose to play seated in a chair, standing, or in their own manual wheelchair. Leaning movements of the trunk created corresponding action in the game (ie, lean right to move right). The participants played a total of 5 preselected video games for approximately 5 minutes each. Data were collected to assess the usability of the GAIMplank, along with self-efficacy regarding execution of game play actions, rating of perceived exertion and enjoyment for each game, and overall qualitative feedback. A total of 21 adults (n=15, 71% men; n=6, 29% women) completed the usability testing, with a mean age of 48.8 (SD 13.8; range 21-73) years. Overall, 38% (8/21) of adults played while standing, 33% (7/21) of adults played while seated in a chair, and 29% (6/21) played in their own manual wheelchair. Scores from the System Usability Scale indicated above average (74.8, SD 14.5) usability, with scores best for those who played seated in a chair, followed by those standing, and then individuals who played seated in their own wheelchairs. Inconsistencies in the responsiveness of the controller and general feedback for minor improvements were documented. Rating of perceived exertion scores ranged from light to moderate intensity, with the highest scores for those who played seated in a chair. Participants rated their experience with playing each game from above average to very enjoyable. The GAIMplank video game controller was found to be usable and accessible, providing an enjoyable option for light-to-moderate intensity exercise among adults with mobility impairments. Minor issues with inconsistencies in controller responsiveness were also recorded. Following further development and refinement, the next phase will include a pilot exercise intervention using the GAIMplank system.

The mammalian brain consists of millions to billions of cells that are organized into many cell types with specific spatial distribution patterns and structural and functional properties 1 – 3 . Here we report a comprehensive and high-resolution transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The cell-type atlas was created by combining a single-cell RNA-sequencing (scRNA-seq) dataset of around 7 million cells profiled (approximately 4.0 million cells passing quality control), and a spatial transcriptomic dataset of approximately 4.3 million cells using multiplexed error-robust fluorescence in situ hybridization (MERFISH). The atlas is hierarchically organized into 4 nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. We present an online platform, Allen Brain Cell Atlas, to visualize the mouse whole-brain cell-type atlas along with the single-cell RNA-sequencing and MERFISH datasets. We systematically analysed the neuronal and non-neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell-type organization in different brain regions—in particular, a dichotomy between the dorsal and ventral parts of the brain. The dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. Our study also uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types. Finally, we found that transcription factors are major determinants of cell-type classification and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole mouse brain transcriptomic and spatial cell-type atlas establishes a benchmark reference atlas and a foundational resource for integrative investigations of cellular and circuit function, development and evolution of the mammalian brain.  A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Beyond their role in horizontal gene transfer, conjugative plasmids commonly encode homologues of bacterial regulators. Known plasmid regulator homologues have highly targeted effects upon the transcription of specific bacterial traits. Here, we characterise a plasmid translational regulator, RsmQ, capable of taking global regulatory control in Pseudomonas fluorescens and causing a behavioural switch from motile to sessile lifestyle. RsmQ acts as a global regulator, controlling the host proteome through direct interaction with host mRNAs and interference with the host’s translational regulatory network. This mRNA interference leads to large-scale proteomic changes in metabolic genes, key regulators, and genes involved in chemotaxis, thus controlling bacterial metabolism and motility. Moreover, comparative analyses found RsmQ to be encoded on a large number of divergent plasmids isolated from multiple bacterial host taxa, suggesting the widespread importance of RsmQ for manipulating bacterial behaviour across clinical, environmental, and agricultural niches. RsmQ is a widespread plasmid global translational regulator primarily evolved for host chromosomal control to manipulate bacterial behaviour and lifestyle.

In this multicenter, placebo-controlled, randomized trial of intravenous magnesium sulfate in women at imminent risk for delivery between 24 and 31 weeks of gestation, magnesium sulfate did not significantly reduce the primary composite outcome of moderate or severe cerebral palsy or death. However, it did result in a reduced rate of cerebral palsy among survivors (a prespecified secondary outcome), which may suggest the possibility of benefit. In women at imminent risk for delivery between 24 and 31 weeks of gestation, magnesium sulfate did not significantly reduce the primary composite outcome of moderate or severe cerebral palsy or death. However, it did result in a reduced rate of cerebral palsy among survivors. Cerebral palsy is characterized by abnormal control of movement and posture that results in limitation of activity. It is caused by nonprogressive damage or dysfunction of the developing fetal or infant brain 1 and is a leading cause of chronic childhood disability, with profound medical, emotional, and economic consequences. 2 Preterm birth is a risk factor for cerebral palsy, and the magnitude of the risk is inversely correlated with gestational age at birth. 3 During the past 20 to 30 years, the survival of infants born markedly preterm has improved dramatically, and whereas some data suggest that the rate of cerebral palsy among . . .

Abstract Plasmids drive bacterial evolutionary innovation by transferring ecologically important functions between lineages, but acquiring a plasmid often comes at a fitness cost to the host cell. Compensatory mutations, which ameliorate the cost of plasmid carriage, promote plasmid maintenance in simplified laboratory media across diverse plasmid–host associations. Whether such compensatory evolution can occur in more complex communities inhabiting natural environmental niches where evolutionary paths may be more constrained is, however, unclear. Here, we show a substantial fitness cost of carrying the large conjugative plasmid pQBR103 in Pseudomonas fluorescens SBW25 in the plant rhizosphere. This plasmid fitness cost could be ameliorated by compensatory mutations affecting the chromosomal global regulatory system gacA/gacS, which arose rapidly in plant rhizosphere communities and were exclusive to plasmid carriers. These findings expand our understanding of the importance of compensatory evolution in plasmid dynamics beyond simplified lab media. Compensatory mutations contribute to plasmid survival in bacterial populations living within complex microbial communities in their environmental niche. Compensatory mutations reducing the cost of plasmid carriage occur in the plant rhizosphere.

The use of chemical grouts to stabilize soils adjacent to shafts, tunnels and excavations is a proven technique for providing increased strength and stiffness and permeability reductions in predominantly granular soils. Of the many types of grout, sodium silicate grouts are used in over 90% of chemical grouting applications. Current sodium silicate grouting technology applies sodium silicate grouts with organic reagents to provide greater control over grout placement. Analysis of the reaction chemistry of three organics; formamide, ethyl acetate and a combination of three dibasic esters known as DBE, with aqueous sodium silicate indicates that the organics theoretically function as a mechanism for silica gelation and should not chemically remain as part of the final silica gel. However, during the grout reaction, the organics are transformed into several organic by-products which are theoretically not bound to the silica gel. Leaching tests using laboratory prepared sodium silicate grout specimens have shown that between 70% and 90% (by mass) of the organics initially present within each specimen are released to leaching solutions. Microtox and Daphnia magna acute toxicity tests using leaching solutions for specimens containing the DBE reagent indicate that the released chemicals are only mildly toxic. Biodegradability tests showed that the DBE organics are highly aerobically biodegradable. A review of concepts pertinent to the transport of dissolved solutes from grouted soil is presented. Diffusion is identified as the dominant transport mechanism for the in-situ release of grout chemicals from sodium silicate grouted soil. Other traditional groundwater modeling parameters, including sorption, dispersion, and biodegradation will influence the transport of the chemical plumes after the release or leaching from the grouted soil. A laboratory testing program was used to measure these properties for chemically grouted soil. Large scale soil column tests were used to monitor the release and down-gradient transport of grout chemicals from DBE reagent specimens under hydraulic conditions similar to in-situ. Using data obtained from the experimental program, the computer based solute transport model, MT3D, was considered for its application to the data set. Several solutions provided reasonable results numerically, however, these results did not correlate with the observed laboratory data.

The 2004–05 eruption of Mount St Helens exhibited sustained, near-equilibrium behaviour characterized by relatively steady extrusion of a solid dacite plug and nearly periodic shallow earthquakes. Here we present a diverse data set to support our hypothesis that these earthquakes resulted from stick-slip motion along the margins of the plug as it was forced incrementally upwards by ascending, solidifying, gas-poor magma. We formalize this hypothesis with a dynamical model that reveals a strong analogy between behaviour of the magma–plug system and that of a variably damped oscillator. Modelled stick-slip oscillations have properties that help constrain the balance of forces governing the earthquakes and eruption, and they imply that magma pressure never deviated much from the steady equilibrium pressure. We infer that the volcano was probably poised in a near-eruptive equilibrium state long before the onset of the 2004–05 eruption. Rumbling on The explosive eruption of Mount St Helens in May 1980 was an extraordinary event, triggered in part by a massive landslide that rapidly depressurized volatile-rich magma. More typical of the history of this volcano is the less energetic eruption that began in October 2004 and is still going on. This eruption is building a new lava dome inside the volcanic crater, accompanied by periodic shallow earthquakes and low emissions of steam, volcanic gases and ash. In this issue a multidisciplinary team of scientists presents a detailed report on the current eruption and shows that the eruption quickly settled into persistent near-equilibrium behaviour. Numerical modelling suggests that the near-periodic earthquakes observed are linked mechanistically to the solid-state extrusion that is rebuilding the dome. On the cover, a view of the volcano from the northwest, photographed on 8 June 2005 by John S. Pallister of the US Geological Survey.

Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further \"how\" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 × 10 −12 ), and reduced proenkephalin (PENK), a surrogate marker for the state of striatal medium spiny neurons (FDR = 2.6 × 10 −3 ), accompanied by brain atrophy, predominantly in the caudate (FDR = 5.5 × 10 −10 ) and putamen (FDR = 1.2 × 10 −9 ). Longitudinal increase in somatic CAG repeat expansion ratio (SER) in blood was a significant predictor of subsequent caudate (FDR = 0.072) and putamen (FDR = 0.148) atrophy. Atypical loss of interruption HTT repeat structures, known to predict earlier age at clinical motor diagnosis, was associated with substantially faster caudate and putamen atrophy. We provide evidence in living humans that the influence of CAG length on HD neuropathology is mediated by somatic CAG repeat expansion. These critical mechanistic insights into the earliest neurodegenerative changes will inform the design of preventative clinical trials aimed at modulating somatic expansion. ClinicalTrials.gov registration: NCT06391619 . A comprehensive longitudinal analysis of individuals with preclinical Huntington’s disease identifies biomarkers of neurodegeneration and somatic expansion in blood DNA, detectable years before symptom onset.